dalfampridine

Action and Spectrum

Actions and Spectrum: 

• dalfampridine is a medication used for the symptomatic improvement of walking in patients with multiple sclerosis (MS). Its mechanism of action is not fully understood, but it is believed to work by blocking potassium channels in demyelinated axons, which improves nerve conduction velocity. 
• dalfampridine is a potassium channel blocker that specifically targets voltage-gated potassium channels. In demyelinated axons, these channels are exposed to the extracellular space, which can reduce the conduction velocity of the action potential. By blocking these channels, dalfampridine can improve nerve conduction, improving motor function. 
• The spectrum of dalfampridine activity is limited to MS patients with difficulty walking. It is not indicated for other conditions or symptoms and is ineffective in all patients with MS. In clinical trials, dalfampridine has been shown to improve walking speed and distance in some patients with MS. Still; it does not improve other MS symptoms such as muscle weakness, spasticity, or fatigue. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Urinary tract infection (12%) 

1-10% 

Dizziness 

Nausea 

Back pain 

Balance disorder 

Paresthesia 

Constipation 

Pharyngolaryngeal pain 

Insomnia 

Headache 

Asthenia 

Multiple sclerosis relapse 

Nasopharyngitis 

Dyspepsia 

Dose-related increased risk of seizures 

Post-marketing reports 

Vomiting 

Seizures 

Vertigo 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: dalfampridine is contraindicated in patients with known hypersensitivity to the drug or its components. 

• Moderate or Severe Renal Impairment: dalfampridine is contraindicated in patients with moderate or severe renal impairment (creatinine clearance less than 50 mL/min), as the kidneys primarily eliminate the drug, and its safety and efficacy have not been established in this population. 

• History of Seizures: dalfampridine may lower the seizure threshold and is contraindicated in patients with a history of seizures. 

• Concurrent Use of Other Potassium Channel Blockers: dalfampridine should not be used concurrently with other drugs known to block potassium channels, such as amiodarone or quinidine, as it may increase the risk of adverse effects. 

• Pregnancy and Breastfeeding: The safety and efficacy of dalfampridine have not been established in pregnant or breastfeeding women. The drug should only be used in these populations if the potential benefits outweigh the potential risks. 

Caution: 

• Renal impairment: dalfampridine is primarily eliminated by the kidneys, and its safety and efficacy have not been established in patients with mild renal impairment (creatinine clearance 51-80 mL/min). Close monitoring is recommended in these patients. 
• History of Seizures: dalfampridine may lower the seizure threshold and increase the risk of seizures. Patients with a history of seizures should be closely monitored while taking dalfampridine. 
• Drug Interactions: dalfampridine is primarily metabolized by the liver, and caution should be taken when co-administering with other drugs metabolized by the same pathway, such as cimetidine or famotidine. 
• Pregnancy and Breastfeeding: The safety and efficacy of dalfampridine have not been established in pregnant or breastfeeding women. The drug should only be used in these populations if the potential benefits outweigh the potential risks. 
• Cardiovascular risk: dalfampridine may increase the risk of cardiovascular events such as atrial fibrillation and myocardial infarction. Patients with a history of cardiovascular disease should be closely monitored while taking dalfampridine. 
• Gastrointestinal Side Effects: dalfampridine may cause gastrointestinal side effects such as nausea, vomiting, and diarrhea. These side effects may be managed by taking the medication with food. 
• Allergic Reactions: dalfampridine may cause allergic reactions in some patients, and patients should be monitored for signs of an allergic reaction such as rash, itching, or swelling. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation:  

• Excretion of the drug in human breast milk is unknown 
• The drug should only be used in these populations if the potential benefits outweigh the potential risks. 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

dalfampridine is a potassium channel blocker used for the symptomatic improvement of walking in patients with multiple sclerosis (MS). The exact mechanism of action of dalfampridine has yet to be fully understood. Still, it is believed to work by blocking voltage-gated potassium channels, which are exposed in demyelinated axons. This leads to an improvement in nerve conduction velocity and motor function. 

Pharmacodynamics: 

• dalfampridine is a potassium channel blocker that blocks voltage-gated potassium channels exposed in demyelinated axons. This leads to improved nerve conduction velocity and motor function, particularly in the lower extremities, resulting in improved walking speed and distance in patients with multiple sclerosis (MS). 
• In MS, damage to the myelin sheath surrounding nerve fibers leads to impaired nerve conduction velocity and motor function. Dalfampridine works by blocking potassium channels on the axons of demyelinated nerves, which allows for a more significant influx of calcium ions and an increase in neurotransmitter release. This leads to an improvement in nerve conduction velocity and motor function. 

Pharmacokinetics: 

Absorption 

dalfampridine is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours. The absolute bioavailability of dalfampridine is approximately 90%. 

Distribution 

dalfampridine is highly protein-bound (approximately 30%) and has a volume of distribution of approximately 0.7 L/kg. 

Metabolism 

dalfampridine is primarily metabolized in the liver by the cytochrome P450 system, specifically by the CYP1A2 and CYP2E1 isoenzymes. The significant metabolites of dalfampridine are 3-hydroxy-4-aminopyridine and 3-hydroxy-4-aminopyridine N-oxide. 

Elimination and Excretion 

dalfampridine is primarily eliminated in the urine, with approximately 80% of the drug eliminated in the urine and approximately 10% eliminated in the feces. The half-life of dalfampridine is approximately 4-6 hours. 

Adminstartion

Administration: 

• dalfampridine is available as an oral tablet, and the recommended dosage is one 10 mg tablet twice daily, with a 12-hour interval between doses. The tablets should be swallowed whole, not crushed, chewed, or broken. 
• dalfampridine can be taken with or without food, but it should not be taken simultaneously with other forms of 4-aminopyridine, as this may increase the risk of adverse effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dalfampridine 

Pronunciation: [ dal-FAM-pri-deen ] 

Why do we use dalfampridine? 

• dalfampridine is indicated for the symptomatic improvement of walking in adult patients with multiple sclerosis (MS). It improves walking speed and distance in MS patients with walking difficulties. 
• MS is a chronic neurological disease affecting the central nervous system, damaging the myelin sheath surrounding nerve fibers. This damage can lead to various symptoms, including impaired motor function and walking difficulties.  
• dalfampridine improves nerve conduction velocity and motor function, particularly in the lower extremities, improving walking speed and distance in patients with MS.