Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Mirati Therapeutics B.V., Locatellikade 1, 1076 AZ Amsterdam, Netherlands
KRAZATI as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and disease progression after at least one prior systemic therapy.
Treatment with KRAZATI should be initiated by a physician experienced in the use of anti-cancer medicinal products.
The presence of a KRAS G12C mutation must be confirmed using a validated test prior to initiation of therapy with KRAZATI.
The recommended dose of KRAZATI is 600 mg (three 200 mg tablets) twice daily.
Treatment with KRAZATI is recommended until disease progression or unacceptable toxicity.
Patients should be advised that if less than 4 hours have passed since the scheduled time of dosing, the patient should take the dose as normal. If a dose is missed by more than 4 hours, the dose should be skipped, and dosing should resume at the next scheduled dose. If vomiting occurs after taking a dose, patients should be advised not to take an additional dose. The next dose should be taken as prescribed.
The recommended dose reduction levels for the management of adverse reactions are outlined in Table 1.
Table 1. Recommended dose reduction levels for adverse reactions:
| Dose reduction level | Reduced dosage |
|---|---|
| First dose reduction | Two 200 mg tablets (400 mg) twice daily |
| Second dose reduction | Three 200 mg tablets (600 mg) once daily |
The recommended dose modifications for adverse reactions are provided in Table 2. Severe (e.g., Grade 3) or intolerable adverse reactions require interruption of KRAZATI until sufficient improvement is observed before dosing is resumed.
Table 2. Recommended dosage modifications for adverse reactions:
| Adverse reaction | Severitya | Treatment modification |
|---|---|---|
| Nausea or vomiting despite appropriate supportive care (including anti-emetic therapy) | Grade 3 or 4 | Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline Resume KRAZATI at the next lower dose level |
| Diarrhoea despite appropriate supportive care (including anti-diarrhoeal therapy) | Grade 3 or 4 | Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline Resume KRAZATI at the next lower dose level |
| Hepatotoxicity | Grade 2 AST or ALT (3 to 5 times the ULN) | Decrease KRAZATI to the next lower level |
| Grade 3 or 4 AST or ALT (>5 times the ULN) | Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline Resume KRAZATI at the next lower dose level | |
| AST or ALT >3 × ULN with total bilirubin >2 × ULN in the absence of alternative causes | Permanently discontinue KRAZATI | |
| QTc Prolongation | Grade 3 (QTc ≥501 ms or >60 ms change from baseline) | Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline Resume KRAZATI at the next lower dose level |
| Grade 4 (ventricular arrhythmia) | Permanently discontinue KRAZATI | |
| Other adverse reactions | Grade 3 or 4 | Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline Resume KRAZATI at the next lower dose level |
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal
a Grading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
No clinically relevant difference was observed among patients older and younger than 65 years of age. There are limited safety and efficacy data in patients 75 years or older. No dose adjustment is recommended (see Special populations in section 4.8).
No clinically significant differences in the pharmacokinetics of adagrasib are expected in patients with mild to severe hepatic impairment (Child-Pugh classes A to C). No dose adjustment is recommended in patients with mild, moderate, or severe hepatic impairment (see section 5.2).
No dose adjustment is recommended in patients with mild, moderate, or severe renal impairment (see section 5.2).
The safety and efficacy of adagrasib in children aged 0 to 18 years have not been established. No data are available (see section 5.1).
KRAZATI is for oral use. The tablets can be taken with or without food and should be swallowed whole with water. Administration with food may improve tolerability.
Patients may disperse tablets in 120 mL of non-carbonated, room-temperature water, without crushing them. Other liquids must not be used. Patients should stir until the tablets are dispersed and drink immediately. The appearance of the mixture may be white with small pieces of the tablets that should not be chewed. The container must be rinsed with an additional 120 mL of water, which should be taken immediately.
In case of overdose, treatment should be interrupted, and general supportive measures initiated as appropriate. There is no specific antidote or treatment for adagrasib overdose.
2 years.
This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture.
Keep the bottle tightly closed.
Each carton contains one white opaque HDPE bottle with a white, child resistant polypropylene closure and an aluminium foil heat induction seal. Each HDPE bottle contains two 1 g of silica gel desiccant containers.
Pack sizes: bottles with 120 and 180 film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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