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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(BAK loe fen)
Generic Available (U.S.)
Yes: Tablets
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of reversible spasticity associated with multiple sclerosis or spinal cord lesions
Orphan drug: Intrathecal: Treatment of intractable spasticity caused by spinal cord injury, multiple sclerosis, and other spinal disease (spinal ischemia or tumor, transverse myelitis, cervical spondylosis, degenerative myelopathy)
Use: Unlabeled
Intractable hiccups, intractable pain relief, bladder spasticity, trigeminal neuralgia, cerebral palsy, short-term treatment of spasticity in children with cerebral palsy, Huntington's chorea
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal reproduction studies. Withdrawal symptoms in the neonate were noted in a case report following the maternal use of oral baclofen 20 mg 4 times/day throughout pregnancy (Ratnayaka, 2001). Plasma concentrations following administration of intrathecal baclofen are significantly less than those with oral doses; exposure to the fetus is expected to be limited (Morton, 2009).
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Very small amounts of baclofen were found in the breast milk of a woman 14 days postpartum after oral use. Following a single oral dose of baclofen 20 mg, the total amount of baclofen excreted in breast milk within 26 hours was 22 mcg (Eriksson, 1981). Adverse events were not observed in a nursing infant following maternal use of intrathecal baclofen 200 mcg/day throughout pregnancy and while nursing (Morton, 2009).
Contraindications
Hypersensitivity to baclofen or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Abrupt withdrawal: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder. Use with caution in patients with a history of seizure disorder.
Special populations:
• Elderly: Use with caution in the elderly; may be more sensitive to adverse CNS effects, especially at higher doses.
Other warnings/precautions:
• Abrupt withdrawal: [U.S. Boxed Warning]: Avoid abrupt withdrawal of the drug; abrupt withdrawal of intrathecal baclofen has resulted in severe sequelae (hyperpyrexia, obtundation, rebound/exaggerated spasticity, muscle rigidity, and rhabdomyolysis), leading to organ failure and some fatalities. Risk may be higher in patients with injuries at T-6 or above, history of baclofen withdrawal, or limited ability to communicate.
• Intrathecal use: Cases (most from pharmacy compounded preparations) of intrathecal mass formation at the implanted catheter tip have been reported; may lead to loss of clinical response, pain or new/worsening neurological effects. Neurosurgical evaluation and/or an appropriate imaging study should be considered if a mass is suspected.
Adverse Reactions
>10%:
Central nervous system: Drowsiness, vertigo, psychiatric disturbances, insomnia, slurred speech, ataxia, hypotonia
Neuromuscular & skeletal: Weakness
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Fatigue, confusion, headache
Dermatologic: Rash
Gastrointestinal: Nausea, constipation
Genitourinary: Polyuria
<1%: Palpitation, chest pain, syncope, euphoria, excitement, depression, hallucinations, xerostomia, anorexia, abnormal taste, abdominal pain, vomiting, diarrhea, enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, paresthesia, hematuria, dyspnea
Withdrawal reactions have occurred with abrupt discontinuation (particularly severe with intrathecal use).
Metabolism/Transport Effects
None known.
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola.
Compatibility
Stable in sterile, preservative-free NS.
Mechanism of Action
Inhibits the transmission of both monosynaptic and polysynaptic reflexes at the spinal cord level, possibly by hyperpolarization of primary afferent fiber terminals, with resultant relief of muscle spasticity
Pharmacodynamics/Kinetics
Onset of action: 3-4 days
Peak effect: 5-10 days
Absorption (dose dependent): Oral: Rapid
Protein binding: 30%
Metabolism: Hepatic (15% of dose)
Half-life elimination: 3.5 hours
Time to peak, serum: Oral: Within 2-3 hours
Excretion: Urine and feces (85% as unchanged drug)
Dosage
Oral (avoid abrupt withdrawal of drug):
Children (unlabeled use):
Spasticity: Caution: Pediatric dosing expressed as a daily amount, and NOT in mg/kg. Limited published data in children; the following is a compilation of small prospective studies (Albright, 1996; Milla, 1977; Scheinberg, 2006) and one large retrospective study (Lubsch, 2006):
<2 years: 10-20 mg daily divided every 8 hours; titrate dose every 3 days in increments of 5-15mg/day to a maximum of 40 mg daily
2-7 years: Initial: 20-30 mg daily divided every 8 hours; titrate dose every 3 days in increments of 5-15 mg/day to a maximum of 60 mg daily
≥8 years: 30-40 mg daily divided every 8 hours; titrate dose every 3 days in increments of 5-15 mg/day to a maximum of 120 mg daily
Note: Baclofen dose may need to be increased over time. One retrospective analysis (Lubsch, 2006) suggested that increased doses were needed as the time increased from spasticity onset, as age increased, and as the number of concomitant antispasticity medications increased. A small number of patients required daily doses exceeding 200 mg.
Spasticity in cerebral palsy (unlabeled use): Initial: 5-10 mg/day in 3 divided doses (Delgado, 2010)
Adults: 5 mg 3 times/day, may increase 5 mg/dose every 3 days to a maximum of 80 mg/day
Hiccups (unlabeled use): Usual effective dose: 10-20 mg 2-3 times/day
Intrathecal: Children and Adults:
Test dose: 50-100 mcg, doses >50 mcg should be given in 25 mcg increments, separated by 24 hours. A screening dose of 25 mcg may be considered in very small patients. Patients not responding to screening dose of 100 mcg should not be considered for chronic infusion/implanted pump.
Maintenance: After positive response to test dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump. Initial dose via pump: Infusion at a 24-hour rate dosed at twice the test dose. Avoid abrupt discontinuation.
