ZOKINVY- lonafarnib capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

LONAFARNIB (UNII: IOW153004F) (LONAFARNIB - UNII:IOW153004F)

Available from:

Eiger BioPharmaceuticals, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

ZOKINVY is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 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 - Heterozygous LMNA mutation with progerin-like protein accumulation - Homozygous or compound heterozygous ZMPSTE24 mutations Limitations of Use ZOKINVY is not indicated for other Progeroid Syndromes or processing-proficient Progeroid Laminopathies. Based upon its mechanism of action, ZOKINVY would not be expected to be effective in these populations. ZOKINVY is contraindicated in patients taking: - Strong CYP3A inhibitors [see Drug Interactions (7.1)] - Strong or moderate CYP3A inducers [see Drug Interactions (7.1)] - Midazolam [see Drug Interactions (7.2)] - Lovastatin, simvastatin, or atorvastatin [see Drug Interactions (7.2)] Risk Summary Based on findings from animal studies, ZOKINVY can cause embryofetal harm when administered to a pregnant woman. There are no human data on ZOKINVY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the risk to a fetus. In animal reproduction studies, oral administration of lonafarnib to pregnant rats during organogenesis produced embryo-fetal toxicity at exposures that were 1.2-times the human exposure at the recommended dose of 150 mg/m2 twice daily. In pregnant rabbits, oral administration of lonafarnib during organogenesis produced skeletal malformations and variations at exposures lower than the human exposure at 150 mg/m2 twice daily, and maternal toxicity at 26 times the human exposure at 150 mg/m2 twice daily (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study in rats, oral administration of lonafarnib during organogenesis produced an increase in post-implantation loss (resorptions) and decreases in fetal body weight and number of live fetuses at 30 mg/kg/day (1.2 times the AUC [area under the plasma concentration-time curve] in humans at the recommended dose of 150 mg/m2 twice daily). No effects on embryo-fetal development in rats were observed at systemic exposures lower than the human AUC at 150 mg/m2 twice daily. In rabbits, oral administration of lonafarnib during organogenesis resulted in skeletal malformations and variations at systemic exposures lower than the human AUC at the recommended dose of 150 mg/m2 twice daily, and maternal toxicity (body weight loss and abortion) at 120 mg/kg/day (26 times the human AUC at 150 mg/m2 twice daily). No effects in offspring were observed in a pre- and postnatal development study in rats with maternal administration of up to 20 mg/kg/day orally (AUC lower than the human AUC at 150 mg/m2 twice daily) during organogenesis through lactation. Risk Summary There are no data on the presence of ZOKINVY in human milk, the effects on the breastfed infant, or the effects on milk production. Lonafarnib is excreted in rat milk (see Data) . When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOKINVY and any potential adverse effects of the breastfed infant from ZOKINVY or from the underlying maternal condition. Data Lonafarnib is excreted in milk following oral administration in lactating rats, with a mean milk to plasma concentration ratio of 1.5 at 12 hours. Contraception ZOKINVY can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use appropriate effective contraception during treatment with ZOKINVY. Infertility Based on findings in rats, ZOKINVY may reduce fertility in females and males of reproductive potential [see Warnings and Precautions (5.6), Nonclinical Toxicology (13.1)] . The safety and effectiveness of ZOKINVY for the treatment of HGPS and processing-deficient Progeroid Laminopathies (with either heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations) have been established in pediatric patients 12 months of age and older. Use of ZOKINVY for these indications is supported by adequate and well-controlled studies in pediatric patients 2 years of age and older [see Clinical Studies (14)] . The safety and effectiveness of ZOKINVY in pediatric patients less than 12 months of age have not been established. The safety and effectiveness of ZOKINVY for the treatment of HGPS and processing-deficient Progeroid Laminopathies (with either heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations) have been established in adults. Use of ZOKINVY in adults for these indications is based on adequate and well-controlled studies in pediatric patients 2 years of age and older [see Clinical Studies (14)] . INSTRUCTIONS FOR USE ZOKINVY™ (ZO-kinvy) (lonafarnib) capsules, for oral use This Instructions for Use contains information on how to mix and give or take a dose of ZOKINVY if the capsules cannot be swallowed whole. Read this Instructions for Use before you start giving or taking ZOKINVY and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about you or your child’s medical condition or treatment Supplies needed to prepare and give or take a dose of ZOKINVY   Before mixing a dose of ZOKINVY, gather the following supplies: - the prescribed number of ZOKINVY capsules for you or your child’s dose. Place the capsule or capsules on a clean flat surface. - either Ora-Blend SF, Ora-Plus, orange juice or applesauce for mixing. Do not mix with juice that contains grapefruit or Seville oranges. Seville oranges may also be called bitter or sour oranges. - if mixing with Ora-Blend SF, Ora-Plus or orange juice: a clean medicine cup with 5 milliliter (mL) and 10 mL measurement levels, OR if mixing with applesauce: a clean teaspoon. - clean cup(s) for each ZOKINVY capsule to be mixed. - a clean spoon for stirring the mixture. How to open ZOKINVY capsules and mix the capsule contents Step 1: If mixing with Ora-Blend SF, Ora-Plus or orange juice: Use a clean medicine cup to measure either 5 mL or 10 mL of Ora-Blend SF, Ora-Plus or orange juice. If mixing with applesauce: measure either 1 or 2 teaspoonfuls of applesauce. You can choose to use 5 mL or 10 mL of liquid or 1 or 2 teaspoonfuls of applesauce (See Figure A). Step 2: Place the Ora-Blend SF, Ora-Plus, orange juice or applesauce measured in Step 1 into a clean cup (See Figure B). Step 3: Hold a ZOKINVY capsule above the clean cup containing the liquid or applesauce. Hold the ZOKINVY capsule on both sides between your thumb and forefinger. Gently twist and pull apart the capsule (See Figure C). Empty the contents of the capsule directly into the clean cup (See Figure D). Step 4: Using a clean spoon, mix the ZOKINVY capsule contents well (See Figure E) . If only 1 capsule is to be taken, skip to Step 6 . If 2 capsules are to be taken, go to Step 5 . Step 5: If 2 capsules will be taken, repeat Steps 1 through 4 for the second capsule. After completing the mixing process for the second capsule, the 2 servings can either be placed together in a single cup or remain in 2 serving cups for you or your child to take the full dose of ZOKINVY. After you finish, go to Step 6 . Step 6: Give or take all of the ZOKINVY mixture with morning and evening meals within about 10 minutes of preparing. How should I store ZOKINVY? - Store at room temperature between 68°F to 77°F (20°C to 25°C) Keep ZOKINVY and all medicines out of reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured for: Eiger BioPharmaceuticals, Inc., 2155 Park Boulevard Palo Alto, CA 94306 ©2020 Eiger BioPharmaceuticals Issued: 11/2020

