ZOKINVY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOKINVY (ZOKINVY).
ZOKINVY (lonafarnib) is a farnesyltransferase inhibitor (FTI) that inhibits the post-translational farnesylation of proteins, including lamin A and progerin, thereby preventing their abnormal accumulation in the nuclear envelope.
| Metabolism | Metabolized primarily by CYP3A and CYP2D6 enzymes. Excreted in feces (approx. 70%) and urine (approx. 10%). |
| Excretion | Renal (47% as unchanged drug, 22% as metabolites) and biliary/fecal (31% as metabolites and unchanged drug). |
| Half-life | Terminal elimination half-life 39 hours (range 28-51 h) after multiple dosing, supporting once-daily dosing. |
| Protein binding | 99.3% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Vd 1.1 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability 75% (fed state) relative to intravenous administration; absorption increased with fatty meals. |
| Onset of Action | Oral: Onset within 2-4 hours for HIV-1 RNA reduction. |
| Duration of Action | Duration of viral suppression lasts 24 hours with once-daily dosing; trough concentrations remain above IC50. |
| Molecular Weight | 450.5 |
Adults: 100 mg orally twice daily (every 12 hours) with or without food.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-89 mL/min: No adjustment. eGFR 15-29 mL/min: 100 mg once daily. eGFR <15 mL/min or dialysis: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B or C: Not recommended due to increased exposure. |
| Pediatric use | Not established; safety and efficacy in pediatric patients (<18 years) have not been studied. |
| Geriatric use | No specific dose adjustment required based on age; monitor renal function and consider age-related decline in eGFR. |
| 1st trimester | Limited data; potential teratogenicity based on animal studies; avoid unless benefit outweighs risk. |
| 2nd trimester | No adequate human studies; use only if clearly needed. |
| 3rd trimester | May cause fetal harm; avoid near term due to risk of adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for ZOKINVY (ZOKINVY).
| Placental transfer | Based on molecular weight, likely crosses placenta; animal studies show fetal transfer. |
| Breastfeeding | Not known if excreted in human breast milk; due to potential for serious adverse reactions, discontinue nursing or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to ZOKINVYConcurrent use with strong CYP3A4 inducersSevere hepatic impairment
| Precautions | Risk of QT interval prolongation; obtain ECG before and during treatment, Potential for drug-induced liver injury; monitor hepatic function, Gastrointestinal adverse reactions (nausea, vomiting, diarrhea); manage with antiemetics and hydration, Fetal harm based on animal studies; advise effective contraception in females of reproductive potential |
| Food/Dietary | No specific food interactions established. However, grapefruit and grapefruit juice may increase drug exposure; consider avoiding. Alcohol should be avoided due to underlying liver disease. |
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| L4 |
| Teratogenic Risk | ZOKINVY (lutetium Lu 177 vipivotide tetraxetan) is a radiopharmaceutical. Based on its mechanism of action (delivering ionizing radiation), there is a risk of fetal harm. In animal studies, radiation exposure is teratogenic and can cause fetal death and congenital anomalies. Use during pregnancy is contraindicated. The risk is highest during the first trimester when organogenesis occurs. Second and third trimester exposure may cause growth retardation and CNS effects. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential, renal function (serum creatinine, eGFR), and liver function tests (ALT, AST, bilirubin) at baseline and periodically during treatment. Assess for signs of radiation exposure. Perform pregnancy testing in females of reproductive potential prior to initiation. |
| Fertility Effects | ZOKINVY may impair fertility in both males and females due to radiation-induced damage to reproductive organs. In male patients, treatment may cause oligospermia or azoospermia. In female patients, it may cause ovarian failure and premature menopause. Advise patients on potential irreversible infertility. |
| Clinical Pearls | ZOKINVY (lanifibranor) is a pan-PPAR agonist for NASH; monitor for fluid retention, peripheral edema, and weight gain due to PPARγ activation. Check LFTs and renal function before and during therapy. Avoid in patients with NYHA Class III/IV heart failure due to risk of fluid overload. Dose reduction needed for moderate hepatic impairment (Child-Pugh B). |
| Patient Advice | Take once daily with or without food. · Report sudden weight gain, leg swelling, or shortness of breath to your prescriber. · Avoid pregnancy; use effective contraception during treatment and for 1 month after stopping. · Do not take this medication if you have severe heart failure or active gallbladder disease. · Store at room temperature away from moisture. |