Catapres

ADHD Adjunct Agents
Agents for Opioid Withdrawal
Centrally Acting Alpha Agonists
Other Analgesics

Oral Administration

Administer last dose of the day immediately prior to bedtime to ensure maximum overnight blood pressure control; the largest portion of the daily dose should also be taken just before bedtime.

Oral Solid Formulations

Immediate-release tablets (e.g., Catapres): May be taken with or without food. Upon discontinuation, slowly taper dose over 2—4 days to avoid withdrawal symptoms and rebound hypertension.
Extended-release tablets (e.g., Kapvay): May be taken with or without food. Swallow whole; do not crush, cut, or chew. Upon discontinuation, slowly taper dose every 3—7 days to avoid withdrawal symptoms and rebound hypertension.

Oral Liquid Formulations

NOTE: Enteral administration of clonidine solution for injection is not approved by the FDA.
The 100 mcg/mL clonidine solution for epidural administration, diluted to a concentration of 5 mcg/mL, has been administered orally to neonatal patients for the treatment of neonatal abstinence syndrome.

Extemporaneous Compounding-Oral

Extemporaneous 0.02 mg/mL Clonidine Oral Solution Preparation
Triturate six (6) 0.1-mg clonidine hydrochloride tablets (total: 0.6 mg) in a glass mortar.
Levigate with 1 to 2 mL Simple Syrup NF and combine with sufficient additional syrup to yield 30 mL.
Storage: The resulting solution is stable in an amber plastic bottle for 35 days under refrigeration (2 to 8 degrees C).
 
Extemporaneous 0.01 mg/mL Clonidine Oral Suspension Preparation
Crush and grind twenty-five (25) 0.1-mg clonidine hydrochloride tablets (total: 2.5 mg clonidine) to a fine powder using a mortar and pestle.
Add Ora-Blend in geometric amounts until approximately half of the total volume (125 ml) is added.
Transfer the suspension to a graduated cylinder, rinse the mortar and pestle with additional Ora-Blend, and continue to add Ora-Blend to a final volume of 250 ml.
Shake until well suspended before transferring to appropriate storage container.
Storage: The resulting suspension is stable for 91 days when stored in clear plastic syringes at either 4 or 25 degrees C.
 
Extemporaneous 0.1mg/mL Clonidine Oral Suspension Preparation
Crush and grind thirty (30) 0.2-mg clonidine hydrochloride tablets (total: 6 mg clonidine) to a fine powder in a glass mortar.
Add enough Purified Water, USP to form a paste (roughly 2 mL).
Add 15 mL Simple Syrup, NF to the paste and triturate well.
Transfer mortar contents to a 60 mL amber glass bottle.
Continue to add Simple Syrup, NF in increments to a total of 60 mL; shake after each increment until well suspended.
Storage: The resulting suspension is stable for 28 days when stored in 60 mL amber glass bottles at 4 degrees C and protected from light.

Injectable Administration Other Injectable Administration

Epidural Injection
Epidural clonidine is preservative-free.
Epidural clonidine is usually administered in combination with other opiate analgesics such as fentanyl or morphine.
Health care professionals should be familiar with epidural infusion devices when administering epidural infusions.

Topical Administration Transdermal Patch Formulations

NOTE: The amount of active drug released after application of a clonidine transdermal system is directly proportional to the area covered by the system. 'Patches' are available as 3.5 cm2 (total clonidine content 2.5 mg, delivering 100 mcg/day); 7 cm2 (total clonidine content 5 mg, delivering 200 mcg/day); and 10.5 cm2 (total clonidine content 7.5 mg, delivering 300 mcg/day) over a period of 7 days. The total amount of drug in each system is greater than that delivered, to ensure constant release of the drug over 7 days.
Do not cut or trim patch.
Clonidine is absorbed better from the patch if applied on the upper arm or torso.
Apply to any hairless site at the same time each week. Avoid applying to areas with cuts or calluses. Wash area with soap and water. Dry thoroughly. Apply patch using firm pressure over patch to ensure contact with skin, especially around edges. If patch becomes loose during the 7-day wearing period, apply the adhesive overlay over the patch. If patch is overly loose or falls off, apply another patch. Rotate sites each week.
Instruct patient on proper application of patch. Patches should not be affected by showering, bathing, or swimming.
Patches must be removed prior to cardioversion or defibrillation to prevent burns to the patient. Also, removal of the Catapres-TTS patch before undergoing magnetic resonance imaging (MRI) is recommended because the patch contains aluminum.

Severe

bradycardia / Rapid / 0-4.0
stroke / Early / 0-1.0
angioedema / Rapid / 0-1.0
ileus / Delayed / 0-1.0
GI obstruction / Delayed / 0-1.0
AV block / Early / Incidence not known
heart failure / Delayed / Incidence not known
arrhythmia exacerbation / Early / Incidence not known

Moderate

orthostatic hypotension / Delayed / 32.0-47.0
hypotension / Rapid / 44.0-47.0
confusion / Early / 13.0-38.0
erythema / Early / 0.5-26.0
constipation / Delayed / 1.0-10.0
dyspnea / Early / 6.0-6.0
chest pain (unspecified) / Early / 5.3-5.3
hallucinations / Early / 5.0-5.0
contact dermatitis / Delayed / 5.0-5.0
urinary incontinence / Early / 0-4.0
sinus tachycardia / Rapid / 0-3.0
edema / Delayed / 0.5-3.0
impotence (erectile dysfunction) / Delayed / 2.0-3.0
hypoventilation / Rapid / 2.6-2.6
depression / Delayed / 1.0-1.0
hepatitis / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 1.0-1.0
parotitis / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
palpitations / Early / 0.5-0.5
skin ulcer / Delayed / 0.5-0.5
urinary retention / Early / 0.1-0.1
fluid retention / Delayed / 0.1-0.1
hyperesthesia / Delayed / Incidence not known
delirium / Early / Incidence not known
QT prolongation / Rapid / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
blurred vision / Early / Incidence not known
meningitis / Delayed / Incidence not known
withdrawal / Early / Incidence not known

