FORZINITY

Clinical summary

Indications and usage 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. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Benzyl alcohol toxicity : Do not use in neonates. ( 5.1 ) 5.1 Risk of Benzyl Alcohol Toxicity in Neonates FORZINITY is not approved for use in neonates. Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight neonates (less than 2,500 grams) and preterm neonates (gestational age less than 34 weeks) who received benzyl alcohol (BA)-containing drugs intravenously. FORZINITY is not approved for intravenous use [see Dosage and Administration (2.1) ] . Gasping syndrome is a life-threatening condition in neonates caused by BA toxicity and is primarily characterized by multiorgan dysfunction secondary to metabolic acidosis, which leads to gasping respirations and death. The minimum amount of BA at which these serious adverse reactions, including fatal reactions, may occur is not known (FORZINITY contains 20 mg of BA per mL). [See Use in Specific Populations (8.4) .] 5.2 Hypersensitivity Hypersensitivity reactions, including serious allergic reactions requiring emergency medical intervention, have been reported in patients receiving FORZINITY. These reactions have included skin manifestations such as rash, papular lesions, and eczematous dermatitis, as well as respiratory symptoms including cough [see Adverse Reactions (6.1) ] . Reactions may occur within minutes to months after treatment initiation. Monitor patients for signs and symptoms of hypersensitivity reactions during treatment. If a serious hypersensitivity reaction occurs, do not administer further doses of FORZINITY and institute app