Zokinvy lonafarnib 50 mg Capsule, 30-count — NDC 42358-450-30 (Billing 42358-0450-30)
This is a package of 30 capsules of Zokinvy lonafarnib 50 mg Capsule from Sentynl Therapeutics, Inc., marketed since Jul 2025 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 42358-450-30 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 42358 labeler · 450 product · 30 package
- Package marketed since
- Jul 2, 2025
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 30 EA per package
- Barcode (UPC)
- 0342358450305, 0342358475308
- FDA record last changed
- Oct 8, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 081705
- GCN: 48901
- GPI-14 (Medi-Span): 99463045000120
- HICL (First Databank): 046991
- AHFS class code: 44:04.00.00
- RxCUI (RxNorm): 2467582
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 8, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 8, 2026
RxNorm drug class
This medicine belongs to the Farnesyltransferase Inhibitor class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 8, 2026
Clinical
Lonafarnib is used to reduce the risk of death in children 1 year of age or older with Hutchinson-Gilford progeria syndrome (HGPS, Hutchinson-Gilford syndrome; an inherited disorder that causes certain proteins to build up in the body which causes children to age rapidly). Lonafarnib is also used to treat certain processing-deficient progeroid laminopathies (PDPL; inherited disorders that cause certain proteins to build up in the body which cause children to age rapidly). Lonafarnib is in a class of medications called farnesyltransferase inhibitors. It works by preventing proteins from buildin...
Read the full MedlinePlus article ↗- Lonafarnib (Zokinvy) is used to reduce the risk of death in Hutchinson-Gilford Progeria Syndrome. It also treats certain processing-deficient progeroid laminopathies with specific...
- Take it by mouth twice a day with your morning and evening meals. Swallow the capsules whole with enough water. If swallowing is hard, your pharmacist can show you how to mix the c...
- Take it as soon as you can with food if there are more than 8 hours until your next dose. If less than 8 hours remain, skip it and take your next dose on schedule.
- Vomiting, diarrhea and nausea are very common, especially in the first few months. Tell your doctor if they cause dehydration or weight loss. Call right away about fainting, a poun...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Lonafarnib — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $912.03 | $27,360.96 / 30 capsules |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 9, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 42358-0450-30 You're viewing this Main listing | 1 BOTTLE, PLASTIC in 1 CARTON / 30 CAPSULE in 1 BOTTLE, PLASTIC | 2025-07-02 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zokinvy 50 mgthis 42358-0450-30 | Sentynl | 30 capsules | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Orange Book · refreshed Oct 9, 2026
- CMS NADAC weekly file
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 7838531 ↗ | Method of use | U-3070 | Jul 26, 2029 |
| US 7838531 ↗ | Method of use | U-3070 | Jul 26, 2029 |
| Code | What it grants | Expires |
|---|---|---|
| ODE-324 | Orphan Drug Exclusivity (7-year) | Nov 20, 2027 |
| ODE-324 | Orphan Drug Exclusivity (7-year) | Nov 20, 2027 |
Is there a generic version of ZOKINVY 50 MG CAPSULE?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 9, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Lonafarnib inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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10.0 mg
UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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0.616 mg
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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12.50 mg
UNII LQA7B6G8JG
A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
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50 mg
UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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1.85 mg
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 8, 2026
- FDA openFDA NDC Directory · synced Oct 8, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
More NDCs from Sentynl Therapeutics, Inc. labeler code 42358
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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: ( 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 ) 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Start at 115 mg/m 2 twice daily with morning and evening meals. ( 2.1 ) After 4 months, increase to 150 mg/m 2 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 )
2.1Recommended Dosage The starting dosage of ZOKINVY for patients with a BSA of 0.39 m 2 and above is 115 mg/m 2 twice daily with morning and evening meals (see Table 1 ) to reduce the risk of gastrointestinal adverse reactions [see Adverse Reactions ( 6.1 )] . An appropriate dosage strength of ZOKINVY is not available for patients with a BSA of less than 0.39 m 2 [see Indications and Usage ( 1 )] . After 4 months of treatment, increase the dosage to 150 mg/m 2 twice daily with morning and evening meals (see Table 2 ).
Round all total daily dosages to the nearest 25 mg increment (see Table 1 and Table 2 ). If a dose is missed, take the dose as soon as possible with food, up to 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next scheduled dose, skip the missed dose, and resume taking ZOKINVY at the next scheduled dose.
Table 1 provides the BSA-based dosage recommendations for the starting dosage of 115 mg/m 2 twice daily. Table 1: Recommended Dosage and Administration for 115 mg/m 2 Body Surface Area-Based Dosing BSA (m 2 ) Total Daily Dosage Rounded to Nearest 25 mg Morning Dosing Number of Capsule(s) Evening Dosing Number of Capsule(s) ZOKINVY 50 mg ZOKINVY 75 mg ZOKINVY 50 mg ZOKINVY 75 mg 0.39 - 0.48 100 1 1 0.49 - 0.59 125 1 1 0.6 - 0.7 150 1 1 0.71 - 0.81 175 2 1 0.82 - 0.92 200 2 2 0.93 – 1 225 1 1 2 Table 2 provides the BSA-based dosage recommendations for the dosage of 150 mg/m 2 twice daily.
Table 2: Recommended Dosage and Administration for 150 mg/m 2 Body Surface Area-Based Dosing BSA (m 2 ) Total Daily Dosage Rounded to Nearest 25 mg Morning Dosing Number of Capsule(s) Evening Dosing Number of Capsule(s) ZOKINVY 50 mg ZOKINVY 75 mg ZOKINVY 50 mg ZOKINVY 75 mg 0.39 - 0.45 125 1 1 0.46 - 0.54 150 1 1 0.55 - 0.62 175 2 1 0.63 - 0.7 200 2 2 0.71 - 0.79 225 1 1 2 0.8 - 0.87 250 1 1 1 1 0.88 - 0.95 275 2 1 1 0.96 – 1 300 2 2
2.2Dosage Modifications Due to Adverse Reactions and Drug Interactions Table 3: Recommended ZOKINVY Dosage Modifications Adverse Reaction Severity Monitoring and Dose Modifications for ZOKINVY QTc Interval Prolongation [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 )] If the QTc interval is greater than or equal to 500 msec Withhold ZOKINVY until QTc interval is less than 470 msec, then resume ZOKINVY at same dosage. Monitor electrocardiograms (ECGs) prior to initiating ZOKINVY, during treatment, and as clinically indicated.
Gastrointestinal Adverse Reactions [see Adverse Reactions ( 6.1 )] For patients who have increased their dose of ZOKINVY to 150 mg/m 2 twice daily and are experiencing repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss The dose of ZOKINVY can be reduced to the starting dose of 115 mg/m 2 twice daily (see Table 1 ). Ensure ZOKINVY is taken with the morning and evening meals and with an adequate amount of water. CYP3A Drug Interactions [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 ), Drug Interactions ( 7.1 )] When moderate CYP3A inhibitors are added for a patient already on steady state ZOKINVY No dosage adjustment for ZOKINVY is recommended.
When initiating ZOKINVY in a patient who is concurrently on a moderate CYP3A inhibitor The patient may be at increased risk of adverse reactions. Monitor the patient closely for adverse reactions for at least the first 7 days after initiating ZOKINVY. If the patient experiences an adverse reaction during the first 7 days of the starting dose or thereafter, consider an alternative therapy that is not a moderate CYP3A inhibitor.
2.3Temporary D… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules: 50 mg, opaque yellow with “LNF” and “50” printed in black 75 mg, opaque light orange with “LNF” and “75” printed in black Capsules : 50 mg and 75 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS 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 )] Strong CYP3A inhibitors. ( 4 ) Strong or moderate CYP3A inducers. ( 4 ) Midazolam. ( 2.3 , 4 ) Lovastatin, simvastatin, or atorvastatin. ( 4 )
⚠️ Warnings and Cautions ▾
5 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 potential for drug interactions and review concomitant medications; monitor for adverse reactions.
( 5.2 , 7 ) Laboratory Abnormalities: Monitor for changes in electrolytes, complete blood counts, and liver enzymes. ( 5.3 ) Nephrotoxicity: Caused nephrotoxicity in rats. Monitor renal function at regular intervals.
( 5.4 , 13.2 ) 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. ( 5.5 , 13.2 ) Impaired Fertility: Caused impaired fertility in female rats, impaired fertility and testicular toxicity in male rats, and toxicity in the male reproductive tract in monkeys.
Advise females and males of reproductive potential of the animal fertility findings. ( 5.6 , 13.1 , 13.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the risk to a fetus and to use effective contraception.
( 5.7 , 8.1 , 8.3 )
5.1QTc Interval Prolongation ZOKINVY prolongs the QTc interval. Prolongation of the QTc interval increases the risk of Torsade de pointes, other serious arrhythmias, and sudden death. Avoid use of ZOKINVY in patients with a history of cardiac arrhythmias, as well as in other circumstances that may increase the risk of the occurrence of Torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia, or hypomagnesemia.
Avoid use of ZOKINVY in combination with other drugs known or suspected to prolong the QTc interval [see Drug Interactions ( 7.1 )] . Monitor ECGs prior to initiating ZOKINVY, during treatment, and as clinically indicated. If QTc interval is greater than 500 msec, withhold ZOKINVY until QTc interval is less than 470 msec, then resume ZOKINVY at same dosage.
Obtain serum electrolytes prior to initiating ZOKIVNY and during treatment as clinically indicated. Correct serum electrolyte abnormalities.
5.2Risk of Reduced Efficacy or Adverse Reactions Due to Drug Interactions Coadministration of ZOKINVY with other drugs may result in clinically significant drug interactions [see Dosage and Administration ( 2.2 , 2.3 ), Contraindications ( 4 ), Drug Interactions ( 7.1 , 7.2 )] . These drug interactions can lead to: Reduced efficacy of ZOKINVY Increased risk of adverse reactions from ZOKINVY or co-administered drugs See Table 5 and Table 6 for steps to prevent or manage these clinically significant drug interactions, including dosage recommendations [see Drug Interactions (7.1, 7.2 ) ] .
Consider the potential for drug interactions prior to and during ZOKINVY therapy; review concomitant medications during ZOKINVY therapy; and monitor for adverse reactions.
5.3Laboratory Abnormalities Some patients treated with ZOKINVY developed laboratory abnormalities [see Adverse Reactions ( 6.1 )] . These included: Electrolyte abnormalities (43%), such as hyperkalemia, hypokalemia, hyponatremia, or hypercalcemia Myelosuppression (35%), such as reductions in absolute neutrophil count, white blood cell counts, lymphocytes, hemoglobin, or hematocrit Increased liver enzymes, such as aspartate aminotransferase (35%), or alanine aminotransferase (27%) These laboratory abnormalities often improved while continuing ZOKINVY, but it is not possible to exclude ZOKINVY as a cause of the abnormalities.
Periodically monitor electrolytes, complete blood counts, and liver enzymes, and manage abnormalities accordingly.