Mild

xerostomia / Early / 0-40.0
anxiety / Delayed / 38.0-38.0
drowsiness / Early / 12.0-33.0
pruritus / Rapid / 0.7-26.0
headache / Early / 1.0-20.0
infection / Delayed / 5.0-20.0
dizziness / Early / 2.0-16.0
fatigue / Early / 4.0-16.0
abdominal pain / Early / 0-15.0
nausea / Early / 1.0-13.0
vomiting / Early / 5.0-10.5
nightmares / Early / 4.0-9.0
irritability / Delayed / 6.0-9.0
vesicular rash / Delayed / 7.0-7.0
insomnia / Early / 0.5-6.0
anorexia / Delayed / 1.0-6.0
diaphoresis / Early / 5.0-5.0
skin hyperpigmentation / Delayed / 5.0-5.0
tremor / Early / 1.0-4.0
nasal congestion / Early / 2.0-4.0
agitation / Early / 3.0-3.0
lethargy / Early / 3.0-3.0
libido decrease / Delayed / 3.0-3.0
throat irritation / Early / 3.0-3.0
emotional lability / Early / 2.0-2.0
rash / Early / 1.0-2.0
maculopapular rash / Early / 0-1.0
nocturia / Early / 1.0-1.0
gynecomastia / Delayed / 1.0-1.0
dysgeusia / Early / 1.0-1.0
nasal dryness / Early / 0-1.0
urticaria / Rapid / 0.5-0.5
alopecia / Delayed / 0.2-0.2
weight gain / Delayed / 0.1-0.1
paresthesias / Delayed / Incidence not known
fever / Early / Incidence not known
malaise / Early / Incidence not known
restlessness / Early / Incidence not known
asthenia / Delayed / Incidence not known
syncope / Early / Incidence not known
pallor / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
arthralgia / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
xerophthalmia / Early / Incidence not known

Catapres, Catapres-TTS, Duraclon, Kapvay, NEXICLON XR

Rx

Centrally-acting alpha2-agonist
Oral and transdermal drug for HTN and autonomic hyperactivity (e.g., drug withdrawal syndromes); also used orally for ADHD
Epidural product is used for refractory pain

For the treatment of hypertension. Oral dosage (immediate-release tablets) Adults

0.1 mg PO twice daily, initially. May increase dose by 0.1 mg/day every 7 days if further control is needed. Usual dosage range: 0.1 to 0.8 mg/day. Max: 2.4 mg/day.

Children and Adolescents 12 years and older†

0.1 mg PO twice daily, initially. May increase dose by 0.1 mg/day every 7 days if further control is needed. Usual adult dosage range: 0.1 to 0.8 mg/day. Max: 2.4 mg/day.

Children younger than 12 years†

Generally not recommended in children younger than 12 years. Initial doses of 5 to 10 mcg/kg/day PO in divided doses every 8 to 12 hours then titrated based on clinical response (Max: 25 mcg/kg/day or 0.9 mg/day) has been reported.

Transdermal dosage Adults

0.1 mg/24 hours transdermally every 7 days. May increase dose by 0.1 mg/24 hours after 7 to 14 days if further control is needed. Usual dosage range: 0.1 to 0.3 mg/24 hours every 7 days. Max: 0.6 mg/24 hours every 7 days.

Children† and Adolescents†

Initial dosing recommendations for pediatric patients are not available. Although not studied specifically in children with hypertension, in children with psychiatric disorders such as Tourette's and ADHD, it has been suggested that once patients are stabilized on an oral dose, they can be converted to the transdermal patch that provides an approximately equivalent daily dose. While the manufacturer recommends patches be changed once every 7 days in adult patients, it is suggested that patches may need to be changed earlier (i.e., every 5 days) in pediatric patients due to variable absorption in this population. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.

For the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients as monotherapy or as adjunctive therapy to a psychostimulant. Oral dosage (Kapvay extended-release tablets) Children and Adolescents 6 years and older

Initially, 0.1 mg/day PO at bedtime. Increase by 0.1 mg/day increments weekly as needed to attain the desired response. Max: 0.4 mg/day. Divide doses larger than 0.1 mg/day into 2 doses taken in the morning and at bedtime. If the morning and bedtime doses are not equal, the larger dose should be given at bedtime. When extended-release clonidine is added to a psychostimulant, the dosage of the psychostimulant may be adjusted according to patient response. Measure heart rate and blood pressure prior to beginning therapy, after dose increases, and periodically while on therapy. If a patient misses a dose, they should skip that dose and take the next dose as scheduled. When discontinuing, taper the dose in decrements of no more than 0.1 mg/day every 3 to 7 days to avoid rebound hypertension. Extended-release clonidine tablets are not interchangeable with the immediate-release formulation.

Oral dosage (immediate-release tablets)† Children and Adolescents 6 years and older weighing more than 45 kg

Initially, 0.1 mg PO at bedtime, then titrate by increments of 0.1 mg/day to 0.1 mg PO twice daily, then 0.1 mg PO 3 times per day, then 0.1 mg PO 4 times per day. Max: 0.4 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of patients with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO (alone) and 0.28 mg/day PO (with methylphenidate about 26 mg/day PO). The greatest ADHD benefit and improved tic severity compared to baseline was seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. Sedation was common (28%) in the clonidine groups.

