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Rozlytrek is a brand name for Entrectinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Neurotrophic tyrosine receptor kinase (NTRK) gene fusion Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients older than 1 month with solid tumours that have a NTRK gene fusion, • who have a disease that is locally advanced, metastatic or where surgical resection is likely to result…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Rozlytrek should be initiated by a physician experienced in the use of anticancer medicinal products. Patient selection NTRK gene fusion A validated assay is required for the selection of patients with NTRK gene fusion-positive solid tumours.
1). ROS1 gene fusion A validated assay is required for the selection of adult patients with ROS1-positive NSCLC. 1). Posology Rozlytrek is available as hard capsules or film-coated granules. The physician should prescribe the most appropriate pharmaceutical form according to the dose required and patient needs.
• Whole capsules are recommended for patients who can swallow whole capsules and where the required dose is 100 mg or a multiple of 100 mg. , gastric or nasogastric) may receive treatment with Rozlytrek capsules administered as an oral suspension.
6. • Rozlytrek film-coated granules are recommended for paediatric patients who have difficulty, or are unable, to swallow capsules but can swallow soft food and where the required dose is 50 mg or a multiple of 50 mg. Film-coated granules should be sprinkled on soft food.
Refer to the Rozlytrek film-coated granules SmPC for prescribing information. Adults The recommended dose for adults is 600 mg entrectinib once daily. 4 Paediatric population Paediatric population > 6 months of age The recommended dose for paediatric patients > 6 months of age is based on body surface area (BSA) (see Table 1).
Patients who have difficulty or are unable to swallow capsules but can swallow soft food, may receive treatment with Rozlytrek film-coated granules. Refer to the Rozlytrek film-coated granules SmPC for prescribing information. 51 m2 600 mg *BSA categories and recommended dosing in Table 1 are based on closely matching exposures to a target dose of 300 mg/m2 **To enable dosing increments of 10 mg, capsules prepared as an oral suspension may be used.
6. Paediatric patients > 1 month to ≤ 6 months of age The recommended dose for paediatric patients > 1 month to ≤ 6 months of age is 250 mg/m2 BSA entrectinib once daily, using capsules prepared as an oral suspension. Capsules administered as an oral suspension (oral or enteral use) enable dosing increments of 10 mg.
6. 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.
Summary of the safety profile The most common adverse reactions (≥20%) were fatigue, constipation, diarrhoea, dizziness, dysgeusia, oedema, increased weight, anaemia, increased blood creatinine, nausea, dysaesthesia, pain, vomiting, pyrexia, arthralgia, increased aspartate aminotransferase and dyspnoea, cognitive disorders, cough, and increased alanine aminotransferase.
5%). 0% of patients. Tabulated list of adverse reactions Table 4 summarises the adverse drug reactions (ADRs) occurring in 762 adult and 91 paediatric patients treated with Rozlytrek in three clinical trials in adults (ALKA, STARTRK-1, and STARTRK-2) and one clinical trial in paediatric patients (STARTRK-NG) and one clinical trial in adult and paediatric patients (TAPISTRY).
6 months. Table 5 includes paediatric patients from three clinical studies; STARTRK-NG, STARTRK-2 and TAPISTRY. 1 months. Paediatric data in the description of selected adverse reactions reflect exposure to Rozlytrek in this expanded paediatric safety population (n=91).
The safety profile observed in the expanded paediatric population was consistent with the known paediatric safety profile from the integrated safety population in Table 4 below. Adverse drug reactions are listed by MedDRA system organ class.
The following categories of frequency have been used: very common ≥1/10, common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000). Within each system organ class, the adverse reactions are presented in order of decreasing frequency.
9 * Grades 3 to 5, inclusive of fatal adverse reactions (including 4 reactions of pneumonia, 3 reactions of dyspnoea, 1 reaction of cardiac failure, and 1 reaction of tumour lysis syndrome). 1 Lung infection (bronchitis, lower respiratory tract infection, lung infection, pneumonia, respiratory tract infection, upper respiratory tract infection) 2 Neutropenia (neutropenia, neutrophil count decreased) 3 Dizziness (dizziness, vertigo, dizziness postural) 4 Dysaesthesia (paresthesia, hyperesthesia, hypoesthesia, dysesthesia) 5 Cognitive disorders (cognitive disorder, confusional state, memory impairment, disturbance in attention, amnesia, mental status changes, hallucination, delirium, disorientation, brain fog, attention deficit hyperactivity disorder, ‘visual hallucination’,‘auditory hallucination’, mental impairment, mental disorder) 6 Periphery sensory neuropathy (neuralgia, neuropathy peripheral, peripheral motor neuropathy, peripheral sensory neuropathy) 7 Ataxia (ataxia, balance disorder, gait disturbances) 8 Sleep disturbances (hypersomnia, insomnia, sleep disorder, somnolence) 9 Mood disorders (anxiety, affect lability, affective disorder, agitation, depressed mood, euphoric mood, mood altered, mood swings, irritability, depression, persistent depressive disorder, psychomotor retardation) 10 Vision blurred (diplopia, vision blurred, visual impairment) 11 Congestive heart failure (acute right ventricular failure, cardiac failure, cardiac failure congestive, chronic right ventricular failure, ejection fraction decreased, pulmonary oedema) 12 Hypotension (hypotension, orthostatic hypotension) 13 Rash (rash, rash maculopapular, rash pruritic, rash erythematous, rash papular) 14 Fractures (acetabulum […]
Efficacy across tumour types The benefit of Rozlytrek has been established in single-arm trials encompassing a relatively small sample of patients whose tumours exhibit NTRK gene fusions. Favourable effects of Rozlytrek have been shown based on overall response rate and response duration in a limited number of tumour types.
