Amifampridine

Lambert-Eaton Myasthenic Syndrome

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 Consider dosage modification or discontinuation if needed based on effect and tolerability

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 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

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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

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

History of seizures Hypersensitivity to amifampridine phosphate or another aminopyridine

Hypersensitivity reactions 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 Monitoring Parameters Clinical and ECG monitoring required at treatment initiation and yearly thereafter.

Not Classi 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

Drugs that lower seizure threshold: Coadministration may increase risk of seizures Drugs with cholinergic effects: Coadministration may increase risk of adverse cholinergic effects

>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%)

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