Rozlytrek Dosage/Direction for Use

General: Patient Selection: Solid Tumors: A validated assay is required for the selection of patients with NTRK fusion-positive locally advanced or metastatic solid tumors. NTRK fusion-positive status should be established prior to initiation of ROZLYTREK therapy.
NSCLC: A validated assay is required for the selection of patients with ROS1-positive locally advanced or metastatic NSCLC. ROS1-positive status should be established prior to initiation of ROZLYTREK therapy.
Dosage: ROZLYTREK hard capsules can be taken with or without food, swallowed whole and must not be opened or dissolved.
Adults: The recommended dose of ROZLYTREK for adults is 600 mg given orally, once daily (see PHARMACOLOGY: Pharmacokinetics under Actions).
Pediatric patients: The recommended dose of ROZLYTREK for pediatric patients who have the ability to swallow capsules is 300 mg/m² orally, once daily (see Table 9). (See PHARMACOLOGY: Pharmacokinetics under Actions.) (See Table 9.)

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Duration of Treatment: It is recommended that patients are treated with ROZLYTREK until disease progression or unacceptable toxicity.
Delayed or Missed Doses: If a planned dose of ROZLYTREK is missed, patients can make up that dose unless the next dose is due within 12 hours. If vomiting occurs immediately after taking a dose of ROZLYTREK, patients may repeat that dose.
Dose Modifications: Management of adverse events may require temporary interruption, dose reduction, or discontinuation of treatment with ROZLYTREK, based on the prescriber's assessment of the patient's safety or tolerability.
Adults: For adults, the dose of ROZLYTREK may be reduced up to 2 times, based on tolerability. Table 10 provides general dose reduction advice for adult patients. ROZLYTREK treatment should be permanently discontinued if patients are unable to tolerate a dose of 200 mg once daily. (See Table 10.)

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Pediatric Patients: Table 11 provides specific dose reduction advice for pediatric patients. For pediatric patients, the dose of ROZLYTREK may be reduced up to 2 times, based on tolerability.
For some patients an intermittent dosing schedule is required to achieve the recommended reduced total weekly pediatric dose. ROZLYTREK treatment should be permanently discontinued if patients are unable to tolerate the lowest reduced dose. (See Table 11.)

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Dose Modifications for Specific Adverse Reactions: Recommendations for ROZLYTREK dose modifications for adults and pediatric patients for specific adverse reactions are provided in Table 12. (See Precautions and Adverse Reactions.) (See Table 12.)

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Dose Modifications for Specific Drug Interactions: Concomitant strong or moderate CYP3A inhibitors: Adults: The concomitant use of strong or moderate CYP3A inhibitors and ROZLYTREK in adults should be avoided or limited to 14 days or less. If concomitant use of strong or moderate CYP3A inhibitors cannot be avoided, ROZLYTREK dose should be reduced to 100 mg once daily for use with strong CYP3A inhibitors and to 200 mg once daily for use with moderate CYP3A inhibitors.
After discontinuation of the concomitant strong or moderate CYP3A inhibitors, ROZLYTREK dose that was taken prior to initiating the strong or moderate CYP3A inhibitor can be resumed. A wash out period may be required for CYP3A4 inhibitors with long half-life. (See Interactions.)
Pediatric patients: The concomitant use of strong or moderate CYP3A inhibitors in pediatric patients should be avoided. (See Interactions.)
Concomitant CYP3A inducers: Co-administration of ROZLYTREK with CYP3A inducers in adult and pediatric patients should be avoided. (See Interactions.)
Special Dosage Instructions: Pediatric use: Pediatric patients must have the ability to swallow whole ROZLYTREK capsules. Dosage for patients is based on body surface area (mg/m²) with a maximum daily dose of 600 mg (see Table 9 as previously shown for pediatric dosing).
Geriatric use: No dose adjustment of ROZLYTREK is required in patients ≥ 65 years of age. (See PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.)
Renal Impairment: No dose adjustment is required in patients with mild or moderate renal impairment. The safety and efficacy of ROZLYTREK have not been studied in patients with severe renal impairment. However, since entrectinib elimination via the kidney is negligible, no dose adjustment is required in patients with severe renal impairment. (See Precautions and PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.)
Hepatic Impairment: No dose adjustment is required in patients with underlying mild, moderate or severe hepatic impairment based on a study in subjects with hepatic impairment. (See Precautions and PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.)
Other Special Patient Populations: Ethnicity: No dose adjustment is necessary for patients of different ethnicities (see PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).