Metadate ER

Psychostimulants, Methylphenidate Derivatives
Stimulant Narcolepsy Agents

Oral Administration Oral Solid Formulations

Methylin chewable tablets: Administer 30 to 45 minutes before meals in divided doses 2 to 3 times daily. Chewable tablets should be taken with at least 8 ounces of fluid to avoid choking. Twice-daily dosages may be administered in the morning and around noon. Individualized timing of the midday dose is usually necessary, as determined by the loss of positive drug effect, which occurs 2 to 6 hours after the morning dose. Administer the last dose of the day prior to 6 PM.[45982]
Immediate-release dosage forms (Ritalin, Methylin, Metadate, generic equivalents): Administer 30 to 45 minutes before meals in divided doses 2 to 3 times daily. Twice-daily dosages may be administered in the morning and around noon. Individualized timing of the midday dose is usually necessary, as determined by the loss of positive drug effect, which occurs 2 to 6 hours after the morning dose. Administer the last dose of the day prior to 6 PM.[28518]
Extended-release tablets (Ritalin SR, Metadate ER, generic methylphenidate ER): May be administered without regard to meals. Administer whole; do not cut, crush, or chew. Extended-release tablets have a duration of action of approximately 8 hours. Administer the last dose of the day several hours before bedtime.[28518]
Once-daily extended-release tablets (Concerta, Relexxii): Administer once daily in the morning with an adequate amount of fluid. May be administered without regard to meals. Administer whole; do not cut, crush, or chew. The biologically inert portion of this tablet may appear intact in the stool; this is normal.[33387]
Once-daily extended-release capsules (Metadate CD, Ritalin LA, Aptensio XR): May be administered without regard to meals; however, the manufacturer of Aptensio XR recommends that patients establish a routine pattern with regard to meals. Administer with an adequate amount of fluid. Do not cut, crush, or chew. If swallowing is difficult, the capsule may be opened, and the contents gently sprinkled on 1 tablespoon of applesauce and swallowed immediately. The capsule contents (beads) should not be crushed or chewed.[31289] [34475] [59540] Instruct the patient to drink fluids (e.g., water, milk, or juice) after the intake of the sprinkles with applesauce.[34475]
The Institute for Safe Medication Practices states the capsule contents of Metadate CD and Ritalin LA may be administered via a nasogastric tube as long as they are not crushed and an adequate amount of fluid is used to wash the full dose down the tube.[53771]
Once-daily extended-release chewable tablets (QuilliChew ER): Administer once daily in the morning with or without food. The 10 mg and 15 mg doses can be achieved by breaking in half the scored 20 mg and 30 mg tablets, respectively.[60401]
Once-daily extended-release orally disintegrating tablets (Cotempla XR-ODT): Administer once daily in the morning consistently either with or without food. Do not remove tablet from the blister pack until just prior to dosing; use dry hands when opening the blister pack. Remove the tablet by peeling back the foil; do not push the tablet through the foil. Place the whole tablet on the tongue and allow it to disintegrate without chewing or crushing. No liquid is needed to take the tablet.[62034]
Once-daily extended-release capsules (Jornay PM): Administer once daily in the evening consistently either with or without food. Initiate dosing at 8:00 PM and adjust the timing of administration between 6:30 PM and 9:30 PM to optimize tolerability and efficacy the next morning and throughout the day. If a dose is missed, advise the patient to take it as soon as it's remembered that same evening. If a patient remembers the missed dose the next morning, skip the dose and do not give until the next scheduled evening administration. If swallowing is difficult, the capsule may be opened and the contents gently sprinkled on applesauce and swallowed immediately. Do not crush or chew the capsule contents (beads).[63424]
Once-daily extended-release capsules (Adhansia XR): Administer once daily in the morning consistently either with or without food. Do not cut, crush, or chew. If swallowing is difficult, the capsule may be opened, and the contents gently sprinkled on 1 tablespoon of applesauce or yogurt and swallowed immediately or within 10 minutes. If not consumed within 10 minutes after mixing, it should be discarded and not stored. The capsule contents (beads) should be taken in its entirety without chewing. The single dose capsules should not be divided.[63983]

Oral Liquid Formulations

Immediate-release oral solution (Methylin)
Measure methylphenidate dosage with an oral syringe or calibrated measuring device.
Administer 30 to 45 minutes before meals in divided doses 2 to 3 times daily. Twice-daily dosages may be administered in the morning and around noon. Individualized timing of the midday dose is usually necessary, as determined by the loss of positive drug effect which occurs 2 to 6 hours after the morning dose. Administer the last dose of the day prior to 6 PM.
 
Once-daily extended-release oral suspension (Quillivant XR)
Vigorously shake the bottle of suspension for a minimum of 10 seconds.
Measure dosage with the calibrated oral dosing dispenser provided.
Administer in the morning without regard to meals.
 
Reconstitution of once-daily extended-release oral suspension (Quillivant XR)
Review the manufacturer's reconstitution instructions for the particular product and package size.
Prior to reconstitution, tap the bottle several times to loosen the powder.
To prepare the suspension, add the specified amount of water to the bottle, fully insert the bottle adapter into the bottle neck, replace the cap, and vigorously shake the bottle for at least 10 seconds.
Storage: Store reconstituted suspension at 77 degrees F; dispense in original packaging (bottle in container). The reconstituted suspension is stable for 4 months from date of reconstitution.

Topical Administration Transdermal Patch Formulations

Daytrana transdermal system:
Patch should be applied 2 hours before the effect is needed.
Do not cut or trim patch.
Apply patch immediately after opening the pouch and removing protective liner. Do not use if pouch seal is broken. Do not touch the adhesive side of the patch during application to avoid absorption of methylphenidate. Wash hands immediately if adhesive side of the patch is touched. Discard the patch if difficulty is encountered in separating the patch from the release liner, or if tearing or other damage occurs. Discard patch if adhesive containing medication has transferred to the liner during removal of the patch from the liner.
Place on a dry, clean area of the hip and hold in place for 30 seconds with the palm of the hand. Do not apply to oily, damaged, or irritated skin. Do not apply topical preparations to the application site immediately prior to patch application. Avoid the waistline area where the patch could be rubbed by clothing.
Applications sites should be alternated from one hip to the next each day, avoiding sites where a patch was recently placed, when possible.
Instruct patient on proper application and disposal of patch. Adherence of the patch may be affected by showering, bathing, or swimming. The carton contains an administration chart that can help the patient monitor application and removal time, which the patient and/or caregiver should be encouraged to use. If a patch was removed without the caregiver's knowledge, or if a patch is missing from the tray, the caregiver should be encouraged to ask the child when and how the patch was removed.
Avoid exposing the application site to hair dryers, heating pads, electric blankets, heated water beds, or other direct external heat sources. The rate and extent of absorption of methylphenidate are significantly increased during application of heat to the patch during use. Temperature-dependent increases in absorption may be greater than 2-fold, potentially resulting in overdose.
Do not apply or re-apply the patch with dressings, tape, or adhesives. If the patch is not fully adhered to the skin during application or wear time, discard the patch according to disposal instructions and apply a new patch.
The total daily wear time should not exceed 9 hours, regardless of patch replacement.
Patches should be peeled off slowly. Patch removal may be aided by applying an oil-based product (i.e., petroleum jelly, mineral oil, olive oil) to the patch edges and gently working the oil underneath the edges of the patch.
Disposal: Instruct patient and/or caregiver to fold used patches, so that the adhesive side of the patch adheres to itself, and then flush it down the toilet or dispose of in an appropriate lidded container. If the patient stops using the prescription, each unused patch should be removed from its pouch, separated from the protective liner, folded onto itself, and flushed down the toilet or disposed of in an appropriate lidded container. Do not flush pouch and protective liner down the toilet. Instead, dispose of them in an appropriate container with a lid.

