COMETRIQ Capsule Ref.[27457] Active ingredients: Cabozantinib

2.1 Recommended Dosage

Do NOT substitute COMETRIQ capsules with cabozantinib tablets.

The recommended daily dose of COMETRIQ is 140 mg once daily without food until disease progression or unacceptable toxicity. Instruct patients not to eat for at least 2 hours before and at least 1 hour after taking COMETRIQ.

Swallow COMETRIQ capsules whole. Do not open COMETRIQ capsules.

Do not take a missed dose within 12 hours of the next dose.

Do not ingest foods (e.g., grapefruit, grapefruit juice) or nutritional supplements that are known to inhibit cytochrome P450 while taking COMETRIQ.

2.2 Dosage Modifications for Adverse Reactions

Withhold COMETRIQ for NCI CTCAE Grade 4 hematologic adverse reactions, Grade 3 or greater non-hematologic adverse reactions, intolerable Grade 2 adverse reactions, or osteonecrosis of the jaw.

Upon resolution/improvement of the adverse reaction (i.e., return to baseline or resolution to Grade 1), reduce the dose as follows:

• If previously receiving 140 mg daily dose, resume treatment at 100 mg daily
• If previously receiving 100 mg daily dose, resume treatment at 60 mg daily
• If previously receiving 60 mg daily dose, resume at 60 mg if tolerated, otherwise, discontinue COMETRIQ

Permanently discontinue COMETRIQ for any of the following:

• development of gastrointestinal (GI) perforation or Grade 4 fistula
• severe hemorrhage
• acute myocardial infarction or arterial or venous thromboembolic events that require medical intervention
• nephrotic syndrome
• severe hypertension that cannot be controlled with anti-hypertensive therapy or hypertensive crisis
• reversible posterior leukoencephalopathy syndrome

2.3 Dosage Modifications For Coadministration With Strong CYP3A4 Inhibitors

Reduce the daily COMETRIQ dose by 40 mg (for example, from 140 mg to 100 mg daily or from 100 mg to 60 mg daily). Resume the dose that was used prior to initiating the CYP3A4 inhibitor 2 to 3 days after discontinuation of the strong inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

2.4 Dosage Modifications For Coadministration With Strong CYP3A4 Inducers

Increase the daily COMETRIQ dose by 40 mg (for example, from 140 mg to 180 mg daily or from 100 mg to 140 mg daily) as tolerated. Resume the dose that was used prior to initiating the CYP3A4 inducer 2 to 3 days after discontinuation of the strong inducer. The daily dose of COMETRIQ should not exceed 180 mg [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for Patients with Hepatic Impairment

The recommended starting dose of COMETRIQ for patients with mild to moderate hepatic impairment is 80 mg [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

One case of overdosage was reported in a patient who inadvertently took twice the intended dose (200 mg daily) for nine days. The patient suffered Grade 3 memory impairment, Grade 3 mental status changes, Grade 3 cognitive disturbance, Grade 2 weight loss, and Grade 1 increase in BUN. The extent of recovery was not documented.

Store COMETRIQ at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].