DALFAMPRIDINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DALFAMPRIDINE (DALFAMPRIDINE).
Potassium channel blocker that enhances neuronal transmission by prolonging repolarization and increasing neurotransmitter release in demyelinated neurons.
| Metabolism | Primarily metabolized via CYP2E1 and CYP3A4; also undergoes N-acetylation and glucuronidation. |
| Excretion | Renal excretion of unchanged drug (95%); fecal (<5%). |
| Half-life | 5-6 hours in patients with normal renal function; prolonged to 15-20 hours in moderate renal impairment. |
| Protein binding | 98-99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 2.6 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 95% (immediate-release formulation). |
| Onset of Action | Oral: Clinical effect on walking speed observed within 1-2 weeks. |
| Duration of Action | 12-24 hours; requires twice-daily dosing for sustained effect. |
10 mg orally twice daily, 12 hours apart.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated if CrCl <= 50 mL/min. If CrCl > 50 mL/min, no adjustment needed; monitor renal function. |
| Liver impairment | No adjustment required in mild to moderate hepatic impairment; not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific adjustment, but monitor for adverse effects due to potential age-related renal function decline; contraindicated if CrCl <= 50 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DALFAMPRIDINE (DALFAMPRIDINE).
| Breastfeeding | Unknown if distributed in human milk. No M/P ratio available. Caution advised due to potential for CNS excitability in infant. Consider alternative treatments or discontinue breastfeeding. |
| Teratogenic Risk | Pregnancy category C. No adequate studies in pregnant women. In animal studies, dalfampridine caused increased fetal resorptions and reduced fetal body weight at doses similar to human therapeutic exposure. Risk cannot be ruled out; use only if potential benefit outweighs fetal risk. First trimester: Potential for teratogenicity based on animal data; avoid if possible. Second and third trimesters: Possible fetal harm from maternal seizures if drug discontinued; weigh risks. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of seizures or epilepsy","Moderate to severe renal impairment (CrCl ≤50 mL/min)","Concurrent use of other medications containing fampridine (4-aminopyridine)","Hypersensitivity to fampridine or any component of the formulation"]
| Precautions | ["Seizure risk: Increased risk of seizures, especially in patients with a history of seizures or renal impairment.","Renal impairment: Contraindicated in moderate to severe renal impairment (CrCl ≤50 mL/min); dose adjustment required in mild impairment.","QT prolongation: May prolong QT interval; avoid in patients with QT prolongation or concurrent use of QT-prolonging drugs.","Hypersensitivity reactions: Discontinue if signs of angioedema or anaphylaxis occur."] |
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| Fetal Monitoring | Monitor maternal renal function (creatinine clearance) before and during therapy; dalfampridine is renally eliminated. Monitor for seizures, especially in patients with history. Fetal monitoring: standard prenatal care; consider fetal growth ultrasound if prolonged exposure. |
| Fertility Effects | Animal studies: No effects on fertility or reproductive performance in rats at doses up to 3 mg/kg/day. Human data lacking. No known impact on human fertility. |