Entrectinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of entrectinib.
Drugs List
Therapeutic Indications
Uses
Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion +ve solid tumours
ROS1-positive advanced non-small cell lung cancer (NSCLC)
Monotherapy treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, and who have no satisfactory treatment options.
Monotherapy treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.
Dosage
Adults
600mg once daily.
Children
Children aged 12 years and older
300mg per metre squared body surface area (BSA).
BSA between 1.11 metres squared to 1.50 metres squared
400mg once daily.
BSA greater than or equal to 1.51 metres squared
600mg once daily.
Additional Dosage Information
Dose reduction in adult patients
Recommended dose: 600mg once daily.
First dose reduction: 400mg once daily.
Second dose reduction: 200mg once daily.
Dose reduction in paediatric patients
BSA of 1.11 to 1.50 metres squared
Recommended dose: 400mg once daily.
First dose reduction: 300mg once daily.
Second dose reduction: 200mg once daily, for 5 days each week.
BSA equal to or greater than 1.51 metres squared
Recommended dose: 600mg once daily.
First dose reduction: 400mg once daily.
Second dose reduction: 200mg once daily, for 5 days each week.
Delayed or missed doses
If a dose is missed, patients can take the missed dose unless the next dose is due within 12 hours. If vomiting occurs immediately after taking a dose, patients may repeat that dose.
Dose modifications for adverse reactions
Congestive heart failure
Symptomatic with middle to moderate activity or exertion, including where intervention is indicated (Grade 2 or 3) - Withhold until recovered to less than or equal to Grade 1, then resume at reduced dose.
Severe with symptoms at rest, minimal activity, or exertion or where intervention is indicated (Grade 4) - Withhold until recovered to less than or equal to Grade 1, then resume at reduced dose or discontinue as clinically appropriate.
Cognitive disorders
Intolerable, but moderate changes interfering with activities of daily living (Intolerable Grade 2) - Withhold until recovery to less than or equal to Grade 1 or baseline, then resume at same dose or reduced dose as clinically needed.
Severe changes limiting activities of daily living (Grade 3) - Withhold until recovery to less than or equal to Grade 1 or baseline, then resume at reduced dose.
Urgent intervention indicated for event (Grade 4) - Discontinue as clinically appropriate.
Hyperuricaemia
Symptomatic or Grade 4 - Initiate urate lowering medication and withhold until improvement of signs or symptoms, then resume at same dose or reduced dose.
QT interval prolongation
QTc from 481 to 500 ms - Withhold until QTc interval recovers to baseline, then resume at same dose.
QTc greater than 500 ms - Withhold until QTc interval recovers to baseline. Then resume at same dose if factors that cause QT prolongation are identified and corrected or resume at reduced dose if other factors that cause QT prolongation are not identified.
Torsade de pointes, polymorphic ventricular tachycardia, signs/symptoms of serious arrhythmia - Permanently discontinue.
Transaminase elevations
Grade 3 - Withhold until recovery to less than or equal to Grade 1 or to baseline, then resume at same dose if resolution occurs within 4 weeks, or permanently discontinue if the Grade 3 transaminase elevations do not resolve within 4 weeks.
Recurrent Grade 3 - Withhold until recovery to less than or equal to Grade 1 or to baseline, then resume at reduced dose if resolution occurs within 4 weeks.
Grade 4 - Withhold until recovery to less than or equal to Grade 1 or to baseline, then resume at same dose if resolution occurs within 4 weeks, or permanently discontinue if the Grade 4 transaminase elevations do not resolve within 4 weeks.
Recurrent Grade 4 - Permanently discontinue.
ALT/AST greater than 3 times ULN with concurrent total bilirubin greater than 2 times ULN (in the absence of cholestasis or haemolysis) - Permanently discontinue.
Anaemia or neutropenia
Grade 3 or 4 - Withhold until recovery to less than or equal to Grade 2 or baseline, then resume at the same dose or reduced dose, as clinically needed.
Other adverse reactions
Grade 3 or 4 - Withhold until recovery to less than or equal to Grade 1 or to baseline, then resume at same dose or reduced dose if resolution occurs within 4 weeks. Consider permanently discontinuation if the Grade 3 or 4 adverse reactions do not resolve within 4 weeks.
Recurrent Grade 4 - Permanently discontinue.
Contraindications
Children under 12 years
Breastfeeding
Galactosaemia
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
History of treatment with anthracyclines
Bradyarrhythmia
Congestive cardiac failure
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Lactose intolerance
Moderate hepatic impairment
QT interval greater than 450 milliseconds
Recent myocardial infarction
Severe cardiac disorder
Severe renal impairment
Unstable angina
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Confirm positive NTRK gene fusion status of tumour prior to treatment
Confirm ROS1-positive status prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Contains sunset yellow (E110) - may cause allergic reaction
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Evaluate LVEF before each treatment if cardiomyopathy suspected
Exclude pregnancy prior to initiation of treatment
Perform ECG before and during treatment
Monitor for impaired motor &/or cognitive function especially in elderly
Monitor patients for signs and symptoms of cardiac failure
Monitor serum electrolytes
Monitor uric acid levels
Advise patient to report bone pain, pain in extremities or fractures
Consider treatments to prevent hyperuricaemia
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Advise patient to seek advice at first indications of pregnancy
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if Torsade de Pointes should occur during treatment
Interrupt treatment if QTc exceeds 500msec and consider dose modification
Suspend treatment and/or reduce dose if grade 3 or greater neutropenia
Suspend treatment if grade 3 or greater adverse reaction occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Advise patient to avoid Seville (sour) orange products
Female: Contraception required during and for 5 weeks after treatment
Male & female: Two methods of contraception required (including barrier)
Male: Contraception required during and for 3 months after treatment
Pregnancy and Lactation
Pregnancy
Entrectinib is contraindicated during pregnancy.
The manufacturer recommends that entrectinib is not used during pregnancy and in women of childbearing potential not using contraception. There are no available data form the use of entrectinib in pregnant women, however, based on animal studies, entrectinib may cause foetal harm when administered to pregnant women.
Lactation
Entrectinib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with entrectinib. Its is unknown whether entrectinib or its metabolites are excreted in human milk, therefore a risk to the breast-fed child cannot be excluded.
Side Effects
Abdominal pain
Anaemia
Anxiety
Arthralgia
Asthenia
Ataxia
Blurred vision
Changes in mood
Cognitive impairment
Confusion
Congestive cardiac failure
Constipation
Cough
Decreased appetite
Dehydration
Delirium
Depression
Diarrhoea
Disturbance of fluid balance
Dizziness
Dysaesthesia
Dysgeusia
Dysphagia
Dyspnoea
Fatigue
Fractures
Headache
Hyperuricaemia
Hypotension
Impaired memory
Increase in serum ALT/AST
Lung infection
Muscle weakness
Myalgia
Nausea
Neutropenia
Oedema
Pain
Peripheral oedema
Peripheral sensory neuropathy
Photosensitivity
Pleural effusion
Prolongation of QT interval
Psychiatric disorders
Pulmonary oedema
Pyrexia
Rash
Serum creatinine increased
Sleep disturbances
Somnolence
Syncope
Tumour lysis syndrome
Urinary retention
Urinary tract infections
Vertigo
Vomiting
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2020
Reference Sources
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 July 2021
Summary of Product Characteristics: Rozlytrek 100mg hard capsules. Roche Products Limited. Revised June 2021.
Summary of Product Characteristics: Rozlytrek 200mg hard capsules. Roche Products Limited. Revised June 2021.
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