Children and Adolescents 6 years and older weighing 40.5 to 45 kg

Initially, 0.05 mg PO at bedtime, then titrate in increments of 0.05 mg/day to 0.05 mg PO twice daily, then 0.05 mg PO 3 times per day, then 0.05 mg PO 4 times per day. Max: 0.3 mg/day.

Children and Adolescents 6 years and older weighing 27 to 40.5 kg

Initially, 0.05 mg PO at bedtime, then titrate in increments of 0.05 mg/day to 0.05 mg PO twice daily, then 0.05 mg PO 3 times per day, then 0.05 mg PO 4 times per day. Max: 0.2 mg/day.

Transdermal dosage† Children and Adolescents 6 years and older

Initial dosing recommendations for pediatric patients are not available; however, it has been suggested that once patients are stabilized on an oral dose they may be converted to the transdermal patch that provides an approximately equivalent daily dose (e.g., 0.1, 0.2, or 0.3 mg/day). Patches are changed once every 7 days in adults; however, due to variable absorption in pediatric patients, patches may need to be changed earlier (i.e., every 5 days). Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.

For the treatment of severe pain. In cancer patients when the pain is not adequately relieved by opiate analgesics alone including neuropathic pain.
NOTE: Clonidine has been designated an orphan drug by the FDA for this indication.
NOTE: Epidural clonidine has been effective primarily in the subgroup of patients with neuropathic pain. Epidural dosage Adults

Initially, 30 mcg/hour by continuous epidural infusion in combination with opioid analgesics, is recommended by the manufacturer. Dosage may be titrated up or down depending on pain relief and occurrence of adverse events; however, there is limited experience above the maximum rate of 40 mcg/hour. In clinical trials, bolus doses of epidural clonidine range from 100 to 900 mcg per dose. The dosage should be titrated to pain relief and incidence of side effects. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

Children and Adolescents

Initially, 0.5 mcg/kg/hour by continuous epidural infusion and adjusted cautiously based upon pain relief and incidence of side effects. It is recommended that epidural clonidine be restricted to pediatric patients with severe intractable pain from malignancy that is unresponsive to epidural or spinal opiates or other more conventional analgesic techniques. Epidural clonidine has been effective primarily in the subgroup of patients with neuropathic pain.

In postoperative patients in combination with opiate analgesics.
NOTE: FDA-approved labeling does not recommend the use of epidural clonidine in obstetrical, post-partum, or peri-operative analgesia due to the risk of hemodynamic instability.
Epidural dosage Adults

Epidural clonidine 150 mcg in combination with fentanyl has been studied. This dose provided similar pain relief and increased the analgesia duration as compared to epidural fentanyl alone as a single dose. Epidural clonidine 450 mcg/day has been studied in combination with morphine. This dose resulted in improved pain relief and less rescue doses of morphine in comparison to epidural morphine alone in patients with postoperative pain. Consider dosage reduction in elderly patients, as they may be more sensitive to the sedative and hypotensive effects.

For the treatment of hypertensive urgency† or hypertensive emergency†. Oral dosage (immediate-release tablets) Adults

0.1 to 0.2 mg PO every hour as required to a total of 0.6 mg. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

Children and Adolescents

2 to 5 mcg/kg/dose PO every 6 to 8 hours as needed (Max: 10 mcg/kg/dose) for severely hypertensive patients with non-life-threatening symptoms. Alternatively, 0.05 to 0.1 mg/dose PO, which can be repeated hourly as needed, up to a total dose of 0.8 mg PO.

For the treatment of opiate agonist withdrawal†. Oral dosage (immediate-release) Adults

0.1 to 0.2 mg PO every 4 to 6 hours, initially, as needed or as a standing dose in cases of severe withdrawal. Adjust dose until withdrawal symptoms are reduced. Monitor blood pressure and withhold dose if blood pressure is 90/60 mmHg or lower. Dose range: 0.1 to 0.3 mg PO every 4 to 8 hours. Max: 1.2 mg/day on day 1, then 2 mg/day. To discontinue, taper dose over several days while monitoring for signs of withdrawal.   

Infants, Children, and Adolescents

Limited data available. 2 to 4 mcg/kg/dose PO every 4 to 6 hours as needed.

For the treatment of neonatal abstinence syndrome†. Oral dosage Neonates

0.5 to 1 mcg/kg/dose PO every 3 to 6 hours (Max: 8 mcg/kg/day PO) is recommended by the American Academy of Pediatrics (AAP). Dosages of 2 to 6 mcg/kg/day PO given in divided doses every 4 to 6 hours have been effective in treating opiate agonist withdrawal symptoms in neonates addicted to opiates secondary to intrauterine exposure to methadone or heroin and in neonates being weaned from opiate infusions. Premature neonates (n = 11, gestational age 24 to 35 weeks) were included in 1 small study.

For pheochromocytoma diagnosis†. Oral dosage Adults

A single 0.3 mg PO dose administered after 30 minutes of inactivity successfully differentiated 10 patients with pheochromocytoma from 15 hypertensive patients without pheochromocytoma. Blood pressure, heart rate, and plasma catecholamines were assessed at 30, 60, 120, and 180 minutes post-dose. At 3 hours post-dose, norepinephrine concentrations were suppressed to normal or below normal in all patients without pheochromocytoma but in none of the 10 patients with the disease.

For the symptomatic treatment of diabetic neuropathy†. Oral dosage Adults

Initially, 0.1 mg PO at bedtime. Gradually increase to 0.5 mg PO each night.

Geriatric

Consider dosage reduction (see adult dosage). Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

For the treatment of diabetic diarrhea†. Oral dosage Adults

0.1 mg PO every 12 hours, initially. Increase dose over 3 days up to 0.5 to 0.6 mg PO every 12 hours.

For the treatment of alcohol withdrawal†. Oral dosage Adults

0.2 mg PO at 9PM on day 1; at 9AM, 1PM, and 6PM on day 2; at 9AM and 6PM on day 3; and a final dose at 9AM on day 4.

