Lioresal

Muscle Relaxants, Centrally Acting, Plain

Oral Administration

Baclofen may be administered with food or milk to minimize gastric irritation.
Whenever baclofen is discontinued, the daily dosage should be gradually decreased; abrupt discontinuation may result in adverse reactions.

Oral Solid Formulations

Oral granules (Lyvispah)
Empty the entire contents of the packet into the mouth. The granules will dissolve in the mouth or can be swallowed. The granules can be administered with liquids or soft foods if needed.
Alternatively, the granules may be mixed with up to 15 mL of liquid or soft food (such as apple sauce, yogurt, or pudding), and administered within 2 hours following mixing. When using multiple packets, mix each packet with a separate volume of liquid or soft food.
 
Oral granules (Lyvispah) Feeding Tube Administration
Oral granules can be administered via enteral feeding tubes including nasogastric (NG) tubes at sizes 8 French (FR) or higher, gastrostomy tubes at sizes 12 FR or higher, percutaneous endoscopic gastrostomy (PEG) tubes at sizes 14 FR or higher, and gastrojejunostomy (GJ) tubes at sizes 16 FR or higher.
Flush the feeding tube with up to 15 mL of water using a catheter tip syringe.
Mix each packet of granules with 15 mL of a preferred liquid (e.g., apple juice or milk) in a clean container; ensure the granules are wetted. Draw up the suspension into an oral dosing syringe administer within 2 hours following mixing. Invert the syringe 3 times to ensure mixing if the suspension stands for 15 minutes or more.
Flush the feeding tube with 15 mL or water following administration.
When using multiple packets, mix each packet with a separate volume of liquid.

Oral Liquid Formulations

Oral Solution (Ozobax)
Measure using a calibrated oral dosing cup, spoon, syringe, or other oral device to ensure accurate dosage.
Must keep refrigerated.
 
Oral Suspension (Fleqsuvy)
Verify strength and dosage of the product prior to administration. The suspension is a concentrated formulation.
Shake well before each administration.
Measure using a calibrated oral dosing cup, spoon, syringe, or other oral device to ensure accurate dosage.
Storage: Store at room temperature. Discard any unused suspension 2 months after opening.

Injectable Administration

For intrathecal administration only via injection or continuous infusion; do not give parenterally or by epidural routes.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intrathecal Administration

Only use implantable pumps FDA-approved for the administration of continuous intrathecal baclofen infusions. Refer to the implantable pump manual for the specific instructions and precautions regarding pump programming and filling the reservoir.
Before pump implantation and initiation of chronic intrathecal baclofen therapy, patients must demonstrate a positive response to a baclofen intrathecal dose in a screening trial.
IMPORTANT: Avoid use of baclofen prefilled syringes for intrathecal injection (Gablofen) in an aseptic setting (e.g., operating room) to fill sterile intrathecal pumps before implantation in patients due to the non-sterile external surface of the syringe and the potential for contamination. Baclofen injection in vials may be used with conventional aseptic technique to fill intrathecal pumps before implantation. If prefilled syringes are used to fill intrathecal pumps before implantation, the external surface of the syringe must be treated to ensure sterility.
Procedures should also be in place to avoid contamination of sterile surfaces through contact with the non-sterile external surface of prefilled syringes when refilling implantable intrathecal pumps in the outpatient setting.[42610] [42609]
 
Dilution:
Dilution of baclofen injection is not required prior to use. However, if a baclofen concentration that is not commercially available is needed, dilute only with sterile, preservative-free 0.9% Sodium Chloride Injection.
The specific concentration that should be used depends upon the total daily dose required as well as the delivery rate of the pump. Baclofen intrathecal injection may require dilution when used in certain pumps. Consult the manufacturer's manual for specific recommendations.[42609] [42610]
 
