Dalfampridine

Pronunciation: dal-FAM-pri-deen
Class: Potassium channel blocker

Trade Names

Ampyra
- Tablets, ER 10 mg

Pharmacology

Unknown. Is a broad-spectrum potassium channel blocker that has been shown to increase conduction of action potentials in demyelinated axons.

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Pharmacokinetics

Absorption

Rapidly and completely absorbed from the GI tract. Relative bioavailability is 96%. C _max for a 10 mg dose ranged from 17.3 to 21.6 ng/mL and T _max from approximately 3 to 4 h. When taken with food, there is a slight increase in C _max (12% to 17%) and a slight decrease in AUC (4% to 7%).

Distribution

Largely unbound to plasma proteins (97% to 98%); apparent Vd is 2.6 L/kg.

Metabolism

CYP2E1 is the major enzyme responsible for the 3-hydroxylation of dalfampridine.

Elimination

Dalfampridine and metabolites elimination is nearly complete after 24 h, with 95.9% of the dose recovered in urine and 0.5% recovered in feces. The elimination half-life is 5.2 to 6.5 h and the plasma half-life is about 7.6 h.

Special Populations

Renal Function Impairment

Total body Cl of dalfampridine is reduced by approximately 45% in patients with mild renal impairment (CrCl 51 to 80 mL/min), by approximately 50% in patients with moderate renal impairment (CrCl 30 to 50 mL/min), and by approximately 75% in patients with severe renal impairment (CrCl less than 30 mL/min). Dalfampridine is contraindicated in patients with moderate to severe renal impairment.

Hepatic Function Impairment

The pharmacokinetics in patients with hepatic impairment have not been studied.

Elderly

Cl modestly decreased with increasing age, but not significantly enough to necessitate a modification in dose.

Gender

A pharmacokinetic analysis suggested that women would be expected to have higher C _max than men.

Race

There were too few nonwhite patients to evaluate the effect of race.

Indications and Usage

For the treatment to improve walking in patients with multiple sclerosis (MS).

Contraindications

History of seizure; moderate to severe renal impairment.

Dosage and Administration

Adults

PO 10 mg twice daily (max, 20 mg/day).

General Advice

• May administer with or without food.
• Doses should be taken approximately 12 h apart.
• Tablets should only be taken whole; do not divide, crush, chew, or dissolve.

Storage/Stability

Store at 77°F.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Insomnia (9%); asthenia, dizziness, headache (7%); balance disorder (5%); MS relapse, paresthesia (4%).

EENT

Nasopharyngitis (4%); pharyngolaryngeal pain (2%).

GI

Nausea (7%); constipation (3%); dyspepsia (2%).

Miscellaneous

UTI (12%); back pain (5%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy in patients younger than 18 yr of age not established.

Elderly

Dalfampridine Cl modestly decreased with increasing age, but not sufficient enough to necessitate a modification of dose. Because elderly patients are more likely to have decreased renal function, it is particularly important to know the CrCl in these patients.

Renal Function

Dalfampridine Cl is decreased; contraindicated in patients with moderate or severe renal impairment (CrCl 50 mL/min or less). Calculate CrCl prior to initiating therapy with dalfampridine.

Seizures

Contraindicated in patients with a history of seizures. Discontinue therapy and do not restart in patients who experience a seizure while on treatment.

Urinary tract infections

Were reported.

Overdosage

Symptoms

Altered mental state, amnesia, complex partial seizure, confusion, diaphoresis, hypophonic speech, limbic encephalitis, memory loss, reduced awareness, status epilepticus, temporal lobe hyperintensities, tremulousness, and weakness.

Patient Information

• Inform patients that dalfampridine causes seizures in a dose-dependent fashion, and that they must discontinue use if they experience a seizure.
• Instruct patients to take the drug exactly as prescribed and to take the dose approximately 12 h apart, and not to double the dose if a dose is missed.
• Instruct patients that they may take the drug without regard to meals, but to take with food if stomach upset occurs.
• Advise patients not to take dalfampridine with other forms of 4–aminopyridine (4–AP, fampridine) because the active ingredient is the same.

Copyright © 2009 Wolters Kluwer Health.