For use as an adjunct to psychosocial interventions in the management of tobacco cessation† (smoking cessation†). Oral dosage Adults

0.1 mg PO once or twice daily initially. Dose range in clinical trials: 0.1 mg/day to 0.75 mg/day, in divided doses. Begin clonidine shortly before (up to 3 days) or on the quit date. The dose may be increased by 0.1 mg/day per week if needed. Dividing the total daily dose is suggested to increase tolerability. Consider a dosage reduction in elderly patients due to greater sensitivity to clonidine at usual dosages. Treatment duration has varied across clinical trials, generally ranging from 3 to 10 weeks. Common side effects include dry mouth, sedation, dizziness, drowsiness, and constipation. There is no clear dose-response relationship; however, dose-related adverse effects limit the clinical usefulness of the drug. DISCONTINUATION: Reducing the dose gradually over 2 to 4 days may mitigate a rebound phenomenon of rapid increase in blood pressure, agitation, confusion, and/or tremor. According to the Agency for Healthcare Research and Quality (AHRQ) treatment guidelines, clonidine is appropriate as a second-line medication for treating tobacco use.

Transdermal dosage Adults

Initially, 0.1 mg/24 hours applied transdermally once weekly. May increase the dose by 0.1 mg/24 hours weekly if needed. Transdermal doses ranging from 0.1 mg/24 hours to 0.2 mg/24 hours strength patch applied once weekly have been used in clinical trials.  Consider low doses and slow titration in elderly patients because they may be more sensitive to common side effects of clonidine at usual dosages. Treatment duration has varied across clinical trials, generally ranging from 3 to 10 weeks. Common side effects include dry mouth, sedation, dizziness, drowsiness, and constipation. There is no clear dose-response relationship; however, dose-related adverse effects limit the clinical usefulness of the drug. According to the Agency for Healthcare Research and Quality (AHRQ) treatment guidelines, clonidine is appropriate as a second-line medication for treating tobacco use.

For the treatment of hot flashes† due to menopause†. Oral dosage (immediate-release tablets) Adult females

Initially, 0.05 mg PO twice daily or 0.1 mg PO once daily at bedtime. Higher doses of 0.1 mg PO twice daily or more may be necessary for some patients. Max studied: 0.2 mg PO twice daily. In a study of 194 postmenopausal women with breast cancer receiving tamoxifen, clonidine 0.1 mg PO once daily at bedtime reduced the number of hot flashes per day compared with placebo (p = 0.006); quality of life also improved. A meta-analysis estimates clonidine provides approximately a 1 hot flash/day reduction when compared to control groups; improvements in quality of life are also reported. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy consider clonidine effective for vasomotor symptoms of menopause; however, it is typically not used as a first-line agent in the treatment of hot flashes as it is less effective and associated with more adverse effects compared to other non-hormonal pharmacologic therapies (e.g., paroxetine, gabapentin, venlafaxine).

Transdermal dosage Adult females

A dose of one Catapres TTS-1 patch (delivers clonidine 0.1 mg/24 hours) once weekly has been suggested. A meta-analysis estimates clonidine (oral or transdermal) provides approximately a 1 hot flash/day reduction when compared to control groups; improvements in quality of life are also reported. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy consider clonidine effective for vasomotor symptoms of menopause; however, it is typically not used as a first-line agent in the treatment of hot flashes as it is less effective and associated with more adverse effects compared to other non-hormonal pharmacologic therapies (e.g., paroxetine, gabapentin, venlafaxine).

For the treatment of hypertension and the subsequent decline in renal function associated with scleroderma renal crisis (SRC)†. Oral dosage Adults

Initially, 0.1 mg PO twice daily, increased by 0.1—0.2 mg/day PO to attain blood pressure response.

Geriatric

Consider dosage reduction (see adult dosage). Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

For minimization of nephrotoxicity in patients receiving cyclosporine (i.e., cyclosporine nephrotoxicity prophylaxis†) and low-dose methotrexate for allogeneic bone marrow transplant. Transdermal dosage Adults

A small study compared the effect of transdermal clonidine patches on cyclosporine-induced nephrotoxicity in allogeneic bone marrow transplant patients. Transdermal clonidine 0.1 mg/day (from 4 days prior to 31 days after transplantation), titrated to 0.2 mg/day (if DBP not < 90 mm Hg), has been studied in 8 transplant patients. Twenty-three allogeneic BMT patients did not receive clonidine. Data from 23 autologous BMT patients were also included in the evaluation. At the end of the study, mean serum creatinine in the allogeneic group receiving clonidine was significantly lower than the allogeneic group not receiving clonidine (1.1 mg/dL vs 1.6 mg/dL) and was not significantly different from the autologous BMT group (0.9 mg/dL). NOTE: The Catapres-TTS-1 transdermal patch delivers clonidine 0.1 mg/day over 7 days; whereas the Catapres-TTS-2 patch delivers clonidine 0.2 mg/day over 7 days.

Geriatric

See adult dosage. Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

For use in peripheral nerve block† including brachial plexus†, intercostal† and peribulbar† blocks in combination with local anesthetics. Peripheral nerve block dosage Adults

Epidural clonidine 30 to 150 mcg has been used to enhance the effects of lidocaine in peripheral nerve blocks. In cataract surgery, clonidine 2 mcg/kg in combination with 3 to 4 mL of 2% lidocaine resulted in decreased intraocular pressure and longer post-operative analgesia and akinesia than lidocaine alone. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.

Children and Adolescents 2 years and older

Limited data available; 1 mcg/kg/dose (Max: 100 mcg) as a single-shot nerve block in combination with a local anesthetic significantly prolonged the mean duration of sensory blockade (17.2 hours vs. 13.2 hours) and the mean duration of analgesia (10 hours vs. 6.8 hours) compared to nerve block with a local anesthetic alone in patients undergoing various surgeries.