5.4Nephrotoxicity Lonafarnib caused nephrotoxicity in rats at plasma drug exposures approximately equal to that achieved with the human dose [ see Nonclinical Toxicology ( 13.2 )] . Monitor renal function at reg… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sentynl Therapeutics, Inc. at 1-888-507-5206 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 84 subjects were treated with at least one dose of ZOKINVY with or without additional therapy, of which 8 were treated at a dosage of at least 115 mg/m 2 twice daily for greater than or equal to 10 years. The safety profile of ZOKINVY is based on 128 patient-years of treatment exposure (62 patients with HGPS and 1 patient with processing-deficient Progeroid Laminopathy with LMNA heterozygous mutation) and pooled results from two Phase 2 open-label, single-arm trials (n=63: 28 patients from Study 1 and 35 treatment naïve patients from Study 2).
In Study 1, ZOKINVY treatment was initiated at 115 mg/m 2 twice daily and increased to 150 mg/m 2 twice daily after approximately 4 months for a total treatment duration of 24 to 30 months. Treatment naïve patients in Study 2 received ZOKINVY 150 mg/m 2 twice daily for up to 36 months. In both studies, ZOKINVY was administered orally via capsules or the capsule contents were mixed with Ora Blend SF or Ora-Plus and administered orally as a suspension.
In these two studies, a total of 63 patients received ZOKINVY for a median duration of 2.2 years, with approximately 1.9 years at the recommended dose of 150 mg/m 2 twice daily. The population was 2 to 17 years old, with a similar proportion of males (33 [52%] patients) and females (30 [48%] patients). Most patients had classic HGPS (60 [95%] patients) compared to non-classic HGPS (2 [3%] patients) and 1 (2%) patient had Progeroid Laminopathy with LMNA heterozygous mutation.
Table 4 summarizes adverse reactions reported in the clinical trials. The most common adverse reactions (≥25%) in the clinical trials were 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. Table 4: Adverse Reactions in ≥5% of Patients in Study 1 and Treatment-Naïve Patients in Study 2 Receiving ZOKINVY Adverse Reactions ZOKINVY n=63 n (%) 1 Abdominal pain includes stomach pain and abdominal pain.
2 Infection includes abdominal infection, candidiasis, chicken pox, Clostridium difficile colitis, colitis, croup, dengue fever, flu syndrome, flu-like symptoms, fungal infection, gastroenteritis, gastrointestinal infection, Helicobacter pylori infection, infection, infection viral, influenza, nail infection, otitis media, parotitis, perirectal abscess, pneumonia, small intestine infection, submandibular lymphadenitis, tonsillitis, viral infection. 3 Upper respiratory infection includes bronchial infection, bronchitis, sinus infection, and upper respiratory infection.
4 Electrolyte abnormalities include hypermagnesemia, hypokalemia, hyperkalemia, hyponatremia, hypercalcemia, hyperphosphatemia, hypocalcemia, and hypernatremia. 5 Myelosuppression includes absolute neutrophil count decreased, low total white blood cells, lymphopenia, decreased hemoglobin, and hematocrit low. 6 Musculoskeletal pain includes arth… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS QTc Interval Prolongation Drugs : Avoid concomitant use with ZOKINVY. ( 2.2 , 5.2 , 7.1 , 12.3 ) See full prescribing information for additional clinically significant drug interactions with ZOKINVY and recommended dosage modifications for drug interactions. ( 2.2 , 7 )
7.1Effect of Other Drugs on ZOKINVY Table 5 presents clinically significant drug interactions involving drugs that affect ZOKINVY. Table 5: Clinically Significant Drug Interactions (Drugs that Affect ZOKINVY) CYP3A Inhibitors Clinical Impact Lonafarnib is metabolized by CYP3A. Concomitant use of ZOKINVY with a strong CYP3A inhibitor may increase lonafarnib area under curve (AUC) and maximum concentration (C max ) [see Clinical Pharmacology ( 12.3 )] , which may increase the incidence and severity of adverse reactions, including QTc interval prolongation.
Prolongation of the QTc interval increases the risk of Torsade de pointes, other serious arrhythmias, and sudden death [see Warnings and Precautions ( 5.1 )] . Prevention or Management Strong CYP3A inhibitors Use of ZOKINVY with strong CYP3A inhibitors is contraindicated [see Contraindications ( 4 )] . Avoid consumption of grapefruit or Seville oranges.
Moderate CYP3A inhibitors No dosage adjustment for ZOKINVY is recommended when moderate CYP3A inhibitors are added to steady-state ZOKINVY [see Dosage and Administration ( 2.2 )] . When initiating ZOKINVY in a patient who is currently on a moderate CYP3A inhibitor, the patient may be at increased risk of adverse reactions [see Dosage and Administration ( 2.2 )]. CYP3A Inducers Clinical Impact Coadministration of ZOKINVY with a strong CYP3A inducer decreases lonafarnib C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may reduce ZOKINVY efficacy.
Prevention or Management Strong or moderate CYP3A inducers Use of ZOKINVY with strong or moderate CYP3A inducers is contraindicated [see Contraindications ( 4 )] . Weak CYP3A inducers No ZOKINVY dosage adjustment is recommended. QTc Prolongation Drugs Clinical Implication ZOKINVY causes QTc interval prolongation [see Clinical Pharmacology ( 12.2 )] .
Concomitant use of ZOKINVY with other products that prolong the QTc interval may result in a greater increase of the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsade de pointes, other serious arrythmias, and sudden death [see Warnings and Precautions ( 5.1 )] . Prevention or Management Avoid concomitant use of ZOKINVY with other drugs with a known potential to prolong the QTc interval. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated [see Warnings and Precautions ( 5.1 )] .
7.2ZOKINVY's Effect on Other Drugs Table 6 presents clinically significant drug interactions involving drugs affected by ZOKINVY. Table 6: Clinically Significant Drug Interactions (Drugs Affected by ZOKINVY) CYP3A Substrates Clinical Impact Lonafarnib is a strong CYP3A mechanism-based inhibitor. Coadministration of ZOKINVY with a CYP3A substrate increases the AUC and C max of the CYP3A substrate [see Clinical Pharmacology ( 12.3 )] which may increase the risk of the CYP3A substrate's adverse reactions, including myopathy or rhabdomyolysis (with statins), or extreme sedation or respiratory depression (with midazolam).
