Products
Fampridine was approved in the United States in 2010, in the EU in 2011 (2017), and in many countries in 2019 in sustained-release tablet form (Fampyra). In the US, it is referred to as dalfampridine (Ampyra).
Structure and properties
Fampridine (C5H6N2, Mr = 94.1 g/mol) is a pyridine bearing an amino group at position 4 (4-aminopyridine). It exists as a fine white powder that is soluble in water. Fampridine has a pKa of 9.1 and is predominantly protonated at physiological pH.
Effects
The effects of fampridine (ATC N07XX07) are primarily attributed to the blockade of voltage-gated potassium channels. By reducing the outward potassium current through the channels in demyelinated axons, it prolongs repolarization and enhances the action potential. As a result, axon function is improved and more impulses are transmitted in the nervous system. In addition, other mechanisms of action are discussed, particularly enhanced release of neurotransmitters such as acetylcholine. Fampridine does not cause prolongation of the QT interval. The half-life is approximately 6 hours. Unlike most other MS medications, fampridine is primarily effective against symptoms and not at the immune system level.
Indications
To improve walking ability in adult patients with multiple sclerosis with walking disability.
Dosage
According to the drug label. Tablets are taken twice daily, i.e., morning and evening, 12 hours apart and fasting.
Contraindications
- Hypersensitivity.
- Concurrent treatment with other drugs containing fampridine.
- Seizures in the patient’s history or current seizures. This is because fampridine increases the risk for seizures.
- Renal dysfunction.
- Concurrent treatment with OCT2 inhibitors, such as cimetidine.
For complete precautions, see the drug label.
Interactions
Fampridine is an organic cation and is excreted via the kidney. It is actively secreted to a relevant extent via the organic cation transporter OCT2. OCT2 inhibitors or substrates such as cimetidine, carvedilol, propranolol, and metformin may inhibit the excretion of fampridine and increase the risk for adverse effects.
Adverse effects
Urinary tract infections were most commonly observed in clinical trials. Other common adverse effects include: