What is the recommended use and dosage of Dalfampridine (Dalfampridine) for patients with multiple sclerosis?

Dalfampridine for Multiple Sclerosis: Recommended Use and Dosage

Dalfampridine is indicated to improve walking in adult patients with multiple sclerosis (MS) at a maximum recommended dosage of 10 mg twice daily, taken approximately 12 hours apart. 1

Mechanism and Indication

• Dalfampridine (also known as fampridine outside the US) is a potassium channel blocker that improves conduction in demyelinated neurons, specifically addressing walking impairment in MS patients 1, 2
• It is the only medication FDA-approved specifically for improving walking ability in MS patients 3
• Dalfampridine is distinct from other MS treatments and is not indicated for treating spasticity, which is typically managed with medications such as tizanidine, dantrolene, or oral baclofen 4

Dosing Guidelines

• The recommended dose is 10 mg twice daily (approximately 12 hours apart) 1
• Tablets should be taken whole; they should not be divided, crushed, chewed, or dissolved 1
• Can be taken with or without food 1
• Patients should not take double or extra doses if they miss a dose 1
• There is no evidence of additional benefit with doses higher than 10 mg twice daily, and adverse reactions (including seizures) are more frequent at higher doses 1, 5

Efficacy

• In clinical trials, dalfampridine improved walking speed in approximately one-third of MS patients 3
• Phase III trials demonstrated that the proportion of "timed walk responders" was significantly higher with dalfampridine (42.9% and 35%) compared to placebo (9.3% and 8%) 6
• Among responders, walking speed improved by approximately 25% from baseline 6
• Improvements in walking ability have been sustained for up to 2.5 years in extension studies 7

Contraindications

• History of seizures 1
• Moderate or severe renal impairment (creatinine clearance ≤50 mL/min) 1
• History of hypersensitivity to dalfampridine or 4-aminopyridine 1

Important Safety Considerations

• Seizure risk: Dalfampridine can cause seizures; the risk increases with higher doses 1, 5
• Renal function: Estimated creatinine clearance should be known before initiating treatment 1
• In patients with mild renal impairment (CrCl 51-80 mL/min), dalfampridine may reach plasma levels associated with greater seizure risk 1
• Avoid concomitant use with other forms of 4-aminopyridine (4-AP, fampridine) 1
• Dalfampridine can cause anaphylaxis; discontinue and do not restart if this occurs 1
• OCT2 inhibitors may increase dalfampridine exposure and potential seizure risk 1

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
  • Nasopharyngitis
  • Constipation
  • Dyspepsia
  • Pharyngolaryngeal pain

Special Populations

• Elderly patients: More likely to have decreased renal function; particularly important to know estimated CrCl before initiating treatment 1
• Pregnancy: Based on animal data, may cause fetal harm 1
• Patients with mild renal impairment: Carefully consider potential benefits against seizure risk 1

Clinical Pearls

• Dalfampridine has a narrow therapeutic range but an acceptable safety profile when used at the therapeutic dose 5
• The drug is nearly completely (approximately 96%) eliminated unchanged in urine, with limited transformation to inactive metabolites 5
• Patients should be monitored for improvement in walking ability; if no improvement is seen, consider discontinuation 3
• The risk of seizures appears to be dose-related with low incidence at the recommended dose of 10 mg twice daily 3, 5