Prevention or Management HMG CoA reductase inhibitors (“Statins”) Coadministration of ZOKINVY with lovastatin, simvastatin, or atorvastatin is contraindicated [see Contraindications ( 4 )] . Midazolam Coadministration of ZOKINVY with midazolam is contraindicated [see Contraindications ( 4 )] . Temporarily discontinue ZOKINVY for 10-14 days before and 2 days after administration of midazolam [see Dosage and Administration ( 2.3 )] .
Other sensitive CYP3A substrates Avoid coadministration of ZOKINVY with sensitive CYP3A substrates. As noted above, use with lovastatin, simvastatin, or atorvastatin, and midazolam is contraindicated [see Contraindicati… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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/m 2 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/m 2 twice daily, and maternal toxicity at 26 times the human exposure at 150 mg/m 2 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/m 2 twice daily). No effects on embryo-fetal development in rats were observed at systemic exposures lower than the human AUC at 150 mg/m 2 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/m 2 twice daily, and maternal toxicity (body weight loss and abortion) at 120 mg/kg/day (26 times the human AUC at 150 mg/m 2 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/m 2 twice daily) during organogenesis through lactation.
8.2Lactation 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.
8.3Females and Males of Reproductive Potential 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 )] .
8.4Pediatric Use 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 studi… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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/m 2 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/m 2 twice daily, and maternal toxicity at 26 times the human exposure at 150 mg/m 2 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/m 2 twice daily). No effects on embryo-fetal development in rats were observed at systemic exposures lower than the human AUC at 150 mg/m 2 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/m 2 twice daily, and maternal toxicity (body weight loss and abortion) at 120 mg/kg/day (26 times the human AUC at 150 mg/m 2 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/m 2 twice daily) during organogenesis through lactation.
🧒 Pediatric Use ▾
8.4Pediatric Use 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.
12.2Pharmacodynamics Cardiac Electrophysiology The effect of lonafarnib on the QTc interval was evaluated in a randomized, double-blind, placebo- and positive-controlled (moxifloxacin 400 mg single dose), multiple-dose, QTc study in 64 healthy subjects. Subjects received 200 mg lonafarnib twice daily for 9 consecutive days and a single 200 mg dose in the morning on Day 10, with food. The largest mean increase in QTc interval was 19 msec (upper bound of 90% confidence interval = 27 msec) on Day 10 at 48 hours after administration of the morning dose of lonafarnib 200 mg.
The C max on Day 10 was 2233 ng/mL, which is similar to the mean C max of 2695 ng/mL observed in the HGPS patient population [see Clinical Pharmacology ( 12.3 )] .
12.3Pharmacokinetics The pharmacokinetics of lonafarnib at steady state in patients with HGPS following oral administration of lonafarnib twice daily with food are summarized in Table 7 . Table 7: Summary of Pharmacokinetic Parameters of Lonafarnib at Steady State after Oral Administration Twice Daily to Patients with HGPS Lonafarnib Dose Median (range) t max (hr) Mean (SD) C max (ng/mL) Mean (SD) AUC 0-8hr (ng*hr/mL) Mean (SD) AUC tau (ng*hr/mL) 115 mg/m 2 N 23 23 23 15 Results 2 (0, 6) 1777 (1083) 9869 (6327) 12365 (9135) 150 mg/m 2 N 18 18 18 8 Results 4 (0, 12) 2695 (1090) 16020 (4978) 19539 (6434) Absorption The absolute bioavailability of lonafarnib following oral administration has not been determined.
Following oral administration of lonafarnib 75 mg and 100 mg twice daily in healthy subjects under fasted conditions, the geometric mean (CV%) maximum peak plasma concentrations of lonafarnib were 834 (32%) ng/mL and 964 (32%) ng/mL, respectively. Effect of Food Following a single oral dose of 75 mg lonafarnib in healthy subjects, the C max decreased 55% and AUC decreased 29% with a high-fat meal (approximately 43% fat of the total 952 calories) compared to fasted conditions. C max decreased 25% and AUC decreased 21% with a low-fat meal (approximately 12% fat of the total 421 calories) compared to fasted conditions.
Distribution In vitro plasma protein binding of lonafarnib was greater than or equal to 99% over the concentration range between 0.5 to 40.0 μg/mL. The apparent volumes of distribution were
87.8 L and
97.4L, respectively, at steady state following oral administration of lonafarnib 100 mg and 75 mg twice daily in healthy subjects. Elimination The mean half-life was approximately 4 to 6 hours following oral administration of lonafarnib 100 mg twice daily in healthy subjects. Metabolism Lonafarnib is primarily metabolized by CYP3A and to a lesser extent by CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1 in vitro.
In a Phase 1 study in healthy subjects, autoinhibition activity of lonafarnib was demonstrated following repeated dosing of lonafarnib. Specifically, the clearance of lonafarnib following multiple-dose lonafarnib administration was reduced by 75% compared with that following single-dose lonafarnib administration. Excretion Following an oral administration of 104 mg [ 14 C]-lonafarnib under fasted conditions in healthy subjects, approximately 62% of the total radiolabeled dose was recovered in feces and <1% of the total radiolabeled dose was recovered in urine up to 240 hours post-dose.