Product summary:

ZOKINVY is supplied as: Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30ºC (59°F-86°F) [see USP Controlled Room Temperature].

Authorization status:

New Drug Application

Summary of Product characteristics

ZOKINVY- LONAFARNIB CAPSULE
EIGER BIOPHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZOKINVY SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ZOKINVY.
ZOKINVY (LONAFARNIB) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2020
RECENT MAJOR CHANGES
Dosage and Administration (2.2)
03/2024
Warnings and Precautions (5.1)
03/2024
INDICATIONS AND USAGE
ZOKINVY is a farnesyltransferase inhibitor indicated in patients 12
months of age and older with a body
surface area of 0.39 m and above: (1)
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.
Limitations of Use
Not indicated for other Progeroid Syndromes or processing-proficient
Progeroid Laminopathies. Based
upon its mechanism of action, ZOKINVY would not be expected to be
effective in these populations. (1)
DOSAGE AND ADMINISTRATION
Start at 115 mg/m twice daily with morning and evening meals. (2.1)
After 4 months, increase to 150 mg/m twice daily. (2.1)
Round all total daily doses to nearest 25 mg increment. (2.1)
See full prescribing information for dosage modifications due to
adverse reactions. (2.2)
See full prescribing information for preparation and administration
instructions. (2.4)
DOSAGE FORMS AND STRENGTHS
_Capsules:_ 50 mg and 75 mg. (3)
CONTRAINDICATIONS
Strong CYP3A inhibitors. (4)
Strong or moderate CYP3A inducers. (4)
Midazolam. (2.3, 4)
Lovastatin, simvastatin, or atorvastatin. (4)
WARNINGS AND PRECAUTIONS
_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. (5.1)
_Risk of Reduced Efficacy or Adverse Reactions Due to Drug
Interactions:_ Prior to and during treatment,
consider potentia