baclofen LIORESAL/GABLOFEN
Class: Skeletal Muscle RelaxantFDA Indications: Spasticity Resulting From Multiple Sclerosis
Off-Label Use: Alcoholic Liver Disease, Alcohol Abstinence, Gastroesophageal Reflux Disease, Hiccups, Nystagmus, Trigeminal Neuralgia
Prescribing
Forms: 10, 20mg tablet; 40,000 mcg/20 mLmg Intrathecal; 1 mg/mL, 5 mg/mL po solnDose Range: 15-80 mg/day
Starting: Spasticity: 5 mg PO q8°; may ↑ by 5 mg/dose q3Days to maximum 80 mg/day
Precautions
Serious Side Effects: Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which in rare cases has advanced to rhabdomyolysis, multiple organ-system failure, and death.Side Effects: sedation/somnolence, weakness/asthenia, vertigo, confusion, headache, insomnia, hypotension, nausea, constipation, urinary frequency
Pharmacodynamics
1° MOA: Centrally acting skeletal muscle relaxant and antispastic, inhibits spinal cord monosynaptic and polysynaptic reflexes via GABAB receptor-mediated opening of neuronal K+ channels that leads to hyperpolarization of primary afferent fiber terminalsTarget: GABAB receptor agonist
Pharmacokinetics
t½: 2.5 (1.5-4)° TMAX: 1°Substrate of: Renal (70-80%); hepatic/deamination (15%)
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - caution with coprescribed CNS depressants
Misc
- - The only drug currently in clinical use that selectively interacts with GABAB receptors
- - there is some data suggesting 30-60 mg qd may be safe and effective for the treatment of alcohol-dependent individuals with normal renal function who have not been diagnosed with a psychiatric illness and do not carry a history of seizures
- - Activation of GABAB receptors may result in local inhibition of surrounding DA neurons that are thought to be involved in the mediation of alcohol intake and reinforcement & through this mechanism, alcohol-stimulated DA release would be ↓'d, ∴ ↓-ing positive reinforcement from alcohol
Special Populations
Category C—Human data suggests risk; a comparison of 134 pregnant women who had taken baclofen in early pregnancy and 400 pregnant controls showed an increased risk of major malformations. Several infants exposed to baclofen until birth exhibited withdrawal symptoms.
Limited human data — probably compatible
Use with caution in elderly patients; may be more sensitive to adverse CNS effects, especially at higher doses.
CrCl >80 mL/min: No initial dosage adjustment necessary
CrCl 50-80 mL/min: Initial: 5 mg every 12°
CrCl 30-50 mL/min: Initial: 2.5 mg every 8°
CrCl <30 mL/min(not on dialysis): Initial: 2.5 mg q12°
There are no dosage adjustments provided in the manufacturer's labeling.
References
Foye's Principles Of Medicinal ChemistryPackage Insert
UpToDate
A Controlled Pharmacokinetic Evaluation Of Tizanidine And Baclofen At Steady State
Clinical Effectiveness Of Baclofen For The Treatment Of Alcohol Dependence: A Review
Baclofen And Pregnancy: Birth Defects And Withdrawal Symptoms.
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