The two most predominant metabolites were HM17 and HM21 (an active metabolite) accounting for 15% and 14% of plasma radioactivity, respectively. Specific Populations Patients with Renal Impairment or Hepatic Impairment ZOKINVY has not been studied in patients with renal impairment or in patients with hepatic impairment. Male and Female Patients Following a single oral dose of 100 mg lonafarnib in healthy subjects, the plasma lonafarnib AUC and C max were 44% and 26% higher in fema… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ZOKINVY is supplied as: 50 mg capsules: Size 4 hard capsule, opaque yellow with “LNF” and “50” printed in black. Bottles of 30 capsules each (NDC 42358-450-30) 75 mg capsules: Size 3 hard capsule, opaque light orange with “LNF and “75” printed in black. Bottles of 30 capsules each (NDC 42358-475-30) Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30ºC (59°F-86ºF) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION ZOKINVY (lonafarnib) is a farnesyltransferase inhibitor. The chemical name for lonafarnib is 4-[2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H- benzo[1,2] cyclohepta [2,4-b]pyridin-11-yl]piperidin-1-yl]-2- oxoethyl]piperidine-1-carboxamide. Its molecular formula is C 27 H 31 Br 2 ClN 4 O 2 , molecular mass is 638.8 g/mol, and its chemical structure is depicted below.
ZOKINVY (lonafarnib) capsules for oral administration contain 50 mg or 75 mg of lonafarnib as the active ingredient and the following inactive ingredients: croscarmellose sodium, magnesium stearate, poloxamer 188, povidone, and silicon dioxide. The capsule shells of both strengths contain gelatin, titanium dioxide, and yellow iron oxide; the 75 mg capsule also contains red iron oxide. The imprinting ink contains ammonia solution, black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, and shellac.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Dosing [see Dosage and Administration ( 2.1 )] Advise patients and caregivers that ZOKINVY should be taken twice daily with the morning and evening meals. Inform patients and caregivers that if a dose is missed, the next dose should be given as soon as possible up to 8 hours prior to the next scheduled dose.
If less than 8 hours remain before the next scheduled dose, the patient should skip the missed dose and resume taking ZOKINVY at the next scheduled dose. Preparation and Administration [see Dosage and Administration ( 2.4 ), Drug Interactions ( 7 )] Advise patients to swallow the capsule whole with water. The capsules should not be chewed.
For patients unable to swallow capsules, advise patients and caregivers that the contents of ZOKINVY can be mixed with Ora Blend SF or Ora-Plus. For patients unable to access or tolerate Ora Blend SF or Ora-Plus, the contents of ZOKINVY can be mixed with orange juice or applesauce. Advise patients not to mix the contents of ZOKINVY with juice containing grapefruit or Seville oranges.
Advise patients and caregivers that the mixture must be prepared fresh for each dose and taken within approximately 10 minutes of mixing. Advise patients and caregivers to read and carefully follow the instructions for administering the capsule contents in Ora Blend SF, Ora-Plus, orange juice or applesauce [see Instructions for Use ] . Advise patients and caregivers to call their healthcare provider or pharmacist if they have any questions.
QTc Interval Prolongation [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.2 )] Inform patients and caregivers that ZOKINVY causes QTc interval prolongation and may increase the risk of Torsades de pointes, other ventricular arrhythmias, and sudden death. Instruct patients or caregivers to notify their healthcare provider if they experience symptoms such as dizziness, lightheadedness, heart palpitations, or loss of consciousness. Instruct patients to inform their healthcare provider if they are taking any other medications that may prolong the QTc interval.
Drug Interactions [see Dosage and Administration ( 2.2 , 2.3 ), Contraindications ( 4 ), Warnings and Precautions ( 5.1 , 5.2 ), Drug Interactions ( 7.1 )] Inform patients and caregivers that ZOKINVY may interact with several drugs. Advise patients and their caregivers to inform their healthcare provider before starting or discontinuing a prescription or non-prescription drug, supplement, or strong CYP3A inhibitor. Nephrotoxicity [see Warnings and Precautions ( 5.4 ), Nonclinical Toxicology ( 13.2 )] Inform the patient and caregiver of the risk of kidney damage.
Retinal Toxicity [see Warnings and Precautions ( 5.5 ), Nonclinical Toxicology ( 13.2 )] Inform the patient and caregiver of the risk of developing difficulty with night vision. Advise patients and caregivers to contact their healthcare provider if they experience a change in vision. Gastrointestinal Adverse Reactions [see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 )] Inform patients and caregivers that gastrointestinal adverse reactions are common with ZOKINVY.
These include, but are not limited to, vomiting, diarrhea, and nausea. Advise patients and caregivers to contact their healthcare provider if these adverse reactions persist. Hypertension [see Adverse Reactions ( 6.1 )] Inform patients and caregivers that blood pressure may increase while taking ZOKINVY.
Symptoms of hypertension may include headaches, shortness of breath, nosebleeds, flushing, dizziness, or chest pain. Advise patients and caregivers to contact their healthcare provider if these adverse reactions occur. Impaired Fertility [see Warnings and Precautions ( 5.6 ), Nonclinical Toxicology ( 13.1 )] Inform females and males of reproductive potential that ZOKINVY may impact pubertal development… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics The pharmacokinetics of lonafarnib at steady state in patients with HGPS following oral administration of lonafarnib twice daily with food are summarized in Table 7 . Table 7: Summary of Pharmacokinetic Parameters of Lonafarnib at Steady State after Oral Administration Twice Daily to Patients with HGPS Lonafarnib Dose Median (range) t max (hr) Mean (SD) C max (ng/mL) Mean (SD) AUC 0-8hr (ng*hr/mL) Mean (SD) AUC tau (ng*hr/mL) 115 mg/m 2 N 23 23 23 15 Results 2 (0, 6) 1777 (1083) 9869 (6327) 12365 (9135) 150 mg/m 2 N 18 18 18 8 Results 4 (0, 12) 2695 (1090) 16020 (4978) 19539 (6434) Absorption The absolute bioavailability of lonafarnib following oral administration has not been determined.
