Drug Interactions between aluminum hydroxide and taletrectinib

Citrate, or citric acid, can increase the absorption of aluminum hydroxide. This may lead to elevated blood levels of aluminum, particularly in individuals with reduced kidney function, since aluminum is primarily eliminated by the kidneys. Excess aluminum may deposit and cause problems in various tissues including bone, brain, heart, liver, muscles, and spleen. Over time, weak bones, bone pain, fractures, skeletal deformity, brain disorders, and anemia may develop. Talk to your doctor before using aluminum hydroxide if you have kidney impairment or are on hemodialysis. You should avoid or limit the consumption of citrate-containing foods and beverages (e.G., soft drinks, citrus fruits, fruit juices) during treatment with aluminum hydroxide. Be aware that some effervescent and dispersible drug formulations may also contain citrate and should be restricted as well. Even if you do not have kidney problems, it may be best to separate the dosing of aluminum hydroxide and citrate-containing products by 2 to 3 hours. Talk to a healthcare professional if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

When aluminum hydroxide is taken during enteral nutrition therapy (tube feeding), the tube may get clogged. Therefore, aluminum hydroxide should not be mixed with or given after high-protein tube feedings. The dose should be separated from the feeding by as much as possible, and the tube should be thoroughly flushed before administration of the dose.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of taletrectinib. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. In a clinical study, taletrectinib peak plasma concentration (Cmax) increased by 1.8-fold and systemic exposure (AUC) increased by 3.3-fold following concomitant administration of itraconazole, a potent CYP450 3A inhibitor. According to the product labeling, administration of taletrectinib with a moderate CYP450 3A inhibitor is predicted to increase taletrectinib Cmax and AUC by up to 1.5- and 2.6-fold, respectively. Increased exposure to taletrectinib may increase the risk and/or severity of adverse effects such as hepatotoxicity with liver enzyme elevations, lung toxicities, QT prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, and skeletal fractures.

ADJUST DOSING INTERVAL: Coadministration with high-fat food (1000 calories, 50% fat) increased taletrectinib Cmax and AUC by 1.5-fold, and the predicted increase in the QTc interval is 20.5 msec.

MANAGEMENT: The manufacturer recommends avoiding food or drink containing grapefruit during treatment with taletrectinib. In addition, taletrectinib should be administered on an empty stomach at about the same time each day, at least 2 hours before or 2 hours after food intake.