Zokinvy (lonafarnib)

Zokinvy (lonafarnib) is a farnesyltransferase inhibitor indicated in patients 12 months of age and older with a body surface area of 0.39 m2 and above to reduce risk of mortality in Hutchinson-Gilford Progeria Syndrome; and for treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations.

Zokinvy (lonafarnib) is used to reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome. It also blocks the production of the protein Progerin, which may be responsible for the process of premature aging that characterizes the syndrome.

Side effects of Zokinvy include:

• vomiting,
• diarrhea,
• infection,
• nausea,
• decreased appetite,
• fatigue,
• upper respiratory tract infection,
• abdominal pain,
• musculoskeletal pain,
• electrolyte abnormalities,
• weight loss,
• headache,
• myelosuppression,
• increased aspartate aminotransferase,
• decreased blood bicarbonate,
• cough,
• high blood pressure (hypertension), and
• increased alanine aminotransferase

Recommended Dosage

• The starting dosage of Zokinvy for patients with a BSA of 0.39 m² and above is 115 mg/m² twice daily with morning and evening meals (see Table 1) to reduce the risk of gastrointestinal adverse reactions. An appropriate dosage strength of Zokinvy is not available for patients with a BSA of less than 0.39 m².
• After 4 months of treatment, increase the dosage to 150 mg/m² 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 remains 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/m² twice daily.

Table 1: Recommended Dosage and Administration for 115 mg/m² Body Surface Area-Based Dosing

Table 2: Recommended Dosage and Administration for 150 mg/m² Body Surface Area-Based Dosing

Table 2 provides the BSA-based dosage recommendations for the dosage of 150 mg/m² twice daily.

Dosage Modifications For Gastrointestinal Adverse Reactions

• For patients who have increased their dose of Zokinvy to 150 mg/m² twice daily and are experiencing repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss, Zokinvy can be dose reduced to the starting dose of 115 mg/m² twice daily (see Table 1).
• Ensure Zokinvy is taken with the morning and evening meals and with an adequate amount of water.

Dosage Modifications For Drug Interactions

CYP3A Inhibitors

If concomitant use of Zokinvy with a weak CYP3A inhibitor is unavoidable:

• Reduce to or continue Zokinvy at the starting dosage of 115 mg/m² twice daily (see Table 1).
• Resume the previous Zokinvy dosage 14 days after discontinuing the concomitant use of the weak CYP3A inhibitor.

Temporary Discontinuation For Midazolam Use

• Temporarily discontinue Zokinvy for 10 to 14 days before and 2 days after administration of midazolam.

Preparation And Administration Instructions

• Administer Zokinvy orally with the morning and evening meals.

Patients Able To Swallow Capsules

• Administer Zokinvy capsules whole with a sufficient amount of water. Do not chew the capsules.

Patients Unable To Swallow Capsules

• The entire contents of Zokinvy capsules can be mixed with Ora Blend SF or Ora-Plus or, for patients unable to access or tolerate Ora Blend SF or Ora-Plus, the contents of Zokinvy capsules can be mixed with orange juice or applesauce (see preparation instructions below).
• Do not mix with juice containing grapefruit or Seville oranges.
• The mixture must be prepared fresh for each dose and taken within approximately 10 minutes of mixing.

Preparation of Dose in Ora Blend SF, Ora-Plus, or Orange Juice

1. For each capsule, empty contents of the capsule into a container containing 5 mL to 10 mL of the liquid.
2. Mix thoroughly with a spoon.
3. Consume entire serving.

Preparation of Dose in Applesauce

1. For each capsule, empty contents of the capsule into a container containing 1 teaspoonful to 2 teaspoonfuls of applesauce.
2. Mix thoroughly with a spoon.
3. Consume entire serving.

Effect Of Other Drugs On Zokinvy

Table 4 presents clinically significant drug interactions involving drugs that affect Zokinvy.

Table 4: Clinically Significant Drug Interactions (Drugs that Affect Zokinvy)

Zokinvy’s Effect On Other Drugs

Table 5 presents clinically significant drug interactions involving drugs affected by Zokinvy.

Table 5: Clinically Significant Drug Interactions (Drugs Affected by Zokinvy)

• 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.
• 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.