Usage
- Dalfampridine is prescribed to improve walking in adults with multiple sclerosis (MS). This is measured by an increase in walking speed.
- Pharmacological Classification: Potassium channel blocker.
- Mechanism of Action: Dalfampridine blocks potassium channels on demyelinated axons, which improves nerve conduction by prolonging the action potential duration and enhancing signal transmission.
Alternate Names
- Fampridine (specifically, 4-aminopyridine or 4-AP). The term “dalfampridine” represents the extended-release formulation of fampridine.
- Brand Name: Ampyra
How It Works
- Pharmacodynamics: Dalfampridine improves the conduction of nerve impulses in demyelinated nerve fibers, likely by increasing the duration of action potentials. This enhanced conduction can lead to improved muscle function and walking ability in some MS patients.
- Pharmacokinetics:
- Absorption: Well-absorbed after oral administration.
- Metabolism: Primarily excreted unchanged by the kidneys. Limited hepatic metabolism.
- Elimination: Renal excretion.
- Mode of Action: Binds to open voltage-gated potassium channels, delaying repolarization, thereby increasing the duration of action potentials in demyelinated axons.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Blocks voltage-gated potassium channels, but doesn’t directly bind to receptors, inhibit enzymes, or modulate neurotransmitters in the classical sense.
- Elimination Pathways: Primarily renal excretion (over 90%).
Dosage
Standard Dosage
Adults:
- 10 mg orally twice daily, approximately 12 hours apart.
- Maximum dose: 20 mg per day. Do not exceed this limit.
Children:
- Safety and efficacy have not been established in children under 18 years of age. Use is not recommended.
Special Cases:
- Elderly Patients: Renal function should be assessed before initiating therapy, as elderly patients are more likely to have age-related renal impairment.
- Patients with Renal Impairment: Contraindicated in moderate to severe renal impairment (creatinine clearance ≤50 mL/min). Caution is advised in mild renal impairment (creatinine clearance 51–80 mL/min) due to potential increased risk of seizures. Creatinine clearance should be calculated before starting treatment and monitored regularly.
- Patients with Hepatic Dysfunction: No specific dosage adjustments recommended, as hepatic metabolism is limited.
- Patients with Comorbid Conditions: Evaluate for seizure history. Patients with a history of seizures should not take this medication.
Clinical Use Cases
Dalfampridine is specifically indicated for improving walking in adults with MS. Its use is not recommended in the following settings:
- Intubation: Not applicable.
- Surgical Procedures: Not applicable.
- Mechanical Ventilation: Not applicable.
- Intensive Care Unit (ICU) Use: Not applicable.
- Emergency Situations: Not applicable.
Dosage Adjustments
- Dose adjustment is primarily based on renal function. See “Special Cases” above.
Side Effects
Common Side Effects:
- Urinary tract infection
- Insomnia
- Dizziness
- Headache
- Nausea
- Asthenia
- Back pain
- Balance disorder
- MS relapse
- Paresthesia
- Nasopharyngitis
- Constipation
- Dyspepsia
- Pharyngolaryngeal pain
Rare but Serious Side Effects:
- Seizures (dose-related)
- Allergic reactions (including anaphylaxis and angioedema)
Long-Term Effects:
- Long-term effects are still being investigated, though open-label extension studies indicate a continued improvement in walking speed for up to two years.
Adverse Drug Reactions (ADR):
Contraindications
- History of seizures
- Moderate to severe renal impairment (creatinine clearance ≤50 mL/min)
- Hypersensitivity to dalfampridine
Drug Interactions
- Cimetidine (and other OCT2 inhibitors): May increase dalfampridine exposure and seizure risk.
- Other forms of 4-aminopyridine: Should not be used concomitantly.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Fetal Risks: Animal data suggests potential fetal harm. Use only if the potential benefit outweighs the risk.
- Breastfeeding: Excretion into human milk is unknown. Due to the potential for adverse effects in the nursing infant, breastfeeding is not recommended while taking dalfampridine.
Drug Profile Summary
- Mechanism of Action: Potassium channel blocker; improves nerve conduction in demyelinated axons.
- Side Effects: Urinary tract infections, insomnia, dizziness, headache, nausea, seizures (rare but serious).
- Contraindications: Seizures, moderate to severe renal impairment.
- Drug Interactions: OCT2 inhibitors (e.g., cimetidine), other forms of 4-aminopyridine.
- Pregnancy & Breastfeeding: Category C; not recommended.
- Dosage: 10 mg twice daily, not to exceed 20 mg/day. Adjust dose based on renal function.
- Monitoring Parameters: Renal function (creatinine clearance), monitor for seizure activity.
Popular Combinations
- No established popular drug combinations.
Precautions
- General Precautions: Assess renal function before starting therapy and monitor regularly. Evaluate for seizure history.
- Specific Populations: See “Dosage - Special Cases” and “Pregnancy and Breastfeeding” above.
- Lifestyle Considerations: No specific restrictions. Maintain a healthy lifestyle, which can benefit overall well-being in MS patients.
FAQs
Q1: What is the recommended dosage for Dalfampridine?
A: 10 mg orally twice daily (approximately 12 hours apart), not to exceed 20 mg/day. Dosage adjustments may be necessary in patients with renal impairment.
Q2: What is the mechanism of action of Dalfampridine?
A: It blocks potassium channels in demyelinated axons, improving nerve conduction by prolonging action potential duration.
Q3: Is Dalfampridine safe during pregnancy?
A: Pregnancy Category C. Animal studies suggest a potential risk of fetal harm. Use only if the potential benefit outweighs the risk.
Q4: Can Dalfampridine be used in children?
A: Safety and efficacy have not been established in children under 18 years of age. Use is not recommended.
Q5: What are the most common side effects of Dalfampridine?
A: Urinary tract infection, insomnia, dizziness, headache, nausea.
Q6: What is the most serious side effect of Dalfampridine?
A: Seizures. The risk is dose-related and may be increased in patients with renal impairment.
Q7: Are there any contraindications to using Dalfampridine?
A: History of seizures, moderate to severe renal impairment, and hypersensitivity to dalfampridine.
Q8: Does Dalfampridine interact with other medications?
A: Yes, it can interact with OCT2 inhibitors (e.g., cimetidine) and other forms of 4-aminopyridine.
Q9: How should Dalfampridine be administered?
A: Orally, as an extended-release tablet. Swallow the tablet whole; do not crush, chew, divide, or dissolve.
Q10: How long does it take to see the effects of Dalfampridine?
A: Effects on walking speed are typically seen within 2-4 weeks.
