What is LEMS?
Lambert Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disease with the primary symptoms of muscle weakness. Muscle weakness in LEMS is caused by autoantibodies to voltage gated calcium channels leading to a reduction in the amount of acetylcholine released from nerve terminals.
Patients with LEMS typically suffer from fatigue, muscle pain, and stiffness. The weakness is generally more marked in the proximal muscles particularly of the legs and trunk. Other problems include reduced reflexes, drooping of the eyelids, facial weakness and problems with swallowing. Patients often report a dry mouth, impotence, constipation and feelings of light headedness on standing. On occasion these problems can be life threatening when the weakness involves respiratory muscles.
In the European Union, LEMS occurs in 1 in 100,000 patients, according to Orphanet. Approximately half of all LEMS patients diagnosed have small cell lung cancer.
Diagnosis of LEMS
A diagnosis of LEMS is generally made on the basis of clinical symptoms, specific neuromuscular changes through electromyographic testing and the presence of autoantibodies against voltage gated calcium channels.
Patients are also screened for small lung cancer due to the high prevalence of LEMS patients diagnosed with small cell lung cancer.
Patients with LEMS should be examined and then treated by both a neurologist and if appropriate, an oncologist. When a cancer is identified, the first concern should be the appropriate treatment of that malignancy.
Secondarily, treatment of LEMS may include immunosuppressant agents, but success is limited by toxicity and difficulty administering the regimens.
Approaches for Treating LEMS
Patients with LEMS should be examined and then treated by a neurologist, and, if appropriate, an oncologist.
- If a cancer is identified, the first concern will be the appropriate treatment of that cancer.
- Treatment of LEMS symptoms may include medications to improve transmission of nerve impulses as well as agents to reduce the number of antibodies.
Therapeutic interventions in LEMS:
- Treatments aimed at reducing the number of antibodies to allow more muscle function:
- Intravenous immunoglobulin—removes antibodies
- Plasmapheresis—blood is filtered to remove the antibodies
- Corticosteroids, cyclosporine or azathioprine—suppresses the immune system
- Monoclonal Antibodies—attach to the antibodies and disable them
- Treatments aimed at increasing the amount of acetylcholine received by the muscle:
- Cholinesterase inhibitors—the breakdown of acetylcholine is reduced, allowing an increase of generated signals to reach the muscle
- Treatments aimed at increasing the amount of acetylcholine released:
- Aminopyridines—increases the number of nerve impulses
- Firdapse™ (currently approved in the EU) (amifampridine), also known as 3,4 DAP is an aminopyridine—it is the first and only approved treatment option for LEMS
- Firdapse™ was approved for marketing in the European Union on Jan 5, 2010
- Firdapse™ development for the U.S. market is ongoing
For additional information about LEMS, please visit the following websites and others listed in the Patient/Physician Resource Library:
- European Society for Immunodeficiencies
- Myasthenia Gravis Association (UK)
- Association Française contre les Myopathies (France)
Important Safety Information
Abbreviated Prescribing Information
Refer to Summary of Product Characteristics for full information.
Presentation: Each tablet contains amifampridine phosphate equivalent to 10 mg of amifampridine.
Therapeutic indication: Symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults.
Dosage and Administration: Treatment should be initiated under supervision of a physician experienced in the treatment of the disease. FIRDAPSE™ (currently approved in the EU) should be given in divided doses, three or four times a day. The recommended starting dose is 15 mg a day, which can be increased in 5 mg increments every 4 to 5 days, to a maximum of 60 mg per day. No single dose should exceed 20 mg. Tablets are to be taken with food. For oral use only.
Contraindications: Hypersensitivity to the active substance, or to any of the excipients; epilepsy; uncontrolled asthma; Concomitant use with sultopride; concomitant use with medicinal products with a narrow therapeutic window; concomitant use with medicinal products with a known potential to cause QT prolongation; in patients with congenital QT syndromes.
Precautions: No studies have been conducted in patients with renal or hepatic impairment. In view of the risk of markedly increased exposure to medicinal product, patients with renal or hepatic impairment must be carefully monitored. The dose of amifamipridine should be titrated more slowly in patients with renal and hepatic impairment than those with normal renal and hepatic function.
Exposure to amifampridine is associated with an increased risk for epileptic seizures. The risk of seizures is dose-dependent and is increased in patients with risk factors which lower the epileptic threshold; including use in combination with other medicinal products known to lower the epileptic threshold.
Amifampridine has not been fully tested in carcinogenicity models, and the carcinogenicity risk associated with treatment has not been determined. The use of amifampridine in patients with the non-paraneoplastic form of LEMS should only be commenced following a thorough assessment of the risk-benefit to the patient.
Clinical and electrocardiogram (ECG) monitoring are indicated at the initiation of the treatment and yearly thereafter. In case of signs and symptoms indicative of cardiac arrhythmias, ECG should be performed immediately.
Undesirable Effects: The most commonly reported adverse reactions in the published literature are paraesthesias (such as peripheral and peribucal paraesthesias) and gastro-intestinal disorders (such as epigastralgia, diarrhoea, nausea and abdominal pain). The intensity and incidence of most adverse reactions is dose-dependent.
Legal Category: Prescription Only Medicine.
Marketing Authorisation Holder: BioMarin Europe Limited, 164 Shaftesbury Avenue, London, WC2H 8HL, United Kingdom.
Marketing Authorisation Number: EU/1/09/601/001.
Date of Preparation of Text: January 2010.