Severe

stroke / Early / 0-1.0
myocardial infarction / Delayed / 0-1.0
neuroleptic malignant syndrome / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
seizures / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
vasculitis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
pancytopenia / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
visual impairment / Early / Incidence not known
serotonin syndrome / Delayed / Incidence not known

Moderate

sinus tachycardia / Rapid / 0.7-8.0
palpitations / Early / 2.0-3.1
depression / Delayed / 1.7-1.7
constipation / Delayed / 1.4-1.4
confusion / Early / 1.2-1.2
physiological dependence / Delayed / 0-1.0
contact dermatitis / Delayed / 0.3-0.3
psychosis / Early / 0.1-0.1
blurred vision / Early / 1.7
euphoria / Early / Incidence not known
migraine / Early / Incidence not known
teeth grinding (bruxism) / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
mania / Early / Incidence not known
hostility / Early / Incidence not known
supranormalization / Delayed / Incidence not known
hallucinations / Early / Incidence not known
dyskinesia / Delayed / Incidence not known
angina / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypertension / Early / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
erythema / Early / Incidence not known
bullous rash / Early / Incidence not known
chemical leukoderma / Delayed / Incidence not known
skin erosion / Delayed / Incidence not known
atopic dermatitis / Delayed / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
skin ulcer / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
dyspnea / Early / Incidence not known
priapism / Delayed / Incidence not known
hot flashes / Early / Incidence not known
tolerance / Delayed / Incidence not known
psychological dependence / Delayed / Incidence not known
withdrawal / Early / Incidence not known

Mild

insomnia / Early / 2.0-41.0
anorexia / Delayed / 1.7-35.0
headache / Early / 2.4-22.2
emotional lability / Early / 2.0-22.0
abdominal pain / Early / 4.0-15.0
xerostomia / Early / 3.0-14.0
nausea / Early / 3.8-13.0
vomiting / Early / 1.7-13.0
weight loss / Delayed / 3.0-12.0
irritability / Delayed / 6.0-11.0
anxiety / Delayed / 2.0-8.2
dizziness / Early / 0-6.7
hyperactivity / Early / 0-5.0
restlessness / Early / 2.0-3.1
diarrhea / Early / 3.0-3.0
back pain / Delayed / 0-3.0
pharyngitis / Delayed / 0-3.0
dyspepsia / Early / 2.2-2.2
agitation / Early / 2.0-2.2
infection / Delayed / 0-2.2
fever / Early / 2.0-2.2
vertigo / Early / 1.7-2.0
rash / Early / 2.0-2.0
ocular pain / Early / 0-2.0
cough / Delayed / 1.9-1.9
libido decrease / Delayed / 1.7-1.7
paresthesias / Delayed / 0-1.2
tremor / Early / 2.0
drowsiness / Early / Incidence not known
asthenia / Delayed / Incidence not known
fatigue / Early / Incidence not known
lethargy / Early / Incidence not known
syncope / Early / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
purpura / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
skin irritation / Early / Incidence not known
xerosis / Delayed / Incidence not known
skin hypopigmentation / Delayed / Incidence not known
ecchymosis / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
mydriasis / Early / Incidence not known
diplopia / Early / Incidence not known
sinusitis / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known

Alcoholism, potential for overdose or poisoning, substance abuse

Central nervous system (CNS) stimulants, such as methylphenidate, have a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction.[28518] [31289] [32121] [33387] [34475] [51955] [59540] [60401] [62034] Caution is recommended in patients with a known history of substance abuse, including alcoholism.[28518] [31289] [32121] [33387] [34475] [51955] [59540] [60401] [62034] Assess each individual's risk for abuse, misuse, or addiction before prescribing a CNS stimulant, and monitor for the development of these behaviors or conditions throughout treatment.[28518] [31289] [32121] [33387] [34475] [51955] [59540] [60401] [62034] Children and adolescents with attention-deficit hyperactivity disorder (ADHD) are more prone to substance abuse compared to those without ADHD, and those with co-occurring mental health conditions (e.g., depression, disruptive behavior disorders) are at even greater risk; however, appropriate treatment of ADHD with medication and behavior therapy may reduce the risk of developing a substance abuse disorder.The American Academy of Pediatrics recommends an active substance abuse disorder be treated appropriately before beginning stimulant medication. In patients with well-documented ADHD that predates the onset of substance abuse, a careful risk/benefit assessment must be conducted and appropriate consultation (e.g., a psychiatrist or addiction specialist) is suggested. To reduce the risk of substance abuse in patients who are prescribed stimulants, prescribers should take special care to 1.) confirm an accurate diagnosis of ADHD, 2.) screen older children and adolescents for use of alcohol, marijuana, and other drugs, 3.) provide age-appropriate anticipatory guidance (e.g., discuss proper medication use, risk of misuse, diversion, and abuse, safe storage of medication, appropriate transition to self-administration in older children), and 4.) carefully document and monitor prescription records closely.[57647] Prescribing and dispensing the smallest appropriate quantity may help to minimize abuse, misuse, and overdosage. CNS stimulants can be diverted for non-medical use into illicit channels or distribution. The most common source of non-medical use is sharing from family or friends with misuse of the patient's own prescription or obtaining from illicit channels occurring less frequently. Sharing of CNS stimulant medications can lead to substance abuse disorder and addiction in those they are shared with. Misuse and abuse of CNS stimulants can result in potential for overdose or poisoning and death; the risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Educate patients and their families about these risks, proper storage, and proper disposal of any unused medication. Misuse or abuse may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with stimulant abuse or misuse.[28518] [31289] [32121] [33387] [34475] [51955] [59540] [60401] [62034]

Adhansia XR, Aptensio XR, Concerta, Cotempla XR, Daytrana, Jornay, Metadate CD, Metadate ER, Methylin, QuilliChew ER, Quillivant XR, RELEXXII, Ritalin, Ritalin LA, Ritalin SR

Rx, schedule II

CNS stimulant chemically similar to but with milder peripheral sympathomimetic actions than amphetamines
Used for attention-deficit hyperactivity disorder (ADHD) and narcolepsy
Pediatric patients with structural heart defects, cardiomyopathy, or heart-rhythm disturbances may be at risk for adverse cardiac events

For the treatment of attention-deficit hyperactivity disorder (ADHD). For once-daily product dosing. Oral dosage (extended-release once-daily tablets; Concerta, Relexxii) Adults up to 65 years not currently taking methylphenidate

Initially, 18 to 36 mg PO once daily in the morning. Dose may be increased by 18 mg increments at weekly intervals. Max: 72 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.[33387]

Adults up to 65 years currently taking 10 to 15 mg/day methylphenidate

Initially, 18 mg PO once daily in the morning. Dose may be increased by 18 mg increments at weekly intervals. Max: 72 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Adults up to 65 years currently taking 20 to 30 mg/day methylphenidate

Initially, 36 mg PO once daily in the morning. Dose may be increased by 18 mg increments at weekly intervals. Max: 72 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Adults up to 65 years currently taking 30 to 45 mg/day methylphenidate

Initially, 54 mg PO once daily in the morning. Dose may be increased by 18 mg increments at weekly intervals. Max: 72 mg/day. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug. 

