baclofen
Lioresal

Available forms
Available by prescription only
Intrathecal kit: 500 mcg/ml, 2,000 mcg/ml
Tablets: 10 mg, 20 mg

Indications and dosages
 Spasticity in multiple sclerosis and other spinal cord lesions. Adults: Initially, 5 mg P.O. t.i.d. for 3 days. Dosage may be increased (based on response) at 3-day intervals by 15 mg (5 mg/dose) daily up to maximum of 80 mg daily. For geriatric patients, increase oral dose more gradually.
 Intrathecal administration
 Must be diluted with sterile preservative-free normal saline solution.
Adults: Initial intrathecal bolus of 50 mcg in 1 ml over not less than 1 minute. Observe patient for response over subsequent 4 to 8 hours. A positive response consists of a significant decrease in muscle tone or frequency or severity of spasm. If initial response is inadequate, repeat dose with 75 mcg in 1.5 ml 24 hours after last injection. Repeat observation of patient over 4 to 8 hours. If the response is still inadequate, repeat dosing at 100 mcg in 2 ml 24 hours later. If still no response, patient shouldn’t be considered for an implantable pump for long-term baclofen administration. Ranges for long-term doses are 12 to 2,000 mcg daily.
Children younger than age 12: Test dose is the same as for adults (50 mcg); but for very small children, an initial dose of 25 mcg may be given. Maintenance dose averages 274 mcg daily (range 24 to 1,200 mcg daily).
Postimplant dosage adjustment
 If the screening dose produces the desired effect for over 8 hours, the initial intrathecal dose is the same as the test dose; this dose is infused intrathecally for 24 hours. If the screening dose produces the desired effect for less than 8 hours, the initial intrathecal dose is twice the test dose, followed slowly by 10% to 30% increments at 24-hour intervals.

Pharmacodynamics
Skeletal muscle relaxant action: Precise mechanism of action is unknown, but drug appears to act at the spinal cord level to inhibit transmission of monosynaptic and polysynaptic reflexes, possibly through hyperpolarization of afferent fiber terminals. It also may act at supraspinal sites because baclofen at high doses produces generalized CNS depression. Baclofen decreases the number and severity of spasms and relieves pain, clonus, and muscle rigidity and therefore improves mobility.

Pharmacokinetics
Absorption: Rapidly and extensively absorbed from the GI tract but is subject to individual variation. As dose increases, rate and extent of absorption decreases. Onset of therapeutic effect may not be immediately evident; varying from hours to weeks. Peak effect is seen at 2 to 3 hours.
Distribution: Studies indicate that baclofen is widely distributed throughout the body, with small amounts crossing the blood-brain barrier. About 30% is plasma protein-bound.
Metabolism: About 15% is metabolized in the liver via deamination.
Excretion: 70% to 80% is excreted in urine unchanged or as its metabolites; remainder is excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with renal impairment or seizure disorders or when spasticity is used to maintain motor function.

Interactions
Drug-drug. Antidiabetics, insulin: May increase blood glucose level and require dosage adjustments of antidiabetic or insulin. Monitor serum glucose level.
CNS depressants, including antipsychotics, anxiolytics, general anesthetics, narcotics: May add to CNS effects of drug. Use together cautiously.
MAO inhibitors, tricyclic antidepressants: May cause CNS depression, respiratory depression, and hypotension. Avoid use together.
Drug-lifestyle. Alcohol use: May add to CNS effects of drug. Discourage alcohol use.

Adverse reactions
Early signs of abrupt baclofen withdrawal: return of baseline spasticity, pruritus, hypotension, and paresthesias.
CNS: CNS depression, drowsiness, dizziness, headache, slurred speech, weakness, fatigue, hypotonia, confusion, insomnia, dysarthria, SEIZURES; high fever, paresthesia with intrathecal administration.
CV: CV collapse, hypotension, hypertension.
EENT: blurred vision, nasal congestion.
GI: nausea, constipation, vomiting.
GU: urinary frequency.
Hepatic: liver dysfunction.
Metabolic: hyperglycemia, weight gain.
Musculoskeletal: muscle rigidity or spasticity, rhabdomyolysis with intrathecal administration.
Respiratory: respiratory failure, dyspnea.
Skin: rash, pruritus, excessive perspiration.
Other: multiple organ failure with intrathecal administration.

Effects on lab test results
• May increase AST, alkaline phosphatase, and glucose levels.

Overdose and treatment
Signs and symptoms of overdose include absence of reflexes, vomiting, muscular hypotonia, marked salivation, drowsiness, visual disorders, seizures, respiratory depression, and coma.
 Treatment involves supportive measures, including endotracheal intubation and positive-pressure ventilation. If patient is conscious, remove drug by inducing emesis followed by gastric lavage. If patient is comatose, don’t induce emesis. Gastric lavage may be performed after endotracheal tube is in place with cuff inflated. Don’t use respiratory stimulants. Monitor vital signs closely.

Special considerations
• Intrathecal administration should be performed only by qualified individuals familiar with administration techniques and patient management problems.
• Adverse reactions may be reduced by slowly decreasing the dose. Abrupt withdrawal can result in hallucinations or seizures and acute exacerbation of spasticity.
• Monitor blood glucose levels routinely in diabetic patients.
• Observe patient’s response to drug. Signs of effective therapy may appear in a few hours to 1 week and may include diminished frequency of spasms and severity of foot and ankle clonus, increased ease and range of joint motion, and enhanced performance of daily activities.
 ALERT Increased seizures may occur in patients with a seizure disorder. Closely monitor patients with seizure disorder using EEG and clinical observation. Assess patient for possible loss of seizure control.
• For intrathecal baclofen withdrawal, readminister it at or near the same dosage as before therapy was interrupted. However, if delayed, treat with P.O. or enteral baclofen, or P.O., enteral, or I.V. benzodiazepines to prevent potentially fatal sequelae. P.O. or enteral baclofen alone shouldn’t be relied on to stop the progression of the withdrawal.
 ALERT Seizures may occur during overdose of baclofen, with withdrawal from intrathecal baclofen, and in patients maintained on therapeutic doses of intrathecal baclofen.
• Baclofen is used investigationally to reduce choreiform movements in Huntington’s chorea; to reduce rigidity in Parkinson’s disease; to reduce spasticity in CVA, cerebral lesions, cerebral palsy, and rheumatic disorders; for analgesia in trigeminal neuralgia; and for treatment of unstable bladder.
• In some patients, smoother response may be obtained by giving daily dose in four divided doses.
• Patient may need supervision during walking. The initial loss of spasticity induced by baclofen may affect patient’s ability to stand or walk. (In some patients, spasticity helps patient to maintain upright posture and balance.)
• Discontinue drug if signs of improvement don’t occur within 1 to 2 months.
• Implantable pump or catheter failure can result in sudden loss of effectiveness of intrathecal baclofen.
• During prolonged intrathecal baclofen therapy for spasticity, about 10% of patients become refractory to baclofen therapy requiring a temporary suspension of treatment to regain sensitivity to its effects.
• Store tablets in a tight container.
• Store baclofen at temperatures below 86° F (30° C). Don’t freeze. Each vial is for individual use. Use only sterile, preservative-free normal saline solution for dilution. Baclofen must be diluted to 50 mcg/ml before injecting into the subarachnoid space.
Pregnant patients
• There are no adequate and controlled studies in pregnant women.
Pediatric patients
• Use of oral form isn’t recommended for children younger than age 12. Safety of intrathecal administration in children younger than age 4 hasn’t been established.
Geriatric patients
• Geriatric patients are especially sensitive to drug. Observe carefully for adverse reactions, such as mental confusion, depression, and hallucinations. Lower doses are usually indicated.

Patient education
• Advise patient to report adverse reactions promptly. Most can be reduced by decreasing dosage. Drowsiness, dizziness, and ataxia are more common in patients older than age 40.
• Warn patient of additive effects with use of other CNS depressants, including alcohol.
• Caution patient to avoid hazardous activities that require mental alertness.
• Tell diabetic patient that baclofen may elevate blood glucose levels and may require adjustment of insulin dosage during treatment with baclofen. Urge patient to promptly report changes in urine or blood glucose tests.
• Caution patient against taking OTC drugs without medical approval. Explain that hazardous drug interactions are possible.
• Inform patient that drug should be withdrawn gradually over 1 to 2 weeks. Abrupt withdrawal after prolonged use of drug may cause anxiety, agitated behavior, auditory and visual hallucinations, severe tachycardia, and acute spasticity.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use