Skip to Content

Ruzurgi

Generic Name: Amifampridine
Class: Other Miscellaneous Therapeutic Agents
Chemical Name: pyridine-3,4-diamine
Molecular Formula: C5H7N3
CAS Number: 54-96-6

Medically reviewed by Drugs.com. Last updated on Jul 8, 2019.

Introduction

Amifampridine is a broad spectrum potassium channel blocker.1

Uses for Ruzurgi

Amifampridine has the following uses:

Amifampridine is a potassium channel blocker indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age.1

Ruzurgi Dosage and Administration

General

Amifampridine is available in the following dosage form(s) and strength(s):

Tablets: 10 mg, functionally scored1

Clinicians should be aware that there are 2 different formulations of amifampridine: amiframpidine (Ruzurgi) and amifampridine phosphate (Firdapse).1 2 Both are available as scored tablets containing 10 mg of amifampridine and are labeled for use in the treatment of Lambert-Eaton myasthenic syndrome (LEMS).1 2 Amiframpidine (Ruzurgi) is labeled for use in pediatric patients 6 to less than 17 years of age,1 and amifampridine phosphate (Firdapse) is labeled for use in adults.2

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration in Pediatric Patients 6 to Less Than 17 Years of Age
  • The recommended oral dosage for pediatric patients 6 to less than 17 years of age is dependent on body weight. Dosage should be increased based on clinical response and tolerability.1

  • Patients 6 to less than 17 years of age weighing 45 kg or more: Initial dosage is 15 mg to 30 mg daily, in divided doses (2 or 3 times per day). Increase daily in 5 mg to 10 mg increments, divided in up to 5 doses daily. Maximum single dose is 30 mg; maximum daily dosage is 100 mg.1

  • Patients 6 to less than 17 years of age weighing less than 45 kg: Initial dosage is 7.5 mg to 15 mg daily, in divided doses (2 or 3 times per day). Increase daily in 2.5 mg to 5 mg increments, divided in up to 5 doses daily. Maximum single dose is 15 mg; maximum daily dosage is 50 mg.1

  • For patients with renal impairment (creatinine clearance 15 to 90 mL/min), those with any degree of hepatic impairment, or those who are known N-acetyltransferase 2 poor metabolizers, use the lowest recommended initial dosage (15 mg daily in those weighing 45 kg or more, 7.5 mg daily in those weighing less than 45 kg).1

  • When patients require a dosage in less than 5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL suspension can be prepared.1

  • If a dose is missed, patients should not take double or extra doses.1

  • Amifampridine can be taken without regard to food.1

Cautions for Ruzurgi

Contraindications

  • History of seizures.1

  • Hypersensitivity to amifampridine or other aminopyridine.1

Warnings/Precautions

Seizures

Amifampridine can cause seizures. Seizures have been observed in patients with and without a history of seizures taking amifampridine at the recommended doses, and at various times after initiation of treatment. Many of the patients were taking medications or had comorbid medical conditions that may have lowered the seizure threshold. Seizures may be dose-dependent. Because seizure events were captured retrospectively from expanded access programs, it is not possible to reliably estimate their frequency with use of amifampridine. Consider discontinuation or dose reduction of amifampridine in patients who have a seizure while on treatment. Amifampridine is contraindicated in patients with a history of seizures.1

Hypersensitivity

In clinical trials, hypersensitivity reactions and anaphylaxis associated with amifampridine administration have not been reported. Anaphylaxis has been reported in patients taking another aminopyridine; therefore, it may occur with amifampridine. If anaphylaxis occurs, administration of amifampridine should be discontinued and appropriate therapy initiated.1

Specific Populations

Pregnancy

Risk Summary: There are no data on the developmental risk associated with the use of amifampridine in pregnant women.1

Animal studies to assess the potential adverse effects of amifampridine on embryofetal development have not been conducted.1

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.1

Lactation

Risk Summary: There are no data on the presence of amifampridine or the 3-N-acetyl-amifampridine metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.1

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 breastfed infant from amifampridine or from the underlying maternal condition.1

Pediatric Use

Safety and effectiveness of amifampridine have been established in patients 6 to less than 17 years of age. Use of amifampridine in patients 6 to less than 17 years of age is supported by evidence from 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 to less than 17 years of age.1