For the treatment of tics associated with Tourette's syndrome† and chronic tic disorders†. Oral dosage (immediate-release tablets) Adults

Initially, 0.025 to 0.05 mg/day PO. Gradually titrate according to blood pressure and heart rate. Range: 0.025 to 0.6 mg/day PO. Max: 0.6 mg/day PO, usually given in 3 to 4 divided doses. Clonidine is recommended in evidence-based guidelines (strong recommendation, moderate-quality evidence). Consider a dose reduction in elderly patients, as they may be more sensitive to adverse effects at the usual dosages. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions.

Children and Adolescents 6 years and older

Initially, 0.025 to 0.05 mg/day PO; titrate gradually in increments of 0.025 mg to the target dose of 0.2 to 0.3 mg/day PO given in 3 to 4 divided doses. Max: 0.4 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of patients with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO (alone) and 0.28 mg/day PO (with methylphenidate about 26 mg/day PO). The greatest ADHD benefit and improved tic severity compared to baseline were seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions. The effect size of clonidine on tics appears larger in children with tics and ADHD compared to individuals with tics and without ADHD.

Oral dosage (extended-release tablets) Children and Adolescents 6 years and older

Initially 0.1 mg/day PO at bedtime. Increase the dose in 0.1 mg/day increments weekly as needed to attain the desired response (Max: 0.4 mg/day). Divide doses larger than 0.1 mg/day into 2 doses taken in the morning and at bedtime. If the morning and bedtime doses are not equal, the larger dose should be given at bedtime. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions.

Transdermal dosage Children and Adolescents 6 years and older

Initial dosing recommendations for pediatric patients are not available; however, some patients stabilized on an oral dose may then be converted to the transdermal patch that provides an approximately equivalent daily dose (i.e., 0.1, 0.2, or 0.3 mg/day). Patches are changed once every 7 days in adults; however, due to variable absorption, patches may need to be changed earlier (i.e., every 5 days) in pediatric patients. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions. The effect size of clonidine on tics appears larger in children with tics and ADHD compared to individuals with tics and without ADHD.

For the treatment of aggressive behavior and hyperactivity/inattentiveness in patients with autistic disorder†. Oral dosage Children and Adolescents 5 years and older

Initially, 0.05 mg PO once daily in the evening. Increase to 0.05 mg PO twice daily after 3 days. Then continue to increase by 0.05 mg/day PO every 3 days as needed for symptom control. Usual dose range is 0.1 to 0.4 mg/day PO given in 3 to 4 divided doses (Max: 0.4 mg/day PO).

Transdermal dosage Children and Adolescents 5 years and older

Initial doses of 0.005 mg/kg/day rounded to the nearest available patch strength (patches are available in 3 strengths delivering doses of approximately 0.1, 0.2, or 0.3 mg/day over 7 days) were used in a small study including 7 pediatric patients (age range 5 to 12 years, weight range 19.1 to 52.7 kg). Patients weighing less than 25 kg were started on half a 0.1 mg/day patch for 3 days to minimize adverse reactions. The mean dose of clonidine used in the study was 0.16 +/- 0.09 mg/day. Although patches in this study were changed every 7 days, other authors have suggested that pediatric patients may require patches be changed earlier (i.e., every 5 days) due to variable absorption. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.

For growth hormone deficiency diagnosis†. Oral dosage Children and Adolescents

5 mcg/kg PO as a single dose (Max: 250 mcg PO). Maximal growth hormone secretion usually occurs 60 minutes after the dose. Blood should be drawn at 0, 30, 60, and 90 minutes after the dose of clonidine is given. Similarly, blood pressure should be measured at these same time intervals.

For the treatment of hot flashes† due to prostate cancer† and associated induced androgen deficiency† ("andropause†") in men who have had surgical or medication induced castration. Transdermal dosage Adult males

Apply one Catapres TTS-1 patch (delivers clonidine 0.1 mg/24 hours) once weekly. Limited data from a pilot study indicate that transdermal clonidine may have some benefit in reducing the frequency of hot flashes in men after bilateral orchiectomy; however a randomized clinical trial of transdermal clonidine showed no benefit compared to placebo.

For the treatment of benzodiazepine withdrawal†. Oral dosage (immediate-release) Infants, Children, and Adolescents

Limited data available. 2 to 4 mcg/kg/dose PO every 4 to 6 hours as needed.

†Indicates off-label use

Hepatic Impairment

No quantitative recommendations are available. Because clonidine is substantially metabolized by the liver, monitor patients for sedation and hypotension and adjust the dose if necessary.

Renal Impairment

A lower initial dose may be beneficial; patients should be carefully monitored for bradycardia, sedation, and hypotension.
 
Intermittent hemodialysis
Clonidine is minimally removed by hemodialysis. In general, no supplemental dosage is needed following hemodialysis. Adjust dosage based on clinical response.