Adults up to 65 years currently taking 40 to 60 mg/day methylphenidate

72 mg PO once daily in the morning. Max: 72 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older not currently taking methylphenidate

Initially, 18 mg PO once daily in the morning. Dose may be increased by 18 mg increments at weekly intervals. A 27-mg tablet is available for prescribers who wish to utilize a dosage between 18 and 36 mg. FDA-approved Max: 54 mg/day in children and 72 mg/day (not to exceed 2 mg/kg/day) in adolescents; however, some experts recommend doses up to 108 mg, which may be appropriate in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older currently taking 10 to 15 mg/day methylphenidate

Initially, 18 mg PO once daily in the morning. Titrate dose by 18 mg increments at weekly intervals as needed. A 27-mg tablet is available for patients who may benefit from a dosage between 18 and 36 mg. FDA-approved Max: 54 mg/day in children and 72 mg/day (not to exceed 2 mg/kg/day) in adolescents; however, some experts recommend doses up to 108 mg, which may be appropriate in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older currently taking 20 to 30 mg/day methylphenidate

Initially, 36 mg PO once daily in the morning. Titrate dose by 18 mg increments at weekly intervals as needed. FDA-approved Max: 54 mg/day in children and 72 mg/day (not to exceed 2 mg/kg/day) in adolescents; however, some experts recommend doses up to 108 mg, which may be appropriate in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older currently taking 30 to 45 mg/day methylphenidate

Initially, 54 mg PO once daily in the morning. Titrate dose by 18 mg increments at weekly intervals as needed and as clinically appropriate. FDA-approved Max: 54 mg/day in children and 72 mg/day (not to exceed 2 mg/kg/day) in adolescents; however, some experts recommend doses up to 108 mg, which may be appropriate in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Adolescents currently taking 40 to 60 mg/day methylphenidate

Initially, 72 mg PO once daily in the morning. While the FDA-approved maximum dosage is 72 mg/day (not to exceed 2 mg/kg/day), some experts recommend doses up to 108 mg, which may be appropriate in patients weighing more than 50 kg. Titrate dosage by 18 mg increments no more frequently than weekly intervals as clinically appropriate. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily capsules; Metadate CD) Adults not currently taking methylphenidate

Initially, 20 mg PO once daily in the morning. When in the judgment of the clinician a lower dosage is indicated for initial treatment, it is recommended that patients begin treatment with an immediate-release product first. Dose may be increased by 10 to 20 mg increments at weekly intervals. Max: 60 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Adults currently taking other dosage forms of methylphenidate

Initially, 20 mg PO once daily in the morning. Alternatively, give an equivalent total daily dosage as the previous methylphenidate product PO once daily, rounded to the closest available capsule size. For example, patients already taking 10 mg of immediate-release methylphenidate twice daily (20 mg/day) should start with 20 mg Metadate CD once daily; those taking 20 mg twice daily (40 mg/day) should start with 40 mg Metadate CD once daily. Dose may be increased by 10 to 20 mg increments at weekly intervals. Max: 60 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older not currently taking methylphenidate

Initially, 20 mg PO once daily in the morning. Dose may be increased by 10 to 20 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts recommend doses up to 100 mg/day for patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older currently taking other dosage forms of methylphenidate

Initially, 20 mg PO once daily in the morning. Alternatively, give no more than the equivalent total daily dose of the previous methylphenidate product, rounded to the nearest available capsule size, PO once daily. For example, patients already taking 10 mg of immediate-release methylphenidate twice daily (20 mg/day) should start with 20 mg Metadate CD once daily; those taking 20 mg twice daily (40 mg/day) could start with 40 mg Metadate CD once daily. Dose may be increased by 10 to 20 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts recommend doses up to 100 mg/day for patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily capsules; Ritalin LA) Adults not currently taking methylphenidate

Initially, 20 mg PO once daily in the morning. If a lower initial dose is desired, patients may begin treatment with 10 mg PO once daily. Dose may be increased by 10 mg increments at weekly intervals. Max: 60 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Adults currently taking other dosage forms of methylphenidate

Initially, give no more than the total daily dosage of the previous methylphenidate product PO once daily in the morning. Dose may be increased by 10 mg increments at weekly intervals. Max: 60 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older not currently taking methylphenidate

Initially, 20 mg PO once daily in the morning. If a lower initial dose is desired, 10 mg PO once daily may be used. Dose may be increased by 10 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts recommend doses up to 100 mg/day in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older currently taking other dosage forms of methylphenidate

Initially, give no more than the total daily dosage of the previous methylphenidate product PO once daily in the morning. For example, patients already taking 10 mg of immediate-release methylphenidate twice daily (20 mg/day) should start with 20 mg Ritalin LA once daily; those taking 20 mg of extended-release methylphenidate once daily (20 mg/day) should also start with 20 mg of Ritalin LA once daily. Dose may be increased by 10 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts recommend doses up to 100 mg/day in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily capsules; Aptensio XR) Children and Adolescents 6 years and older

Initially, 10 mg PO once daily in the morning. Dose may be increased by 10 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts have recommended doses up to 100 mg/day of other methylphenidate formulations in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily chewable tablets; QuilliChew ER) Children and Adolescents 6 years and older

Initially, 20 mg PO once daily in the morning. Dose may be titrated up or down in increments of 10 mg, 15 mg, or 20 mg at weekly intervals. The 10 mg and 15 mg doses can each be achieved by breaking in half the functionally scored 20 mg and 30 mg tablets, respectively. FDA-approved Maximum: 60 mg/day PO; however, some experts have recommended doses up to 100 mg/day of other methylphenidate formulations in patients weighing more than 50 kg. If switching from another methylphenidate product, discontinue that treatment and titrate with QuilliChew ER as previously described; do not substitute QuilliChew ER for other methylphenidate products on a mg-for-mg basis. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily suspension; Quillivant XR) Children and Adolescents 6 years and older

Initially, 20 mg PO once daily in the morning. Dose may be increased by 10 to 20 mg increments at weekly intervals. FDA-approved Max: 60 mg/day; however, some experts have recommended doses up to 100 mg/day of other methylphenidate formulations in patients weighing more than 50 kg. If switching from another methylphenidate product, discontinue that treatment and titrate with Quillivant XR as previously described; do not substitute Quillivant XR for other methylphenidate products on a mg-for-mg basis. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release orally disintegrating tablets; Cotempla XR-ODT) Children and Adolescents 6 years and older

Initially, 17.3 mg PO once daily in the morning; take consistently with or without food. Dose may be increased by 8.6 to 17.3 mg increments at weekly intervals. FDA-approved Max: 51.8 mg/day. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Transdermal dosage (transdermal system; Daytrana) Children and Adolescents 6 years and older

Initially, apply a 10 mg/9-hour patch topically once daily in the morning, 2 hours before an effect is needed, regardless of previous methylphenidate therapy. If response is not maximized after 1 week, titrate to the next available patch strength in weekly intervals. The suggested upward titration schedule is Week 1: apply 10 mg/9-hour patch once daily; Week 2: apply 15 mg/9-hour patch once daily; Week 3: apply 20 mg/9-hour patch once daily; Week 4: apply 30 mg/9-hour patch once daily. Dose titration, final dosage, and wear time should be individualized according to the needs and response of the patient. Maximum: 30 mg/9-hour patch once daily. In clinical trials, there was no additional benefit of increasing the patch dose from 20 mg/9-hours to 30 mg/9-hours. Remove the patch 9 hours after application or may remove earlier if late day side effects appear and shorter duration of effect is desired.

