Firdapse (amifampridine phosphate)

Dosage of amifampridine phosphate is expressed in terms of amifampridine.

No dosing information is available for this tab.

No dosing information is available for this tab.

Amifampridine is extensively metabolized by N-acetyltransferase 2 (NAT2) to 3-N-acetyl-amifampridine, an inactive major metabolite.

In vitro studies suggest that amifampridine and its major metabolite are not substrates or inhibitors or inducers of major cytochrome P-450 (CYP) isoenzymes or transporters.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Sodium Channel Blocker; Potassium Channel Blocker/Lacosamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Lacosamide may enhance the slow inactivation of voltage-gated sodium channels and may cause dose-dependent bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1)

CLINICAL EFFECTS: Concurrent use of lacosamide and agents that affect cardiac conduction (sodium channel blockers and potassium channel blockers) may increase the risk of bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Lacosamide should be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers and potassium channel blockers.(1) If concurrent use is needed, obtain an ECG before lacosamide therapy and after lacosamide dose is titrated to steady-state.(1) Patients should be monitored closely when lacosamide is given intravenously.(1)

DISCUSSION: In a clinical trial in patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block occurred in 4/944 (0.4%) of patient who received lacosamide compared to 0/364 (0%) with placebo.(1) In a clinical trial in patients with diabetic neuropathy, asymptomatic first-degree AV block occurred in 5/1023 (0.5%) of patients who received lacosamide compared to 0/291 (0%) with placebo.(1) Second-degree and complete AV block have been reported in patients with seizures.(1) One case of profound bradycardia was observed in a patient during a 15-minute infusion of 150 mg of lacosamide.(1) A case report of a 49 year old male with refractory complex partial and generalized seizures described the development of ventricular tachycardia four months after addition of lacosamide 400 mg/day to the existing regimen of carbamazepine, lamotrigine, clonazepam, and valproate. The patient's ECG showed first-degree AV block, posterior left fascicular block, and severe widening of the QRS complex, all of which resolved upon discontinuation of lacosamide.(2)

*History of seizures.

*Hypersensitivity to amifampridine phosphate or another aminopyridine.

• Seizure disorder

• Chronic kidney disease stage 1 (mild) GFR 90ml/min or higher with signs of kidney damage
• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Disease of liver
• NAt2 poor metabolizer

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

The most common (>10%) adverse effects of amifampridine include paresthesia, upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension, and muscle spasms.

Less Frequent

• Anemia
• Cataracts
• Hypersensitivity drug reaction
• Pneumonia

Rare or Very Rare

• Abnormal hepatic function tests
• Cardiac arrhythmia
• Chorea
• Influenza
• Seizure disorder
• Viral infection

More Frequent

• Acute abdominal pain
• Dizziness
• Dysesthesia
• Dyspepsia
• Hyperhidrosis
• Hypoesthesia
• Nausea
• Oral hypoesthesia
• Paresthesia
• Upper respiratory infection

Less Frequent

• Accidental fall
• Arthralgia
• Back pain
• Bronchitis
• Constipation
• Depression
• Diarrhea
• Dysphagia
• Dyspnea
• Gastroesophageal reflux disease
• Insomnia
• Lymphadenopathy
• Muscle spasm
• Muscle weakness
• Pain
• Pain in extremities
• Sensation of cold
• Upper abdominal pain

Rare or Very Rare

• Blurred vision
• Cough
• Drowsy
• Erythema
• Fatigue
• Fever
• General weakness
• Headache disorder
• Hypercholesterolemia
• Increased bronchial secretions
• Increased creatine kinase level
• Peripheral edema
• Raynaud's phenomenon
• Sleep disorder
• Symptoms of anxiety
• Urinary tract infection

No enhanced messaging available.

Safety and effectiveness of amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) have been established in pediatric patients >=6 years of age. The supporting evidence includes adequate and well-controlled studies of amifampridine in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients >=6 years of age.

In pediatric patients >=6 years of age, body weight significantly correlates with amifampridine clearance. Clearance of the drug increased with increasing body weight and a weight-based dosing regimen is necessary to achieve amifampridine exposures in such patients, similar to the exposures observed in adults at recommended doses.

Safety and effectiveness in pediatric patients <6 years of age have not been established.

There are no data on risk associated with the use of amifampridine in pregnant women. Administration of amifampridine phosphate to rats during pregnancy and lactation resulted in developmental toxicity (e.g., increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development) at doses associated with maternal plasma drug levels lower than therapeutic levels.

If a patient is exposed to amifampridine during pregnancy, enrollment in a pregnancy registry is encouraged by contacting the Pregnancy Coordinating Center at (855-212-5856, firdapsepregnancyregistry@ubc.com, or https://www.firdapsepregnancystudy.com).

There are no data on the presence of amifampridine in human milk, the effects on the breastfed infant, or the effects on milk production.

Amifampridine is distributed into the milk of lactating rats and achieves drug levels similar to those in maternal plasma.

The manufacturer states that the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for amifampridine and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

An insufficient number of patients >=65 years of age (19 of 63 patients) were included in the principal efficacy studies of amifampridine; it is unknown whether these patients respond differently compared to younger adults. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.