Version May 2024
Jacobus Pharmaceutical Company's new drug application for Ruzurgi (amifampridine) was approved in May 2019 for the treatment of Lambert-Eaton myasthenic syndrome in patients 6 to younger than 17 years of age. However, due to a January 2022 court ruling, the FDA has converted the final approval of the Ruzurgi new drug application to a tentative approval. Therefore, Ruzurgi may not be legally marketed or distributed in the United States at this time.
Further information may be found at https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/209321Orig1s000TA_ltr.pdf.
Lambert-Eaton myasthenic syndrome (LEMS):
Firdapse: Oral: Initial: 15 to 30 mg/day in 3 to 4 divided doses; may increase based on response and tolerability in 5 mg increments every 3 to 4 days (maximum: 80 mg/day; maximum single dose: 20 mg).
Ruzurgi [Canadian product]:
<45 kg: Oral: Initial: 5 to 10 mg/day in 2 to 3 divided doses; may increase based on response and tolerability in 2.5 to 5 mg/day increments; daily dose may be divided in up to 5 doses/day (maximum: 40 mg/day; maximum single dose: 10 mg).
≥45 kg: Oral: Initial: 10 to 20 mg/day in 2 to 3 divided doses; may increase based on response and tolerability in 5 to 10 mg/day increments; daily dose may be divided in up to 5 doses/day (maximum: 100 mg/day; maximum single dose: 20 mg).
Dosage adjustment for N-acetyltransferase 2 (NAT2) poor metabolizers:
Firdapse: Oral: Initial: 15 mg/day in 3 divided doses; may adjust dose or discontinue use based on response and tolerability.
Ruzurgi [Canadian product]:
<45 kg: Oral: Initial: 5 mg/day in 2 to 3 divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
≥45 kg: Oral: Initial: 10 mg/day in 2 to 3 divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥90 mL/minute: No dosage adjustment necessary.
CrCl ≥15 to <90 mL/minute:
Firdapse: Oral: Initial: 15 mg/day in 3 divided doses; may adjust dose or discontinue use based on response and tolerability.
Ruzurgi [Canadian product]:
<45 kg: Oral: Initial: 7.5 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability (maximum: 20 mg/day).
≥45 kg: Oral: Initial: 15 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability (maximum: 40 mg/day).
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment:
Firdapse: Oral: Initial: 15 mg/day in 3 divided doses; may adjust dose or discontinue use based on response and tolerability.
Ruzurgi [Canadian product]:
<45 kg: Oral: Initial: 5 mg/day in 2 to 3 divided doses; may adjust dose or discontinue use based on response and tolerability (maximum: 20 mg/day).
≥45 kg: Oral: Initial: 10 mg/day in 2 to 3 divided doses; may adjust dose or discontinue use based on response and tolerability (maximum: 40 mg/day).
Severe impairment:
Firdapse: Oral: Initial: 15 mg/day in 3 divided doses; may adjust dose or discontinue use based on response and tolerability.
Ruzurgi [Canadian product]: There are no specific dosage adjustments provided in the manufacturer’s labeling; use with caution.
Refer to adult dosing.
(For additional information see "Amifampridine: Pediatric drug information")
Lambert-Eaton myasthenic syndrome (LEMS):
Children ≥6 years and Adolescents: Firdapse:
<45 kg: Oral: Initial: 5 to 15 mg/day in 3 to 4 divided doses; titrate by 2.5 mg/day increments at 3- to 4-day intervals based on clinical response and tolerability; maximum single dose: 10 mg/dose; maximum daily dose: 40 mg/day. Note: For individual doses <5 mg, an oral suspension may be prepared.
≥45 kg: Oral: Initial: 15 to 30 mg/day in 3 to 4 divided doses; titrate by 5 mg/day increments at 3- to 4-day intervals based on clinical response and tolerability; maximum single dose: 20 mg/dose; maximum daily dose: 80 mg/day.
Dosage adjustment for N-acetyltransferase 2 (NAT2) poor metabolizers:
Children ≥6 years and Adolescents: Initiate therapy at the lowest initial dose for weight; if individual dose <5 mg, an oral suspension (1 mg/mL) may be prepared.
