Rozlytrek^® (Capsules) Instructions for Use

Marketing Authorization Holder

F. Hoffmann-La Roche, Ltd (Switzerland)

Manufactured By

Catalent Greenville, Inc (USA)

ATC Code

L01EX14 (Entrectinib)

Active Substance

Entrectinib (Rec.INN registered by WHO)

Dosage Forms

	Rozlytrek®	Capsules 100 mg: 30 pcs.
		Capsules 200 mg: 90 pcs.

Dosage Form, Packaging, and Composition

Capsules size 2, yellow opaque body and cap; the capsule body is imprinted with the blue inscription “ENT 100”; capsule contents – powder or powder with lumps from white to almost white, pale pink or pale orange in color.

Excipients: anhydrous lactose, microcrystalline cellulose, tartaric acid, hypromellose, crospovidone, magnesium stearate, colloidal silicon dioxide.

Capsule shell composition: hypromellose, titanium dioxide (E171, CI77891), yellow iron oxide (E172, CI77492).
Ink composition for capsule imprint: shellac, propylene glycol, concentrated ammonia solution, FD&C Blue No. 2 aluminum lake.

30 pcs. – high-density polyethylene bottles (1) – cardboard packs with first-opening control (holographic sticker).

Capsules size 0, orange opaque body and cap; the capsule body is imprinted with the blue inscription “ENT 200”; capsule contents – powder or powder with lumps from white to almost white, pale pink or pale orange in color.

Excipients: anhydrous lactose, microcrystalline cellulose, tartaric acid, hypromellose, crospovidone, magnesium stearate, colloidal silicon dioxide.

Capsule shell composition: hypromellose, titanium dioxide (E171, CI77891), FD&C Yellow No. 6 (E110, CI15985).
Ink composition for capsule imprint: shellac, propylene glycol, concentrated ammonia solution, FD&C Blue No. 2 aluminum lake.

90 pcs. – high-density polyethylene bottles (1) – cardboard packs with first-opening control (holographic sticker).

Clinical-Pharmacological Group

Antitumor drug. Protein kinase inhibitor

Pharmacotherapeutic Group

Antineoplastic agents; protein kinase inhibitors; other protein kinase inhibitors

Pharmacological Action

Antitumor agent, protein kinase inhibitor.

It blocks the action of abnormal enzymes, the presence of which is due to changes in the neurotrophic receptor tyrosine kinase NTRK or ROS1 genes that encode these enzymes. Abnormal enzymes promote the growth of cancer cells. Entrectinib may slow or stop tumor growth and also helps to reduce tumor size.

Indications

In adults and children aged 12 years and older as monotherapy: solid tumors expressing the NTRK fusion gene, if the disease is locally advanced, metastatic, or if surgical resection is likely to result in severe complications; patients who have not previously received an NTRK inhibitor; patients who have no other treatment options.

As monotherapy in adults with ROS1-positive advanced non-small cell lung cancer (NSCLC) who have not previously been treated with an NTRK inhibitor.

ICD codes

Dosage Regimen

For oral administration. Take capsules once daily at the same time each day.

Swallow capsules whole with water. Do not chew, crush, or open capsules.

Take on an empty stomach. Do not eat for at least 2 hours before and at least 1 hour after taking the dose.

For adults, the recommended dose is 600 mg once daily.

Select the appropriate combination of 100 mg and 200 mg capsules to achieve the total 600 mg dose.

For children aged 12 years and older, the dose is based on body surface area (BSA). Calculate the dose using the formula: 600 mg multiplied by the patient’s BSA.

Administer the calculated dose once daily. The maximum daily dose must not exceed 600 mg.

Continue treatment until disease progression or unacceptable toxicity occurs.

In case of a missed dose, take it only if more than 12 hours remain before the next scheduled dose. If less than 12 hours remain, skip the missed dose and take the next dose at the regular time. Do not take a double dose to make up for a missed one.

Manage adverse reactions with dose modifications, which may include temporary interruption, dose reduction, or permanent discontinuation.

For management of specific adverse reactions, refer to the full prescribing information for detailed dose modification guidelines.

Adverse Reactions

From the cardiovascular system very common – manifestations of congestive heart failure (cough, shortness of breath and swelling of the arms and legs due to fluid retention); common – arrhythmia, QT interval prolongation on ECG, arterial hypotension.

From the nervous system very common – confusion, mood changes, memory impairment, hallucinations; common – dizziness, peripheral sensory neuropathy, headache, dysesthesia, ataxia, sleep disorder, mood disorders, syncope.

From the musculoskeletal system common – joint pain, bone pain, deformities, changes in mobility (these may be signs of fractures), pain including back pain, neck pain, musculoskeletal pain, limb pain, muscle weakness.

From the urinary system common – increased blood creatinine levels, urinary tract infection, incomplete bladder emptying.

From metabolism common – severe hyperuricemia, which can lead to impaired renal function and arthritis, weight gain, dehydration; uncommon – tumor lysis syndrome.

From the digestive system common – constipation, dysgeusia, diarrhea, nausea, vomiting, increased ALT and AST activity, decreased appetite, abdominal pain, dysphagia.

From the skin and subcutaneous tissues common – photosensitivity.

From the organ of vision common – blurred vision.

From the hematopoietic system common – anemia, neutropenia.

From the respiratory system common – shortness of breath, cough, lung infection, pleural effusion.

General reactions common – fatigue, edema, increased body temperature.

Contraindications

Hypersensitivity to entrectinib, children under 12 years of age, pregnancy, breastfeeding period.

With caution

History of memory loss, confusion, hallucinations, or altered consciousness; osteoporosis, osteopenia. Use of drugs to reduce uric acid levels in the blood, heart failure, current or history of QT interval prolongation on ECG, low levels of electrolytes in the blood (potassium, magnesium, calcium or phosphorus).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in hepatic impairment.

Use in Renal Impairment

Use with caution in renal impairment.

Pediatric Use

Do not use in children under 12 years of age.

Special Precautions

Effect on ability to drive vehicles and operate machinery

During treatment, in case of cognitive impairment, blurred vision, dizziness, fainting, the patient should not drive vehicles or operate machinery until the adverse reactions disappear. Consult your doctor or pharmacist about the possibility of driving vehicles and operating machinery.

Drug Interactions

Adverse reactions may develop with the concomitant use of entrectinib with the following drugs: ketoconazole, itraconazole, voriconazole, posaconazole; ritonavir or saquinavir; St. John’s wort preparations; phenytoin, carbamazepine or phenobarbital; rifampicin, rifabutin; topotecan, lapatinib, mitoxantrone, apalutamide, methotrexate; ergotamine; fentanyl; pimozide; quinidine; warfarin, dabigatran etexilate; cisapride, omeprazole; atorvastatin, pravastatin, rosuvastatin; sirolimus, tacrolimus, cyclosporine; paroxetine, fluvoxamine; repaglinide, tolbutamide; bosentan, felodipine, nifedipine, verapamil.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.