Amifampridine (Firdapse) Side Effects: What to Expect and When to Call Your Doctor

Starting a new medication for a serious condition like Lambert-Eaton Myasthenic Syndrome (LEMS) comes with natural concerns about side effects. Understanding what amifampridine (Firdapse) can cause — and which effects require immediate medical attention — helps you get the most out of treatment while staying safe. Here's a complete picture of what to expect.

The Most Common Side Effect: Paresthesia (Tingling or Numbness)

The most frequently reported side effect of amifampridine is paresthesia or dysesthesia — tingling, numbness, or abnormal sensations, often in the mouth or face (oral paresthesia) and sometimes in the hands and feet. This occurs in approximately 69% of patients and is directly related to the drug's mechanism of blocking potassium channels, which can affect sensory nerves.

For most patients, this tingling is noticeable but not severely uncomfortable and tends to occur shortly after taking a dose. It typically improves or becomes tolerable as your body adjusts to the medication. If the tingling is bothersome, discuss dose timing or dose adjustment with your neurologist.

Other Common Side Effects (Occurring in 10–14% of Patients)

The following side effects were reported in 10% or more of patients in clinical trials:

Elevated liver enzymes (14%): Increases in ALT, AST, LDH, or GGT may occur. Your doctor should periodically monitor liver function tests during treatment.

Back pain (14%): Back discomfort is commonly reported. Discuss with your doctor if it's severe or limiting.

Headache (14%): Headaches are frequently reported, particularly around the time of dosing.

Muscle spasm (12%): Some patients experience muscle cramping or spasms.

Muscle weakness (10%): A challenging side effect given that LEMS already causes weakness. Report any new or worsening weakness to your doctor.

Dizziness (10%): Dizziness may occur, particularly when changing positions. Rise slowly from seated or lying positions.

Asthenia/fatigue (10%): General weakness and fatigue are reported in about 10% of patients.

Pain in extremities (10%): Arm or leg pain or discomfort occurs in approximately 10% of patients.

Serious Side Effects: When to Call Your Doctor Immediately

While most side effects of amifampridine are manageable, two serious risks require prompt medical attention:

Seizures: This is the most important safety warning for amifampridine. Seizures have been reported in approximately 2% of patients taking Firdapse at recommended doses, even in patients with no prior seizure history. Amifampridine is contraindicated in patients with a seizure history. If you experience a seizure, stop taking the medication immediately and seek emergency care. Many cases occurred in patients who were also taking other medications that lower the seizure threshold (e.g., antibiotics, antidepressants, antipsychotics, stimulants).

Allergic reactions / anaphylaxis: Although anaphylaxis to amifampridine itself has not been widely reported, it has been seen with related aminopyridine drugs. Seek emergency care immediately if you experience hives, difficulty breathing, swelling of the face, lips, tongue, or throat, or severe rash after taking amifampridine.

Respiratory Side Effects in Asthma Patients

Amifampridine can cause bronchial hypersecretion and has been associated with asthma attacks in patients with asthma or a history of asthma. If you have asthma, make sure your neurologist and pulmonologist are aware before starting amifampridine.

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Tips for Managing Side Effects

Take amifampridine with food if it causes stomach upset

Stay well hydrated to reduce headache risk

Tell your doctor about ALL other medications you take — several drugs can increase seizure risk when combined with amifampridine

Attend all scheduled follow-up appointments — liver enzymes and clinical response should be monitored regularly

Do not take more than 2 tablets at one dose and no more than 8 tablets in 24 hours (for adults on standard dosing)

See also: Amifampridine Drug Interactions: What to Avoid and What Is Amifampridine? Uses, Dosage, and What You Need to Know.