Elderly: Oral (the lowest effective dose is recommended): Initial: 5 mg 2-3 times/day, increasing gradually as needed; if benefits are not seen, withdraw the drug slowly.
Dosing adjustment in renal impairment: May be necessary to reduce dosage in renal impairment, but there are no specific guidelines available
Hemodialysis: Poor water solubility allows for accumulation during chronic hemodialysis. Low-dose therapy is recommended. There have been several case reports of accumulation of baclofen resulting in toxicity symptoms (organic brain syndrome, myoclonia, deceleration and steep potentials in EEG) in patients with renal failure who have received normal doses of baclofen.
Administration: Other
Intrathecal: For screening dosages, dilute with preservative-free sodium chloride to a final concentration of 50 mcg/mL for bolus injection into the subarachnoid space. For maintenance infusions, concentrations of 500-2000 mcg/mL may be used.
Administration: I.V. Detail
pH: 5-7
Test Interactions
Increased alkaline phosphatase, AST, glucose, ammonia (B); decreased bilirubin (S)
Patient Education
Abrupt discontinuation may cause hallucinations. Avoid alcohol use. You may experience transient drowsiness, lethargy, or dizziness. Intrathecal use: Keep scheduled pump refill visits; abrupt interruption can cause serious withdrawal symptoms. Report increased spasticity, itching, numbness, unresolved insomnia, painful urination, change in urinary patterns, constipation, high fever, or persistent confusion.
Geriatric Considerations
The elderly are more sensitive to the effects of baclofen and are more likely to experience adverse CNS effects at higher doses.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness and insomnia are common; rare reports of depression, euphoria, and hallucinations
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may produce additive sedation; concurrent use with MAO inhibitors may potentiate their hypotensive effects
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, intrathecal [preservative free]:
Gablofen®: 500 mcg/mL (20 mL); 2000 mcg/mL (20 mL)
Lioresal®: 500 mcg/mL (20 mL); 2000 mcg/mL (5 mL, 20 mL)
Injection, solution, intrathecal [for screening, preservative free]:
Gablofen®: 50 mcg/mL (1 mL)
Lioresal®: 50 mcg/mL (1 mL)
Tablet, oral: 10 mg, 20 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Baclofen)
10 mg (30): $13.99
20 mg (30): $17.99
Extemporaneously Prepared
A 5 mg/mL oral suspension may be made with tablets. Crush thirty 20 mg tablets in a mortar and reduce to a fine powder. Add a small amount of glycerin and mix to a uniform paste. Mix while adding Simple Syrup, NF in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add a sufficient quantity of vehicle to make 120 mL. Label “shake well” and “refrigerate”. Stable for 35 days (Johnson, 1993).
A 10 mg/mL oral suspension may be made with tablets. Crush one-hundred-twenty 10 mg tablets in a mortar and reduce to a fine powder. Add small portions (60 mL) of a 1:1 mixture of Ora-Sweet® and Ora-Plus® and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “refrigerate”. Stable for 60 days (Allen, 1996).
Allen LV Jr and Erickson MA 3rd, "Stability of Baclofen, Captopril, Diltiazem Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(18):2179-84.
Johnson CE and Hart SM, “Stability of an Extemporaneously Compounded Baclofen Oral Liquid,” Am J Hosp Pharm, 1993, 50(11):2353-5.
References
Abarbanel J, Herishanu Y, Frisher S, “Encephalopathy Associated With Baclofen,” Ann Neurol, 1985, 17(6):617-8.
Albright AL, “Baclofen in Treatment of Cerebral Palsy,” J Child Neurol, 1996, 11(2):77-83.
Cooke DE and Glasstone MA, “Baclofen Poisoning in Children,” Vet Hum Toxicol, 1994, 36(5):448-50.
Delgado MR, Hirtz D, Aisen M, et al, “Practice Parameter: Pharmacologic Treatment of Spasticity in Children and Adolescents With Cerebral Palsy (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child,” Neurology, 2010, 74(4):336-43.
Eriksson G and Swahn CG, "Concentrations of Baclofen in Serum and Breast Milk From a Lactating Woman," Scand J Clin Lab Invest, 1981, 41(2):185-7.
Khorasani A and Peruzzi WT, “Dantrolene Treatment for Abrupt Intrathecal Baclofen Withdrawal,” Anesth Analg, 1995, 80(5):1054-6.
Lubsch L, Habersang R, Haase M, et al, “Oral Baclofen and Clonidine for Treatment of Spasticity in Children,” J Child Neurol, 2006, 21(12):1090-2.
May CR, “Baclofen Overdose,” Ann Emerg Med, 1983, 12:171-3.
Milla PJ and Jackson AD, “A Controlled Trial of Baclofen in Children With Cerebral Palsy,” J Int Med Res, 1977, 5(6):398-404.
Morton CM, Rosenow J, Wong C, et al, "Intrathecal Baclofen Administration During Pregnancy: A Case Series and Focused Clinical Review," PM R, 2009, 1(11):1025-9.
Ratnayaka BD, Dhaliwal H, and Watkin S, "Drug Points: Neonatal Convulsions After Withdrawal of Baclofen," BMJ, 2001, 323(7304):85.
Roberge RJ, Martin TG, Hodgman M, et al, “Supraventricular Tachyarrhythmia Associated With Baclofen Overdose,” J Toxicol Clin Toxicol, 1994, 32(3):291-7.
Scheinberg A, Hall K, Lam LT, et al, “Ora Baclofen in Children With Cerebral Palsy: A Double-Blind Cross-Over Pilot Study,” J Paediatr Child Health, 2006, 42(11):715-20.
Tan AK and Tan CB, “The Syndrome of Painful Legs and Moving Toes - A Case Report,” Singapore Med J, 1996, 37(4):446-7.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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