Firdapse:
<45 kg: Oral: Initial: 5 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
≥45 kg: Oral: Initial: 15 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: Oral:
CrCl ≥15 to 90 mL/minute: Initiate therapy at the lowest initial dose for weight:
<45 kg: Initial: 5 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
≥45 kg: Initial: 15 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to severe impairment: Children ≥6 years and Adolescents: Oral: Initiate therapy at the lowest initial dose for weight:
<45 kg: Initial: 5 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
≥45 kg: Initial: 15 mg/day in divided doses; may adjust dose or discontinue use based on response and tolerability; monitor closely for adverse effects.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults. Reported adverse reactions are for adults unless otherwise indicated.
>10%:
Cardiovascular: Hypertension
Gastrointestinal: Abdominal pain, diarrhea, nausea
Hepatic: Increased liver enzymes (including increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Nervous system: Headache, muscle spasm, paresthesia (including oral hypoesthesia, oral paresthesia)
Neuromuscular & skeletal: Back pain
Respiratory: Upper respiratory tract infection
1% to 10%:
Cardiovascular: Peripheral edema
Dermatologic: Erythema of skin
Endocrine & metabolic: Hypercholesterolemia
Gastrointestinal: Constipation, gastroesophageal reflux disease
Genitourinary: Urinary tract infection
Hematologic: Lymphadenopathy
Infection: Influenza, viral infection
Nervous system: Asthenia, depression, dizziness, falling, insomnia, myasthenia, seizure
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, limb pain
Ophthalmic: Cataract
Respiratory: Bronchitis, dyspnea
Miscellaneous: Fever
Frequency not defined: Endocrine & metabolic: Weight loss (children and adolescents)
Hypersensitivity to amifampridine phosphate, aminopyridines, or any component of the formulation; history of seizures.
Canadian labeling: Additional contraindications (not in the US labeling): Concurrent use with other forms of amifampridine or other aminopyridines.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Hypersensitivity: Although hypersensitivity reactions, including anaphylaxis, have not been associated with amifampridine, anaphylaxis has been reported with another aminopyridine and cross-sensitivity may occur. Discontinue use and initiate appropriate therapy if anaphylaxis occurs. Use is contraindicated in patients with known hypersensitivity to another aminopyridine.
• Seizures: May cause seizures, including in patients with no prior history; use caution in patients taking medications or with comorbid conditions that may lower the seizure threshold. Seizures may be dose-dependent. Discontinue use or reduce dose if seizure occurs during treatment. Use is contraindicated in patients with a history of seizures.
Disease-related concerns:
• Asthma: Use with caution in patients with uncontrolled asthma (Lindquist 2011).
• Conduction abnormality: Use with caution in patients with congenital QT syndromes or a prolonged QT interval (Lindquist 2011).
• Hepatic impairment: Use with caution; dosage adjustment required.
• Renal impairment: Use with caution; dosage adjustment may be required.
Special populations:
• N-acetyltransferase 2 (NAT2) poor metabolizers: Use with caution; dosage adjustment may be required.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Firdapse: 10 mg [scored]
Ruzurgi: 10 mg [DSC]
No
Tablets (Firdapse Oral)
10 mg (per each): $262.39
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Firdapse: 10 mg
Ruzurgi: 10 mg
Oral:
Firdapse: May administer without regard to food. Tablets may be divided in half at the score if needed to obtain the appropriate dose. For patients requiring a dose in <5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL oral suspension may be prepared. Place required number of tablets in a 50 to 100 mL container; add 10 mL sterile water for each tablet, wait 5 minutes and shake well for 30 seconds; crushing tablets is not necessary. Do not prepare suspension using anything other than sterile water; do not use other liquids or food. The suspension must be refrigerated between doses. Shake well prior to each dose. Discard the oral suspension 24 hours after preparation; a new suspension must be prepared daily. Withdraw dose into calibrated oral syringe to accurately measure dose. If administered via a feeding tube, must flush feeding tube with 10 mL of sterile water.