Intrathecal Administration:
Administer screening test dose intrathecally over at least 1 minute using barbotage. Following determination of patient response, baclofen may be administered by continuous intrathecal infusion using an implantable controlled-infusion pump.
If patients require multiple infusion rates for optimal symptom control, changes in flow rate should be programmed to start 2 hours before the time of the desired clinical effect.
ALERT: Avoid abrupt discontinuation of intrathecal baclofen therapy as serious, and potential fatal sequela may result. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms.
ALERT: Over-infusion of more drug volume than the programmed rate can result in unexpected overdose or withdrawal caused by early emptying of the reservoir. If over-infusion is suspected, refer to the manufacturer's pump instructions for refilling the reservoir and contact the pump manufacturer. Reducing the dose and concentration is not recommended as a solution for over-infusion. Multiple factors may increase the risk for over-infusion, including the use of nonindicated drug formulations, overfilling of the pump reservoir, operation of the pump with no fluid in the reservoir, catheter occlusion, and pump stops or motor stalls lasting 48 hours or more.[42609] [42610]

Severe

coma / Early / 0-1.5
seizures / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
stroke / Early / Incidence not known
ileus / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
oliguria / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
thrombosis / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
bradycardia / Rapid / Incidence not known
apnea / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
neuroleptic malignant syndrome / Delayed / Incidence not known
malignant hyperthermia / Rapid / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known

Moderate

hypotonia / Delayed / 2.4-34.7
confusion / Early / 0.5-11.0
hypotension / Rapid / 0-9.0
urinary retention / Early / 0.7-8.0
hypertonia / Delayed / 0-6.0
constipation / Delayed / 0.2-6.0
hypoventilation / Rapid / 0.2-4.0
peripheral edema / Delayed / 0-3.3
amblyopia / Delayed / 0.2-2.3
urinary incontinence / Early / 0-2.0
depression / Delayed / 0-1.6
impotence (erectile dysfunction) / Delayed / 0.2-1.6
impaired cognition / Early / 0.5-1.3
dyspnea / Early / 0-1.2
hypertension / Early / 0.2-0.6
hallucinations / Early / 0.3-0.5
dystonic reaction / Delayed / Incidence not known
dyskinesia / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
euphoria / Early / Incidence not known
respiratory depression / Rapid / Incidence not known
psychological dependence / Delayed / Incidence not known
blurred vision / Early / Incidence not known
dysarthria / Delayed / Incidence not known
akathisia / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
psychosis / Early / Incidence not known
hyperglycemia / Delayed / Incidence not known
dysuria / Early / Incidence not known
hematuria / Delayed / Incidence not known
vaginitis / Delayed / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
palpitations / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
meningitis / Delayed / Incidence not known
anemia / Delayed / Incidence not known
withdrawal / Early / Incidence not known
priapism / Early / Incidence not known

Mild

drowsiness / Early / 5.7-63.0
weakness / Early / 5.0-15.0
dizziness / Early / 1.7-15.0
nausea / Early / 1.4-12.0
headache / Early / 1.6-10.7
vomiting / Early / 1.6-10.5
insomnia / Early / 0-7.0
paresthesias / Delayed / 0.7-6.7
increased urinary frequency / Early / 0-6.0
pruritus / Rapid / 0-4.0
fatigue / Early / 2.0-4.0
xerostomia / Early / 0-3.3
hypersalivation / Early / 0-2.7
diarrhea / Early / 0-2.3
asthenia / Delayed / 0-2.0
back pain / Delayed / 0.7-2.0
agitation / Early / 0.5-1.3
tremor / Early / 0-1.3
chills / Rapid / 0-1.3
urticaria / Rapid / 0.2-1.2
abdominal pain / Early / 0-1.0
anxiety / Delayed / 0.2-0.9
diplopia / Early / 0-0.9
anorexia / Delayed / 0-0.9
musculoskeletal pain / Early / Incidence not known
hyporeflexia / Delayed / Incidence not known
emotional lability / Early / Incidence not known
miosis / Early / Incidence not known
tinnitus / Delayed / Incidence not known
paranoia / Early / Incidence not known
mydriasis / Early / Incidence not known
flatulence / Early / Incidence not known
weight gain / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
dyspepsia / Early / Incidence not known
libido decrease / Delayed / Incidence not known
nocturia / Early / Incidence not known
orgasm dysfunction / Delayed / Incidence not known
hyperhidrosis / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
rash / Early / Incidence not known
premature atrial contractions (PACs) / Early / Incidence not known
malaise / Early / Incidence not known
hypothermia / Delayed / Incidence not known
influenza / Delayed / Incidence not known
petechiae / Delayed / Incidence not known
leukocytosis / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
rhinitis / Early / Incidence not known
hyperventilation / Early / Incidence not known

