Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Biogen Netherlands B.V., Prins Mauritslaan 13, 1171 LP, Badhoevedorp, The Netherlands
Hypersensitivity to fampridine or to any of the excipients listed in section 6.1.
Concurrent treatment with other medicinal products containing fampridine (4-aminopyridine).
Patients with prior history or current presentation of seizure.
Patients with mild, moderate or severe renal impairment (creatinine clearances <80 ml/min).
Concomitant use of Fampyra with medicinal products that are inhibitors of Organic Cation Transporter 2 (OCT2) for example, cimetidine.
Treatment with fampridine increases seizure risk (see section 4.8).
Fampyra should be administered with caution in the presence of any factors which may lower seizure threshold.
Fampyra should be discontinued in patients who experience a seizure while on treatment.
Fampyra 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 older people in whom renal function might be reduced). Creatinine clearance can be estimated using the Cockroft-Gault formula. Fampyra should not be administered to patients with renal impairment (creatinine clearance <80 ml/min) (see section 4.3).
Caution is required when Fampyra is prescribed concurrently with medicinal products that are substrates of OCT2 for example, carvedilol, propanolol and metformin.
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, Fampyra should be discontinued and not restarted.
Fampyra 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.
The increased incidence of dizziness and balance disorder seen with Fampyra may result in an increased risk of falls. Therefore, patients should use walking aids as needed.
In clinical studies low white blood cell counts were seen in 2.1% of Fampyra patients versus 1.9% of patients on placebo. Infections were seen in the clinical studies (see section 4.8) and increased infection rate and impairment of the immune response cannot be excluded.
Interaction studies have only been performed in adults.
Concurrent treatment with other medicinal products containing fampridine (4-aminopyridine) is contraindicated (see section 4.3).
Fampridine is eliminated mainly via the kidneys with active renal secretion accounting for about 60% (see section 5.2). 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 (see section 4.3) and concomitant use of fampridine with medicinal products that are substrates of OCT2 for example, carvedilol, propanolol and metformin is cautioned (see section 4.4).
Interferon: fampridine has been administered concomitantly with interferon-beta and no pharmacokinetic medicinal product interactions were observed.
Baclofen: fampridine has been administered concomitantly with baclofen and no pharmacokinetic medicinal product interactions were observed.
There are limited amount of data from the use of fampridine in pregnant women.
Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure it is preferable to avoid the use of Fampyra in pregnancy.
It is unknown whether fampridine is excreted in human or animal milk. Fampyra is not recommended during breast-feeding.
In animal studies no effects on fertility were seen.
Fampyra has a moderate influence on the ability to drive and use machines because Fampyra can cause dizziness.
The safety of Fampyra 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 Fampyra 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.
Very Common: Urinary tract infection1
Common: Influenza1, Nasopharyngitis1, Viral infection1
Uncommon: Anaphylaxis, Angioedema, Hypersensitivity
Common: Insomnia, Anxiety
Common: Dizziness, Headache, Balance disorder, Paraesthesia, Tremor
Uncommon: Seizure, Exacerbation of trigeminal neuralgia
Common: Palpitations
Uncommon: Tachycardia
Uncommon: Hypotension2
Common: Dyspnoea, Pharyngolaryngeal pain
Common: Nausea, Vomiting, Constipation, Dyspepsia
Uncommon: Rash, Urticaria
Common: Back pain
Common: Asthenia
Uncommon: Chest discomfort2
1 See section 4.4
2 These symptoms were observed in the context of hypersensitivity
In post-marketing experience, there have been reports of seizure, the frequency is not known (cannot be estimated from the available data). For further information on seizure risk, please refer to sections 4.3 and 4.4.
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. For further information on hypersensitivity reactions, please refer to sections 4.3 and 4.4.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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