Ruzurgi [Canadian product]: May administer without regard to food intake; however, administration with food may lessen paresthesia and abdominal discomfort. Tablets may be divided in half at the score if needed to obtain the appropriate dose. For patients requiring a dose in <5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL oral suspension may be prepared. Place required number of tablets in an appropriately sized container; add 10 mL sterile water for each tablet and shake well for 30 seconds; crushing tablets is not necessary. Do not prepare suspension using anything other than sterile water; do not use other liquids or food. The suspension must be refrigerated between doses. Shake well prior to each dose. Discard the oral suspension 24 hours after preparation; a new suspension must be prepared daily. Withdraw dose into calibrated oral syringe to accurately measure dose. If administered via a feeding tube, must flush feeding tube with 10 mL of sterile water.
Oral: Administer without regard to meals.
Tablets: May be divided in half at the score if needed to obtain the appropriate dose.
Oral suspension (1 mg/mL): For patients who require a dose in <5 mg increments, have difficulty swallowing tablets, or require feeding tubes, a 1 mg/mL oral suspension may be prepared. Do not prepare suspension using anything other than sterile water; do not use other liquids or food. Place required number of tablets in a 50 to 100 mL container; add 10 mL sterile water for each tablet, wait 5 minutes, then shake well for 30 seconds; crushing tablets is not necessary. The suspension must be refrigerated between doses. Shake well prior to each dose. Discard the oral suspension 24 hours after preparation; a new suspension must be prepared daily. Withdraw dose into calibrated oral syringe to accurately measure dose.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Firdapse: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208078s009lbl.pdf#page=12
Ruzurgi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209321s000lbl.pdf#page=15
Lambert-Eaton myasthenic syndrome: Treatment of Lambert-Eaton myasthenic syndrome in adults and pediatric patients ≥6 years of age.
Amifampridine may be confused with amifostine; aminosidine; dalfampridine; fampridine.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy
Agents With Seizure Threshold Lowering Potential: May enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amifampridine and its metabolite cross the placenta and enter fetal circulation and amniotic fluid.
Outcome data related to the use of amifampridine during pregnancy are limited (Pelufo-Pellicer 2006).
Data collection to monitor pregnancy and infant outcomes following exposure to Firdapse is ongoing. Health care providers are encouraged to enroll patients exposed to amifampridine during pregnancy in the pregnancy registry (855-212-5856 or https://firdapsepregnancystudy.com/); patients may also enroll themselves.
It is not known if amifampridine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Renal and hepatic function (as clinically indicated); ECG (as clinically indicated)
Increases acetylcholine release in nerve terminals via potassium channel blockade (Wirtz 2010).
Protein binding: Ruzurgi [Canadian product]: 25.3% (amifampridine); 43.3% (3-N-acetyl amifampridine).
Metabolism: Extensively metabolized by N-acetyltransferase 2 (NAT2) to 3-N-acetyl amifampridine (inactive metabolite).
Half-life elimination: Firdapse: 1.8 to 2.5 hours; Ruzurgi [Canadian product]: 3.6 to 4.2 hours.
Time to peak: Firdapse: 20 minutes to 1 hour; Ruzurgi [Canadian product]: Median: 0.5 hour; increased with high fat meal (1 hour).
Excretion: Urine: Firdapse: 93% to 100% (as amifampridine and 3-N-acetyl amifampridine); Ruzurgi [Canadian product]: >65% (as amifampridine and 3-N-acetyl amifampridine).
Altered kidney function: Firdapse: AUC 2- to 3-fold higher in patients with moderate to severe (CrCl 15 to 59 mL/minute) renal impairment and 36% higher in patients with mild (CrCl 60 to 89 mL/minute) impairment compared to patients with normal renal function.
Hepatic function impairment: Firdapse: AUC 33% higher and Cmax 22% higher in patients with moderate hepatic impairment compared to patients with normal hepatic function.
N-Acetyltransferase gene 2 (NAT2) poor metabolizers:
Firdapse: Cmax 3.5- to 4.5-fold higher and AUC 5.6- to 9-fold higher in poor metabolizers (slow acetylators) compared to normal metabolizers (fast or rapid acetylators).
Ruzurgi [Canadian product]: Poor metabolizers (slow acetylators) had 2.7 times higher mean AUC0-4h and 2.2 times higher mean Cmax than intermediate acetylators and 6.9 times higher mean AUC0-4h and 5.4 times higher mean Cmax than rapid acetylators.
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