ZOKINVY Dosage & Rx Info | Uses, Side Effects

Zokinvy Generic Name & Formulations

Legal Class

General Description

Lonafarnib 50mg, 75mg; caps.

Pharmacological Class

Farnesyltransferase inhibitor.

How Supplied

Caps—30

Manufacturer

Eiger BioPharmaceuticals, Inc.

Generic Availability

Mechanism of Action

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

Zokinvy Indications

Indications

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.

Zokinvy Dosage and Administration

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. Other dose modifications: see full labeling.

Zokinvy Contraindications

Contraindications

Concomitant strong CYP3A inhibitors. Concomitant strong or moderate CYP3A inducers. Concomitant midazolam, lovastatin, simvastatin, or atorvastatin.

Zokinvy Boxed Warnings

Not Applicable

Zokinvy Warnings/Precautions

Warnings/Precautions

Avoid use in patients with a history of cardiac arrhythmias and other circumstances that increase the risk of Torsade de pointes or sudden death (eg, symptomatic bradycardia, hypokalemia, or hypomagnesemia). Withhold therapy if QTc interval is >500msec until interval is <470msec, then resume at same dose. Monitor ECGs prior to initiation, during, and as clinically indicated. Obtain serum electrolytes prior to initiation and during as clinically indicated; correct serum electrolyte abnormalities. 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 Pharmacokinetics

Absorption

Maximum peak plasma concentration: 834 ng/mL (lonafarnib 75mg twice daily) and 964 ng/mL (lonafarnib 100mg twice daily).

Distribution

Volume of distribution: 87.8 L (lonafarnib 75mg twice daily) and 97.4 L (lonafarnib 100mg twice daily). In vitro plasma protein binding: ≥99%.

Metabolism

CYP3A (primarily), CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1.

Elimination

Fecal (62%), renal (<1%). Half-life: 4–6 hours.

Zokinvy Interactions

Interactions

See Contraindications. Temporarily discontinue Zokinvy 10–14 days before and 2 days after administration of midazolam. Avoid grapefruit or Seville oranges. Avoid concomitant drugs known or suspected to prolong QTc interval; if unavoidable, obtain ECGs when initiating, during, and as clinically indicated. Avoid concomitant sensitive CYP3A or CYP2C19 substrates; if unavoidable, monitor and reduce dose of substrate. Potentiated by moderate CYP3A inhibitors: monitor for at least the first 7 days after starting treatment; consider alternative therapy if reaction occurs. 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.

Zokinvy Adverse Reactions

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.

Zokinvy Clinical Trials

See Literature

Zokinvy Note