BACENTRA INTRATHECAL 0,05 mg/ml

Indications

• Severe chronic spasticity of cerebral or spinal origin
• Multiple sclerosis-related spasticity
• Spinal cord injury-related spasticity

Dosage

Children: Child 1 month–11 years: Initially 1–1.5 mg/kg daily in 4 divided doses, increased gradually according to response; maintenance 25–200 micrograms daily.

Adults: Initial dose is usually 5 mg three times daily, which can be increased gradually based on response, with a maximum dose of 80 mg per day in divided doses.

Mechanism of action

Baclofen is a GABA-B receptor agonist, which inhibits neurotransmitter release, leading to decreased excitatory transmission in the spinal cord and ultimately resulting in muscle relaxation.

Pharmacodynamics

Baclofen reduces spasticity and muscle tone by enhancing GABAergic inhibition. This results in decreased muscle contractions and improvement in motor control in patients with spasticity.

Pharmacokinetics

Baclofen is well absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours. It is distributed widely in body tissues and crosses the blood-brain barrier. The elimination half-life is approximately 3-4 hours, and it is primarily excreted unchanged in the urine.

Contra-indications

• Active peptic ulceration
• Local infection
• Systemic infection

Adverse effects

• Gastrointestinal hypermotility
• Muscle cramps
• Rash

Interactions

• Clozapine: Unknown (additive effect)
• Second-generation antipsychotics: Unknown (additive effect)
• Levodopa: Unknown (increases risk of adverse effects)

Precautions

• Dose adjustments required in renal impairment
• Resuscitation equipment must be available for immediate use when administering intrathecal baclofen

Pregnancy

Use with caution; consult relevant guidelines.

Breast-feeding

Use with caution; consult relevant guidelines.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablet
• Oral solution
• Solution for injection

Mechanism of action

The exact mechanism of action of baclofen is unclear. Baclofen is an agonist at the beta subunit of gamma-aminobutyric acid (GABA) receptors expressed on pre- and post-synaptic neurons. Upon binding to GABA_B receptors, baclofen causes an influx of potassium into the neuron, leading to hyperpolarization of the neuronal membrane and decreased calcium influx at presynaptic nerve terminals. This results in a decreased rate of action potential threshold being reached by presynaptic neurons and reduced action potential of postsynaptic motor neurons that innervate the muscle spindles. Baclofen thereby inhibits the transmission of both mono- and polysynaptic reflexes at the spinal cord, relaxing spasticity. Baclofen may act on some voltage-gated calcium channels; however, the clinical significance of this is unclear.

Pharmacodynamics

Baclofen is an antispasmodic agent that induces muscle relaxation. It reduces the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulates inhibitory neuronal signals in the post-synaptic neurons. Oral formulations of baclofen are the most commonly used form of the drug. In one cross-section study, intrathecal baclofen was more effective than oral baclofen in relieving spasticity directly at the level of the spinal cord. Baclofen has CNS depression properties and can cause sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression. Baclofen also mediates some antinociceptive effects and stimulates gastric acid secretion. Baclofen exhibits anti-inflammatory and neuroprotective activities: it inhibits the release of pro-inflammatory cytokines from microglia and astrocytes, and decreases oxidative stress in rats.