Abrupt discontinuation, priapism

Avoid abrupt discontinuation of intrathecal baclofen therapy. Abrupt discontinuation of intrathecal baclofen, regardless of cause, has resulted in severe reactions including high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multi-system organ failure, and death. Priapism may also develop or recur if intrathecal therapy is interrupted. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to at-risk patients (e.g., spinal cord injuries at T6 or above, communication difficulties, or history of withdrawal symptoms from oral or intrathecal baclofen). Rapid, accurate diagnosis and treatment are important to prevent potentially life-threatening central nervous system and systemic effects of intrathecal baclofen withdrawal. When appropriate, oral baclofen and/or oral or intravenous benzodiazepines may be considered for emergency use.[42609] [42610] Also avoid sudden discontinuation of oral baclofen after chronic use; abrupt discontinuation is associated with confusion, hallucinations, other psychiatric disturbances, seizure(s), and exacerbations of spasticity or other neurologic events. Gradual reduction of the oral dosage over a period of 2 weeks or more is recommended. Use baclofen with caution in patients with a history of autonomic dysreflexia (e.g., spinal cord injuries at T6 or above), as abrupt withdrawal or nociceptive stimuli may cause autonomic dysreflexic episodes.

ED Baclofen, FLEQSUVY, Gablofen, Lioresal, Lioresal Intrathecal, LYVISPAH, OZOBAX

Rx

Orally and intrathecally administered skeletal muscle relaxant; derivative of the inhibitory neurotransmitter GABA
Used to treat spasticity in patients with MS and other spinal cord lesions; may improve bowel and bladder function in some patients
Abrupt discontinuation may cause serious and fatal adverse reactions; avoid rapid drug withdrawal

For the treatment of spasticity, muscle spasm (not due to rheumatic conditions), myoclonus, and muscle rigidity in multiple sclerosis and spinal cord injury or other spinal cord diseases. For severe spasticity due to multiple sclerosis, cerebral palsy, spinal cord injury, or traumatic brain injury; or in patients unresponsive to oral baclofen therapy or those who experience intolerable side effects at effective oral doses.
NOTE: Intrathecal baclofen has been designated an orphan drug by the FDA for this indication.
Intrathecal dosage (Screening dose) Adults

Dosage requires special procedures, patient screening, and dosage techniques; consult specialized resources. Recommended initial screening dose is 50 mcg intrathecally by barbotage over a period of at least 1 minute. The patient is observed over 4 to 8 hours. A positive response consists of significant decrease in muscle tone and/or frequency and/or severity of spasms. If the initial response is less than desired, a second bolus of 75 mcg intrathecally may be given 24 hours after the first dose, and observe for 4 to 8 hours. If the response is still inadequate, a final bolus of 100 mcg intrathecally may be given 24 hours later. Patients who do not respond to the 100 mcg dose should not be considered candidates for an implanted pump for chronic infusion.

Children 4 years and older

Dosage requires special procedures, patient screening, and dosage techniques; consult specialized resources. The initial screening dose and procedure is the same as in adults, 50 mcg intrathecally initially. However, for very small patients, a screening dose of 25 mcg intrathecally may be tried first.

Intrathecal dosage (Dose titration) Adults

Dosage requires special dosage techniques and monitoring; consult specialized resources. The screening dose that gave a positive response should be doubled and administered as a continuous intrathecal infusion over a 24-hour period, unless the efficacy of the screening bolus dose was maintained for 8 hours or longer. In this case, the starting daily dose should be the screening dose delivered intrathecally over a 24-hour period. No dose increases should be given in the first 24 hours. After the first 24 hours, the daily dosage should be increased slowly by 10% to 30% increments for spasticity of spinal cord origin or 5% to 15% increments for spasticity of cerebral origin per 24-hour period, until a desired clinical effect is achieved.

Children 4 years and older

Dosage requires special dosage techniques and monitoring; consult specialized resources. The screening dose that gave a positive response should be doubled and administered as a continuous intrathecal infusion over a 24-hour period, unless the efficacy of the screening bolus dose was maintained for 8 hours or longer. In this case, the starting daily dose should be the screening dose delivered intrathecally over a 24-hour period. No dose increases should be given in the first 24 hours. After the first 24 hours, the daily dosage should be increased slowly 5% to 15% increments per 24-hour period, until a desired clinical effect is achieved.

Intrathecal maintenance dosage (Spasticity of spinal origin) Adults

Maintenance dosage for long-term continuous intrathecal infusion has ranged from 12 mcg/day to 2,003 mcg/day, with most patients maintained on dosages of 300 to 800 mcg/day. There is limited experience with doses more than 1,000 mcg/day. Doses are titrated to response with the lowest possible effective dose utilized. During periodic pump refills, the daily dose may be increased by 10% to 40%, but no more than 40%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Children 4 years and older

For children younger than 12 years, the average dose was 274 mcg/day intrathecally (24 to 1,199 mcg/day). Dosage requirements for children older than 12 years are not significantly different from adults. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Intrathecal maintenance dosage (Spasticity of cerebral origin) Adults

Maintenance dosage for long-term continuous intrathecal infusion has ranged from 22 mcg/day to 1,400 mcg/day, with most patients maintained on dosages of 90 to 703 mcg/day. There is limited experience with doses more than 1,000 mcg/day. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Children 4 years and older

For children younger than 12 years, the average dose was 274 mcg/day intrathecally (24 to 1,199 mcg/day). Dosage requirements for children older than 12 years are not significantly different from adults. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Oral dosage Adults

5 mg PO 3 times daily, initially. Increase the dose by 5 mg/dose every 3 days as needed. Usual dose: 40 to 80 mg/day divided in 3 to 4 doses. Max: 80 mg/day. Some clinicians suggest that higher doses are well tolerated and offer a therapeutic advantage. Mean doses of 140 to 160 mg/day PO have been used during clinical experience. Some patients have required up to 240 mg/day.

Children and Adolescents 12 to 17 years

Optimal dosing requires careful titration. Initially, 5 mg PO 3 times daily, increase slowly every 3 days by 5 mg PO 3 times/day up to 40 to 80 mg/day given in 3 to 4 divided doses. Adverse reactions can be minimized by slowly increasing the dosage. A 4-times per day regimen may provide better control in some patients. Some patients require 1 to 2 months of treatment for full benefit. Avoid abrupt discontinuation of therapy. The maximum dose recommended by the manufacturers is 80 mg/day, however some clinicians suggest that doses up to 160 mg/day are well tolerated and offer a therapeutic advantage.

Children 8 to 11 years†

Initially, 10 to 15 mg/day PO in 3 divided doses. Titrate slowly every 3 days in 5 to 15 mg increments to a maximum dose of 60 mg/day.

Children 2 to 7 years†

Initially, 10 to 15 mg/day PO in 3 divided doses. Titrate slowly every 3 days in 5 to 15 mg increments to a maximum dose of 40 mg/day.

For the treatment of persistent singultus (hiccups)†. Oral dosage Adults

Baclofen may be just as effective as other agents already in use. A dose of 10 mg PO 4 times per day has been used.

