Drug information of Amifampridine

Amifampridine

Drug group:

Amifampridine is an orally available potassium channel blocker that increases acetylcholine in synaptic clefts of peripheral nerve endings and is used to treat the Lambert-Eaton myasthenic syndrome. Amifampridine is associated with a low rate of transient serum enzyme elevations during therapy but has not been linked with instances of clinically apparent acute liver injury.

Amifampridine

Mechanism of effect

Amifampridine is a symptomatic treatment that increases acetylcholine concentrations at the neuromuscular junction. It selectively blocks presynaptic fast voltage-gated potassium channels, thereby prolonging cell membrane depolarization and action potential, and augmenting calcium transport into the nerve endings. Increased intracellular calcium enhances the exocytosis of acetylcholine-containing vesicles and enhances impulse transmission at central, autonomic, and neuromuscular synapses . Amifampridine improves muscle strength and resting compound muscle action potential (CMAP) amplitudes with an overall weighted mean difference of 1.69 mV

Pharmacodynamic

Administration of amifampridine to patients with LES in clinical trials resulted in improvement of the compound muscle action potential (CMAP), muscle function, and quantitative myasthenia gravis (QMG) .

Pharmacokinetics

Absorption

Peak plasma time: 20-60 min

Distribution

Vd: Moderate to high

Protein bound: 25.3

Metabolism

Extensively metabolized by N-acetyltransferase gene 2 (NAT2) in the liver to 3-N-acetyl-amifampridine (inactive)

Elimination

Half-life: 1.8-2.5 hr

Oral clearance: 149-214 L/hr

Excretion (as amifampridine or inactive metabolite): 93-100% in urine

Drug indications

Amifampridine is indicated for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and in patients aged 6 to less than 17 years of age. Nevertheless, it is important to note that at the current time only the Firdapse brand of amifampridine is indicated for the treatment of LEMS in adults and the Ruzurgi brand of amifampridine is indicated for the treatment of LEMS in patients aged 6 to less than 17 years.

Dosage

Indicated for Lambert-Eaton myasthenic syndrome (LEMS)

15-30 mg/day PO in divided doses (3-4 times daily) initially; may increase by 5 mg/day q3-4 days; not to exceed 80 mg/day

Maximum single dose: 20 mg

Drug contraindications

Because it affects voltage-gated ion channels in the heart, it is contraindicated in people with long QT syndrome and in people taking a drug that might prolong QT time like sultopride, disopyramide, cisapride, domperidone, rifampicin or ketoconazol. It is also contraindicated in people with epilepsy or badly controlled asthma.

Side effects

  • The dose-limiting side effects include tingling or numbness, difficulty sleeping, fatigue, and loss of muscle strength.
  • Amifampridine can cause seizures, especially but not exclusively when given at high doses and/or in particularly vulnerable individuals who have a history of seizures.

Interactions

The combination of amifampridine with pharmaceuticals that prolong QT time increases the risk of ventricular tachycardia, especially torsade de pointes; and combination with drugs that lower the seizure threshold increases the risk of seizures.

Interactions via the liver's cytochrome P450 enzyme system are considered unlikely.

Alerts

If hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue drug and initiate appropriate therapy

Seizures

  • Can cause seizures; consider discontinuation or dose reduction in patients who have a seizure while on treatment
  • Many instances of seizure were in patients taking medications or who had comorbid conditions that may have lowered seizure threshold
  • Contraindicated in patients with history of seizures
  • Drugs that lower seizure threshold: Coadministration may increase risk of seizures
  • Drugs with cholinergic effects: Coadministration may increase risk of adverse cholinergic effects

Pregnancy level

No data are available in pregnant women

Breast feeding warning

Unknown if distributed in human breast milk

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