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Drug Interactions between lonafarnib and Tyblume

This report displays the potential drug interactions for the following 2 drugs:

  • lonafarnib
  • Tyblume (ethinyl estradiol/levonorgestrel)

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Interactions between your drugs

Moderate

ethinyl estradiol lonafarnib

Applies to: Tyblume (ethinyl estradiol / levonorgestrel) and lonafarnib

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with lonafarnib may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Lonafarnib is a potent CYP450 3A time-dependent and mechanism-based inhibitor in vitro. When a single 3 mg oral dose of midazolam, a sensitive CYP450 3A4 substrate, was administered with lonafarnib (100 mg orally twice daily for 5 days) in healthy subjects, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 180% and 639%, respectively.

MANAGEMENT: Caution is advised when lonafarnib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lonafarnib is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information recommends avoiding concomitant use of lonafarnib and sensitive CYP450 3A4 substrates or substrates with narrow therapeutic ranges when possible. These drugs include, but are not limited to: alfentanil, cisapride, colchicine, cyclosporine, fentanyl, ivacaftor, lovastatin, simvastatin, oral midazolam, triazolam, pimozide, quinidine, sildenafil, ergot derivatives, macrolide immunosuppressants, and vinca alkaloids.

References

  1. "Product Information. Zokinvy (lonafarnib)." Eiger BioPharmaceuticals, Palo Alto, CA.
Moderate

levonorgestrel lonafarnib

Applies to: Tyblume (ethinyl estradiol / levonorgestrel) and lonafarnib

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with lonafarnib may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Lonafarnib is a potent CYP450 3A time-dependent and mechanism-based inhibitor in vitro. When a single 3 mg oral dose of midazolam, a sensitive CYP450 3A4 substrate, was administered with lonafarnib (100 mg orally twice daily for 5 days) in healthy subjects, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 180% and 639%, respectively.

MANAGEMENT: Caution is advised when lonafarnib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lonafarnib is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information recommends avoiding concomitant use of lonafarnib and sensitive CYP450 3A4 substrates or substrates with narrow therapeutic ranges when possible. These drugs include, but are not limited to: alfentanil, cisapride, colchicine, cyclosporine, fentanyl, ivacaftor, lovastatin, simvastatin, oral midazolam, triazolam, pimozide, quinidine, sildenafil, ergot derivatives, macrolide immunosuppressants, and vinca alkaloids.

References

  1. "Product Information. Zokinvy (lonafarnib)." Eiger BioPharmaceuticals, Palo Alto, CA.

Drug and food interactions

Major

lonafarnib food

Applies to: lonafarnib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lonafarnib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single 50 mg oral dose of lonafarnib was administered following pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 5 days) in healthy study subjects, lonafarnib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 270% and 425%, respectively, compared to lonafarnib administered alone. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to lonafarnib may increase the risk and/or severity of adverse effects such as nausea, vomiting, diarrhea, anorexia, electrolyte disturbances, liver enzyme elevations, myelosuppression, infection, and hypertension.

ADJUST DOSING INTERVAL: Food does not have clinically relevant effects on the oral bioavailability of lonafarnib. When a single 75 mg oral dose of lonafarnib was administered with a high-fat meal (952 calories; approximately 43% from fat) in healthy subjects, lonafarnib Cmax and AUC decreased by 55% and 29%, respectively, compared to administration under fasted conditions. When administered with a low-fat meal (421 calories; approximately 12% from fat), lonafarnib Cmax decreased by 25% and AUC decreased by 21% relative to fasting. However, administration with food may help improve gastrointestinal tolerance to lonafarnib, which may commonly cause nausea, vomiting, diarrhea, and abdominal pain.

MANAGEMENT: Lonafarnib should be administered with the morning and evening meals and an adequate amount of water. Patients should avoid consumption of grapefruit or grapefruit juice and Seville oranges (also known as bitter or sour oranges).during treatment with lonafarnib.

References

  1. "Product Information. Zokinvy (lonafarnib)." Eiger BioPharmaceuticals, Palo Alto, CA.
Moderate

levonorgestrel food

Applies to: Tyblume (ethinyl estradiol / levonorgestrel)

Grapefruit juice may increase the blood levels of certain medications such as levonorgestrel. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with levonorgestrel. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

Switch to professional interaction data

Minor

ethinyl estradiol food

Applies to: Tyblume (ethinyl estradiol / levonorgestrel)

Information for this minor interaction is only available at a professional reading level.

For clinical details see professional interaction data.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.