Lonafarnib

Lonafarnib is a prescription medication used for the treatment of Hutchinson-Gilford's progeria syndrome and progeroid laminopathies.

• Lonafarnib is available under the following different brand names: Zokinvy.

Common side effects of Lonafarnib 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)
• increased alanine aminotransferase

Serious side effects of Lonafarnib include:

• headaches
• shortness of breath
• nosebleeds
• flushing
• dizziness
• chest pain
• vision changes
• watery, red, itchy eyes
• decreased urine output

Rare side effects of Lonafarnib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule

• 50 mg
• 75 mg

Hutchinson-Gilford progeria syndrome

Adult and pediatric dosage

• Initial: 115 mg/m2 orally two times a day with morning and evening meals.
• After 4 months: Increase to 150 mg/m2 orally two times a day.
• Round all total daily doses to the nearest 25-mg increment.

Progeroid laminopathies

Adult and pediatric dosage

• Initial: 115 mg/m2 orally two times a day with morning and evening meals
• After 4 months: Increase to 150 mg/m2 orally two times a day.
• Round all total daily doses to the nearest 25-mg increment.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Lonafarnib has severe interactions with at least 108 other drugs.
• Lonafarnib has serious interactions with at least 250 other drugs.
• Lonafarnib has moderate interactions with at least 94 other drugs.
• Lonafarnib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • ganaxolone

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• strong or moderate CYP3A inhibitors or inducers
• midazolam
• lovastatin, simvastatin, or atorvastatin

Effects of drug abuse

• none

Short-Term Effects

• See “What Are Side Effects Associated with Using Lonafarnib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lonafarnib?”

Cautions

• Laboratory abnormalities reported, including electrolyte abnormalities (eg, hyperkalemia, hypokalemia, hyponatremia, hypercalcemia), myelosuppression (eg, decreased ANC, WBC count, lymphocytes, hemoglobin, hematocrit), and increased liver enzymes; periodically monitor for these abnormalities and correct accordingly
• Nephrotoxicity observed in rats at plasma drug exposures like humans
• Retinal toxicity (rod-dependent, low-light vision decline) observed in monkeys at plasma drug exposures like humans
• Fertility impairment observed in female and male rats
• Based on animal reproduction studies, can cause embryofetal toxicity
• Drug interaction overview
  • CYP3A4 inhibitors
    • Lonafarnib is a sensitive substrate of CYP3A4
    • Strong or moderate inhibitors: Contraindicated
    • Weak inhibitors: If unable to avoid coadministration, reduce or continue Lonafarnib at the starting dose
  • CYP3A4 inducers
    • Lonafarnib is a sensitive substrate of CYP3A4
    • Strong or moderate: Contraindicated
  • CYP2C9 inhibitors
    • Lonafarnib is a CYP2C9 substrate
    • Coadministration may increase lonafarnib AUC and peak concentration.
    • Avoid coadministration with CYP2C9 inhibitors
    • If unavoidable, closely monitor patients for arrhythmias and events (eg, syncope, heart palpitations); the effect of increased Lonafarnib systemic exposure on the QT interval is unknown
  • CYP3A4 substrates
    • Lonafarnib is a strong CYP3A inhibitor
    • HMG CoA reductase inhibitors: Coadministration is contraindicated with lovastatin, simvastatin, or atorvastatin
    • Midazolam: Coadministration is contraindicated; temporarily discontinue Lonafarnib for 10-14 days before and 2 days after administration of midazolam
    • Loperamide: Loperamide is contraindicated in patients aged under 2 years; when Lonafarnib is coadministered with loperamide, do not exceed loperamide 1 mg once a day when first coadministered; slowly increase loperamide dosage with caution by its approved product labeling
    • Other sensitive CYP3A substrates: Avoid coadministration; if coadministration is unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose by their approved product labeling
    • Certain CYP3A substrates: If coadministered with certain CYP3A substrates where minimal concentration changes may lead to serious or life-threatening toxicities, monitor for adverse reactions, and reduce the CYP3A substrate dose by its approved product labeling
  • CYP2C19 substrates
    • Avoid coadministration
    • Lonafarnib may increase the AUC and peak concentration of CYP2C19 substrates.
    • If coadministration is unavoidable, monitor for adverse reactions and reduce the CYP2C19 substrate dose by its approved product labeling
  • P-gp substrates
    • Lonafarnib is a weak P-gp inhibitor
    • Monitor for adverse reactions if coadministered with P-gp substrates (eg, digoxin, dabigatran) where minimal concentration changes may lead to serious or life-threatening toxicities
    • Reduce the P-gp substrate dose by its approved product labeling

Pregnancy and Lactation

• Based on findings from animal studies, can cause embryofetal harm when administered to pregnant women
• Advise pregnant women of fetal risk
• Fertility
  • Fertility impairment observed in female and male rats
  • Advise women and men of the reproductive potential of the animal fertility findings.
  • The impact on pubertal development and the potential for impaired fertility in humans have not been adequately evaluated
• Lactation
  • Data are unavailable on the presence of the drug in human milk, its effects on breastfed infants or on milk production
  • Lonafarnib is excreted in rat milk; when a drug is present in animal milk, the drug will likely be present in human milk
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects of the breastfed infant from Lonafarnib or the underlying maternal condition