1). , for which clinical benefit has not been established, or where such treatment options have been exhausted). 8). Patients over the age of 65 years experienced a higher incidence of these events than younger patients. Patients should be monitored for signs of cognitive changes.
2. Patients should be counselled on the potential for cognitive changes with Rozlytrek treatment. 7). 8). Bone fractures mostly occurred in paediatric patients less than 12 years of age and were localised in the lower extremity (with a predilection for femur, tibia, foot, and fibula).
In both adult and paediatric patients, some fractures occurred in the setting of a fall or other trauma to the affected area. Fourteen paediatric patients had more than one occurrence of a fracture. 8). Five paediatric patients had Rozlytrek treatment interrupted due to a fracture.
Six paediatric patients discontinued treatment due to fractures. , pain, abnormal gait, changes in mobility, deformity) should be evaluated promptly. Hyperuricemia Hyperuricemia has been observed in patients treated with entrectinib.
Serum uric acid levels should be assessed prior to initiating Rozlytrek and periodically during treatment. Patients should be monitored for signs and symptoms of hyperuricemia. Treatment with urate-lowering medicinal products should be initiated as clinically indicated and Rozlytrek withheld for signs and symptoms of hyperuricemia.
2. 8). 0% of those patients upon institution of appropriate clinical management and/or Rozlytrek dose reduction/interruption. For patients with symptoms or known risk factors of CHF, left ventricular ejection fraction (LVEF) should be assessed prior to initiation of Rozlytrek treatment.
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For whole capsules, if vomiting occurs immediately after taking a dose of Rozlytrek, patients may repeat that dose. , caregivers or parents) and partial or total vomiting/spitting occurs immediately after taking an administered dose, caregivers should consult the healthcare professional for the next steps.
Dose modifications Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with Rozlytrek, in case of specified adverse reactions (see Table 3) or based on the prescriber’s assessment of the patient’s safety or tolerability.
5 Adults For adults, the dose of Rozlytrek may be reduced up to 2 times, based on tolerability (see Table 2). Rozlytrek treatment should be permanently discontinued if patients are unable to tolerate a dose of 200 mg once daily. Paediatric population For paediatric patients older than 1 month, the dose of Rozlytrek may be reduced up to 2 times, based on tolerability (see Table 2).
Table 2:
Dose reduction schedule for adult and paediatric patients Starting dose once daily First dose reduction Second dose reduction Permanently discontinue Rozlytrek in patients who are unable to tolerate Rozlytrek after two dose reductions.
250 mg/m2 Reduce the once daily dose to two thirds of the starting dose* Reduce the once daily dose to one third of the starting dose* 100 mg 50 mg or 100 mg once daily, according to schedule** 50 mg once daily 200 mg 150 mg once daily 100 mg once daily 300 mg 200 mg once daily 100 mg once daily 400 mg 300 mg once daily 200 mg once daily 600 mg 400 mg once daily 200 mg once daily *To enable dosing increments of 10 mg, capsules prepared as an oral suspension may be used.
6. **Monday (100 mg), Tuesday (50 mg), Wednesday (100 mg), Thursday (50 mg), Friday (100 mg), Saturday (50 mg), and Sunday (100 mg). 8).
Table 3:
Recommended Rozlytrek dose modifications for adverse reactions in adult and paediatric patients Adverse reaction Severity* Dosage modification Congestive heart failure Symptomatic with middle to moderate activity or exertion, including where intervention is indicated (Grade 2 or 3) • Withhold Rozlytrek until recovered to less than or equal to Grade 1 • Resume at reduced dose Severe with symptoms at rest, minimal activity, or exertion or where intervention is indicated (Grade 4) • Withhold Rozlytrek […]
Patients receiving Rozlytrek should be carefully monitored and those with clinical signs and symptoms of CHF, including shortness of breath or oedema, should be evaluated and treated as clinically appropriate. 2. 8). Use of Rozlytrek should be avoided in patients with a baseline QTc interval longer than 450 ms, in patients with congenital long QTc syndrome, and in patients taking medicinal products that are known to prolong the QTc interval.
Rozlytrek should be avoided in patients with electrolyte imbalances or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias. If, in the opinion of the treating physician, the potential benefits of Rozlytrek in a patient with any of these conditions outweigh the potential risks, additional monitoring should be performed and a specialist consultation should be considered.
Assessment of ECG and electrolytes at baseline and after 1 month of treatment with Rozlytrek are recommended. Periodic monitoring of ECGs and electrolytes as clinically indicated throughout Rozlytrek treatment, are also recommended.
2. Women of childbearing potential Rozlytrek may cause foetal harm when administered to a pregnant woman. Women of childbearing potential must use highly effective contraception methods during treatment and up to 5 weeks after the last dose of Rozlytrek.
3). 5), which could increase the frequency or severity of adverse reactions. Co-administration of Rozlytrek with a strong or moderate CYP3A inhibitor should be avoided. 2). During treatment with Rozlytrek, the consumption of grapefruit, grapefruit products, and Seville oranges should be avoided.
5), which may reduce efficacy of […]