FIRDAPSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FIRDAPSE (FIRDAPSE).
FIRDAPSE (amifampridine) is a potassium channel blocker that increases the release of acetylcholine from nerve terminals by prolonging the depolarization phase of the action potential, thereby enhancing neuromuscular transmission.
| Metabolism | FIRDAPSE is primarily metabolized by N-acetyltransferase 2 (NAT2). In patients who are slow acetylators, reduced metabolism leads to higher drug exposure, increasing the risk of adverse effects. |
| Excretion | Primarily renal excretion as unchanged drug (~96%) with minor fecal elimination (~4%). |
| Half-life | Terminal elimination half-life is approximately 7-8 hours in adults with normal renal function; may be prolonged in renal impairment. |
| Protein binding | Approximately 25-30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.6-3.5 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 73-80%. |
| Onset of Action | Oral administration: Clinical effect typically observed within 1-2 hours. |
| Duration of Action | Duration of clinical effect is approximately 3-5 hours based on controlled clinical trials; may vary with dose and individual response. |
15 mg orally twice daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if creatinine clearance < 30 mL/min. No adjustment for 30-80 mL/min. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). No adjustment for mild/moderate (Child-Pugh A/B). |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment, but monitor renal function; start at lower dose if GFR < 60 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FIRDAPSE (FIRDAPSE).
| Breastfeeding | It is not known whether amifampridine is excreted in human milk. The molecular weight (low) suggests potential for excretion. No M/P ratio is available. Caution is advised; breast-feeding should be avoided during treatment due to risk of infant seizures or neuromuscular blockade. |
| Teratogenic Risk | Firdapse (amifampridine) is classified as FDA Pregnancy Category C. Animal studies have shown adverse effects on fetal development at doses below the maximum recommended human dose. In rats, skeletal and visceral abnormalities were observed. No adequate and well-controlled studies in pregnant women exist. Risk cannot be ruled out. During the first trimester, potential for teratogenicity is highest. In second and third trimesters, risks include possible fetal harm from maternal seizures or overdose. Use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
WARNING: SEIZURES. FIRDAPSE can cause seizures, even at recommended doses. The risk of seizures is dose-dependent. Treatment should be discontinued in patients who develop seizures.
| Serious Effects |
["Known hypersensitivity to amifampridine or any excipients.","History of seizures or epilepsy.","Concomitant use with other drugs that increase seizure risk (e.g., bupropion, tramadol).","Caution in patients with renal or hepatic impairment."]
| Precautions | ["Seizures: Risk of dose-dependent seizures; monitor for seizure activity.","Hypersensitivity: May cause serious hypersensitivity reactions including anaphylaxis.","Overdose: Can lead to cholinergic crisis with respiratory depression; monitor closely.","Renal impairment: Use with caution; dose adjustment may be needed.","Hepatic impairment: Not recommended in severe hepatic impairment.","Slow acetylators: Increased risk of adverse effects due to reduced metabolism."] |
Loading safety data…
| Fetal Monitoring | Monitor for maternal seizures, respiratory depression, and cardiac arrhythmias. Fetal monitoring includes serial ultrasound for growth and anatomy. Non-stress testing and biophysical profile in third trimester if used. Monitor maternal liver function and electrolytes due to risk of hypokalemia. |
| Fertility Effects | No human fertility studies. In animal studies, no impairment of fertility was observed in rats at doses up to 5 mg/kg/day. However, the mechanism of action (potassium channel blockade) could theoretically affect sperm motility or ovulation. Unknown clinical significance. |