Cabozantinib Tablets: Adverse Reaction Dose Modifications
1. Renal Cell Carcinoma (RCC)
(1) Elective surgery: Withhold treatment for at least 28 days before scheduled surgery (including dental procedures).
(2) Adverse reactions (Grade 4, Grade 3, or intolerable Grade 2) or ONJ: Withhold until improved to baseline or resolved to Grade 1; then reduce dose as follows: from 60 mg/day to 40 mg/day; from 40 mg/day to 20 mg/day; if already on 20 mg/day, no further reduction is possible; resume at 20 mg/day if tolerated, or discontinue.
(3) Concomitant use with strong CYP3A4 inhibitors: Not recommended. If co‑administration is necessary, reduce the cabozantinib dose by 20 mg (e.g., from 60 mg/day to 40 mg/day). After discontinuation of the strong CYP3A4 inhibitor for 2‑3 days, resume the dose used before co‑administration.
(4) Concomitant use with strong CYP3A4 inducers: Not recommended if alternative therapy is available. If co‑administration is necessary, increase the cabozantinib dose by 20 mg (e.g., from 60 mg/day to 80 mg/day) as tolerated. After discontinuation of the strong CYP3A4 inducer for 2‑3 days, resume the dose used before co‑administration. The daily dose should not exceed 80 mg.
(5) Indications for permanent discontinuation: Uncontrollable fistula or gastrointestinal perforation, severe hemorrhage, arterial thromboembolic events (e.g., myocardial infarction, cerebral infarction), hypertensive crisis or severe hypertension despite optimal medical therapy, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome (RPLS).
2. Thyroid Cancer (DTC) – Adults and Children
(1) Adverse reactions (Grade 4, Grade 3, or intolerable Grade 2): Withhold until improved to baseline or resolved to Grade 1; then reduce dose as follows:
(2) For adult and pediatric patients with BSA ≥ 1.2 m², from 60 mg/day to 40 mg/day; if already on 20 mg every other day, no further reduction is possible; resume at 20 mg every other day if tolerated, or discontinue.
(3) For pediatric patients with BSA < 1.2 m², from 40 mg/day to 20 mg/day; if already on 20 mg every other day, no further reduction is possible; resume at 20 mg every other day if tolerated, or discontinue.
3. RCC in Combination with Nivolumab
(1) Elective surgery: Withhold treatment for at least 3 weeks before scheduled surgery (including dental procedures).
(2) Adverse reactions (Grade 4, Grade 3, or intolerable Grade 2) or ONJ: Withhold until improved to baseline or resolved to Grade 1; then reduce dose as follows: from 40 mg/day to 20 mg/day; from 20 mg/day to 20 mg every other day; if already on 20 mg every other day, no further reduction is possible; resume at 20 mg every other day if tolerated, or discontinue.
(3) Concomitant use with strong CYP3A4 inhibitors: Not recommended. If co‑administration is necessary, reduce the cabozantinib dose by 20 mg (e.g., from 60 mg/day to 40 mg/day). After discontinuation of the strong CYP3A4 inhibitor for 2‑3 days, resume the dose used before co‑administration.
(4) Concomitant use with strong CYP3A4 inducers: Not recommended if alternative therapy is available. If co‑administration is necessary, increase the cabozantinib dose by 20 mg (e.g., from 60 mg/day to 80 mg/day) as tolerated. After discontinuation of the strong CYP3A4 inducer for 2‑3 days, resume the dose used before co‑administration. The daily dose should not exceed 80 mg.
(5) Indications for permanent discontinuation (of cabozantinib): Gastrointestinal perforation or Grade 4 fistula, severe hemorrhage, acute myocardial infarction or arterial/venous thromboembolic events requiring medical intervention, severe hypertension or hypertensive crisis uncontrolled by antihypertensive therapy, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome (RPLS).
Cabozantinib Precautions
1. Special Populations
Safety and efficacy in patients under 12 years of age have not been established.
2. Dialysis
Data are not yet available.