For the treatment of trigeminal neuralgia†. Oral dosage Adults

10 mg PO 3 times daily for 1 week, initially. Increase the dose by 10 mg/day every other day as needed. Usual dose: 40 to 80 mg/day divided in 3 to 4 doses. Max: 80 mg/day.

For the treatment of central vestibular nystagmus†. Oral dosage Adults

Initially, 5 mg PO 3 times per day. Increase dosage by 5 mg per week not to exceed 80 mg/day. It is advisable to individualize the dosage based upon clinical response and tolerability.

For prevention of stuttering priapism† (i.e., recurrent priapism). Oral dosage Adults

Two case reports suggest 40 mg PO at bedtime is effective. Complete resolution of priapism occurred in 2 patients with idiopathic priapism. In both patients, baclofen was initiated at 10 mg PO at bedtime and titrated to effect; priapism was eliminated at a dosage of 40 mg/day. Priapism has not recurred with chronic administration (longer than 5 months in 1 patient and longer than 12 months in the other); sexual function has remained intact.

For the adjunct treatment of symptomatic gastroesophageal reflux disease (GERD)† in refractory patients. Oral dosage Adults

5 to 20 mg PO 3 times daily may be considered in patients with objective documentation of continued symptomatic GERD despite optimal PPI therapy. Limited data from uncontrolled, short-term studies suggests benefits such as a reduction in transient LES relaxation, reflux episodes, postprandial acid and non-acid reflux events, nocturnal reflux activity, and belching episodes. Long-term efficacy and safety data are not available.

For the treatment of severe muscle cramps in persons with hepatic cirrhosis†. Oral dosage Adults

10 mg PO once daily, initially. Increase the dose by 10 mg/day every week up to 30 mg/day as tolerated or until disappearance of cramps for 3 months. Taper dose by 10 mg/day every week to discontinue.

†Indicates off-label use

Hepatic Impairment

No dosage adjustment necessary.

Renal Impairment

CrCl more than 80 mL/minute: No dosage adjustment necessary.
CrCl 50 to 80 mL/minute: Reduce PO dosage by one-third.
CrCl 30 to 50 mL/minute: Reduce PO dosage by one-half.
CrCl less than 30 mL/minute and not on dialysis: Reduce PO dosage by two-thirds.
 
Use intrathecal baclofen with caution in patients with renal impairment. A dosage reduction may be necessary. Specific guidelines for dosage adjustments in renal impairment are not available.
 
Intermittent hemodialysis
Alternative therapies should be considered due to the potential for serious adverse effects. The pharmacokinetic properties of baclofen (i.e., low protein binding and volume of distribution) and low molecular weight (213 daltons) suggest that hemodialysis should be useful in removing baclofen from the blood in cases of clinical toxicity; although, efficacy of hemodialysis for this purpose has not been established.

