Baclofen

Baclofen Medication Overview

Baclofen is a muscle relaxer and an antispastic agent. It is primarily used in the treatment of muscle spasticity, a condition often associated with multiple sclerosis, spinal cord injuries, or diseases affecting the spinal cord. While administered orally, the medication is available in tablet form and also as a solution for intrathecal injection for use in an implanted pump system.

Chemical Composition

The chemical name for baclofen is 4-amino-3-(4-chlorophenyl) butanoic acid. It appears as a white or almost white crystalline powder, slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform.

Pharmacological Action

Baclofen acts on the central nervous system (CNS) to produce its muscle relaxant effects. Its primary mechanism of action is as an agonist at GABA-B receptors, which inhibits excitatory neurotransmitter release, thereby damping neuronal excitability and reducing muscle spasticity.

Dosage Recommendations

The initial dosage should be individualized according to the patient’s response and tolerability. Oral baclofen therapy may be initiated with doses of 5 mg taken three times daily, gradually increased to 20 mg three times daily if needed. The maximum daily dose should generally not exceed 80 mg. For intrathecal administration, the dosage must be individualized by a skilled clinician.

Pharmacokinetics

Baclofen is rapidly and extensively absorbed after oral administration. It has an onset of action typically within one to two hours and a duration of action of 4 to 8 hours. The elimination half-life ranges from 2.5 to 6 hours, and it is excreted primarily by the kidneys. Baclofen does not undergo significant metabolism and is excreted mainly as unchanged drug.

Indications for Use

Baclofen is indicated in the treatment of spastic movement disorders, especially due to multiple sclerosis or spinal cord lesions, muscular rigidity, and spasms. It can be used in adults and children aged 1 year and above for chronic severe spasticity resulting from multiple sclerosis, spinal cord lesions, or neurological diseases.

Administration Routes

Baclofen can be administered orally in tablet or liquid form, or intrathecally directly into the spinal fluid via an implanted pump, designed for the controlled delivery of the drug into the CNS.

Drug Interactions

Potential interactions include additive CNS depression when combined with alcohol, benzodiazepines, opioids, or other CNS depressants. Caution is advised when used concurrently with antihypertensive agents, as enhanced antihypertensive effect can occur. Monoamine oxidase inhibitors may also interact with baclofen.

Adverse Effects

Common side effects of baclofen include drowsiness, dizziness, weakness, fatigue, headache, insomnia, nausea, increased urinary frequency, and constipation. More serious side effects may include seizures, confusion, respiratory depression, and hallucinations, particularly at high doses or with abrupt discontinuation of the drug.

Specially Controlled Dosage Adjustment

In patients with renal impairment, caution should be exercised, and dosage reduction may be necessary as baclofen is primarily eliminated by the kidneys. Lower initial dosages and slower dosage titration are recommended to avoid drug accumulation and associated side effects.

Pregnancy and Lactation Considerations

Baclofen is classified as FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is known to pass into breast milk, so caution should be exercised when baclofen is administered to a nursing woman.

Overdosage Symptoms

Symptoms of baclofen overdose might include profound CNS depression, respiratory depression, hypotension, seizures, and coma. Treatment of overdose consists of appropriate supportive measures, as there is no specific antidote. In severe cases, hemodialysis may be considered to facilitate drug removal.

Storage and Handling

Baclofen tablets and solutions should be stored at controlled room temperature, away from moisture and heat, and out of reach of children. For intrathecal delivery, the specific instructions provided by the pump manufacturer for both the baclofen solution and device should be followed.

Patient Counseling Information

Patients prescribed baclofen should be advised regarding the gradual dosage escalation to minimize adverse effects and cautioned about the potential for CNS depression, especially in relation to activities requiring alertness such as driving or operating machinery. They should also be educated on the potential for withdrawal symptoms upon abrupt discontinuation and the necessity to adhere to prescribed dosage schedules.