Inborn errors of metabolism:
Indications for ZOKINVY:
To reduce the risk of mortality in Hutchinson-Gilford progeria syndrome. Treatment of processing-deficient progeroid laminopathies with either: heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations.
Limitations of Use:
Not for other progeroid syndromes or processing-proficient progeroid laminopathies.
Adults and Children:
<12months (or BSA <0.39m2): not established. Swallow whole with water; if unable to swallow, mix contents with Ora Blend SF®, Ora-Plus®, orange juice or applesauce. ≥12 months (with BSA ≥0.39m2): initially 115mg/m2 twice daily with morning and evening meals; increase to 150mg/m2 twice daily after 4 months; see full labeling. Round all total daily dosages to the nearest 25mg increment. Concomitant weak CYP3A inhibitors (if unavoidable): reduce to or continue Zokinvy at initial dose of 115mg/m2 twice daily. Other dose modifications: see full labeling.
Concomitant strong or moderate CYP3A inhibitors or inducers. Concomitant midazolam, lovastatin, simvastatin, or atorvastatin.
Periodically monitor electrolytes, CBCs, liver enzymes, and renal function during therapy. Perform ophthalmological evaluation regularly and at onset of new visual changes during therapy. Renal or hepatic impairment. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during therapy. Pregnancy: avoid. Nursing mothers.
See Contraindications. Temporarily discontinue Zokinvy 10–14 days before and 2 days after administration of midazolam. Avoid concomitant weak CYP3A inhibitors (see Adults and Children), CYP2C9 inhibitors; if unavoidable, monitor closely for arrhythmias, syncope, heart palpitations. Avoid grapefruit or Seville oranges. Avoid concomitant sensitive CYP3A or CYP2C19 substrates; if unavoidable, monitor and reduce dose of substrate. Potentiates loperamide; do not exceed loperamide 1mg once daily when first coadministered; increase cautiously. Potentiates P-gp substrates (eg, digoxin, dabigatran); monitor and reduce dose of substrate.
Vomiting, diarrhea, infection, nausea, decreased appetite, fatigue, upper respiratory tract infection, abdominal pain, musculoskeletal pain, electrolyte abnormalities, decreased weight, headache, myelosuppression, increased AST/ALT, decreased blood bicarbonate, cough, hypertension; nephrotoxicity, retinal toxicity, impaired fertility.
Generic Drug Availability: