Fampridine

Oral
Multiple sclerosis

CrCl (mL/min)	Dosage
≤50	Contraindicated.

Hypersensitivity. History of seizures. Moderate to severe renal impairment (CrCl ≤50 mL/min).

Patient w/ arrhythmia, SA/AV conduction disorder. Mild renal impairment (CrCl 51-80 mL/min).

Significant: Anaphylaxis or severe allergic reactions (e.g. resp compromise, urticaria, tongue/throat angioedema), seizures, UTI.
Nervous: Insomia, dizziness, headache, anxiety, asthenia, paraesthesia, balance disorder, fatigue, risk of fall, tremor, exacerbation of multiple sclerosis.
CV: Palpitations, tachycardia, peripheral oedema.
GI: Constipation, dyspepsia, nausea, vomiting.
Resp: Nasopharangytis, dyspnoea, pharyngolaryngeal pain.
Musculoskeletal: Back pain, weakness, muscle spasm.

PO: C

This drug may cause dizziness, if affected, do not drive or operate machinery.

Assess risk of seizures, walking ability. Monitor EEG, renal function before initiation of therapy and monitor thereafter.

Symptoms: Confusion, tremulousness, diaphoresis, seizures, status epilepticus, amnesia, involuntary and choreoathetoid movements, cardiac arrhythmias (e.g. supraventricular tachycardia/bradycardia), ventricular tachycardia, hypotension. Management: Supportive treatment. Repeated seizure activity may be treated w/ benzodiazepines, phenytoin or other anti-seizure therapy.

Increased risk of seizures w/ drugs that lower seizure threshold (e.g. TCA, SSRI(s), phenothiazines, butyrophenones, tramadol). Increased serum concentration w/ organic cation transporter-2 (OCT2) inhibitor (e.g. cimetidine) or substrate (e.g. metformin, carvedilol, propranolol).

Description:
Mechanism of Action: Fampridine is a potassium channel blocker. The exact mechanism of action has not been fully elucidated, but it is thought that the inhibition of potassium channel reduces leakage of ionic current, thereby delaying repolarization and increasing conduction of action potentials in demyelinated axons. This results in improved peripheral motor neurologic function and strengthening of muscle fibre twitch activity.
Pharmacokinetics:
Absorption: Rapidly and extensively absorbed from the GI tract. Bioavailability: 96%. Time to peak plasma concentration: 3-4 hr.
Distribution: Crosses blood-brain barrier. Volume of distribution: 2.6 L/kg. Plasma protein binding: 1-3%.
Metabolism: Small portion (<10%) is metabolised in the liver via oxidation by CYP2E1 into 3-hydroxy-4-aminopyridine and conjugated 3-hydroxy-4-aminopyridine sulfate.
Excretion: Mainly via urine (96%, 90% as unchanged drug; 4.3% as 3-hydroxy-4-aminopyridine, 2.6% as 3-hydroxy-4-aminopyridine sulfate); faeces (0.5%). Elimination half-life: 5.2-6.5 hr.

Source: National Center for Biotechnology Information. PubChem Database. 4-Aminopyridine, CID=1727, https://pubchem.ncbi.nlm.nih.gov/compound/4-Aminopyridine (accessed on Jan. 20, 2020)

Store below 25°C. Protect from light and moisture.

Neuromuscular Disorder Drugs

N07XX07 - fampridine ; Belongs to the class of other nervous system drugs.

Ampyra Tab, Film Coated, Extended Release (Acroda Therapeutics, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/09/2017.

Anon. Dalfampridine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/09/2017.

Buckingham R (ed). Fampridine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/09/2017.

Joint Formulary Committee. Fampridine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/09/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Dalfampridine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 08/09/2017.

Preston CL (ed). Fampridine (Dalfampridine) + Miscellaneous. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/09/2017.