Amifampridine for LEMS: How This First-Line Therapy Works

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that affects communication between nerves and muscles, causing symptoms such as muscle weakness and fatigue.

“The goal of treatment is to improve strength, reduce symptoms, and help people stay as active and independent as possible while keeping side effects to a minimum,” says Abdullah “Abdul” AlQahtani, MD, MPH, neurologist at Johns Hopkins Medicine in Baltimore.

Here’s what to know about what causes LEMS symptoms, how amifampridine works, and what to expect when you’re taking the medication.

In LEMS, the immune system mistakenly targets voltage-gated calcium channels at the nerve endings, says Dr. AlQahtani.

Those channels help calcium enter the nerve endings, which is an important step in releasing acetylcholine, the chemical messenger that tells muscles to contract. When the channels are disrupted, the nerve releases less acetylcholine, and the muscle gets a weaker signal, AlQahtani says.

“That weaker signal leads to symptoms such as muscle weakness, difficulty climbing stairs or rising from a chair, fatigue, and sometimes autonomic symptoms such as dry mouth, constipation, or erectile dysfunction in men,” he says.

One unusual feature of LEMS is that strength may briefly improve with repeated effort or exercise, he says.

LEMS can be tumor related or not tumor related. “About half of cases are linked to an underlying cancer, most commonly small cell lung cancer, so cancer screening at diagnosis and ongoing monitoring are a critical part of care,” says AlQahtani.

The drug helps compensate for the nerve-to-muscle signaling problem in LEMS. By blocking potassium channels at the nerve terminal, amifampridine helps the nerve signal last longer, which then allows more calcium to enter the nerve ending and increases the release of acetylcholine, says AlQahtani.

“In simple terms, amifampridine helps the nerve send a stronger signal to the muscle,” he says. The drug doesn’t stop the immune system from making the antibodies involved in LEMS.

Current dosing guidance includes:

Adults The recommended starting dose is 15 to 30 milligrams (mg) per day, divided into three to five doses. The dose may be increased by 5 mg every three or four days. The maximum single dose is 20 mg, and the maximum total daily dose is 100 mg.

Children Age 6 and Older Who Weigh About 99 Pounds or More The recommended starting dose is 15 to 30 mg per day, divided into three to five doses. The dose may be increased by 5 mg every three or four days. The maximum single dose is 20 mg, and the maximum total daily dose is 100 mg.

Children Age 6 and Older Who Weigh Less Than About 99 Pounds The recommended starting dose is 5 to 15 mg per day, divided into three to five doses. The dose may be increased by 2.5 mg every three or four days. The maximum single dose is 10 mg, and the maximum total daily dose is 50 mg.

Children Younger Than 6 Safety and effectiveness have not been established in this age group.

People with kidney impairment, liver impairment, or known NAT2 poor metabolizer status (meaning they break down certain medications slowly) are generally started at the lowest recommended starting dose for their age and weight category.

The tablets are scored and can be split if needed. A liquid suspension can also be prepared for people who need a dose smaller than 5 mg increments, have difficulty swallowing tablets, or use a feeding tube.

The expected benefit of amifampridine is better muscle strength and day-to-day function.

“Many people have improvements in muscle strength, walking ability, stamina, and performance of everyday activities,” AlQahtani says, adding that some people notice improvement in symptoms such as dry mouth.

If symptoms aren’t well managed or remain bothersome, the first step is usually making sure that the dose has been optimized within recommended safety limits, says AlQahtani.

If amifampridine is not tolerated or not available, pyridostigmine (Mestinon) may be considered, and it can also be added to amifampridine for extra symptom relief.

“Pyridostigmine slows the breakdown of acetylcholine at the neuromuscular junction, which can leave more of that chemical messenger available to help muscles contract,” says AlQahtani.

When LEMS is associated with cancer, treating the cancer is a central part of therapy and may also improve LEMS symptoms, he says.

• Tingling or numbness around the mouth, fingers, toes, or other body parts
• Stomach pain, nausea, or diarrhea
• Headache
• Back pain
• High blood pressure
• Muscle spasms
• Increased liver enzymes
• Trouble sleeping

Most side effects are mild and manageable, says AlQahtani.

Taking too much amifampridine can be dangerous. Symptoms reported with overdose have included weakness, tingling, nausea, vomiting, palpitations, seizures, abnormal heart rhythm, and cardiac arrest. Take amifampridine exactly as prescribed and contact your doctor or seek emergency care right away if you think you may have taken too much.