dalfampridine

Dalfampridine is a drug used to improve walking in patients with multiple sclerosis (MS), an autoimmune neurological disorder.

Multiple sclerosis is a potentially disabling disease in which the immune cells mistakenly attack and eventually destroy myelin, a substance that forms a protective sheath over nerve fibers (axons). Axons are hair-like projections from nerve cells (neurons) responsible for transmission of electrical impulses, and damage to myelin and axon can disrupt the conduction of nerve signals.

Depending on the region of the central nervous system that is affected, MS can cause many symptoms including impaired coordination, vision loss, pain, and fatigue. Dalfampridine improves motor function in patients with MS by enhancing the conduction of nerve impulses in the demyelinated axons. Dalfampridine is a potassium channel blocker that prevents the influx of potassium ions into the neurons. This prolongs the duration of action potential and delays the repolarization of the neurons, thereby improving nerve conduction and muscle function.

Dalfampridine is a relatively new drug approved by the FDA in 2010 for improving motor function in patients with MS. In addition, dalfampridine is undergoing clinical trials for use in other conditions caused by damage to the nervous system, including:

• Ataxia, a condition that affects balance, coordination, and speech
• Spinal cord injuries
• Spinocerebellar degeneration
• Parkinson’s disease

• Do not use dalfampridine to treat patients with hypersensitivity to any component of the formulation.
• There have been reports of severe allergic reactions (anaphylaxis) with symptoms that included respiratory difficulty, hives, and swelling of throat or tongue. In the event, a patient develops allergic reactions, discontinue dalfampridine immediately, institute appropriate treatment, and do not restart dalfampridine.
• Do not use dalfampridine in patients with a history of seizure. Dalfampridine was observed to increase the incidence of seizures. Discontinue dalfampridine and do not restart if a patient experiences seizures during treatment.
• Do not use dalfampridine in patients with moderate or severe kidney impairment, it can increase the risk of seizure. The risk for seizure in patients with mild kidney impairment is not known, but is likely. Evaluate creatinine clearance in patients before initiating dalfampridine treatment.
• Do not concurrently use other formulations of dalfampridine, it can increase the risk for dose-related adverse reactions. Dalfampridine is also referred to by its chemical name 4-aminopyridine and is known as fampridine in Canada.
• There have been more frequent reports of urinary tract infections with dalfampridine when compared to placebo.

Common side effects of dalfampridine include:

• Urinary tract infection
• Headache
• Weakness (asthenia)
• Dizziness
• Insomnia
• Abnormal skin sensations (paresthesia)
• Multiple sclerosis relapse
• Nausea
• Constipation
• Indigestion (dyspepsia)
• Nose and throat inflammation (nasopharyngitis)
• Throat pain
• Back pain
• Balance disorder

Less common side effects of dalfampridine include:

• Confusion
• Seizure
• Vertigo
• Vomiting
• Hypersensitivity reactions
• Swelling under the skin and in the mucous tissue (angioedema)
• Severe allergic reactions (anaphylaxis)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet, extended-release

• 10 mg

Adult:

Multiple Sclerosis

• Indicated to improve walking in patients with multiple sclerosis by increasing walking speed
• 10 mg orally twice daily with or without food; take doses 12 hours apart
• Extended-release tablet; swallow tablet whole and do not chew, crush, divide, or dissolve tablets

Renal and Hepatic Impairment

Renal impairment

• Moderate-to-severe (Creatinine Clearance [CrCl] 50 mL/minute or lower): Contraindicated due to increased risk of seizures
• Mild (CrCl 51-80 mL/minute): Risk of seizure unknown, but plasma levels may be similar to levels of 15 mg orally twice daily, a dose that is possibly associated with increased seizure risk

Hepatic impairment

• Not studied, but not expected to change dosing recommendations (primarily renal excretion)

Geriatric:

Multiple Sclerosis

• It is important to know the estimated CrCl in the elderly prior to initiating therapy because the elderly are more likely to have decreased renal function
• 10 mg orally twice daily with or without food in normal renal function; take doses 12 hours apart
• Extended-release tablet; swallow tablet whole and do not chew, crush, divide, or dissolve tablets

Renal and Hepatic Impairment

• Mild renal impairment (CrCl 51-80 mL/minute), Risk of seizure unknown, but plasma levels may be similar to levels of 15 mg orally twice daily, a dose that is possibly associated with increased seizure risk
• Moderate or severe renal impairment (CrCl 50 mL/minute or lower): Contraindicated due to increased risk of seizures
• Hepatic impairment: Not studied but not expect

Pediatric:

• Safety and efficacy not established

Overdose

• Dalfampridine overdose can cause confusion, loss of memory (amnesia), excessive sweating (diaphoresis), tremulousness, and seizures, and in some instances, there have been reports of prolonged state of seizure (status epilepticus).
• Overdose is treated with supportive care and anticonvulsant therapy if required.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Dalfampridine has no listed severe interactions with other drugs.
• Serious interactions of dalfampridine include:
  • Trilaciclib
• Moderate interactions of dalfampridine include:
  • Dolutegravir
  • Metformin
• Dalfampridine has no listed mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• There are no adequate and well-controlled studies of dalfampridine use in pregnant women, however, animal studies suggest it can cause fetal harm if used during pregnancy. Dalfampridine should be used with caution in pregnant women, only if clearly needed and if potential benefits outweigh potential harm to the fetus.
• It is not known if dalfampridine is present in breastmilk, but many drugs are excreted in breastmilk. Decision to discontinue dalfampridine or breastfeeding should be made based on the importance of the drug to the mother, because of the potential for serious adverse reactions in the breastfed infant.

• Take dalfampridine exactly as prescribed.
• Do not double the dose or take an extra dose if you miss a dose.
• Report immediately to your physician if you develop severe allergic reactions, symptoms of which may include hives, swelling of throat and tongue, and/or breathing difficulty.
• Store dalfampridine safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.