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Drug Interactions between Epitol and riociguat

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

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Interactions between your drugs

Moderate

carBAMazepine riociguat

Applies to: Epitol (carbamazepine) and riociguat

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of riociguat, which is partially metabolized by the isoenzyme. According to the product labeling, administration of riociguat with the moderate CYP450 3A4 inducer bosentan resulted in an approximately 30% decrease in riociguat systemic exposure (AUC). The magnitude of interaction is expected to be greater with more potent inducers.

MANAGEMENT: The potential for diminished therapeutic effects of riociguat should be considered when prescribed in combination with CYP450 3A4 inducers. Patients should be closely monitored, and the dosage of riociguat adjusted as necessary. Data are not available to guide dosing of riociguat when coadministered with potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort. Alternative agents with no or minimal CYP450 3A4-inducing activity should be considered whenever possible.

References

  1. (2013) "Product Information. Adempas (riociguat)." Bayer Pharmaceutical Inc

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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Moderate

riociguat food

Applies to: riociguat

ADJUST DOSE: Smoking may decrease the plasma concentrations of riociguat. The proposed mechanism is induction of the CYP450 1A1-mediated metabolism of riociguat by polycyclic aromatic hydrocarbons present in cigarette smoke. CYP450 1A1 is responsible for the formation of the major active metabolite, M1, which has just 1/3 to 1/10 the pharmacologic activity of riociguat. According to the product labeling, plasma concentrations of riociguat are reduced by 50% to 60% in smokers compared to nonsmokers.

MANAGEMENT: Riociguat dosages higher than 2.5 mg three times a day may be considered in cigarette smokers, if tolerated, so as to match the exposure seen in nonsmoking patients. However, safety and effectiveness of higher dosages have not been established. A dosage reduction should be considered in patients who stop smoking during treatment with riociguat.

References

  1. (2013) "Product Information. Adempas (riociguat)." Bayer Pharmaceutical Inc

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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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