Following oral administration of lonafarnib 75 mg and 100 mg twice daily in healthy subjects under fasted conditions, the geometric mean (CV%) maximum peak plasma concentrations of lonafarnib were 834 (32%) ng/mL and 964 (32%) ng/mL, respectively. Effect of Food Following a single oral dose of 75 mg lonafarnib in healthy subjects, the C max decreased 55% and AUC decreased 29% with a high-fat meal (approximately 43% fat of the total 952 calories) compared to fasted conditions. C max decreased 25% and AUC decreased 21% with a low-fat meal (approximately 12% fat of the total 421 calories) compared to fasted conditions.
Distribution In vitro plasma protein binding of lonafarnib was greater than or equal to 99% over the concentration range between 0.5 to 40.0 μg/mL. The apparent volumes of distribution were
87.8 L and
97.4L, respectively, at steady state following oral administration of lonafarnib 100 mg and 75 mg twice daily in healthy subjects. Elimination The mean half-life was approximately 4 to 6 hours following oral administration of lonafarnib 100 mg twice daily in healthy subjects. Metabolism Lonafarnib is primarily metabolized by CYP3A and to a lesser extent by CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1 in vitro.
In a Phase 1 study in healthy subjects, autoinhibition activity of lonafarnib was demonstrated following repeated dosing of lonafarnib. Specifically, the clearance of lonafarnib following multiple-dose lonafarnib administration was reduced by 75% compared with that following single-dose lonafarnib administration. Excretion Following an oral administration of 104 mg [ 14 C]-lonafarnib under fasted conditions in healthy subjects, approximately 62% of the total radiolabeled dose was recovered in feces and <1% of the total radiolabeled dose was recovered in urine up to 240 hours post-dose.
The two most predominant metabolites were HM17 and HM21 (an active metabolite) accounting for 15% and 14% of plasma radioactivity, respectively. Specific Populations Patients with Renal Impairment or Hepatic Impairment ZOKINVY has not been studied in patients with renal impairment or in patients with hepatic impairment. Male and Female Patients Following a single oral dose of 100 mg lonafarnib in healthy subjects, the plasma lonafarnib AUC and C max were 44% and 26% higher in female subjects, respectively, compared to male subjects.
The observed exposure difference by sex in healthy subjects is not considered clinically meaningful. Geriatric Patients Following a single oral dose of 100 mg lonafarnib in healthy subjects, the plasma lonafarnib AUC and C max were 59% and 27% higher in subjects ≥65 years, respectively, compared to subjects 18 to 45 years of age. The observed higher exposure in geriatric subjects is not considered clinically relevant.
Drug Interaction Studies In Vitro Studies Lonafarnib is a CYP3A substrate and a potent CYP3A time-dependent and mechanism-based inhibitor. Lonafarnib is an inhibitor of CYP2C8 and CYP2C19. Lonafarnib is not considered an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, or CYP2D6.
Lonafarnib is unlikely to be an inducer of CYP1A2, CYP2B6, and CYP3A. Lonafarnib is not a substrate of transporters OATP1B1, OATP1B3, or BCRP, but is likely a marginal substrate of P-gp. Lonafarnib is a… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Cardiac Electrophysiology The effect of lonafarnib on the QTc interval was evaluated in a randomized, double-blind, placebo- and positive-controlled (moxifloxacin 400 mg single dose), multiple-dose, QTc study in 64 healthy subjects. Subjects received 200 mg lonafarnib twice daily for 9 consecutive days and a single 200 mg dose in the morning on Day 10, with food. The largest mean increase in QTc interval was 19 msec (upper bound of 90% confidence interval = 27 msec) on Day 10 at 48 hours after administration of the morning dose of lonafarnib 200 mg.
The C max on Day 10 was 2233 ng/mL, which is similar to the mean C max of 2695 ng/mL observed in the HGPS patient population [see Clinical Pharmacology ( 12.3 )] .
🔬 Clinical Studies ▾
14 CLINICAL STUDIES The efficacy of ZOKINVY is based on results from the Observational Cohort Survival Study, which retrospectively compared survival data from two Phase 2 studies in patients with HGPS to those from a natural history cohort. Study 1 (NCT00425607) was a Phase 2 open-label, single-arm trial that evaluated the efficacy of ZOKINVY in 28 patients (26 with classic HGPS, one with non-classic HGPS, and one with processing-deficient Progeroid Laminopathy with LMNA heterozygous mutation with progerin-like protein accumulation).
Patients received ZOKINVY for 24 to 30 months. Patients initiated treatment with ZOKINVY 115 mg/m 2 twice daily. After 4 months of treatment, patients who tolerated treatment had an increase in dose to 150 mg/m 2 twice daily.
Among the 28 patients treated, 27 patients with HGPS (16 females, 11 males) were included in the survival assessment. The median age at treatment initiation for the 27 patients was 7.5 years (range: 3 to 16 years). The body weight range was 6.6 to 17.6 kg and the BSA range was 0.38 to 0.75 m 2 (ZOKINVY is not indicated in patients with a BSA less than 0.39 m 2 because the appropriate dosage strength is not available for this population).
Following completion of Study 1, 26 patients enrolled in a second Phase 2 open label, single-arm trial (Study 2, NCT00916747) which consisted of two study phases. In the first phase of Study 2, patients received ZOKINVY with additional therapies for about 5 years. In the second phase of Study 2, patients received ZOKINVY 150 mg/m 2 twice daily for a period of up to 3 years.
There were 35 treatment naïve patients with HGPS enrolled into the second phase of Study 2. Among the 35 treated patients (22 males, 13 females), 34 (97.1%) patients had classic HGPS and 1 (2.9%) patient had non-classic HGPS. The median age was 6 years (range: 2 to 17 years).
