3,4-Diaminopyridine safety in clinical practice: an observational, retrospective cohort study

Abstract

Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS) and has a significant, often underestimated, impact on patients' quality of life. Current management is mainly symptomatic. 3,4-diaminopyridine (3,4-DAP) is a voltage-dependent potassium channel blocker that has been used on a named patient basis in Europe for many years to improve motor function and fatigue in patients with MS and other neuromuscular disorders, and it is undergoing the European approval process for Lambert-Eaton myasthenic syndrome (LEMS). The efficacy and safety of 3,4-DAP as symptomatic therapy in MS have not been widely evaluated. This study aimed to assess the safety profile of 3,4-DAP in routine clinical practice in an observational, retrospective study. The study involved 669 patients of the Rennes Multiple Sclerosis Clinic, France, who were treated with 3,4-DAP for the relief of fatigue during the period 1998-2003. Overall, 18.2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months. The majority of ADRs were mild to moderate and transient or reversible at the end of treatment (mean treatment duration = two months) or after dose adjustment. Most did not require discontinuation. The most commonly observed ADRs were paraesthesias. There was one case of epileptic seizure, one of hepatotoxicity and one of heart palpitations thought 'possibly' to be linked to 3,4-DAP. These underline the need for continued monitoring during treatment with 3,4-DAP.

Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome

“…25 3,4-DAP increases calcium entry to the presynaptic terminal via blockade of potassium channels, and reduces weakness in patients with LEMS 26 and other neuromuscular disorders. 27 Both of our patients reported a reduction in fatigable weakness, and several objective measures on the CMSS improved during 3,4-DAP treatment. Furthermore, neurophysiologic testing revealed an improvement in synaptic transmission.…”

Recent advances in the diagnosis and treatment of balance disorders

“…Paraesthesias are the most common side effects. As aminopyridines can cause heart palpitations and prolonged QT-time, however, continual monitoring by electrocardiography during treatment is recommended [10]. Also, 4-AP reduces upbeat nystagmus, which only rarely causes chronic symptoms.…”

Current therapy for Lambert–Eaton myasthenic syndrome: development of 3,4-diaminopyridine phosphate salt as first-line symptomatic treatment

“…A study by Flet et al 45 reviewed safety outcomes of 665 patients with multiple sclerosis (MS), three patients with LEMS and one patient with Steinert's disease, who initiated treatment with 3,4-DAP over a five year period. The cumulative daily dose of 3,4-DAP was 20 or 30 mg for 77.6% of patients with a mean cumulative daily dose of 28.6 mg.…”