Acebutolol: (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.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression is possible if skeletal muscle relaxants are used concomitantly with other CNS depressants. Dosage adjustments of one or both medications may be necessary.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Alfentanil: (Major) Concomitant use of alfentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Alprazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Amiloride: (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.
Amiloride; Hydrochlorothiazide, HCTZ: (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.
Amlodipine: (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.
Amlodipine; Atorvastatin: (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.
Amlodipine; Benazepril: (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.
Amlodipine; Celecoxib: (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.
Amlodipine; Olmesartan: (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.
Amlodipine; Valsartan: (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.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (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.
Amobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Amoxapine: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive CNS depressant effects. Skeletal muscle relaxants may produce additive CNS depression or other additive effects when combined with tricyclic antidepressants. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Angiotensin II receptor antagonists: (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.
Angiotensin-converting enzyme inhibitors: (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.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Atenolol: (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.
Atenolol; Chlorthalidone: (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.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with baclofen can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of opioid agonists with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
Benazepril: (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.
Benazepril; Hydrochlorothiazide, HCTZ: (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.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Beta-adrenergic blockers: (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.
Betaxolol: (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.
Bisoprolol: (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.
Bisoprolol; Hydrochlorothiazide, HCTZ: (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.
Botulinum Toxins: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Brimonidine; Timolol: (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.
Buprenorphine: (Major) Reserve concomitant prescribing of buprenorphine and baclofen for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Buprenorphine; Naloxone: (Major) Reserve concomitant prescribing of buprenorphine and baclofen for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Butabarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as baclofen, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Calcium-channel blockers: (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.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and baclofen. CNS depressants can potentiate the effects of cannabidiol.
Captopril: (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.
Captopril; Hydrochlorothiazide, HCTZ: (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.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. 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.
Carteolol: (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.
Carvedilol: (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.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and baclofen. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (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.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Chlordiazepoxide: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Chlorpromazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Clevidipine: (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.
Clonazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clorazepate: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clozapine: (Moderate) Skeletal muscle relaxants should be combined cautiously with clozapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. 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.
Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as baclofen, may have additive effects and worsen drowsiness or sedation.
Dexmedetomidine: (Moderate) Due to the anesthetic effects of dexmedetomidine, concurrent use with other CNS depressants, such as skeletal muscle relaxants, could result in additive sedative effects and possibly prolong recovery from anesthesia. Dosage adjustments of either or both medications may be necessary.
Diazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
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.
Diltiazem: (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.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with baclofen can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dorzolamide; Timolol: (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.
Doxazosin: (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.
Dronabinol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Droperidol: (Moderate) Concomitant use of baclofen with other CNS depressants like droperidol can result in additive CNS depression.
Enalapril, Enalaprilat: (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.
Enalapril; Hydrochlorothiazide, HCTZ: (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.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. 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.
Eplerenone: (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.
Epoprostenol: (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.
Esketamine: (Major) Closely monitor patients receiving esketamine and skeletal muscle relaxants for sedation and other CNS depressant effects. Patients who receive a dose of esketamine should not drive or engage in other activities requiring alertness until the next day after a restful sleep.
Esmolol: (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.
Estazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Eszopiclone: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Felodipine: (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.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and baclofen. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of fentanyl with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Fluphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Flurazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
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.
Fosinopril: (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.
Fosinopril; Hydrochlorothiazide, HCTZ: (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.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and baclofen. Concomitant use of gabapentin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
General anesthetics: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Hydrochlorothiazide, HCTZ; Moexipril: (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.
Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
Hydromorphone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Iloprost: (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.
Isoflurane: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Isradipine: (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.
Ketamine: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Labetalol: (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.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and baclofen. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and baclofen. Dosage adjustments of lemborexant and baclofen 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.
Levamlodipine: (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.
Levobunolol: (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.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Levorphanol: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial levorphanol dosage by 50% or more.
Lisinopril: (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.
Lisinopril; Hydrochlorothiazide, HCTZ: (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.
Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and baclofen. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known. In the use of intrathecal baclofen, hypotension is possible, so the additive effects of lofexidine on blood pressure should be considered. Carefully monitor blood pressure and heart rate in such patients.
Loop diuretics: (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.
Lorazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Loxapine: (Moderate) Loxapine is a central nervous system (CNS) depressant. The concurrent use of loxapine with other CNS depressants (e.g., muscle relaxants such as baclofen) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with loxapine.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Maprotiline: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Mecamylamine: (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.
Meperidine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Meprobamate: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Methadone: (Major) Concomitant use of methadone with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of baclofen and methocarbamol. Concurrent use may result in additive CNS depression.
Methohexital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Methscopolamine: (Moderate) CNS depression can be increased when methscopolamine is combined with other CNS depressants such as skeletal muscle relaxants.
Metoprolol: (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.
Metoprolol; Hydrochlorothiazide, HCTZ: (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.
Midazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Mirtazapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and mirtazapine due to the risk for additive CNS depression.
Moexipril: (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.
Molindone: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as molindone, can increase CNS depression. In addition, antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Morphine: (Major) Concomitant use of morphine with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Major) Concomitant use of morphine with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nabilone: (Major) Avoid use together if possible. Use of nabilone with skeletal muscle relaxants can potentiate the CNS depressant effects of nabilone on sedation, dizziness and other side effects, which can impair the ability to undertake tasks requiring mental alertness.
Nadolol: (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.
Nalbuphine: (Major) Concomitant use of nalbuphine with baclofen may cause excessive sedation and somnolence. Limit the use of nalbuphine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Nebivolol: (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.
Nebivolol; Valsartan: (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.
Nicardipine: (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.
Nifedipine: (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.
Nimodipine: (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.
Nisoldipine: (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.
Oliceridine: (Major) Concomitant use of oliceridine with baclofen may cause excessive sedation and somnolence. Limit the use of oliceridine with baclofen 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.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (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.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. 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.
Oxazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Oxymorphone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half.
Pentazocine: (Major) Concomitant use of pentazocine with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
Pentobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Perindopril: (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.
Perindopril; Amlodipine: (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.
Perphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Phenobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Phenothiazines: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Phenoxybenzamine: (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.
Phentolamine: (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.
Pindolol: (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.
Potassium-sparing diuretics: (Moderate) Baclofen has been associated with hy

potension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Prazosin: (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.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and baclofen. Concomitant use of pregabalin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primidone: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Prochlorperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Promethazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Promethazine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Propofol: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Propranolol: (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.
Propranolol; Hydrochlorothiazide, HCTZ: (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.
Quazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Quinapril: (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.
Quinapril; Hydrochlorothiazide, HCTZ: (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.
Ramipril: (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.
Remifentanil: (Major) Concomitant use of remifentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Remimazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Secobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Sedating H1-blockers: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including skeletal muscle relaxants, such as baclofen.
Sevoflurane: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Spironolactone: (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.
Spironolactone; Hydrochlorothiazide, HCTZ: (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.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and baclofen. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of sufentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tapentadol: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Telmisartan; Amlodipine: (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.
Temazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Terazosin: (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.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as skeletal muscle relaxants due to the potential for additive sedative effects.
Thiazide diuretics: (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.
Thioridazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Timolol: (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.
Tizanidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of baclofen and tizanidine. Concurrent use may result in additive CNS depression.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. 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.
Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Trandolapril: (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.
Trandolapril; Verapamil: (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.
Trazodone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and trazodone due to the risk for additive CNS depression.
Treprostinil: (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.
Triamterene: (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.
Triamterene; Hydrochlorothiazide, HCTZ: (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.
Triazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of baclofen and tricyclic antidepressants due to the risk for additive CNS depression.
Trifluoperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Valerian, Valeriana officinalis: (Moderate) Concomitant use of baclofen with the phytomedicinals valerian, Valeriana officinalis can result in additive CNS depression.
Vasodilators: (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.
Verapamil: (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.
Zaleplon: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ziprasidone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including baclofen.
Zolpidem: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.

Baclofen/ED Baclofen/Lioresal Oral Tab: 5mg, 10mg, 20mg
Baclofen/FLEQSUVY Oral Susp: 1mL, 5mg
Baclofen/Gablofen/Lioresal/Lioresal Intrathecal Intrathecal Inj Sol: 0.05mg, 0.5mg, 1mL, 2mg, 1000mcg
Baclofen/OZOBAX Oral Sol: 5mg, 5mL
Gablofen Intrathecal Sol: 1mL, 50mcg, 500mcg, 1000mcg, 2000mcg
LYVISPAH Oral Gran: 5mg, 10mg, 20mg

Adults

80 mg/day PO is the labeled maximum; however, up to 240 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

Geriatric

80 mg/day PO is the labeled maximum; however, up to 240 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

Adolescents

80 mg/day PO is the labeled maximum; however, up to 160 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

Children

12 years: 80 mg/day PO is the labeled maximum; however, up to 160 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.
8 to 11 years: 60 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.
2 to 7 years: 40 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen. Safe and effective use of intrathecal baclofen has not been established for children less than 4 years.
Less than 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by stimulation of the GABA B receptor subtype. In people, as well as in animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.

Baclofen is given orally or intrathecally. Baclofen crosses the placenta and is excreted into breast milk. Protein binding is low (roughly 30%). Approximately 15% of a baclofen dose is metabolized in the liver, mostly by deamination. The serum half-life ranges from 2.5 to 5.7 hours. The kidney excretes 70% to 85% of a dose as unchanged drug and metabolites, and the remainder is excreted via the feces.
 
Affected cytochrome P450 enzymes and drug transporters: None

Oral Route

Following oral administration, baclofen is rapidly and almost completely absorbed, although bioavailability varies from patient to patient. Both the rate and extent of absorption is inversely proportional to the dose. Oral baclofen is distributed throughout the body (volume of distribution 2.4 L/kg), but only minimally crosses the blood-brain barrier. Bioavailability for oral solution, oral suspension, oral granules, and oral tablets is similar at the 20 mg dose level under fasting conditions. Maximum concentration occurred at approximately 0.75 hours (Tmax) for the oral solution. Bioavailability of the oral granule was not affected by administration with applesauce. Peak plasma concentrations are achieved within 1 hour following administration of the oral granules. Baclofen exposure following oral granule administration was dose proportional across the dose range of 5 mg, 10 mg, and 20 mg. A 10% decrease in AUC and a 29% decrease in Cmax compared to the fasted state occurred during administration of the oral granules with a high fat meal. Tmax occurred at approximately 1 hour following administration of the oral suspension in the fasted state. The apparent elimination half-life of baclofen in the oral suspension is approximately 5.6 hours. A 9% decrease in AUC and a 33% decrease in Cmax compared to the fasted state occurred during administration of the oral suspension with a high fat meal.

Other Route(s)

Intrathecal Route
When baclofen is introduced directly into the intrathecal space, effective CSF concentrations are achieved with plasma concentrations 100-times less than those occurring with oral administration. The onset of action following intrathecal administration occurs within 0.5 to 1 hour and peak antispasmodic effect is seen approximately 4 hours after dosing and lasts 4 to 8 hours; although, there is considerable interpatient variability. With continuous intrathecal infusion, the initial antispasmodic effect is seen within 6 to 8 hours and peak effects are observed within 24 to 48 hours. CSF clearance of baclofen approximates CSF turnover, suggesting that elimination of the drug occurs via bulk-flow removal of CSF. Following an intrathecal dose of 50 or 100 mcg, the CSF elimination half-life over the first 4 hours is 1.51 hours and the average CSF clearance was approximately 30 mL/hour. The mean CSF clearance for LIORESAL INTRATHECAL (baclofen injection) was approximately 30 mL/hour in a study (n = 10 patients) of continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during intrathecal administration are expected to be low (0 to 5 ng/mL). Limited pharmacokinetic data suggest that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5 patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic efficacy; the interpatient variability was great. The gradient was not altered by position.

Pregnancy

At therapeutic oral doses, baclofen is excreted in human milk; caution is recommended when using the drug during breast-feeding. Withdrawal symptoms in the infant may occur if breast-feeding is stopped or oral baclofen is discontinued. It is not known if baclofen is detectable in breast milk after intrathecal administration; the labeling for intrathecal products recommends that a decision be made whether to discontinue breast-feeding or to discontinue intrathecal baclofen injection, considering the importance of intrathecal baclofen therapy to the mother. Limited information indicates that oral baclofen to the lactating mother appears in low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Low intrathecal doses and topical application are unlikely to affect the nursing infant. If baclofen is continued, monitor the infant for signs of sedation. In one report in a woman given a single 20 mg oral dose of baclofen 14 days postpartum, the highest serum concentration of the drug occurred at 3 hours and the highest milk level was obtained at 4 hours. The total amount of drug recovered from the milk during the 26-hour sampling period was about 0.1% of the maternally ingested dose.