Oral dosage (extended-release once-daily capsules; Jornay PM) Adults up to 65 years

Initially, 20 mg PO once daily in the evening. Dose may be titrated in increments of 20 mg at weekly intervals. Max: 100 mg/day. If switching from another methylphenidate product, discontinue that treatment and titrate with Jornay PM as previously described; do not substitute Jornay PM for other methylphenidate products on a mg-for-mg basis. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older

Initially, 20 mg PO once daily in the evening. Dose may be titrated in increments of 20 mg at weekly intervals. Max: 100 mg/day. If switching from another methylphenidate product, discontinue that treatment and titrate with Jornay PM as previously described; do not substitute Jornay PM for other methylphenidate products on a mg-for-mg basis. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or discontinue the drug.

Oral dosage (extended-release once-daily capsules; Adhansia XR) Adults

Initially, 25 mg PO once daily in the morning. Dose may be titrated in increments of 10 to 15 mg at intervals of no less than 5 days. Max: 100 mg/day. Although 100 mg was efficacious in short-term controlled trials, dosages above 85 mg daily were associated with a disproportionate increase in the incidence of certain adverse reactions. If switching from another methylphenidate product, discontinue that treatment and titrate with Adhansia XR as previously described; do not substitute Adhansia XR for other methylphenidate products on a mg-for-mg basis.[63983] Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or discontinue the drug.[63983]

Children and Adolescents 6 years and older

Initially, 25 mg PO once daily in the morning. Dose may be titrated in increments of 10 to 15 mg at intervals of no less than 5 days. Max: 85 mg/day. Although 85 mg was efficacious in short-term controlled trials, dosages above 70 mg daily were associated with a disproportionate increase in the incidence of certain adverse reactions. If switching from another methylphenidate product, discontinue that treatment and titrate with Adhansia XR as previously described; do not substitute Adhansia XR for other methylphenidate products on a mg-for-mg basis.[63983] Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose.[31591] If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or discontinue the drug.[63983]

Oral dosage (immediate-release preparations; Ritalin, Methylin, Methylin oral solution, Methylin chewable tablets) Adults

Average effective dose is 20 to 30 mg/day PO divided and given in 2 to 3 divided doses 30 to 45 minutes before meals. Range: 10 to 60 mg/day PO. Patients who are unable to sleep if medication is taken late in the day should take the last dose before 6 pm.

Children and Adolescents 6 years and older

Initially, 5 mg PO twice daily before breakfast and lunch. Dose may be increased by 5 to 10 mg/day at weekly intervals; some patients may require dosing up to 3 times daily (administer last dose of day before 6 pm to limit sleep interference). Max: 60 mg/day per FDA-approved labeling; however, some experts state that doses up to 100 mg/day may be needed in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If no improvement within 1 month, discontinue methylphenidate and consider an alternative treatment/therapy. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children 3 to 5 years†

The National Institute of Mental Health's Preschool ADHD Treatment Study (PATS) provides clinical guidance for children with ADHD 3 to 5 years of age. In the PATS, the initial dose of immediate-release methylphenidate was 1.25 mg PO 3 times daily. Doses were increased gradually up to a maximum of 10 mg PO 3 times daily to reach optimum therapeutic response. The mean optimal total daily dose was 14.2 +/- 8.1 mg (0.7 +/- 0.4 mg/kg/day). Max: 30 mg/day. In all cases, treatment should start with a low dose and be titrated upward slowly. Use lowest effective dose. Higher doses have lead to social withdrawal in some children. Behavior therapy, parental training, and a structured preschool environment are considered first line treatment for preschool-aged children with ADHD; lack of significant improvement with such modalities may warrant the addition of methylphenidate.

Oral dosage (extended-release tablets; Ritalin SR, Metadate ER, Methylin ER) Adults

The extended-release (ER) tablets have a duration of action of approximately 8 hours. Use in place of immediate-release (IR) tablets when the 8-hour dosage of these ER tablets corresponds to the previously titrated 8-hour dosage of the IR tablets. Max: 20 mg PO 3 times daily. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

Children and Adolescents 6 years and older

The extended-release (ER) tablets have a duration of action of approximately 8 hours. Use in place of immediate-release (IR) tablets when the 8-hour dosage of the ER tablets corresponds to the previously titrated 8-hour dosage of the IR tablets. Alternatively, some experts recommend an initial dose of 10 mg PO once daily. Ritalin SR may be administered once or twice daily. Max: 60 mg/day per FDA-approved labeling; however, some experts state that doses up to 100 mg/day may be needed in patients weighing more than 50 kg. Individualize dosage based on psychosocial and comorbid factors; use lowest effective dose. If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage or discontinue the drug.

For the treatment of narcolepsy. Oral dosage (immediate-release formulations; e.g., Ritalin, Methylin) Adults

Average dose 20 to 30 mg/day; range 10 to 60 mg/day PO in 2 to 3 divided doses, 30 to 45 minutes before meals. Patients who are unable to sleep if medication is taken late in the day should take the last dose before 6 p.m.

Children and Adolescents 6 years and older

Initially, 5 mg PO twice daily before breakfast and lunch. May increase by 5 to 10 mg/day PO at weekly intervals. Max: 60 mg/day.

Oral dosage (extended-release tablets; e.g., Ritalin SR, Metadate ER) Adults, Adolescents, and Children 6 years and older

The extended-release (ER) tablets have a duration of action of approximately 8 hours. Therefore, use in place of immediate-release (IR) tablets when the 8-hour dosage of the ER tablets corresponds to the previously titrated 8-hour dosage of the IR tablets. Max: 60 mg/day.

For the treatment of major depression† or post-stroke depression refractory to other therapies.
NOTE: The use of stimulants for the treatment of depressive disorders is usually limited to treatment-refractory cases or when standard medical therapies are not tolerated. Stimulants may aggravate coexisting anxiety or agitation in depressed patients.
Oral dose (immediate-release tablets) Adults

Initially, 2.5 mg PO twice daily administered in the morning and at noon; increase by 2.5—5 mg PO every 2 or 3 days as tolerated, until the desired response is achieved. Roughly 50% of patients appear to respond to treatment.

Geriatric

Initially, 2.5 mg PO twice daily administered in the morning and at noon; increase by 2.5—5 mg PO every 2 or 3 days as tolerated, until the desired response is achieved. Dosage in elderly patients with post-stroke depression has ranged from 15—40 mg/day PO after dosage titration for a mean of 15 days. Roughly 50% of patients appear to respond to treatment.

†Indicates off-label use

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Renal clearance is not an important predictor of methylphenidate clearance.

Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acebutolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of dihydrocodeine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Aliskiren: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including aliskiren. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including aliskiren. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alpha-blockers: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Amantadine: (Moderate) Use of amantadine with methylphenidate derivatives, which are CNS stimulants, requires careful observation. Coadministration may increase the risk of stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias.
Ambrisentan: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with methylphenidate derivatives and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Methylphenidate derivatives may increase the risk of seizures.
Amiloride: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Amlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Atorvastatin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Benazepril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Celecoxib: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Olmesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amoxapine: (Moderate) Methylphenidate derivatives and amoxapine may lower the seizure threshold; therefore, caution is particularly advisable when this combination is administered to patients susceptible to seizures. In addition, methylphenidate is thought to exert some of its beneficial effects through dopamine re-uptake blockade while amoxapine has central dopamine antagonist properties. In theory, the therapeutic effects of either agent may be reduced.
Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Angiotensin II: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Angiotensin-converting enzyme inhibitors: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Apomorphine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Armodafinil: (Major) The use of armodafinil with other psychostimulants, including methylphenidate derivatives, has not been studied. Patients receiving combination therapy of armodafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related side effects.
Articaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Aspirin, ASA; Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Atenolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Azilsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Benazepril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Beta-blockers: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Betaxolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
Bisoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Brimonidine; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bromocriptine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Brompheniramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Bumetanide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Bupivacaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Buprenorphine: (Moderate) If concomitant use of buprenorphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Bupropion; Naltrexone: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Caffeine; Sodium Benzoate: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Calcium-channel blockers: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Canagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Canagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Candesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Captopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Carbamazepine: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Carbidopa; Levodopa; Entacapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Carteolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Carvedilol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Celecoxib; Tramadol: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Chlordiazepoxide; Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Chlorpheniramine; Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) If concomitant use of dihydrocodeine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Chlorpheniramine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Citalopram: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Clevidipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Clomipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Clonidine: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Phenylephrine; Promethazine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Codeine; Promethazine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
COMT inhibitors: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Dapagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Desflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Desipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Desvenlafaxine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Dextromethorphan; Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Diltiazem: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
dopamine agonists: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Dopamine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dorzolamide; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Doxazosin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Doxepin: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Droxidopa

: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dulaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Duloxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Empagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Linagliptin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Enalapril, Enalaprilat: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Entacapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Ephedrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Ephedrine; Guaifenesin: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Eplerenone: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as eplerenone.
Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Eprosartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Ergotamine; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Ertugliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Escitalopram: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and methylphenidate or its derivatives. Coadministration of psychostimulants, such as methylphenidates, with esketamine may increase blood pressure, including the possibility of hypertensive crisis.
Esmolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Ethacrynic Acid: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Ethanol: (Major) Alcohol consumption should be avoided during treatment with certain extended-release (ER) dosage forms of methylphenidate (e.g., Ritalin LA, Metadate CD). Results from an in vitro study showed that at an alcohol concentration of 40%, there was a 98% release of extended-release methylphenidate (Ritalin LA) from the 40 mg capsule in the first hour after administration. In addition, concurrent use with alcohol may exacerbate the CNS-related adverse effects of methylphenidate.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Exenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Felodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Fenfluramine: (Moderate) Use fenfluramine and methylphenidate derivatives with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) If concomitant use of fentanyl and methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fluoxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Fluvoxamine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Fosinopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Fosphenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with fosphenytoin and methylphenidate; a fosphenytoin dosage decrease may be necessary. Methylphenidate may inhibit the metabolism of fosphenytoin.
Furosemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Green Tea: (Moderate) The CNS stimulant effects of methylphenidate derivatives can be additive when used concurrently with most other psychostimulants, such as caffeine, including foods, herbal or dietary supplement products containing high amounts of caffeine like green tea. The combination of methylphenidate derivatives with other CNS stimulants may increase the incidence of side effects. Patients should avoid excessive caffeine intake, and observe for signs of nervousness, irritability, insomnia, tremor, arrhythmias, or other stimulant-related problems.
Guaifenesin; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Guanfacine: (Moderate) Psychostimulants, such as methylphenidate and its derivatives, may increase blood pressure and reduce the antihypertensive effects of antihypertensive agents, such as guanfacine. Monitor blood pressure and heart rate periodically when prescribed together. Guanfacine may be used adjunctively to methylphenidate and its derivatives in the treatment of attention deficit hyperactivity disorder (ADHD). Pharmacokinetic studies reveal that guanfacine does not influence methylphenidate pharmacokinetics and methylphenidate does not affect guanfacine pharmacokinetics. No dosage adjustments are required when used together. Patients should be monitored for heart rate, blood pressure, and for sedation during ADHD treatment.
Halogenated Anesthetics: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Homatropine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone; Ibuprofen: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydromorphone: (Moderate) If concomitant use of hydromorphone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Imipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Incretin Mimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Indapamide: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as indapamide. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulins: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Irbesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Isoflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isradipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Ketamine: (Moderate) Closely monitor vital signs when ketamine and methylphenidate derivatives are coadministered; consider dose adjustment individualized to the patient's clinical situation. Methylphenidate derivatives may enhance the sympathomimetic effects of ketamine.
Labetalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Levamlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Levobunolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Levomilnacipran: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Levorphanol: (Moderate) If concomitant use of levorphanol and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Levothyroxine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Lidocaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Linezolid: (Major) Psychostimulants, such as methylphenidate derivatives, exhibit sympathomimetic actions and should be avoided with other drugs, such as linezolid, that enhance the pressor response of sympathomimetic agents. A clinically significant rise in systolic blood pressure is possible. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, a non-selective monoamine oxidase inhibitor (MAOI), and medications that enhance central serotonergic activity. Monoamine oxidase (MAO) is the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Liothyronine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Lisinopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Lithium: (Moderate) Monitor for serotonin syndrome, particularly during lithium initiation, during concomitant methylphenidate use. If serotonin syndrome occurs, consider discontinuation of lithium and/or methylphenidate.
Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Losartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Meperidine: (Moderate) If concomitant use of meperidine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Metformin; Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Methadone: (Moderate) If concomitant use of methadone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Methyclothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methyldopa: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Metoclopramide: (Moderate) In theory, metoclopramide and methylphenidate derivatives may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Patients receiving this combination should be monitored for loss of effectiveness of either agent. Methylphenidate derivatives blocks central dopamine reuptake, which increases central dopaminergic functioning, while metoclopramide is a dopamine antagonist.
Metolazone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Metoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Midodrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Milnacipran: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Mirtazapine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and mirtazapine.
Modafinil: (Major) The use of modafinil with other psychostimulants, including methylphenidate or its derivatives, has not been extensively studied. Patients receiving combination therapy of modafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other CNS stimulant-related side effects. Single dose studies of methylphenidate combined with modafinil noted that the rate of absorption of modafinil was delayed up to one hour by the presence of methylphenidate; no changes occurred in the metabolism and extent of absorption of either medication.
Moexipril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Morphine: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Morphine; Naltrexone: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
Nadolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nalbuphine: (Moderate) If concomitant use of nalbuphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Nebivolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nebivolol; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the eff ectiveness of drugs used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and nefazodone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Nicardipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nifedipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nimodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nisoldipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Nortriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Olanzapine; Fluoxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Oliceridine: (Moderate) If concomitant use of oliceridine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Opicapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxymorphone: (Moderate) If concomitant use of oxymorphone and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ozanimod: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Paroxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Perindopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Perindopril; Amlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Perphenazine; Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Phenobarbital: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as phenobarbital. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenobarbital. More frequent monitoring of phenobarbital concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on phenobarbital concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as phenobarbital. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenobarbital. More frequent monitoring of phenobarbital concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on phenobarbital concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Phenoxybenzamine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phentolamine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Phenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with phenytoin and methylphenidate; a phenytoin dosage decrease may be necessary. Methylphenidate may inhibit the metabolism of phenytoin.
Pimozide: (Major) Pimozide should not be used in patients taking medicines that may, themselves, cause motor and phonic tics (e.g., methylphenidate) until such patients have been withdrawn from these drugs to determine whether or not the drugs, rather than Tourette's Disorder, are responsible for the tics. Once this issue is excluded, use together may proceed with caution.
Pindolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Pramipexole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Prazosin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Prilocaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Primidone: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as primidone. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of primidone, which is metabolized to phenobarbital. More frequent monitoring of drug concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on primidone concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Probenecid; Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
Promethazine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Propranolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Protriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Quinapril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Ramipril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Risperidone: (Moderate) Monitor for extrapyramidal symptoms (EPS) with concomitant use of risperidone and methylphenidate derivatives. Postmarketing cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported in patients when there was a change in dosage of either medication (increase or decrease in dosage) as well as with the initiation or discontinuation of either or both medications.
Ropinirole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sacubitril; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Safinamide: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with methylphenidate and its derivatives due to the risk of serotonin syndrome and hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as methylphenidate. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Selective serotonin reuptake inhibitors: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Selegiline: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Semaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Serdexmethylphenidate; Dexmethylphenidate: (Contraindicated) Avoid coadministration of methylphenidate and serdexmethylphenidate. These drugs represent duplicate treatments. Serious side effects such as nervousness, irritability, arrhythmias, palpitations, seizures, or other stimulant-related adverse effects may occur or get worse during concurrent use.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Sertraline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Sevoflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
SGLT2 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sodium Oxybate: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and methylphenidate derivatives, which are CNS stimulants. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
Sotagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sotalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Spironolactone: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering methylphenidate derivatives and St. John's Wort. There are rare reports of serotonin syndrome occurring during use of other serotonergicagents and methylphenidate or its derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sulfonylureas: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tapentadol: (Moderate) If concomitant use of tapentadol and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tedizolid: (Moderate) Psychostimulants, such as methylphenidate and its derivatives, exhibit sympathomimetic actions and may interact with other drugs, such as tedizolid, that enhance the pressor response of sympathomimetic agents. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, which is structurally related to tedizolid, and medications that enhance central serotonergic activity. Tedizolid inhibits monoamine oxidase (MAO), the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Telmisartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Telmisartan; Amlodipine: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Terazosin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Thiazolidinediones: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Thyroid hormones: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Tirzepatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tolcapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Torsemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Tramadol: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Tramadol; Acetaminophen: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Trandolapril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Trandolapril; Verapamil: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Triamterene: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Tricyclic antidepressants: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Trimipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Vasopressin, ADH: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Vasopressors: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Venlafaxine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Verapamil: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Vilazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and vilazodone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored closely for toxicity. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and vortioxetine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving methylphenidate derivatives with vortioxetine should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Warfarin: (Moderate) A dose adjustment of warfarin and more frequent INR monitoring may be required when initiating or discontinuing methylphenidate derivatives. Case reports suggest a potential interaction between methylphenidate derivatives and coumarin anticoagulants. Human pharmacologic studies have shown that methylphenidate derivatives may inhibit the metabolism of warfarin. The mechanism of the potential interaction is not clear. A dose adjustment of warfarin and more frequent monitoring of the INR may be required when initiating or discontinuing methylphenidate derivatives.

