Skip to main content

Drug Interactions between fexofenadine and tolvaptan

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

fexofenadine tolvaptan

Applies to: fexofenadine and tolvaptan

MONITOR: Coadministration with tolvaptan may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to inhibition of P-glycoprotein-mediated drug efflux in the intestine, liver, and/or kidney by tolvaptan. When the P-gp probe substrate digoxin (0.25 mg once daily for 12 days) was coadministered with tolvaptan (60 mg once daily on days 8 to 12), digoxin peak concentration (Cmax) and systemic exposure (AUC) increased by 30% and 20%, respectively, compared to administration alone. Digoxin had no significant effect on the pharmacokinetics of tolvaptan, which is also a P-gp substrate.

MANAGEMENT: Caution is advised when tolvaptan is prescribed with drugs that are P-gp substrates, particularly those with a narrow therapeutic range such as digoxin and dabigatran etexilate. Alternatives should be considered whenever possible. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate following the initiation or discontinuation of tolvaptan. The prescribing information for the coadministered drug should be consulted for specific dosing recommendations.

References (4)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc
  4. (2020) "Product Information. Jynarque (tolvaptan)." Otsuka American Pharmaceuticals Inc

Drug and food interactions

Moderate

fexofenadine food

Applies to: fexofenadine

GENERALLY AVOID: Coadministration with large amounts of certain fruit juices, including grapefruit, orange and apple, may decrease the oral bioavailability of fexofenadine. The proposed mechanism is inhibition of drug efflux via intestinal organic anion transporting polypeptides (e.g., P-glycoprotein), of which fexofenadine is a substrate. In a five-way crossover study with 10 healthy volunteers, 1/4-strength grapefruit juice, grapefruit juice, orange juice and apple juice (300 mL with drug administration and 150 mL every 1/2 hour for up to 3 hours, total volume 1.2 L) reduced the mean area under the plasma concentration-time curve (AUC) of a 120 mg dose of fexofenadine by 23%, 67%, 72% and 77%, respectively, compared to water. Mean peak plasma concentration (Cmax) was similarly affected. The clinical significance of these changes is unknown. However, results from studies using histamine-induced skin wheals and flares found that the size of wheal and flare was significantly larger when fexofenadine was administered with either grapefruit or orange juices compared to water.

MANAGEMENT: To maximize plasma levels and therapeutic effects, fexofenadine should be taken with water. In addition, patients should refrain from consuming large amounts of grapefruit, orange, or apple juice.

References (2)
  1. Bailey DG, Dresser GK, Munoz C, Freemar DJ, Kim RB (2001) "Reduction of fexofenadine bioavailability by fruit juices." Clin Pharmacol Ther, 69, PI-82
  2. Dresser GK, Bailey DG, Leake BF, et al. (2002) "Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine." Clin Pharmacol Ther, 71, p. 11-20
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)
  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

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