Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Firdapse: 10 mg [scored]
Ruzurgi: 10 mg
Pharmacology
Mechanism of Action
Increases acetylcholine release in nerve terminals via potassium channel blockade (Wirtz 2010).
Pharmacokinetics/Pharmacodynamics
Metabolism
Extensively metabolized by N-acetyltransferase 2 (NAT2) to 3-N-acetyl amifampridine (inactive metabolite)
Excretion
Urine: Firdapse: 93% to 100% (as amifampridine and 3-N-acetyl amifampridine); Ruzurgi: >65% (as amifampridine and 3-N-acetyl amifampridine)
Time to Peak
Firdapse: 20 minutes to 1 hour; Ruzurgi: Median: 0.5 hour; increased with high fat meal (1 hour)
Half-Life Elimination
Firdapse: 1.8 to 2.5 hours; Ruzurgi: 3.6 to 4.2 hours
Protein Binding
Ruzurgi: 25.3% (amifampridine); 43.3% (3-N-acetyl amifampridine)
Use in Specific Populations
Special Populations: Renal Function Impairment
AUC 2- to 3-fold higher in patients with moderate to severe (CrCl 15 to 59 mL/minute) renal impairment and 36% higher in patients with mild (CrCl 60 to 89 mL/minute) impairment compared to patients with normal renal function.
Special Populations Note
N-Acetyltransferase gene 2 (NAT2) poor metabolizers:
Firdapse: Cmax 3.5- to 4.5-fold higher and AUC 5.6- to 9-fold higher in poor metabolizers (slow acetylators) compared to normal metabolizers (fast or rapid acetylators).
Ruzurgi: Cmax 1.3- to 3.7-fold higher in poor metabolizers compared to intermediate metabolizers (intermediate acetylators) and 6.1- to 7.6-fold higher compared to normal metabolizers. Poor metabolizers AUC0-4h was 1.1- to 3.7-fold higher than intermediate metabolizers and 6- to 8.5-fold higher than normal metabolizers.
Use: Labeled Indications
Lambert-Eaton myasthenic syndrome: Treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults (Firdapse) and pediatric patients 6 to <17 years (Ruzurgi).
Contraindications
Hypersensitivity to amifampridine phosphate, aminopyridines, or any component of the formulation; history of seizures.
Dosage and Administration
Dosing: Adult
Lambert-Eaton myasthenic syndrome (LEMS) (Firdapse): Oral: Initial: 15 to 30 mg/day in 3 to 4 divided doses; may increase based on response and tolerability in 5 mg increments every 3 to 4 days (maximum: 80 mg/day; maximum single dose: 20 mg).
Dosage adjustment for N-acetyltransferase 2 (NAT2) poor metabolizers (Firdapse): Oral: Initial: 15 mg/day in 3 divided doses; may adjust dose or discontinue use based on response and tolerability.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Lambert-Eaton myasthenic syndrome (LEMS): Children ≥6 years and Adolescents <17 years: Oral: Ruzurgi:
<45 kg: Initial: 7.5 to 15 mg/day in 2 to 3 divided doses, titrate by 2.5 to 5 mg/day based on clinical response and tolerability; daily dose may be divided in up to 5 doses/day; maximum dose: 15 mg/dose; maximum daily dose: 50 mg/day.
≥45 kg: Initial: 15 to 30 mg/day in 2 to 3 divided doses, titrate by 5 to 10 mg/day based on clinical response and tolerability; daily dose may be divided in up to 5 doses/day; maximum dose: 30 mg/dose; maximum daily dose: 100 mg/day.
Dosage adjustment for N-acetyltransferase 2 (NAT2) poor metabolizers: Children ≥6 years and Adolescents <17 years: Oral: Ruzurgi:
<45 kg: Initial: 7.5 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
≥45 kg: Initial: 15 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
Administration
Oral: May administer without regard to food.
Storage
Firdapse: Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F).
Ruzurgi: Prior to dispensing, store at 2°C to 8°C (36°F to 46°F); protect from moisture and light. After dispensing, store at 20°C to 25°C (68°F to 77°F) for ≤3 months; excursions permitted from 15°C to 30°C (59°F to 86°F).
Drug Interactions
Acetylcholinesterase Inhibitors: May enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Monitor therapy
Agents With Seizure Threshold Lowering Potential: May enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy
Adverse Reactions
>10%:
Cardiovascular: Hypertension (12%)
Central nervous system: Paresthesia (62%), headache (14%), muscle spasm (12%)
Gastrointestinal: Abdominal pain (14%), diarrhea (14%), nausea (14%)
Hepatic: Increased liver enzymes (14%)
Neuromuscular & skeletal: Back pain (14%)
Respiratory: Upper respiratory tract infection (33%)
1% to 10%:
Cardiovascular: Peripheral edema (≥5%)
Central nervous system: Dizziness (10%), myasthenia (10%), falling (7%), depression (≥5%), insomnia (≥5%), seizure (2%)
Dermatologic: Erythema (≥5%)
Endocrine & metabolic: Hypercholesterolemia (≥5%)
Gastrointestinal: Constipation (7%), gastroesophageal reflux disease (≥5%)
Genitourinary: Urinary tract infection (≥5%)
Hematologic: Lymphadenopathy (7%)
Infection: Influenza (≥5%), viral infection (≥5%)
Neuromuscular & skeletal: Asthenia (10%), limb pain (10%), increased creatine phosphokinase in blood specimen (≥5%)
Ophthalmic: Cataract (10%)
Respiratory: Bronchitis (7%), dyspnea (≥5%)
Miscellaneous: Fever (≥5%)
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Although hypersensitivity reactions, including anaphylaxis, have not been associated with amifampridine, anaphylaxis has been reported with another aminopyridine and cross-sensitivity may occur. Discontinue use and initiate appropriate therapy if anaphylaxis occurs. Use is contraindicated in patients with known hypersensitivity to another aminopyridine.
- Seizures: May cause seizures, including in patients with no prior history; use caution in patients taking medications or with comorbid conditions that may lower the seizure threshold. Seizures may be dose-dependent. Discontinue use or reduce dose if seizure occurs during treatment. Use is contraindicated in patients with a history of seizures.
Disease-related concerns:
- Asthma: Use with caution in patients with uncontrolled asthma (Lindquist 2011).
- Conduction abnormality: Use with caution in patients with congenital QT syndromes or a prolonged QT interval (Lindquist 2011).
- Hepatic impairment: Use with caution; dosage adjustment required.
- Renal impairment: Use with caution; dosage adjustment may be required.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- N-acetyltransferase 2 (NAT2) poor metabolizers: Use with caution; dosage adjustment may be required.
Monitoring Parameters
Renal and hepatic function (as clinically indicated); ECG (as clinically indicated)
Pregnancy
Pregnancy Considerations
Information related to the use of amifampridine in pregnancy is limited (Pelufo-Pellicer 2006).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience common cold symptoms, flu-like symptoms, abdominal pain, heartburn, nausea, diarrhea, back pain, muscle spasm, loss of strength and energy, painful extremities, constipation, or difficulty sleeping. Have patient report immediately to prescriber signs of a urinary tract infection (blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain), severe headache, dizziness, passing out, vision changes, seizures, burning or numbness feeling, swollen glands, falls, shortness of breath, swelling of arms or legs, depression, or muscle weakness (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