The body weight range was 6.7 to 22 kg and the BSA range was 0.42 to 0.90 m 2 . Throughout Study 1 and Study 2, ZOKINVY was administered orally via capsules or the capsule contents were mixed with Ora Blend SF or Ora-Plus and administered orally as a suspension. The retrospective survival analysis was based on the mortality data from 62 treated patients (27 patients in Study 1 and 35 treatment-naïve patients in Study 2) and data from matched, untreated patients in a separate natural history cohort.
The mean lifespan of HGPS patients treated with ZOKINVY increased by an average of 3 months through the first three years of follow-up and 2.5 years through the last follow-up time (11 years) compared to untreated patients. The survival analysis summary is provided in Table 8 and Figure 1 . Table 8: Survival Analysis Summary for Patients with HGPS 1 Includes 27 patients in Study 1 and 35 treatment-naïve patients in Study 2.
2 Based on the area under the survival curves up to 11 years of follow-up. 3 Based on a Cox regression model (with treatment as the only covariate) stratified by continent of residency. Note: Treated patients were matched 1:1 to untreated patients (who were alive at the age when the treated patient began ZOKINVY) by mutation status (classic/unknown versus non-classic), sex and continent of residence using a fixed 50th percentile matching algorithm.
In the fixed 50th percentile matching algorithm, candidate untreated patients were first sorted by decreasing last known age and the candidate in the 50th percentile was selected as the match. Follow-up time for a matched pair of treated and untreated patients began at the age of the treated patient at ZOKINVY initiation. Follow-up time censored at 3-years Last follow-up time Summary Untreated (n=62) ZOKINVY 1 (n=62) Untreated (n=62) ZOKINVY 1 (n=62) Number of Deaths (%) 12 (19.4) 5 (8.1) 25 (40.3) 21 (33.9) Mean Survival Time (years) 2 (95% CI) 2.6 (2.4, 2.8) 2.8 (2.7, 3.0) 5.5 (4.3, 6.8) 8.0 (6.9, 9.1) Difference in Mean Survival Time (years) (95% CI) -- 0.24 (-0.03, 0.50) -- 2.5 (0.8, 4.1) Hazard Ratio for Risk of Death 3 (95% CI) -- 0.30… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies have not been conducted with lonafarnib. Mutagenesis Lonafarnib was not genotoxic in the bacterial mutagenicity (Ames) assay, in vitro chromosomal aberration assay in mammalian cells, or in vivo micronucleus assay in mice. Impairment of Fertility Lonafarnib produced impaired fertility in male rats at 90 mg/kg/day or higher (1.5 times the AUC in humans at the recommended dose of 150 mg/m 2 twice daily), with a nearly complete loss of fertility at 180 mg/kg/day (3 times the AUC in humans).
Male rats treated with 180 mg/kg/day exhibited small testes, flaccid testes, and discolored epididymis (84%, 56%, and 24% of males, respectively). No effects on fertility occurred in males at systemic exposures lower than the human AUC at 150 mg/m 2 twice daily. Female rats treated with 30 mg/kg/day lonafarnib or higher (1.2 times the human AUC at the recommended human dose of 150 mg/m 2 twice daily) showed a decrease in fertility, as indicated by reductions in the number of corpora lutea and implantation sites and increases in pre- and post-implantation loss.
No effects on fertility occurred in females at systemic exposures lower than the human AUC at 150 mg/m 2 twice daily [see Warnings and Precautions ( 5.6 )] .
13.2Animal Toxicology and/or Pharmacology Renal toxicity occurred in a 6-month oral toxicity study of lonafarnib in rats, with kidney lesions (interstitial necrosis and mineralization in the inner medulla) and correlating changes in clinical chemistry (e.g., hyperphosphatemia, hyperkalemia) and urinalysis parameters observed at systemic exposures approximately equal to the AUC in humans at the recommended dose of 150 mg/m 2 twice daily. No evidence of renal toxicity was observed at systemic exposures lower than the human AUC at 150 mg/m 2 twice daily [see Warnings and Precautions ( 5.4 )] .
Toxicity in the male reproductive tract occurred in a 1-year oral toxicity study in monkeys at 10 mg/kg/day or higher (AUC lower than the human AUC at the recommended dose of 150 mg/m 2 twice daily). The lesions in the male reproductive tract included aspermia in the epididymis and atrophy of seminiferous tubules, seminal vesicle, and prostate gland. Testicular toxicity was also observed in rats, where severe impairment of male fertility occurred [see Warnings and Precautions ( 5.6 ), Nonclinical Toxicology ( 13.1 )] .
Ocular (retinal) toxicity occurred in a 1-year oral toxicity study in monkeys at 40 mg/kg/day (3.7 times the human AUC at the recommended dose of 150 mg/m 2 twice daily). The retinal injury involved single cell necrosis of photoreceptor cells in the layer of rods and cones and the outer nuclear layer. No retinal toxicity was observed at 20 mg/kg/day (2.1 times the human AUC at 150 mg/m 2 twice daily).
However, in a follow-up study of lonafarnib effects on visual function in monkeys as evaluated by electroretinography, oral administration of 15 mg/kg/day for 13 weeks or 60 mg/kg/day for 6 weeks produced adverse effects on rod-dependent, low-light vision. The effects were observed at several time-points throughout the treatment period. No histological changes in the retina were observed at study termination [see Warnings and Precautions ( 5.5 )] .
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies have not been conducted with lonafarnib. Mutagenesis Lonafarnib was not genotoxic in the bacterial mutagenicity (Ames) assay, in vitro chromosomal aberration assay in mammalian cells, or in vivo micronucleus assay in mice. Impairment of Fertility Lonafarnib produced impaired fertility in male rats at 90 mg/kg/day or higher (1.5 times the AUC in humans at the recommended dose of 150 mg/m 2 twice daily), with a nearly complete loss of fertility at 180 mg/kg/day (3 times the AUC in humans).
