Fampridine

Registered South African indications:

• Multiple sclerosis (MS) with walking disability (Expanded disability status scale [EDSS] 4-7)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Prior history or current presentation of seizure
• Renal impairment (CrCl<80ml/min) (South African manufacturer recommendations)
• Moderate to severe renal impairment (CrCl<50ml/min) (International manufacturer recommendations) 
• Coadministration with other medicines containing fampridine (4-aminopyridine)
• Coadministration with medicines that are inhibitors of organic cation transporter 2 (OCT2) (e.g. cimetidine)

Cautions

• Pregnancy
• Breastfeeding
• Mild renal impairment (CrCl≥50ml/min) (International manufacturer recommendations)
• Elderly
• Factors which may lower seizure threshold
• Previous history of allergic reactions
• Cardiovascular symptoms of rhythm and sinoatrial or atrioventricular conduction cardiac disorders
• Coadministration with medicines that are substrates of OCT2 (e.g. carvedilol, propranolol and metformin)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Fampridine is restricted to prescription and supervision by physicians experienced in the management of multiple sclerosis (MS)

Multiple sclerosis (MS) with walking disability (Expanded disability status scale [EDSS] 4-7) for the improvement of walking

• Oral (tab): 10mg, 12hrly (one tab in the morning and one tab in the evening)

 Fampridine should not be administered more frequently or at higher doses than recommended

Fampridine should be taken without food

Missed dose: The usual dosing regimen should always be followed. A double dose should not be taken if a dose is missed

Starting and evaluating fampridine treatment as well as re-evaluating fampridine treatment (See additional prescribing points)

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• There is limited amount of data from the use of fampridine in pregnant women
• Animal studies have shown reproductive toxicity. As a precautionary measure it is preferable to avoid the use of fampridine in pregnancy

Breastfeeding

• Caution; not recommended 
• It is unknown whether fampridine is excreted in human or animal milk. Fampridine is not recommended during breastfeeding

Fertility

• No effects on fertility were seen in animal studies

Renal Impairment
South African manufacturer recommendations

• CrCl<80ml/min: Contraindicated 

International manufacturer recommendations

• CrCl≥50ml/min: Caution; no dose adjustment recommended 
  Fampridine is primarily excreted unchanged by the kidneys. Patients with renal impairment have higher plasma concentrations which are associated with increased adverse reactions, in particular neurological effects. Determining renal function before treatment and its regular monitoring during treatment is recommended in all patients (particularly in the elderly in whom renal function might be reduced). Creatinine clearance can be estimated using the Cockroft-Gault formula. Caution is required when fampridine is prescribed in patients with mild renal impairment
• CrCl<50ml/min: Contraindicated 

Hepatic Impairment

• No dose adjustment recommended 

Elderly

• Caution; no dose adjustment recommended 
  Renal function should be checked in older people before starting treatment with fampridine. Monitoring renal function to detect any renal impairment is recommended in older people

Porphyria Information 

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness (See additional prescribing points)
• Headache
• Balance disorder (See additional prescribing points)
• Vertigo
• Paraesthesia
• Tremor
• Seizure
• Trigeminal neuralgia
  - De novo symptoms and exacerbation of existing
• Insomnia
• Anxiety
• Asthenia

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Chest discomfort

Respiratory Disorders

• Dyspnoea
• Pharyngolaryngeal pain
• Nasopharyngitis

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Dyspepsia

Genitourinary Disorders

• Urinary tract infection

Musculoskeletal Disorders

• Back pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  -  Hypotension
• Decreased white blood cell count
• Influenza
• Viral infection
• Anaphylaxis
• Angioedema

• Other medicinal agents containing fampridine (4-aminopyridine)
• Organic cation transporter 2 (OCT2) inhibitors
• Cimetidine
• Organic cation transporter 2 (OCT2) substrates
• Carvedilol
• Propranolol
• Metformin

• Renal function (baseline and then, at least yearly)
•  Electroencephalogram (EEG)

Additional observations

• Walking ability

Increased incidence of dizziness and balance disorder

• The increased incidence of dizziness and balance disorder seen with fampridine may result in an increased risk of falls. Therefore, patients should use walking aids as needed

Starting and evaluating fampridine treatment

• Initial prescription should be limited to 2-4 weeks of therapy as clinical benefits should generally be identified within 2-4 weeks after starting fampridine
• An assessment of walking ability, e.g. the timed 25 foot walk (T25FW) or twelve item multiple sclerosis walking scale (MSWS-12), is recommended to evaluate improvement within 2-4 weeks. If no improvement is observed, fampridine should be discontinued
• Fampridine should be discontinued if benefit is not reported by patients

Re-evaluating fampridine treatment

• If decline in walking ability is observed, consider an interruption to treatment in order to reassess the benefits of fampridine. The re-evaluation should include withdrawal of fampridine and performing an assessment of walking ability. Fampridine should be discontinued if patients no longer receive walking benefit

Fampridine is a potassium channel blocker. By blocking potassium channels, fampridine reduces the leakage of ionic current through these channels, thereby prolonging repolarization and thus enhancing action potential formation in demyelinated axons and neurological function. Presumably, by enhancing action potential formation, more impulses might be conducted in the central nervous system.

Tablet 10mg

• Fampyra ( Acino Pharma) originator