Introduction
Dalfampridine (previously known as fampridine) is a potassium channel blocker approved by the FDA in 2010 for the improvement of walking in patients with multiple sclerosis (MS). Marketed under the brand name Ampyra, it represents the first therapy specifically indicated to improve mobility in MS patients. This extended-release formulation is chemically designated as 4-aminopyridine and works by enhancing conduction in demyelinated axons.
Mechanism of Action
Dalfampridine is a broad-spectrum potassium channel blocker that exerts its therapeutic effects through voltage-dependent blockade of potassium channels. In demyelinated axons, potassium channels become exposed, leading to excessive potassium efflux that shortens action potentials and impairs conduction. By blocking these channels, dalfampridine prolongs the duration of action potentials and enhances synaptic transmission. This mechanism improves conduction in demyelinated nerve fibers, resulting in improved neurological function, particularly walking speed in MS patients.
Indications
Dalfampridine is FDA-approved for:
- Improvement of walking in patients with multiple sclerosis (MS)
- This was demonstrated by an increase in walking speed
It is important to note that dalfampridine is not indicated for the treatment of MS itself, but specifically for improving walking ability in patients with various forms of MS (including relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing MS).
Dosage and Administration
Standard dosing: 10 mg orally twice daily (approximately 12 hours apart) Administration:- Tablets should be swallowed whole; do not crush, chew, or divide
- Administer without regard to meals
- Doses should be taken approximately 12 hours apart
- Maximum daily dose: 20 mg
- Renal impairment: Contraindicated in patients with moderate or severe renal impairment (CrCl ≤50 mL/min)
- Hepatic impairment: No dosage adjustment necessary
- Elderly: Use with caution due to increased likelihood of renal impairment
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly and completely absorbed from the GI tract; bioavailability approximately 96% Distribution: Volume of distribution: 2.6 L/kg; 1-3% protein bound Metabolism: Minimal hepatic metabolism; primarily excreted unchanged Elimination: Half-life: 5.2-6.5 hours; primarily renal excretion (96% unchanged in urine) Time to peak concentration: 3-4 hours Food effects: None significantContraindications
1. History of seizures 2. Moderate or severe renal impairment (CrCl ≤50 mL/min) 3. Hypersensitivity to dalfampridine or any component of the formulation
Warnings and Precautions
Seizures: Dalfampridine can cause seizures; risk increases with increasing plasma concentrations. Discontinue immediately if seizure occurs. Renal impairment: Contraindicated in moderate or severe impairment due to increased drug exposure and seizure risk. Urinary tract infections: MS patients have increased risk; monitor closely. Anaphylaxis: Rare cases reported; discontinue if signs occur. Pregnancy: Category C; use only if potential benefit justifies potential risk to fetus. Lactation: Not recommended; excreted in human milk.Drug Interactions
Other 4-aminopyridine derivatives: Increased risk of adverse effects Drugs that lower seizure threshold: (e.g., bupropion, tramadol, antipsychotics) - Increased seizure risk CYP inhibitors/inducers: Minimal interactions expected due to minimal metabolism Nephrotoxic drugs: May worsen renal function, increasing dalfampridine exposureAdverse Effects
Common (≥2% and greater than placebo):- Urinary tract infection (12%)
- Insomnia (9%)
- Dizziness (7%)
- Headache (7%)
- Nausea (7%)
- Asthenia (7%)
- Back pain (5%)
- Balance disorder (4%)
- Multiple sclerosis relapse (4%)
- Paresthesia (4%)
- Nasopharyngitis (4%)
- Constipation (3%)
- Dyspepsia (3%)
- Pharyngolaryngeal pain (3%)
- Seizures (0.6-2.2% in clinical trials)
- Anaphylaxis
- Severe allergic reactions
Monitoring Parameters
1. Renal function (serum creatinine at baseline and annually) 2. Seizure activity 3. Walking speed and mobility assessment (Timed 25-Foot Walk) 4. Signs of urinary tract infection 5. Adverse effects (particularly CNS effects) 6. Therapeutic response
Patient Education
- Take exactly as prescribed: 10 mg twice daily, 12 hours apart
- Swallow tablets whole; do not crush, chew, or break
- Do not take extra doses or double doses
- Immediately report any seizures, allergic reactions, or new symptoms
- Regular monitoring of kidney function is necessary
- Inform all healthcare providers about dalfampridine use
- Store at room temperature away from moisture
- Keep out of reach of children
- Report any changes in urinary habits or signs of infection
- Do not discontinue abruptly without medical supervision
References
1. FDA Prescribing Information: Ampyra (dalfampridine) Extended Release Tablets 2. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition 3. Brunton LL, et al. Pharmacotherapy of Multiple Sclerosis. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics 4. Multiple Sclerosis Council for Clinical Practice Guidelines. Dalfampridine clinical applications. 2013 5. Brown TR, et al. Neurology. 2010;74(17):1333-1340 6. Goodman AD, et al. Lancet. 2009;373(9665):732-738 7. National Multiple Sclerosis Society. Dalfampridine guidelines. 2019 8. UpToDate: Dalfampridine drug information 9. Micromedex: Dalfampridine monograph 10. ClinicalTrials.gov: Dalfampridine phase III studies