Male rats treated with 180 mg/kg/day exhibited small testes, flaccid testes, and discolored epididymis (84%, 56%, and 24% of males, respectively). No effects on fertility occurred in males at systemic exposures lower than the human AUC at 150 mg/m 2 twice daily. Female rats treated with 30 mg/kg/day lonafarnib or higher (1.2 times the human AUC at the recommended human dose of 150 mg/m 2 twice daily) showed a decrease in fertility, as indicated by reductions in the number of corpora lutea and implantation sites and increases in pre- and post-implantation loss.
No effects on fertility occurred in females at systemic exposures lower than the human AUC at 150 mg/m 2 twice daily [see Warnings and Precautions ( 5.6 )] .
📄 Patient Package Insert ▾
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 7/2025 PATIENT INFORMATION ZOKINVY ® (ZO-kinvy) (lonafarnib) capsules, for oral use What is ZOKINVY?
ZOKINVY is a prescription medicine used to: lower the risk of death in adults and children 12 months of age or older with Hutchinson-Gilford Progeria Syndrome (HGPS), who have a certain body surface area. treat adults and children 12 months of age or older with certain types of Progeroid Laminopathies, who have a certain body surface area. ZOKINVY is not for use in people with non-HGPS Progeroid Syndromes or with Progeroid Laminopathies that are processing-proficient. It is not known if ZOKINVY is safe and effective in children under 12 months of age.
Do not take ZOKINVY if you are taking: a strong CYP3A inhibitor a strong or moderate CYP3A inducer midazolam lovastatin, simvastatin, or atorvastatin Ask your healthcare provider if you are not sure if your medicine may be one that is listed above. Before taking ZOKINVY, tell your healthcare provider about all of your medical conditions, including if you: have a history of QTc interval prolongation or other abnormal heartbeat. have slow heartbeat. have low magnesium levels or low potassium levels. have kidney problems. have eye problems. are pregnant or plan to become pregnant.
ZOKINVY can harm your unborn baby. Females who are able to become pregnant should use effective birth control (contraception) during treatment with ZOKINVY. are breastfeeding or plan to breastfeed. It is not known if ZOKINVY can pass into your breast milk.
Talk to your healthcare provider about the best way to feed your baby during treatment with ZOKINVY. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking ZOKINVY with certain other medicines may affect how the other medicines work and other medicines may affect how ZOKINVY works, and may increase your risk of side effects, including a heart rhythm problem called QTc interval prolongation.
Especially tell your healthcare provider if you take any other medicines that may cause QTc interval prolongation. Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when starting a new medicine.
How should I take ZOKINVY? Take ZOKINVY exactly as your healthcare provider tells you to. Do not stop taking ZOKINVY without talking to your healthcare provider.
Your healthcare provider may change your dose of ZOKINVY if needed. Your healthcare provider will prescribe your dose of ZOKINVY based on your body size (height and weight). Take ZOKINVY 2 times a day with morning and evening meals.
Swallow ZOKINVY capsules whole with an adequate amount of water. Do not chew ZOKINVY capsules. If you or your child cannot swallow the ZOKINVY capsule whole, see the detailed Instructions for Use that comes with ZOKINVY for information about how to prepare and give or take a dose of ZOKINVY by mixing the contents of a ZOKINVY capsule with either Ora Blend SF, Ora-Plus, orange juice, or applesauce.
Each dose of ZOKINVY mixture must be prepared fresh and taken within about 10 minutes of mixing. Do not take ZOKINVY with any juice that contains grapefruit or Seville oranges. Seville oranges may also be called bitter or sour oranges.
If you miss a dose of ZOKINVY, take it as soon as possible up to 8 hours before your next scheduled dose with food. If it is less than 8 hours before your next dose of ZOKINVY, skip the missed dose and take ZOKINVY at your next regularly scheduled dose. What are the possible side effects of ZOKINVY?
ZOKINVY may cause serious side effects, including: A serious heart rhythm problem called QTc Interval Prolongation. This condition can cause an abnormal heartbeat in people who take ZOKINVY and may lead to death. Your healthcare provider should check your heart and do blood tests before and during treatment with ZOKINVY.… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
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: Sentynl Therapeutics, Inc., 420 Stevens Ave., Suite 200 Solana Beach, CA 92075 ©2024 Sentynl Therapeutics, Inc. Revised: 7/2025 Figure Figure Figure Figure Figure Figure Figure Figure
📄 Recent Major Changes ▾
Dosage and Administration ( 2.2 ) 3/2024 Warnings and Precautions ( 5.1 ) 3/2024
📄 Package Label / Principal Display Panel ▾
Principal Display Panel - 50 mg Carton Label NDC 42358-450-30 Zokinvy (lonafarnib) capsules 50 mg 30 capsules Rx only Principal Display Panel - 50 mg Carton Label
Principal Display Panel - 50 mg Bottle Label NDC 42358-450-30 Zokinvy (lonafarnib) capsules 5 0 mg Rx only 30 capsules Principal Display Panel - 50 mg Bottle Label
Principal Display Panel - 75 mg Carton Label NDC 42358-475-30 Zokinvy (lonafarnib) capsules 75 mg 30 capsules Rx only Principal Display Panel - 75 mg Carton Label
Principal Display Panel - 75 mg Bottle Label NDC 42358-475-30 Zokinvy (lonafarnib) capsules 75 mg Rx only 30 capsules Principal Display Panel - 75 mg Bottle Label
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| NDC identity (package / product / labeler codes) | ✓ Available |
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| Active ingredient / dosage form / route | ✓ Available |
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| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
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| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |