Drug Interactions between pazopanib and Tuinal

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of pazopanib, which is primarily metabolized by the isoenzyme. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: The use of pazopanib in combination with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided. Alternative treatment lacking CYP450 3A4-inducing activity should be considered in patients receiving pazopanib; otherwise, pazopanib should not be used. Other known CYP450 3A4 inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, dabrafenib, efavirenz, nafcillin, nevirapine, somatrem, somatropin, and various other anticonvulsants, although the extent to which they may interact with pazopanib is unknown.

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of pazopanib, which is primarily metabolized by the isoenzyme. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: The use of pazopanib in combination with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided. Alternative treatment lacking CYP450 3A4-inducing activity should be considered in patients receiving pazopanib; otherwise, pazopanib should not be used. Other known CYP450 3A4 inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, dabrafenib, efavirenz, nafcillin, nevirapine, somatrem, somatropin, and various other anticonvulsants, although the extent to which they may interact with pazopanib is unknown.