Lonafarnib

ZOKINVY is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m 2 and above: To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS) For the treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation Homozygous or compound heterozygous ZMPSTE24 mutations ZOKINVY is a farnesyltransferase inhibitor indicated in patients 12 months of age and older with a body surface area of 0.39 m 2 and above: To reduce risk of mortality in Hutchinson-Gilford Progeria Syndrome. For treatment of processing-deficient Progeroid Laminopathies with either: Heterozygous LMNA mutation with progerin-like protein accumulation. Homozygous or compound heterozygous ZMPSTE24 mutations.

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

Start at 115 mg/m 2 twice daily with morning and evening meals. After 4 months, increase to 150 mg/m 2 twice daily. Round all total daily doses to nearest 25 mg increment. See full prescribing information for dosage modifications due to adverse reactions. See full prescribing information for preparation and administration instructions.

ZOKINVY is contraindicated in patients taking: Strong CYP3A inhibitors Strong or moderate CYP3A inducers Midazolam Lovastatin, simvastatin, or atorvastatin Strong CYP3A inhibitors. Strong or moderate CYP3A inducers. Midazolam. Lovastatin, simvastatin, or atorvastatin.

QTc Interval Prolongation: Increases the QTc interval. Avoid use in patients with symptomatic bradycardia, hypokalemia, or hypomagnesemia, and in combination with other drugs known to prolong the QTc interval. Risk of Reduced Efficacy or Adverse Reactions Due to Drug Interactions: Prior to and during treatment, consider potential for drug interactions and review concomitant medications, monitor for adverse reactions. Laboratory Abnormalities: Monitor for changes in electrolytes, complete blood counts, and liver enzymes. Nephrotoxicity: Caused nephrotoxicity in rats. Monitor renal function at regular intervals. Retinal Toxicity: Caused rod-dependent, low-light vision decline in monkeys. Perform ophthalmological evaluation at regular intervals and at the onset of any new visual changes.

The most common adverse reactions (incidence ≥25%) are vomiting, diarrhea, infection, nausea, decreased appetite, fatigue, upper respiratory tract infection, abdominal pain, musculoskeletal pain, electrolyte abnormalities, decreased weight, headache, myelosuppression, increased aspartate aminotransferase, decreased blood bicarbonate, cough, hypertension, and increased alanine aminotransferase.

QTc Interval Prolongation Drugs: Avoid concomitant use with ZOKINVY. See full prescribing information for additional clinically significant drug interactions with ZOKINVY and recommended dosage modifications for drug interactions.

Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30ºC (59°F-86ºF).