Overview
11 DESCRIPTION MIPLYFFA capsules contain arimoclomol citrate. Arimoclomol citrate is a crystalline powder of white to off-white color that is freely soluble in water. The chemical name is N -[(2R, Z )-2-hydroxy-3-(1piperidyl)propoxy]pyridine-3-carboximidoyl chloride, 1-oxide, citrate. The empirical formula is C 20 H 28 ClN 3 O 10 and the molecular weight is 505.90 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism(s) by which arimoclomol exerts its clinical effects in patients with NPC is unknown. 12.2 Pharmacodynamics The effect of arimoclomol (744 mg/day for 28 days) on serum creatinine was assessed in 16 healthy male subjects. A reversible increase in mean serum creatinine of 19% was observed after 21 days of treatment. No effect on glomerular function (GFR, 125 I-iothalamate clearance) or renal hemodynamics (effective renal plasma flow (ERPF); 131 I-hippuran clearance) was observed [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 ), and Drug Interactions ( 7 )].
Indications
- 1 INDICATIONS AND USAGE MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older. MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older. ( 1 )
Common Doses
- 47 mg
- 62 mg
- 93 mg
- 124 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended MIPLYFFA oral dosage, in combination with miglustat, for patients with actual body weight of ( 2.1 ): 8 kg to 15 kg, is 47 mg three times a day > 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer with or without food. ( 2.1 ) See full prescribing information for recommended dosage in patients with an eGFR ≥ 15 to 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer MIPLYFFA with or...
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warning and Precautions ( 5.1 )]. Increased Creatinine without Affecting Glomerular Function [see Warnings and Precautions ( 5.3 )]. Most common adverse reactions (≥15%) are: Upper respiratory tract infection, diarrhea, and decreased weight. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zevra Therapeutics, Inc. at toll-free phone 1-844-600-2237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS Substrates of the Organic Cationic Transporter 2 (OCT2 substrates) : Monitor for adverse reactions and reduce the dosage of the OCT2 substrate. ( 7.1 ) 7.1 Effect of MIPLYFFA on Other Drugs Arimoclomol is an inhibitor of the organic cationic transporter 2 (OCT2) transporter and may increase the exposure of drugs that are OCT2 substrates [see Clinical Pharmacology ( 12.3 )] . When MIPLYFFA is used concomitantly with OCT2 substrates, monitor for adverse reactions and reduce the dosage of the OCT2 substrate.