inued and appropriate medical management should be implemented.
Warfarin: (Moderate) A dose adjustment of warfarin and more frequent INR monitoring may be required when initiating or discontinuing methylphenidate derivatives. Case reports suggest a potential interaction between methylphenidate derivatives and coumarin anticoagulants. Human pharmacologic studies have shown that methylphenidate derivatives may inhibit the metabolism of warfarin. The mechanism of the potential interaction is not clear. A dose adjustment of warfarin and more frequent monitoring of the INR may be required when initiating or discontinuing methylphenidate derivatives.

Adhansia XR/Aptensio XR/Jornay/Metadate CD/Methylphenidate Hydrochloride/Ritalin LA Oral Cap ER: 10mg, 15mg, 20mg, 25mg, 30mg, 35mg, 40mg, 45mg, 50mg, 55mg, 60mg, 70mg, 80mg, 85mg, 100mg
Concerta/Metadate ER/Methylin/Methylphenidate Hydrochloride/RELEXXII/Ritalin SR Oral Tab ER: 10mg, 18mg, 20mg, 27mg, 36mg, 45mg, 54mg, 63mg, 72mg
Cotempla XR Oral Tab Orally Dis DR: 8.6mg, 17.3mg, 25.9mg
Daytrana/Methylphenidate Hydrochloride Topical Film ER: 1h, 1.1mg, 1.6mg, 2.2mg, 3.3mg
Methylin/Methylphenidate Hydrochloride Oral Sol: 5mL, 5mg, 10mg
Methylin/Methylphenidate Hydrochloride Oral Tab Chew: 2.5mg, 5mg, 10mg
Methylin/Methylphenidate Hydrochloride/Ritalin Oral Tab: 5mg, 10mg, 20mg
QuilliChew ER Oral Tab Chew ER: 20mg, 30mg, 40mg
Quillivant XR Oral Susp ER: 5mL, 25mg

Adults

100 mg/day PO for Adhansia XR; 72 mg/day PO for Concerta and Relexxii; 60 mg/day PO for all other oral formulations.

Geriatric

100 mg/day PO for Adhansia XR; 60 mg/day PO for all other oral formulations. While some dosage forms have not been specifically studied in the elderly, use of stimulants off-label has been described in geriatric adults.

Adolescents

85 mg/day PO for Adhansia XR; 72 mg/day (Max: 2 mg/kg/day) PO for Concerta and Relexxii (FDA-approved labeling); 60 mg/day PO for all other oral formulations excluding Cotempla XR-ODT and Jornay PM (FDA-approved labeling); 51.8 mg/day PO for Cotempla XR-ODT and 100 mg/day PO for Jornay PM; however, doses up to 100 to 108 mg/day PO have been used in patients weighing more than 50 kg for some formulations. For the transdermal patch, 30 mg/9-hour patch per day is the maximum.

Children

6 to 12 years: 85 mg/day PO for Adhansia XR; 54 mg/day PO for Concerta and Relexxii (FDA-approved labeling); 60 mg/day PO for all other oral formulations excluding Cotempla XR-ODT and Jornay PM (FDA-approved labeling); 51.8 mg/day PO for Cotempla XR-ODT and 100 mg/day PO for Jornay PM; however, doses up to 100 to 108 mg/day PO have been used in patients weighing more than 50 kg for some formulations. For the transdermal patch, 30 mg/9-hour patch per day is the maximum.
3 to 5 years: Safety and efficacy have not been established. Maximum doses have not been adequately studied; however, The Preschool ADHD Treatment Study (PATS) has suggested immediate-release doses up to 30 mg/day PO.
1 to 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Methylphenidate is a central nervous system (CNS) stimulant that is chemically similar to the amphetamines. Methylphenidate is a racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. The exact mechanism of action of methylphenidate for the treatment of attention-deficit hyperactivity disorder (ADHD) is not established. Methylphenidate is an indirect agonist; it inhibits the reuptake of dopamine and norepinephrine, facilitating their release into the synaptic cleft. As a result, sympathomimetic activity in the CNS is increased. There is some evidence that the alteration of dopamine transport systems by methylphenidate may indirectly augment the action of serotonin, but further pharmacologic research is needed to understand these processes. The main sites of CNS activity appear to be the brain stem arousal system and the cerebral cortex, including the subcortical structures of the thalamus. Methylphenidate-induced CNS stimulation produces a decreased sense of fatigue, an increase in motor activity and mental alertness, and mild euphoria. Improved attention spans, decreased distractibility, increased the ability to follow directions or complete tasks, and decreased impulsivity and aggression are noted when stimulants are prescribed for the treatment of ADHD. Unlike the amphetamines and cocaine, physical dependence is infrequent with clinical use at therapeutic doses. Chronic use of methylphenidate may lead to tolerance of side effects and psychological dependence, similar to other psychostimulants. Psychological dependence and addiction are more likely with parenteral or inhalational abuse or other illicit use. In the periphery, the sympathomimetic actions of methylphenidate are minimal at therapeutic doses. Heart rate typically increases slightly with normal therapeutic doses of stimulants (about 3 to 6 bpm); however, a reflexive decrease in heart rate in response to increased blood pressure can also occur. At high doses, such as in overdoses, stimulants can cause significant hypertension, tachycardia, arrhythmias, and other serious complications.[33387] [51621] [55038]

