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.
ZOKINVY Contraindications:
Concomitant strong or moderate CYP3A inhibitors or inducers. Concomitant midazolam, lovastatin, simvastatin, or atorvastatin.
ZOKINVY Warnings/Precautions:
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.
ZOKINVY Classification:
Farnesyltransferase inhibitor.
ZOKINVY Interactions:
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.
Adverse Reactions:
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:
NO
How Supplied:
Caps—30
