Fampridine Other names: 4-Aminopyridine 4-AP Dalfampridine

Fampridine is eliminated mainly via the kidneys with active renal secretion accounting for about 60%. OCT2 is the transporter responsible for the active secretion of fampridine. Thus, the concomitant use of fampridine with medicinal products that are inhibitors of OCT2 for example, cimetidine are contraindicated and concomitant use of fampridine with medicinal products that are substrates of OCT2 for example, carvedilol, propanolol and metformin is cautioned.

In post-marketing experience, serious hypersensitivity reactions (including anaphylactic reaction) have been reported, the majority of these cases occurred within the first week of treatment. Particular attention should be given to patients with a previous history of allergic reactions. If an anaphylactic or other serious allergic reaction occurs, fampridine should be discontinued and not restarted.

In clinical studies low white blood cell counts were seen in 2.1% of fampridine patients versus 1.9% of patients on placebo. Infections were seen in the clinical studies and increased infection rate and impairment of the immune response cannot be excluded.

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.

Fampridine should be administered with caution to patients with cardiovascular symptoms of rhythm and sinoatrial or atrioventricular conduction cardiac disorders (these effects are seen in overdose). There is limited safety information in these patients.

There are 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.

It is unknown whether fampridine is excreted in human or animal milk. Fampridine is not recommended during breast-feeding.

Fertility

In animal studies no effects on fertility were seen.

Fampridine has a moderate influence on the ability to drive and use machines because can cause dizziness.

The safety of fampridine has been evaluated in randomised controlled clinical studies, in open label long term studies and in the post marketing setting.

Adverse reactions identified are mostly neurological and include seizure, insomnia, anxiety, balance disorder, dizziness, paraesthesia, tremor, headache and asthenia. This is consistent with fampridine’s pharmacological activity. The highest incidence of adverse reactions identified from placebocontrolled trials in multiple sclerosis patients with fampridine given at the recommended dose, are reported as urinary tract infection (in approximately 12% of patients).

Adverse reactions are presented below by system organ class and absolute frequency. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Infections and infestations

Very Common: Urinary tract infection

Common: Influenza, Nasopharyngitis, Viral infection

Immune system disorders

Uncommon: Anaphylaxis, Angioedema, Hypersensitivity

Psychiatric disorders

Common: Insomnia, Anxiety

Nervous system disorders

Common: Dizziness, Headache, Balance disorder, Paraesthesia, Tremor

Uncommon: Seizure, Exacerbation of trigeminal neuralgia

Cardiac disorders

Common: Palpitations

Uncommon: Tachycardia

Vascular disorders

Uncommon: Hypotension¹

Respiratory, thoracic and mediastinal disorders

Common: Dyspnoea, Pharyngolaryngeal pain

Gastrointestinal disorders

Common: Nausea, Vomiting, Constipation, Dyspepsia

Skin and subcutaneous tissue disorders

Uncommon: Rash, Urticaria

Musculoskeletal and connective tissue disorders

Common: Back pain

General disorders and administration site conditions

Common: Asthenia

Uncommon: Chest discomfort¹

¹ These symptoms were observed in the context of hypersensitivity

Description of selected adverse reactions

Seizure

In post-marketing experience, there have been reports of seizure, the frequency is not known (cannot be estimated from the available data).

Hypersensitivity

In post-marketing experience, there have been reports of hypersensitivity reactions (including anaphylaxis) which have occurred with one or more of the following: dyspnoea, chest discomfort, hypotension, angioedema, rash and urticaria.