Methylphenidate is administered orally and transdermally. It is a racemic mixture comprised of the d- and l-threo enantiomers, the d-enantiomer being more pharmacologically active. The distribution of methylphenidate in humans is unknown, but the agent does cross the blood-brain-barrier with high regional uptake in the striatum. The low degree of protein binding and high lipid solubility indicate that methylphenidate largely penetrates the central nervous system (CNS). Plasma protein binding is 10% to 33%. Therapeutic activity is primarily due to the parent compound. Metabolism of methylphenidate occurs in the liver via de-esterification to the primary metabolite alpha-phenyl-piperidine acetic acid (PPA, ritalinic acid), which has little pharmacologic activity. Small amounts of the hydroxylated metabolites (e.g., hydroxymethylphenidate and hydroxyritalinic acid) are detectable in plasma. In studies with methylphenidate tablets and extended-release capsules (Ritalin LA), the average elimination half-life in adults is approximately 3.5 hours (range: 1.3 to 7.7 hours) and in children is approximately 2.5 hours (range 1.5 to 5 hours). The half-life of methylphenidate after oral administration of Jornay PM is about 5.9 hours. Most of a methylphenidate dose is recovered in urine (90%), primarily as ritalinic acid, which accounts for about 80% of the dose.[31289] [33387] [51622] [51673] [63424]
 
Affected cytochrome P450 isoenzymes: none
Methylphenidate is not metabolized by the cytochrome P450 system to a clinically significant extent and does not appear to be a relevant inhibitor of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A.[31289]

Oral Route

The rapid half-life of immediate-release oral preparations may result in unmeasurable concentrations of the drug between the morning and midday doses; extended-release preparations reduce these peak and trough variances. Extended-release once-daily oral preparations minimize the fluctuations between peak and trough concentrations associated with immediate-release formulations.[31289] The transdermal form of methylphenidate bypasses the liver upon first pass, unlike the oral formulation, resulting in higher serum concentrations with lower initial doses. Additionally, the concentration of l-methylphenidate is roughly equal to that of d-methylphenidate with patch administration, whereas with oral administration little l-methylphenidate is available due to first pass metabolism. However, the pharmacological activity of l-methylphenidate is less than d-methylphenidate.
Immediate-release and extended-release dosage forms dosed more than once per day: Peak serum concentrations are achieved in about 1.9 hours and 4.7 hours for the regular and extended-release forms, respectively. The duration of action ranges from 3 to 6 hours with regular tablets and about 8 hours with the extended-release tablets.
Concerta: These extended-release tablets for once daily administration follow a biphasic pharmacokinetic profile to provide day-long medication availability. After oral administration of Concerta, plasma concentrations of methylphenidate increase rapidly reaching an initial maximum at about 1 hour, followed by a gradual increase in concentration over the next 5 to 9 hours. Thereafter, concentrations gradually decrease. Tmax across all doses occurs between 6 to 10 hours. The half-life of methylphenidate in adolescents after oral administration of Concerta is about 3.5 hours.[33387]
Metadate CD: These extended-release capsules for once-daily administration follow a biphasic pharmacokinetic profile to provide day-long medication availability. Using Diffucaps technology, the capsules contain the drug in both rapid release and continuous release beads such that 30% of the dose is rapidly released and 70% of the dose is continuously released. The product demonstrates an initial peak plasma concentration at about 1.5 hours and a second peak at about 4.5 hours. The Metadate CD capsule, when opened and sprinkled on a tablespoon of cool applesauce, is bioequivalent to the intact capsule. The mean terminal half-life of Metadate CD in adults is 6.8 hours (compared to 2.9 hours for immediate release and 3.4 hours for sustained release).
Ritalin LA: These extended-release capsules for once-daily administration follow a biphasic pharmacokinetic profile to provide day-long medication availability. Using SODAS technology, the capsules contain the drug in both rapid release and continuous release beads such that 50% of the dose is rapidly released and 50% of the dose is continuously released from enteric coated, delayed-release beads. The effects of altered gastric pH on the absorption of Ritalin LA have not been studied. Interactions with antacids or acid blockers are possible. The absolute oral bioavailability in children is 22 +/- 8% for d-methylphenidate and 5 +/- 3% for l-methylphenidate, which is suggestive of significant pre-systemic metabolism. The product demonstrates an initial peak plasma level at about 1 to 3 hours and a second peak at about 5 to 8 hours after dosing. There were no differences in pharmacokinetic parameters when this formulation was given with applesauce, but a high fat breakfast may delay absorption time. However, the capsules may be taken with food without clinically significant effects. The Ritalin LA capsule, when opened and sprinkled on a tablespoon of cool applesauce, is bioequivalent to the intact capsule.
Aptensio XR: Aptensio XR follows an extended-release biphasic pharmacokinetic profile to provide day-long medication availability with once daily administration. Aptensio XR capsules contain multilayer beads, which are composed of an immediate-release layer containing approximately 40% of the methylphenidate dose, and a controlled-release layer which contains the remaining 60% of the dose. After oral administration, an initial peak plasma concentration occurs at about 2 hours, with a gradual descending concentration over the next 4 to 6 hours, after which a gradual increase begins reaching a second peak at about 8 hours. The relative bioavailability of Aptensio XR given once daily compared to a methylphenidate immediate-release oral product given 3 times daily in adults is approximately 102%. The pharmacokinetic profile of Aptensio XR administered as a whole capsule or opened and sprinkled onto applesauce under fasting conditions is similar. After a single dose administered to healthy adults under fasting conditions, the following pharmacokinetic parameters were calculated: Cmax = 23.47 (+/- 11.4) ng/mL, AUC = 258.1 (+/- 94.2) ng x hour/mL, and half-life = 5.09 hours. During pharmacokinetic trials, administration with a high fat meal decreased or diminished the second peak and increased the average Cmax and AUC by 28% and 19%, respectively. At an alcohol concentration up to 40%, there was 96% release of methylphenidate from Aptensio XR capsules within 2 hours; similar results are expected with other capsule strengths.[59540]
QuilliChew ER: After a single 40 mg dose under fasting conditions, Cmax was obtained at a median time of 5 hours. Compared to immediate-release chewable tablets (two 20 mg doses given 6 hours apart), methylphenidate mean peak concentration and exposure (AUC) was about 20% and 11% lower, respectively, after a single dose administration of 40 mg QuilliChew ER. Administration with a high-fat meal had no effect on Tmax, and increased Cmax and AUC by about 20% and 4%, respectively, after a single 40 mg dose. Plasma methylphenidate concentrations declined monophasically. The mean elimination half-life was 5.2 hours in healthy volunteers. The presence of alcohol increases release of methylphenidate. At an alcohol concentration up to 40%, there was 90% release of methylphenidate from QuilliChew ER within half an hour; similar results are expected with other available tablet strengths.[60401]
Quillivant XR: This extended-release suspension for once-daily administration provides a mean peak plasma concentration of 13.6 +/- 5.8 ng/mL over a median time of 5 hours when given to healthy adults. Food has no clinically significant effect on the bioavailability of the suspension. The relative bioavailability of Quillivant XR compared to immediate-release methylphenidate oral solution is 95%. Elimination half-life is approximately 5 hours.[51955]
Cotempla XR-ODT: After a single 51.8 mg dose under fasting conditions, Cmax was obtained at a median time of 5 hours. Compared to an extended-release capsule formulation of methylphenidate, methylphenidate mean peak concentration and exposure (AUC) was about 26% and 6% higher, respectively, after Cotempla XR-ODT administration. Administration with a high-fat meal shorted the median time to peak concentration (Tmax) by 0.5 hours and decreased the Cmax and increased AUC of total methylphenidate by approximately 24% and 16%, respectively. Plasma methylphenidate concentrations declined monophasically. Elimination half-life is approximately 4 hours. The presence of alcohol potentially increases release of methylphenidate. At an alcohol concentration of 40%, an in vitro dissolution study showed alcohol-induced dose dumping potential; dose dumping was not observed with lower alcohol concentrations.[62034]
Jornay PM: After a single 100 mg oral dose of Jornay PM administered to healthy adults at 9 PM, the initial absorption of methylphenidate into plasma was delayed such that no more than 5% of total drug was available within the first 10 hours after dosing. After the lag period, the absorption of methylphenidate occurs with a single peak and a median Tmax of 14 hours, followed by a gradual decline throughout the rest of the day. The relative bioavailability of Jornay PM administered once daily compared to the same daily dose of an oral immediate-release methylphenidate product given 3 times/day in adults is 73.9%. Administration with a high-fat meal at night resulted in a similar mean AUC, a 14% lower mean Cmax, and a median Tmax extended by about 2.5 hours compared to a fasting state. A morning meal has no effect on the kinetics of Jornay PM taken at night. The kinetic parameters of Jornay PM are similar when taken as a whole capsule versus sprinkled on applesauce. The presence of alcohol increases release of methylphenidate in vitro. At an alcohol concentration of 40%, there was a 97% release of methylphenidate from Jornay PM within 2 hours; the increased release rate of methylphenidate was not seen with lower alcohol concentrations.[63424]
Adhansia XR: Adhansia XR produces 2 distinct peak concentrations. After Adhansia XR administration, the first median time to Cmax occurs at about 2 (1 to 4) hours and the second at about 10 (8 to 14) hours in pediatric patients 6 to 12 years and 2 (1 to 4) hours for the first and the 11 (8 to 14) hours for the second in pediatric patients 13 to 17 years. The results of pharmacokinetic studies in pediatric patients (6 to 12 years) were comparable to that in adolescents and adults. Elimination half-life is approximately 4 to 7 hours in pediatric patients (6 to 12 years), 5 hours in adolescents, and 7 hours in adults. The AUC and Cmin of d,l-methylphenidate were about 50% and 288% higher, respectively, for Adhansia XR compared to immediate-release methylphenidate at steady state, which was reached on day 3. Administration with a high-fat, high caloric meal did not affect Cmax and AUC. The presence of alcohol increases release of methylphenidate in vitro. At an alcohol concentration of 40%, there was a 71% and 61% faster release of methylphenidate for Adhansia XR 70 mg and 100 mg, respectively, at 2 hours; the increased release rate of methylphenidate was not seen with lower alcohol concentrations. In fasted healthy adults, administration of Adhansia XR 70 mg capsules with 40% alcohol resulted in a 1.4-fold increase in the peak plasma methylphenidate concentration and a 1.3-fold increase in the extent of absorption.[63983]

