Drug Interactions between berotralstat and Jynarque
This report displays the potential drug interactions for the following 2 drugs:
- berotralstat
- Jynarque (tolvaptan)
Interactions between your drugs
tolvaptan berotralstat
Applies to: Jynarque (tolvaptan) and berotralstat
ADJUST DOSE: Coadministration of berotralstat with drugs that are both inhibitors of the efflux transporters P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) as well as substrates of the isoenzyme CYP450 3A4 may lead to an increase in the plasma concentrations and effects of both drugs. Berotralstat is a substrate of both P-gp and BCRP. Coadministration with potent P-gp and BCRP inhibitor cyclosporine increased berotralstat peak plasma concentration (Cmax) and total systemic drug exposure (AUC 0-inf) by 25% and 69%, respectively. Increased plasma concentrations of berotralstat may increase the risk of adverse effects, including the potential for QT prolongation. Berotralstat may cause concentration-dependent prolongation of the Fridericia-corrected QT interval (QTcF). A mean increase in the QTcF interval of 15.9 milliseconds has been reported at 3-times the recommended dose of berotralstat; however, berotralstat has not been shown to prolong the QT interval to any clinically relevant extent when administered at the recommended daily dose of 150 mg. In addition, berotralstat is considered a moderate CYP450 3A4 inhibitor and has been reported in drug interaction studies to increase the peak plasma concentration (Cmax) and systemic exposure (AUC) of sensitive CYP450 3A4 substrate midazolam by approximately 1.5-fold and 2.25-fold, respectively.
MANAGEMENT: The dosage of berotralstat should be reduced to 110 mg once daily in patients requiring chronic coadministration with drugs that are both inhibitors of P-gp or BCRP as well as substrates of CYP450 3A4, such as cyclosporine. Patients should be advised to contact their physician if they experience any undue adverse effects from their medications. Patients should seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope. In addition, the prescribing information for concomitant medications should be consulted and dosages adjusted as needed.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2021) "Product Information. Orladeyo (berotralstat)." BioCryst Pharmaceuticals Inc
Drug and food interactions
tolvaptan food
Applies to: Jynarque (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
- (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
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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