amifampridine

General

Genetic Implications:

Pronunciation:
am-i-fam-pri-deen

Trade Name(s)

• Firdapse
• Ruzurgi 

Ther. Class.

cholinergic muscle stimulants

Pharm. Class.

potassium channel blockers

Indications

Lambert-Eaton myasthenic syndrome.

Action

Increases acetylcholine release in nerve terminals via potassium channel blockade.

Therapeutic Effect(s):

Decreased progression of muscle weakness.

Pharmacokinetics

Absorption: Rapidly and well absorbed.

Distribution: Widely distributed to tissues.

Metabolism and Excretion: Extensively metabolized by N-acetyltransferase 2 (NAT2) to an inactive metabolite. Primarily eliminated in urine (as either unchanged drug or metabolite).

Half-life: 1.8–2.5 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to amifampridine or another aminopyridine;
• History of seizures;
• End-stage renal disease (CCr <15 mL/min) (↑ risk of seizures).

Use Cautiously in:

• Mild to moderate renal impairment (CCr 15–90 mL/min) (initiate with lowest dose and monitor closely);
• Hepatic impairment (initiate with lowest dose and monitor closely);
•   NAT2 poor metabolizers (initiate with lowest dose and monitor closely);
• OB:   Safety not established in pregnancy;
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:  Children <6 yr (safety and effectiveness not established);
• Geri:  Consider age-related ↓ in renal function.

Adverse Reactions/Side Effects

CV: hypertension, peripheral edema

Derm: erythema

EENT: cataracts

GI: abdominal pain, diarrhea, ↑ liver enzymes, nausea, constipation, dyspepsia

GU: urinary tract infection

Metabolic: hypercholesterolemia

MS: back pain, extremity pain, muscle spasms, muscle weakness, ↑ creatine kinase

Neuro: dizziness, headache, paresthesia, depression, insomnia, SEIZURES, weakness.

Resp: dyspnea

Misc: fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Drugs that lower seizure threshold  may ↑ risk of seizures.
•  Cholinesterase inhibitors (direct or indirect)  may ↑ cholinergic effects.

Route/Dosage

PO (Adults and Children ≥6 yr and ≥45 kg): 15–30 mg/day in 3–5 divided doses; may ↑ by 5 mg/day every 3–4 days based on response and tolerability (not to exceed 20 mg/dose or 100 mg/day).  NAT2 poor metabolizers: 15 mg/day in 3–5 divided doses; may ↑ by 5 mg/day every 3–4 days based on response and tolerability (not to exceed 20 mg/dose or 100 mg/day).

PO (Children ≥6 yr and <45 kg): 5–15 mg/day in 3–4 divided doses; may ↑ by 2.5 mg/day every 3–5 days (not to exceed 10 mg/dose or 50 mg/day).  NAT2 poor metabolizers: 5 mg/day in 3–5 divided doses; may ↑ by 2.5 mg/day every 3–4 days based on response and tolerability (not to exceed 10 mg/dose or 50 mg/day).

Renal Impairment 
PO (Adults and Children ≥6 yr and ≥45 kg): CCr 15–90 mL/min: 15 mg/day in 3–5 divided doses; may ↑ by 5 mg/day every 3–4 days based on response and tolerability (not to exceed 20 mg/dose or 100 mg/day).

Renal Impairment 
(Children ≥6 yr and <45 kg): CCr 15–90 mL/min: 5 mg/day in 3–5 divided doses; may ↑ by 2.5 mg/day every 3–4 days based on response and tolerability (not to exceed 10 mg/dose or 50 mg/day).

Hepatic Impairment 
(Adults and Children ≥6 yr and ≥45 kg): Mild, moderate, or severe hepatic impairment: 15 mg/day in 3–5 divided doses; may ↑ by 5 mg/day every 3–4 days based on response and tolerability (not to exceed 20 mg/dose or 100 mg/day).

Hepatic Impairment 
(Children ≥6 yr and <45 kg): Mild, moderate, or severe hepatic impairment: 5 mg/day in 3–5 divided doses; may ↑ by 2.5 mg/day every 3–4 days based on response and tolerability (not to exceed 10 mg/dose or 50 mg/day).

Availability

Tablets: 10 mg

Assessment

• Initiate seizure precautions. If seizures occur, medication may need to be discontinued.
• Assess stamina and weakness periodically during therapy.

Implementation

• PO Administer without regard to food. Scored tablets may be divided in two. Store tablets in refrigerator; protect from light and moisture. Stable for up to 3 mo.
  • When patients require a dose in <5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL suspension can be prepared by placing the required number of tablets in a 50–100 mL container, adding 10 mL of sterile water for each tablet, waiting for 5 min, and shaking well for 30 sec. Crushing the tablets prior to making the suspension is not necessary. After preparation of the suspension, an oral syringe can be used to draw up and administer the correct dose by mouth or by feeding tube. Refrigerate suspension between doses and shake well before drawing up each dose. Suspension can be stored in refrigerator for up to 24 hr. Discard any unused portion of the suspension after 24 hr.

Patient/Family Teaching

• Instruct patient to take medication as directed and follow dose escalation schedule. Advise patient to omit missed doses. Do not double doses; may increase risk of seizures. Do not change dose or stop medication without consulting health care professional.
• Advise patient to notify health care professionals if seizures or signs and symptoms of hypersensitivity reaction (shortness of breath, trouble breathing, swelling of throat or tongue, hives) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to  Firdapse  during pregnancy. Clinicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the pregnancy registry (855-212-5856) or https://firdapsepregancystudy.com/.

Evaluation/Desired Outcomes

Improved stamina and decreased weakness in patients with Lambert-Eaton myasthenic syndrome.