Other Route(s)

Transdermal Route
The extent of methylphenidate systemic absorption after patch administration is dependent on the length of time the patch is worn and the patch size. Peak plasma concentrations of methylphenidate are reached approximately 8 hours after patch application. Cmax and AUC increase significantly with repeated daily administration compared to single-dose administration. After either a 1-day or 7-day patch administration, the Cmax and AUC of d-methylphenidate were approximately 50% lower in adolescents (13 to 17 years of age) than in children (6 to 12 years of age). In clinical pharmacokinetic studies, when the 10 mg/9-hour methylphenidate patch was worn on the hip for 9 hours per day for 4 weeks, the steady state mean d-methylphenidate Cmax was 15.7 +/- 9.39 ng/mL in children 6 years of age and older and 8.32 +/- 4.6 ng/mL in adolescents, and the Cmin was 1.04 +/- 1.17 ng/mL and 0.544 +/- 0.383 ng/mL in children and adolescents, respectively. In patients who wore the 30 mg/9-hour patch, the mean d-methylphenidate Cmax was 42.9 +/- 22.4 ng/mL in children and 16.5 +/- 6.94 ng/mL in adolescents, and the Cmin was 1.96 +/- 1.73 ng/mL and 1.02 +/- 0.629 ng/mL in children and adolescents, respectively. In children 6 to 12 years of age, mean peak concentrations of transdermal methylphenidate were roughly 1.9 times higher than those observed for once daily oral methylphenidate. However, the Cmax of single dose administration of transdermal methylphenidate is comparable to the Cmax from a single dose of the once daily oral formulations. Transdermal absorption of methylphenidate may increase over time with chronic therapy; these changes cannot be explained by changes in clearance or rate of elimination. On average, steady-state is achieved after approximately 14 days of dosing. The time until any transdermally administered d-methylphenidate is detectable in the circulation averages 3.1 hours (range 1 to 6 hours). The absorption (rate and extent) is increased when methylphenidate patch is applied to inflamed skin or exposed to heat. Absorption characteristics in areas other than the hip are not known.
 
Once the methylphenidate patch is removed after 9 hours of wear time, methylphenidate plasma concentrations decline in a biexponential manner most likely due to distribution of methylphenidate from the skin after patch removal. The transdermal form of methylphenidate bypasses the liver upon first pass, unlike the oral formulation, resulting in higher serum concentrations with lower initial doses. Results from single- and multiple-dose studies indicate that exposure to l-methylphenidate is 46% of the exposure to d-methylphenidate in children and 40% in adolescents. The pharmacological activity of l-methylphenidate is less than d-methylphenidate. With transdermal administration in children and adolescents, the mean elimination half-life of l-methylphenidate was shorter than for d-methylphenidate and ranged from 1.4 to 2.9 hours; whereas the mean elimination half-life of d-methylphenidate was about 4 to 5 hours.

Pregnancy

Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects; however, there may be risks to the fetus associated with the use of CNS stimulants during pregnancy. CNS stimulants can cause vasoconstriction and thereby can decrease placental perfusion. Several cohort studies have reported an increased risk of spontaneous abortion, pre-eclampsia, preterm birth, and perinatal complications associated with the use of methylphenidate during pregnancy while other studies have also shown an increase in these complications in unmedicated women with ADHD. Treatment with methylphenidate has also been associated with a small increased risk of cardiac malformations in some studies, while other studies have shown no increase in risk when controlling for concomitant medications and medical comorbidities in the mother. Premature delivery and low birth weight infants have also been reported in mothers taking stimulants while pregnant. Neonates with in utero exposure to stimulants may experience withdrawal after delivery; monitor the newborn for symptoms of withdrawal such as feeding difficulty, irritability, agitation, and excessive drowsiness. When deciding whether to continue, adjust, or stop the medication in a pregnant patient, it is important to weigh the risk of the medication against the risk of untreated illness and how these issues may affect both the mother and the unborn child. The National Pregnancy Registry for ADHD medications is dedicated to evaluating the safety of ADHD medication exposure during pregnancy. Healthcare providers are encouraged to register patients at https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/ or by calling 1-866-961-2388.