Skip to main content

Drug Interactions between riociguat and tolvaptan

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

tolvaptan riociguat

Applies to: tolvaptan and riociguat

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 or moderate to potent inhibitors of P-glycoprotein (P-gp) or breast cancer resistant protein (BCRP) may increase the plasma concentrations of riociguat, which is partially metabolized by CYP450 3A and also a substrate of the P-gp and BCRP efflux transporters. Increased levels of riociguat may increase the risk for hypotension. When riociguat was administered with ketoconazole, a potent CYP450 3A4 inhibitor that also inhibits P-gp and BCRP, riociguat peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 1.5- and 2.5-fold, respectively. The Cmax and AUC of the active metabolite, M1, which has 1/3 to 1/10 the pharmacologic activity of riociguat, were reduced by approximately 50% and 25%, respectively. Administration with the potent CYP450 3A4 inhibitor clarithromycin increased the AUC of riociguat by about 30%. The Cmax and AUC of M1 were not significantly altered (i.e., <20% increase).

MANAGEMENT: Caution is advised when riociguat is prescribed with potent CYP450 3A4 inhibitors or moderate to potent P-gp or BCRP inhibitors. Patients should be monitored for signs and symptoms of hypotension, and the dosage of riociguat adjusted if necessary.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Adempas (riociguat)." Bayer Pharmaceutical Inc (2013):

Switch to consumer interaction data

Drug and food interactions

Moderate

tolvaptan food

Applies to: tolvaptan

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References

  1. "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc (2009):

Switch to consumer interaction data

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

Switch to consumer 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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer