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Drug Interactions between Orkambi and Ranexa

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

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Interactions between your drugs

Major

ranolazine lumacaftor

Applies to: Ranexa (ranolazine) and Orkambi (ivacaftor / lumacaftor)

CONTRAINDICATED: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ranolazine, which is primarily metabolized by the isoenzyme. In pharmacokinetic studies, the potent inducer rifampin (600 mg once a day) has been shown to reduce the plasma concentrations of ranolazine (1000 mg twice a day) by approximately 95%. No data are available for other CYP450 3A4 inducers.

MANAGEMENT: The manufacturer considers the use of ranolazine to be contraindicated in patients taking potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort. The extent to which other, less potent CYP450 3A4 inducers may interact with ranolazine is unknown. Caution is advised if they are used with ranolazine.

References

  1. "Product Information. Ranexa (ranolazine)." Calmoseptine Inc (2006):

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Moderate

ranolazine ivacaftor

Applies to: Ranexa (ranolazine) and Orkambi (ivacaftor / lumacaftor)

MONITOR: Coadministration with inhibitors of the P-glycoprotein (P-gp) efflux transporter may increase the oral bioavailability of ranolazine, which has been shown in vitro to be a substrate of P-gp. Ranolazine can prolong the QT interval in a dose-dependent manner, thus increased plasma levels may potentiate the risk of ventricular arrhythmias including ventricular fibrillation and torsade de pointes. However, the interaction has not been evaluated in pharmacokinetic studies. Plasma levels of ranolazine (750 mg twice a day) were increased about 2-fold by the CYP450 3A4 and P-gp inhibitor, verapamil (120 mg three times a day), although the extent to which P-gp inhibition actually contributes to the overall interaction is unknown.

MANAGEMENT: Caution is advised if ranolazine is prescribed in combination with P-gp inhibitors. Pharmacologic response to ranolazine should be monitored more closely whenever a P-gp inhibitor is added to or withdrawn from therapy, and the ranolazine dosage adjusted as necessary. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References

  1. "Product Information. Ranexa (ranolazine)." Calmoseptine Inc (2006):

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Drug and food interactions

Major

ranolazine food

Applies to: Ranexa (ranolazine)

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.

References

  1. "Product Information. Ranexa (ranolazine)." Calmoseptine Inc (2006):

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Moderate

ivacaftor food

Applies to: Orkambi (ivacaftor / lumacaftor)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals (2012):
  2. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):
  3. "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals (2022):
  4. "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (2019):
View all 4 references

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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.

See also

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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.

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