Dalfampridine Indications in Multiple Sclerosis
Dalfampridine (Ampyra) is indicated specifically to improve walking in adult patients with multiple sclerosis (MS), as demonstrated by an increase in walking speed. 1
Mechanism and Indication Details
- Dalfampridine is a potassium channel blocker that improves nerve conduction in demyelinated axons, which translates to improved walking ability in MS patients 2
- The medication is FDA-approved only for improving walking in adult MS patients and has no other approved indications 1
- Clinical trials demonstrated that approximately one-third of MS patients (35-43%) show a clinically meaningful response to dalfampridine, characterized by improved walking speed 3, 4
- The improvement in walking was demonstrated through the Timed 25-Foot Walk (T25FW) test, with responders showing approximately 25% increase in walking speed 2, 3
Dosing and Administration
- The maximum recommended dosage is 10 mg twice daily (approximately 12 hours apart) 1
- Higher doses do not provide additional benefit and significantly increase the risk of adverse effects, particularly seizures 1, 5
- Tablets should be taken whole; they should not be divided, crushed, chewed, or dissolved 1
- Dalfampridine can be taken with or without food 1
Contraindications
- History of seizures 1, 6
- Moderate or severe renal impairment (creatinine clearance ≤50 mL/min) 1, 5
- History of hypersensitivity to dalfampridine or 4-aminopyridine 1
Important Considerations and Precautions
- Renal function must be assessed before initiating treatment, as dalfampridine is primarily eliminated unchanged through the kidneys (96%) 5
- Even in patients with mild renal impairment (CrCl 51-80 mL/min), dalfampridine may reach plasma levels associated with increased seizure risk 1
- Concomitant use with other forms of 4-aminopyridine should be avoided 1
- The medication has a narrow therapeutic range, requiring strict adherence to the prescribed dosing regimen 5, 6
- Long-term studies have shown sustained improvements in walking speed for up to 2.5 years of continuous treatment in responders 2
Common Adverse Effects
- The most common adverse events (incidence ≥2% and greater than placebo) include: 1, 5
- Urinary tract infection
- Insomnia
- Dizziness
- Headache
- Nausea
- Asthenia
- Back pain
- Balance disorder
- Multiple sclerosis relapse
- Paresthesia
Clinical Pearls
- Treatment response is typically evident quickly, allowing for rapid determination of therapeutic benefit 6
- If no improvement in walking is observed after 2-4 weeks, discontinuation should be considered 3
- Due to the cost (approximately $1,267 per month in 2012) and limited responder rate, dalfampridine should be continued only in patients who demonstrate a clear clinical response 3
- The risk of seizures at the therapeutic dose in patients with no seizure history appears to be similar to the background seizure risk in the MS population 6