Acarbose: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Aldesleukin, IL-2: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alogliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alpha-glucosidase Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alprazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and central-acting antihypertensive agents may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amiodarone: (Moderate) Monitor for potential bradycardia or atrioventricular block during coadministration with amiodarone. Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate.
Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Amoxapine: (Major) Concurrent use of clonidine with amoxapine should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants; occasionally, the hypertension will occur within the first few days of combined therapy. If coadministration of amoxapine with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of a cyclic antidepressant and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients. In rats, the coadministration of a cyclic antidepressant (amitriptyline) with clonidine resulted in corneal lesions, but the human implications of these animal study findings are unknown.
Amphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine Salts: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Apomorphine: (Moderate) Use of central-acting adrenergic agents and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aripiprazole: (Minor) Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Benzodiazepines: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Benzphetamine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of clonidine. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed.
Beta-blockers: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including clonidine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Canagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Canagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbonic anhydrase inhibitors: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cardiac glycosides: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and clonidine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid concomitant use of ceritinib with clonidine if possible due to the risk of additive bradycardia. Both ceritinib and clonidine can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlordiazepoxide: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines. (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpromazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Clomipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Clonazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clorazepate: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Codeine; Phenylephrine; Promethazine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Codeine; Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and central-acting adrenergic agents use. Concomitant use may result in additive hypotension.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Crizotinib: (Major) Avoid coadministration of crizotinib with agents known to cause bradycardia, such as clonidine, to the extent possible due to the risk of additive bradycardia. If concomitant use is unavoidable, monitor heart rate and blood pressure regularly. An interruption of crizotinib therapy or dose adjustment may be necessary if bradycardia occurs.
Cyclobenzaprine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and cyclobenzaprine; a clonidine dose adjustment may be necessary. Concomitant use may result in decreased clonidine efficacy and/or additive CNS depression. The hypotensive effect of clonidine may be reduced by tricyclic antidepressants, and cyclobenzaprine is structurally related to the tricyclic antidepressants.
Cyclosporine: (Minor) Clonidine can inhibit cyclosporine-induced glomerular vasoconstriction and has been shown to offset cyclosporine-induced nephrotoxicity. Clonidine may adversely affect cyclosporine pharmacokinetics; limited data suggest that cyclosporine concentrations increase - dramatically, in some cases - when clonidine is added. Until more data are available, clinicians should use clonidine cautiously in patients stabilized on cyclosporine.
Dapagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Saxagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Desipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Diazoxide can enhance the hyperglycemic, hyperuricemic and antihypertensive effects of thiazide diuretics.
Diethylpropion: (Major) Sympathomimetics, such as diethylpropion, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Digoxin: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Diltiazem: (Moderate) Avoid concomitant use of diltiazem and extended-release clonidine tablets. Monitor heart rate during concomitant use of diltiazem and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of diltiazem and clonidine.
Dipeptidyl Peptidase-4 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dobutamine: (Major) Sympathomimetics, such as dobutamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dopamine: (Moderate) Sympathomimetics, such as dopamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Doxepin: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Dulaglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Duloxetine: (Moderate) Monitor blood pressure during concomitant duloxetine and central-acting adrenergic agent use. Concomitant use increases the risk for hypotension, including orthostatic hypotension and syncope. Consider reducing the duloxetine dose or discontinuing duloxetine if symptomatic orthostatic hypotension, falls, or syncope occur during treatment.
Empagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Epoprostenol: (Moderate) The concomitant administration of epoprostenol with other antihypertensive agents can result in additive hypotensive effects. This can be therapeutically advantageous, but dosages must be adjusted accordingly.
Ertugliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Sitagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Esketamine: (Major) Closely monitor patients receiving esketamine and clonidine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethanol: (Major) Advise patients to avoid alcohol use while taking clonidine. Clonidine may potentiate the CNS-depressive effects of alcohol.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Exenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and clonidine. Concurrent use may result in additive CNS depression.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Fluphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Flurazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clonidine. Concomitant use of gabapentin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Glipizide; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glyburide; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Haloperidol: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Imipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Incretin Mimetics: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Degludec; Liraglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Glargine; Lixisenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulins: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and clonidine. Concurrent use may result in additive CNS depression. Additionally, monitor heart rate if lasmiditan is coadministered with clonidine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and clonidine. Dosage adjustments of lemborexant and clonidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Levomilnacipran: (Moderate) Because levomilnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Linagliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Liraglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lisdexamfetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and lisdexamfetamine. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Lixisenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lofexidine: (Major) Lofexidine is a central alpha-2 adrenergic agonist, and its effects can be additive to other medications in the same class. Monitor for excessive hypotension, bradycardia, and sedation during coadministration. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Lorazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Lumateperone: (Moderate) Monitor for excessive sedation, somnolence, and orthostatic hypotension during coadministration of lumateperone and clonidine. Concurrent use may result in additive CNS depression or orthostasis.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may transiently elevate growth hormone concentrations, such as clonidine. Healthcare providers are advised to discontinue clonidine therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Maprotiline: (Major) Concurrent use of clonidine with maprotiline should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants, such as maprotiline. If coadministration of maprotiline with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed.
Meglitinides: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Repaglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Rosiglitazone: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Saxagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Sitagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like clonidine, when clonidine is used for blood pressure control. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Methylphenidate Derivatives: (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.
Midazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Miglitol: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blo

od pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Milnacipran: (Moderate) Because milnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mirtazapine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and mirtazapine. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. Mirtazapine and clonidine have pharmacologic actions that potentially oppose one another. Mirtazapine inhibits central alpha-2 autoreceptors (located presynaptically on noradrenergic neurons) and stimulating norepinephrine and stimulates the serotonergic system through antagonism at alpha-2 heteroreceptors. Clonidine exerts its antihypertensive effect by stimulating the central alpha-2 autoreceptors, thereby causing a reduction in the synthesis and release of norepinephrine.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Nabilone: (Major) Monitor for excessive sedation and somnolence during coadministration of nabilone and clonidine. Concurrent use may result in additive CNS depression.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Nateglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Nitrates: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Norepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Nortriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Opiate Agonists: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by clonidine. If these drugs are used together, closely monitor for changes in blood pressure.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and central-acting adrenergic agents who are susceptible to hypotension.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phenothiazines: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phentermine: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phentermine; Topiramate: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Pimozide: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Pioglitazone; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as clonidine due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Pramlintide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clonidine. Concomitant use of pregabalin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Prochlorperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Protriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Quazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Quetiapine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and quetiapine. Coadministration may induce or exacerbate orthostatic regulation disturbances, such as orthostatic hypotension, dizziness, or fatigue, as well as produce additive CNS depression.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rasagiline: (Moderate) Orthostatic hypotension has been reported during administration of rasagiline; caution is advised during concurrent use with antihypertensive agents. Patients receiving rasagiline in combination with an antihypertensive should be instructed to rise slowly from a sitting position, and to report syncope, and changes in heart rate or blood pressure to their health care provider. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious hypertensive reactions with agents affecting catecholamine release (e.g., guanabenz, reserpine, guanethidine) are unlikely.
Remimazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Repaglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Semaglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
SGLT2 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sotagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clonidine. CNS depressants can potentiate the effects of stiripentol.
Sulfonylureas: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Temazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiazolidinediones: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Thioridazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tirzepatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Tizanidine: (Major) The use of tizanidine with other alpha 2-adrenergic agonists (such as central-acting adrenergic agonist antihypertensive agents) should be avoided because hypotensive effects may be cumulative. Tizanidine is an alpha 2-adrenergic agonist that can produce hypotension. Syncope has been reported in the postmarketing setting.
Trandolapril; Verapamil: (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Trazodone: (Moderate) Monitor for unusual drowsiness or excess sedation during coadministration of clonidine and trazodone due to risk for additive CNS depression.
Triazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Tricyclic antidepressants: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Trifluoperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Trimipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Verapamil: (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

Catapres/Clonidine/Clonidine Hydrochloride Oral Tab: 0.1mg, 0.2mg, 0.3mg
Catapres-TTS/Clonidine Percutaneous Film ER: 0.1mg, 0.2mg, 0.3mg, 24h
Clonidine/Clonidine Hydrochloride/Duraclon Epidural Inj Sol: 1mL, 100mcg, 500mcg
Clonidine/Clonidine Hydrochloride/Kapvay/NEXICLON XR Oral Tab ER: 0.1mg, 0.17mg

Adults

2.4 mg/day PO immediate-release tablets; two Catapres-TTS-3 transdermal patches/week (delivers 0.6 mg/day for 7 days) applied topically to skin; or 40 mcg/hour continuous epidural infusion.

Geriatric

2.4 mg/day PO immediate-release tablets; two Catapres-TTS-3 transdermal patches/week (delivers 0.6 mg/day for 7 days) applied topically to skin; or 40 mcg/hour continuous epidural infusion.

Adolescents

0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 2.4 mg/day for hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.

Children

12 years: 0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 2.4 mg/day for the treatment of hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
6 to 11 years: 0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 0.9 mg/day PO for the treatment of hypertension have also been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
1 to 5 years: Safety and efficacy have not been established; however, doses up 0.9 mg/day PO for the treatment of hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.

Infants

Safety and efficacy have not been established; however, doses up to 4 mcg/kg PO have been recommended for the management of the symptoms of opioid or benzodiazepine withdrawal.

Neonates

Neonates: Safety and efficacy have not been established; however, doses up to 12 mcg/kg/day PO have been used off-label for the management of neonatal abstinence syndrome.
Premature Neonates: Safety and efficacy have not been established; however, doses up to 12 mcg/kg/day PO have been used off-label for the management of neonatal abstinence syndrome.

Clonidine is an agonist at presynaptic alpha2-receptors in the medulla, specifically, the nucleus tractus solitarius (i.e., the depressor area of the vasomotor center of the medulla oblongata). Stimulation of these receptors results in the inhibition of sympathetic outflow and tone. Suppression of efferent sympathetic pathways decreases vascular tone in the heart, kidneys, and peripheral vasculature; lowers peripheral resistance; and reduces blood pressure. Reflex tachycardia usually does not occur. Instead, stimulation of the central alpha-receptors by clonidine results in a reciprocal increase in vagal tone, causing an increase in baroreceptor activity and bradycardia. Clonidine is also a partial agonist at presynaptic alpha2-adrenergic receptors of peripheral nerves in vascular smooth muscle, however, this site of action contributes little, if anything, to its antihypertensive effects. Doses higher than those required to lower blood pressure are necessary to demonstrate agonism at this peripheral site. Further, it has been shown that alpha2-agonists that cannot penetrate the blood-brain barrier do not effectively lower blood pressure. Agonism at peripheral presynaptic alpha2-receptors may interfere with the peripheral regulation of norepinephrine.
 
Intravenous administration or large oral doses of clonidine also can stimulate alpha1-receptors in peripheral vascular smooth muscle, resulting in acute vasoconstriction and a transient increase in blood pressure. An accurate correlation between clonidine's plasma concentrations and its antihypertensive effects is evident only at lower plasma concentrations. Higher plasma concentrations of clonidine will result in reduced antihypertensive activity because of the increased contribution of the pressor effect.
 
Inhibition of sympathetic outflow by clonidine results in a variety of pharmacodynamic effects. In the supine position, decreased sympathetic tone reduces heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV), with essentially no change in the total peripheral resistance (TPR), renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR), urinary potassium excretion, or renal vascular resistance (RVR). Urinary sodium and chloride excretion are increased, however. Thus, the principal antihypertensive effect in the supine position is related to the reduction in cardiac output secondary to the reduced stroke volume and heart rate.
 
In the erect position (45-degree tilt), clonidine reduces MAP, CO, HR, and TPR, with no significant change in stroke volume. Cardiac output due to clonidine decreases less in hypertensive patients than in normal patients, and the antihypertensive effects of the drug appear to be related to a reduction in both cardiac output and TPR, with the effects of the reduced TPR predominating in the erect position. Renin and aldosterone output are reduced. Clonidine appears to decrease catecholamine excretion during prolonged therapy, but it does not deplete catecholamine stores. As an antihypertensive, clonidine reduces LVH and does not cause detrimental effects on glucose tolerance, although sexual dysfunction is a significant problem.
 
