Elamipretide Hydrochloride
FDA Drug Information • Also known as: Forzinity
- Brand Names
- Forzinity
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION FORZINITY contains elamipretide, a mitochondrial cardiolipin binder. Elamipretide is isolated as a hydrochloride salt that is freely soluble in water. The chemical name for elamipretide hydrochloride is L-Phenylalaninamide, D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-, hydrochloride (1:3). Its molecular formula is C 32 H 49 N 9 O 5 ∙3HCl and its molecular weight is 749.2. The structure of elamipretide hydrochloride is: All amino acid residues in FORZINITY have the L configuration except for arginine which has the D configuration. The peptide sequence is denoted as D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH 2 . FORZINITY is a ready-to-use sterile, clear, colorless to yellow aqueous solution supplied as single-patient-use vials containing 3.5 mL solution for subcutaneous injection. Each 0.5 mL dose of FORZINITY contains 40 mg of elamipretide (equivalent to 46.8 mg elamipretide hydrochloride), 10 mg benzyl alcohol as a preservative, and 2.07 mg monobasic sodium phosphate (as monohydrate). The product may contain hydrochloric acid or sodium hydroxide to adjust pH. The pH of FORZINITY solution is 4.7 to 6.1. Chemical Structure
What Is Elamipretide Hydrochloride Used For?
1 INDICATIONS AND USAGE FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. FORZINITY™ is a mitochondrial cardiolipin binder indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. ( 1 ) This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint. ( 14 ) Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For patients weighing 30 kg and greater, the recommended dosage is 40 mg subcutaneously once daily. ( 2.1 ) Reduce the dose in adults with severe renal impairment. ( 2.2 , 8.6 ). 2.1 Recommended Dosage The recommended dosage of FORZINITY in patients weighing at least 30 kg is 40 mg subcutaneously once daily. Patients should receive the dose at the same time each day. Missed Dose If a dose is missed, skip the dose and take the next dose of FORZINITY at the scheduled time. Do not take a double dose of FORZINITY. 2.2 Dosage Modifications For Renal Impairment Refer to Table 1 for dosage modifications in adults with renal impairment. Table 1: Recommended Dosage in Adults with Renal Impairment Estimated Glomerular Filtration Rate (eGFR) (mL/minute) Recommended Dosage Greater than or equal to 30 mL/minute 40 mg subcutaneously once daily Less than 30 mL/minute and NOT on dialysis 20 mg subcutaneously once daily There is insufficient information to recommend a dosage regimen in adults with eGFR less than 30 mL/minute and on dialysis. There is insufficient information to recommend a dosage regimen in pediatric patients weighing 30 kg or greater with renal impairment. 2.3 Important Administration Instructions FORZINITY is a clear, colorless to yellow aqueous solution that contains the preservative, benzyl alcohol. Visually inspect each vial of FORZINITY for particulate matter and cloudiness prior to administration, whenever solution and container permit. Do not use if the solution is cloudy or particulate matter is present. Adult patients or caregivers may administer FORZINITY after proper training in preparing FORZINITY vials for administration, if a healthcare provider determines that it is appropriate, and with medical follow-up as necessary. Use aseptic technique to prepare and administer FORZINITY. Administer FORZINITY by subcutaneous injection in the abdomen (at least 2 inches from the navel) or outer thigh and rotate the injection site daily. Do not inject where the skin is tender, bruised, red, or hard. Avoid injecting into scars or stretch marks. Refer to the Instructions for Use for preparation and administration. FORZINITY is for single-patient-use only. Do not mix other products in the same syringe. Discard vials 8 days after first opening.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reactions are injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Stealth BioTherapeutics Inc. at 1-844-444-6486 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the FORZINITY clinical development program, 12 male patients aged 12 to 35 years with genetically-confirmed Barth syndrome received treatment with daily subcutaneous injections of 40 mg FORZINITY. Eleven of these 12 patients were Caucasian. Patients first participated in a double-blind, placebo-controlled crossover trial where they were randomized to one of two sequences: 12 weeks of FORZINITY in Period 1 then a 4-week washout followed by 12 weeks of placebo in Period 2 or 12 weeks of placebo in Period 1 then a 4-week washout followed by 12 weeks of FORZINITY in Period 2 Ten patients completed the randomized trial and entered the open-label extension period where they received FORZINITY once daily. Eight of these patients received FORZINITY for 168 weeks, three of whom received FORZINITY for a total of 192 weeks. Adverse reactions occurring more commonly on FORZINITY than on placebo include injection site reactions such as injection site erythema, pain, induration, pruritus, bruising, and urticaria (Table 2). Table 2: Summary of Adverse Drug Reactions in the Placebo-Controlled Crossover Study, Barth Safety Population Combined (Periods 1 and 2) Elamipretide Placebo N=12 N=12 n (%) n (%) Any local administration reaction 12 (100) 8 (67) Injection site erythema 12 (100) 3 (25) Injection site induration 8 (67) 2 (17) Injection site pruritus 8 (67) 2 (17) Injection site pain 9 (75) 5 (42) Injection site bruising 3 (25) 0 Injection site urticaria 3 (25) 0 Injection site hemorrhage 0 1 (8) Eosinophilia Increases in absolute eosinophil counts were noted frequently in studies where duration of administration of FORZINITY was 30 days or greater. Eosinophil counts generally peaked around 90 days after initial exposure (mean increase from baseline ~0.5 to 0.6 × 10 3 /uL) and returned to baseline levels after 6 to 12 months of continuous exposure or after discontinuation of FORZINITY. The elevation in eosinophils was not associated with clinical manifestations or changes in other laboratory parameters.
Contraindications
4 CONTRAINDICATIONS Serious hypersensitivity to elamipretide or any of the excipients in FORZINITY [see Warnings and Precautions (5.2) ]. Serious hypersensitivity to any of the ingredients ( 4 , 5.2 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Barth Syndrome is a rare, X-linked, recessive, genetic disorder and is not likely to affect females. Therefore, there are no data with FORZINITY use in pregnant women to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental outcomes occurred at any dose tested (see Data ). FORZINITY contains benzyl alcohol as a preservative. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. 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. Data Animal Data In pregnant rats, once-daily intravenous infusion of elamipretide during the period of organogenesis [gestation day (GD) 7 to GD 17] did not result in embryo-fetal developmental toxicity at doses tested up to 10 mg/kg/day, approximately 4 times the clinical exposure at the maximum recommended human dose (MRHD) of 40 mg/day, based on area under the concentration-time curve (AUC). In pregnant rabbits, intravenous infusion with elamipretide once daily during the period of organogenesis (GD 7 to GD 19) did not result in embryo-fetal developmental toxicity at doses tested up to 50 mg/kg/day, approximately 10 times the clinical exposure at the MRHD, based on AUC. In a pre- and postnatal study in rats, elamipretide was subcutaneously administered at doses of 0, 5, 10 or 15 mg/kg/day throughout pregnancy and lactation (GD 6 to Lactation Day 20). No adverse developmental effects were observed at doses up to 15 mg/kg/day, approximately 6-times the clinical exposure at the MRHD, based on AUC.
Overdosage
10 OVERDOSAGE There were no reports of overdose during clinical trials with FORZINITY. Symptoms and signs of overdose are likely to be histamine-related (e.g., decreased blood pressure, presyncope) and should be managed according to standard of care. Interrupt treatment with FORZINITY if there is suspicion of overdose.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied FORZINITY (elamipretide) injection is a sterile, clear, colorless to yellow aqueous solution supplied as: Carton containing four 280 mg/3.5 mL (80 mg/mL) single-patient-use vials (NDC 72507-800-04) 16.2 Storage Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Following the first dose, the opened vial can be stored either refrigerated 2°C to 8°C (36°F to 46°F) or at room temperature between 20°C to 25°C (68°F to 77°F). Discard vials 8 days after first opening.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.