Amifampridine
Indications
Amifampridine is used for:
Lambert-Eaton Myasthenic Syndrome
Adult Dose
Lambert-Eaton Myasthenic Syndrome
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
Hepatic impairment
Not studied
Extensively metabolized by N-acetyltransferase 2 (NAT2), and hepatic impairment may cause an increase in exposure
Recommended starting dose: 15 mg/day PO in 3 divided doses; monitor closely
Consider dosage modification or discontinuation if needed based on effect and tolerability
Child Dose
Lambert-Eaton Myasthenic Syndrome
Oral Suspension only
Indicated for Lambert-Eaton myasthenic syndrome (LEMS) in patients aged 6 to <17 years
<6 years: Safety and efficacy not established
6 to <17 years and weighing <45 kg
7.5-15 mg/day, in divided doses (2-3 times/day) initially
May increase based on clinical response and tolerability by 2.5- to 5-mg increments, divided in up to 5 doses/day
Maximum single dose is 15 mg; not to exceed 50 mg/day
6 to <17 years and weighing >45 kg
15-30 mg PO daily in divided doses (2-3 times/day) initially
May increase based on clinical response and tolerability by 5- to 10-mg increments, divided in up to 5 dose/day
Maximum single dose is 30 mg; not to exceed 100 mg/day
Renal Dose
Renal impairment
CrCl 15-90 mL/min: Recommended starting dose is 15 mg/day PO in 3 divided doses; monitor closely; consider dosage modification or discontinuation if needed based on effect and tolerability
End-stage renal disease (CrCl <15 mL/min): No recommendation can be made
Administration
Oral Suspension Preparation
Patients requiring a dosage in <5-mg increments, have difficulty swallowing, or require feeding tubes: 1 mg/mL suspension can be prepared
Place three 10-mg tablets in a 30-mL container; crushing tablets prior to making the suspension is not necessary
Add 30 mL of sterile water
Shake well for 30 seconds
Oral Administration
May administer with or without food
Contra Indications
History of seizures
Hypersensitivity to amifampridine phosphate or another aminopyridine
Precautions
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
Pregnancy-Lactation
Pregnancy
No data are available in pregnant women
Based on animal studies, can cause fetal harm (eg, still births, reduced fetal weight, delayed sexual development) at doses associated with maternal plasma drug levels lower than therapeutic drug levels
Lactation
Unknown if distributed in human breast milk
In lactating rats, amifampridine was excreted in milk and reached levels similar to those in maternal plasma
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Interactions
Drugs that lower seizure threshold: Coadministration may increase risk of seizures
Drugs with cholinergic effects: Coadministration may increase risk of adverse cholinergic effects
Adverse Effects
Side effects of Amifampridine :
>10% (Firdapse)
Paresthesia (62%)
Upper respiratory tract infection (33%)
Abdominal pain (14%)
Nausea (14%)
Diarrhea (14%)
Headache (14%)
Elevated liver enzymes (14%)
Back pain (14%)
Hypertension (12%)
Muscle spasms (12%)
>10% (Ruzurgi)
Paresthesia/dysesthesia (69%)
Abdominal pain (25%)
Dyspepsia (17%)Dizziness (12%)
1-10% (Firdapse)
Dizziness (10%)
Asthenia (10%)
Muscular weakness (10%)
Pain in extremity (10%)
Cataract (10%)
Constipation (7%)
Bronchitis (7%)
Fall (7%)
Lymphadenopathy (7%)
Seizures (2%)
1-10% (Ruzurgi)
Nausea (10%)
Back pain (8%)
Hypoesthesia (6%)
Muscle spasms (6%)
Mechanism of Action
Blocks voltage-dependent potassium channels, thereby prolonging presynaptic cell membrane depolarization, which enhances calcium transport into nerve endings
The increased intracellular calcium concentrations facilitate exocytosis of acetylcholine-containing vesicles, which, in turn, enhances neuromuscular transmission