Clonidine is used to treat hypertension and the subsequent decline of renal function in patients with scleroderma renal crisis (SRC). SRC is associated with elevated peripheral renin concentrations. Clonidine reduces plasma renin activity by reducing sympathetic activity while increasing parasympathetic activity.
 
Because of clonidine's ability to inhibit sympathetic outflow, it has been used successfully to manage withdrawal from opiate agonists, ethanol, or nicotine; and 'hot flashes' associated with menopause. By inhibiting intrarenal vasoconstriction, clonidine has been used to offset cyclosporine-induced nephrotoxicity. Since pheochromocytomas are not under neurologic control, clonidine has been used successfully to differentiate the presence of these tumors from other hypertension-associated disease states.
 
Clonidine administered epidurally produces a dose-dependent analgesia that is not antagonized by opiate antagonists. By preventing pain signal transmission to the brain, clonidine produces analgesia at presynaptic and postjunctional alpha2-adrenoceptors in the spinal cord. Yohimbine, an alpha2-adrenoreceptor antagonist, will partially reverse the analgesic and sedation effects of epidural clonidine with no effect on clonidine-induced changes in blood pressure or heart rate. Clonidine-induced analgesia occurs only in body regions innervated by spinal segments where analgesic concentrations of clonidine are present. Clonidine enhances epidural or peripheral nerve blocks by blocking the conduction of C and A delta fibers and increasing potassium conductance in neurons and causing local vasoconstriction decreasing the elimination of the local anesthetic.

Clonidine is administered epidurally, orally, and via transdermal patch. Fifty percent (50%) of a circulating dose is metabolized in the liver to inactive compounds. Unchanged drug (40% to 60%) and its metabolites are excreted in the urine and feces.
 
Affected cytochrome P450 isoenzymes: none

Oral Route

Immediate- and extended-release clonidine have different pharmacokinetics characteristics; dose substitution on a mg-for-mg basis will result in differences in exposure. Food does not influence the pharmacokinetics of oral clonidine. The pharmacokinetics of clonidine are dose-proportional in the range of 100 to 600 mcg. Elimination half-life of clonidine is approximately 12 to 16 hours.
 
Immediate-release (IR) formulations
After oral administration of IR formulation, peak plasma concentrations are reached in approximately 1 to 5 hours. The absolute oral bioavailability is 70% to 80%. Blood pressure begins to decrease within 30 to 60 minutes, with maximal hypotensive effects occurring in 2 to 4 hours. Mean single-dose pharmacokinetic parameters in healthy adult patients (fasted-state; n = 15) during clinical trials were as follows: Cmax = 443 pg/mL; AUC = 7,313 hour x pg/mL; Tmax = 2.07 hours; half-life = 12.57 hours.
 
Extended-release (ER) formulations
After oral administration of ER formulation, peak clonidine concentrations were approximately 50% of those achieved with the IR formulation and occurred approximately 5 hours later. Similar half-lives were observed and total systemic bioavailability after the ER formulation was approximately 89% of that after the IR formulation. Mean single-dose pharmacokinetic parameters in healthy adult patients (fasted-state; n = 14) during clinical were as follows: Cmax = 258 pg/mL; AUC = 6,729 hour x pg/mL; Tmax = 6.5 hours; half-life = 12.65 hours.

Other Route(s)

Transdermal Route
The clonidine transdermal system consists of a patch, or 0.2 mm thick film, that contains four layers of a microporous polypropylene membrane. This patch holds a reservoir of clonidine that is released and absorbed across the skin at a constant rate over a 7-day period. The absolute bioavailability of clonidine from the transdermal patch is approximately 60%. Steady-state clonidine plasma concentrations are reached within 3 days after transdermal application to the upper outer arm and increase linearly with increasing size of the transdermal patch. Mean steady-state plasma concentrations with the 3.5 cm2 (0.1 mg clonidine/day), 7 cm2 (0.2 mg clonidine/day) and 10.5 cm2 (0.3 mg clonidine/day) systems are approximately 0.4 ng/mL, 0.8 ng/mL, and 1.1 ng/mL, respectively. Similar clonidine steady-state concentrations are reached after application to the chest. Steady-state clonidine plasma levels remain constant after removal of one system and application of a new system of the same size. After removal of the transdermal system, clonidine plasma concentrations decline slowly with a half-life of approximately 20 hours.
 
Epidural Route
Following epidural administration, peak clonidine plasma and cerebrospinal fluid concentrations were achieved in 19 and 26 minutes, respectively. Epidurally administered clonidine distributes into plasma via the epidural veins. Clonidine is highly lipid soluble and distributes widely throughout the body tissues, including the central nervous system. The CSF elimination half-life of clonidine is 1.3 hours. After an epidural dose of clonidine, women had a lower mean plasma clearance, longer mean plasma half-life, and higher mean peak concentration of clonidine in the plasma and CSF compared to men. The pharmacokinetics of epidural clonidine in children 1 to 9 years of age is similar to adults.

Pregnancy

Clonidine should be administered cautiously to breast-feeding women. Clonidine is excreted in human breast milk. Based on published lactation studies, clonidine is present in human milk at relative infant doses ranging from 4.1% to 8.4% of the maternal weight-adjusted dosage. Although in most cases, there were no reported adverse effects in breastfed infants exposed to clonidine, there is one case report of sedation, hypotonia, and apnea in an infant exposed to clonidine through breast milk. Monitor exposed breastfed infants for symptoms of hypotension and bradycardia, such as sedation, lethargy, tachypnea, and poor feeding. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed child from clonidine or from the underlying maternal condition.