Cabozantinib-Specific Drugs and Foods
1. Antifungals, azoles (e.g., itraconazole, ketoconazole, voriconazole): Potent CYP3A4 inhibitors, may increase cabozantinib exposure. In healthy subjects, ketoconazole (400 mg daily for 27 days) increased single-dose cabozantinib (Cometriq) exposure by 38%. Avoid concomitant use. Cometriq: If concomitant use cannot be avoided, reduce the daily cabozantinib capsule dose by 40 mg. Cabometyx: If concomitant use cannot be avoided, reduce the daily cabozantinib tablet dose by 20 mg. After discontinuation of the potent CYP3A4 inhibitor for 2-3 days, resume the original dose.
2. Antimycobacterials, rifamycins (e.g., rifabutin, rifampin, rifapentine): May decrease cabozantinib exposure. In healthy subjects, rifampin (600 mg daily for 31 days) reduced single-dose cabozantinib (Cometriq) plasma exposure by 77%. If alternative therapy is available, avoid long-term concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
3. Antiretrovirals, HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir): May increase cabozantinib exposure. Avoid concomitant use. Cometriq: If concomitant use cannot be avoided, reduce the daily cabozantinib capsule dose by 40 mg. Cabometyx: If concomitant use cannot be avoided, reduce the daily cabozantinib tablet dose by 20 mg. After discontinuation of the potent CYP3A4 inhibitor for 2-3 days, resume the original dose.
4. Carbamazepine: May decrease cabozantinib exposure. If alternative therapy is available, avoid long-term concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
5. Dexamethasone: May decrease cabozantinib exposure. If alternative therapy is available, avoid long-term concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
6. Grapefruit or grapefruit juice: Grapefruit products inhibit CYP, including CYP3A4; may increase cabozantinib concentrations. Avoid concomitant use.
Macrolides (clarithromycin, telithromycin): May increase cabozantinib exposure. Avoid concomitant use. Cometriq: If concomitant use cannot be avoided, reduce the daily cabozantinib capsule dose by 40 mg. Cabometyx: If concomitant use cannot be avoided, reduce the daily cabozantinib tablet dose by 20 mg. After discontinuation of the potent CYP3A4 inhibitor for 2-3 days, resume the original dose.
7. Reduce the daily cabozantinib tablet dose by 20 mg. After discontinuation of the potent CYP3A4 inhibitor for 2-3 days, resume the original dose.
8. Phenobarbital: May decrease cabozantinib exposure. If alternative therapy is available, avoid long-term concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
9. Phenytoin: May decrease cabozantinib exposure. If alternative therapy is available, avoid long-term concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
10. Rosiglitazone: No effect on the plasma peak concentration and AUC of rosiglitazone (a CYP2C8 substrate); clinically important pharmacokinetic interactions are unlikely.
11. St. John's wort (Hypericum perforatum): May decrease cabozantinib exposure. If alternative therapy is available, avoid concomitant use of potent CYP3A4 inducers. Cometriq: If concomitant use cannot be avoided, increase the daily cabozantinib capsule dose by 40 mg based on tolerability; daily dose should not exceed 180 mg. Cabometyx: If concomitant use cannot be avoided, increase the daily cabozantinib tablet dose by 20 mg based on tolerability; daily dose should not exceed 80 mg. After discontinuation of the potent CYP3A4 inducer for 2-3 days, resume the original dose.
