Interaction between Spironolactone and Pazopanib
Major
Absorption
| ID | DDInter1707 and DDInter1400 |
| Interaction | Coadministration with potent inhibitors of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) may significantly increase the plasma concentrations and risk of toxicity of pazopanib. The proposed mechanism involves inhibition of P-gp- or BCRP-mediated transporters of pazopanib metabolism. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib. |
| Management | Concomitant use of pazopanib with potent inhibitors of P-gp or BCRP should generally be avoided. Selection of an alternate concomitant medication with no or minimal potential to inhibit P-gp or BCRP should be considered. Patients should have liver function tests (ALT, AST, bilirubin), electrocardiograms, and serum electrolyte levels performed at baseline and regular intervals as recommended in the product labeling. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. In addition, they should seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope. |
| References | |
| Alternative for Spironolactone |
C03D
|
| Alternative for Pazopanib |
L01X
More
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.