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Amifampridine

Medically reviewed by Drugs.com. Last updated on Sep 15, 2020.

Pronunciation

(AM i fam pri deen)

Index Terms

  • 3,4-diaminopyridine
  • Amifampridine Phosphate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Firdapse: 10 mg [scored]

Ruzurgi: 10 mg

Brand Names: U.S.

  • Firdapse
  • Ruzurgi

Pharmacologic Category

  • Cholinergic Agonist
  • Potassium Channel Blocker

Pharmacology

Increases acetylcholine release in nerve terminals via potassium channel blockade (Wirtz 2010).

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)

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.

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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 concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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: Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine 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.

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 Considerations

Information related to the use of amifampridine in pregnancy is limited (Pelufo-Pellicer 2006).

Patient Education

What is this drug used for?

• It is used to treat myasthenic syndrome of Eaton-Lambert.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Common cold symptoms

• Flu-like symptoms

• Abdominal pain

• Heartburn

• Nausea

• Diarrhea

• Back pain

• Muscle spasm

• Loss of strength and energy

• Painful extremities

• Constipation

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Urinary tract infection like 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

• Muscle weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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