Safety and effectiveness in pediatric patients below the age of 6 years have not been established.1

Renal Impairment

Renal clearance is an elimination pathway for amifampridine and the inactive metabolite, 3-N-acetyl amifampridine. Therefore, in patients with renal impairment, amifampridine should be initiated at the lowest recommended starting dosage and patients should be closely monitored for adverse reactions. Consider dosage modification or discontinuation of amifampridine for patients with renal impairment as needed based on clinical effect and tolerability. No dosage recommendations for amifampridine can be made for patients with end-stage renal disease (CLcr < 15 mL/min or patients requiring dialysis).1

Hepatic Impairment

The effects of amifampridine have not been studied in patients with hepatic impairment. Amifampridine is extensively metabolized by N-acetyltransferase 2 (NAT2), and hepatic impairment may cause an increase in exposure. Therefore, initiate amifampridine in patients with any degree of hepatic impairment at the lowest recommended starting dosage and monitor for adverse reactions. Consider dosage modification or discontinuation of amifampridine for patients with hepatic impairment as needed based on clinical effect and tolerability.1

Pharmacogenomics: NAT2 Poor Metabolizers

Exposure of amifampridine is increased in patients who are N-acetyltransferase 2 (NAT2) poor metabolizers. Therefore, initiate amifampridine in patients who are known NAT2 poor metabolizers at the lowest recommended starting dosage and monitor for adverse reactions. Consider dosage modification of amifampridine for patients who are known NAT2 poor metabolizers as needed based on clinical effect and tolerability.1

Common Adverse Effects

The most common adverse reactions (incidence at least 10% and at least 2% greater than placebo) are paresthesia/dysesthesia, abdominal pain, dyspepsia, dizziness, and nausea.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Drugs that lower seizure threshold: The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures.1

  • Drugs with cholinergic effects: The concomitant use of amifampridine and drugs with cholinergic effects (e.g., direct or indirect cholinesterase inhibitors) may increase the cholinergic effects of amifampridine and of those drugs, and increase the risk of adverse reactions.1

Actions

Mechanism of Action

The mechanism by which amifampridine exerts its therapeutic effect in LEMS patients has not been fully elucidated. Amifampridine is a broad spectrum potassium channel blocker.1

Advice to Patients

Advise the patient and/or caregiver to read the Food and Drug Administration-approved patient labeling (medication guide and instructions for use).1

Risk of Seizures

Inform patients and/or caregivers that amifampridine can cause seizures, and to notify their healthcare provider if they experience a seizure.1

Amifampridine Dosing

Instruct patients to take amifampridine exactly as prescribed. Patients should carefully follow the dose escalation schedule provided by their healthcare provider to safely achieve the therapeutic dosage. Inform patients that the tablets may be divided in half at the score, if needed. Refer patients and/or caregivers to the instructions for use if they require a dosage in less than 5 mg increments, have difficulty swallowing tablets, or require feeding tubes. Instruct patients not to take a double dose after they miss a dose of amifampridine, as this may increase their risk of seizure.1

Hypersensitivity

Instruct patients and/or caregivers to inform their healthcare provider if they have signs or symptoms of hypersensitivity, and to seek emergency help if signs and symptoms of anaphylaxis occur.1

Drug Interactions

Instruct patients to notify their healthcare provider prior to starting any new medication, including over-the-counter drugs.1

Storage

Advise patients and/or caregivers to store the tablets in the pharmacy dispensed container at controlled room temperature, for a period not to exceed 3 months.1

Instruct patients and/or caregivers who prepare the 1 mg/mL suspension of amifampridine that it should be prepared daily and refrigerated between doses. The suspension can be stored under refrigeration for up to 24 hours. Instruct the patient to discard any unused portion of the suspension after 24 hours.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Amifampridine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet

10 mg

Ruzurgi

Jacobus Pharmaceutical Company Inc.

AHFS Drug Information. © Copyright 2020, Selected Revisions July 8, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Jacobus Pharmaceutical Company, Inc. RUZURGI (amifampridine) ORAL prescribing information. 2019 May. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2731310a-c060-4d3e-ba41-763d791f63a9

2. Catalyst Pharmaceuticals, Inc. Firdapse (amifampridine phosphate) ORAL prescribing information. 2018 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f015fe60-3128-4a43-8c31-19fc6b5def3f

Related questions