entrectinib: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
entrectinib: clinical details
Prescribing considerations
- Initiation should be by a clinician experienced in anticancer treatment.
- Confirm NTRK or ROS1 status with a validated assay before treatment.
- For NTRK fusion-positive tumours, confirm the absence of prior NTRK-inhibitor treatment and satisfactory alternatives.
- Review cardiac history, cognition, fracture risk, hepatic and renal function, concomitant medicines and pregnancy potential.
Contraindications and cautions
- Hypersensitivity to entrectinib or any excipient.
- Avoid where possible with baseline QTc above 450 milliseconds, congenital long-QT syndrome, significant electrolyte disturbance, major cardiac disease or other QT-prolonging medicines.
- Contains lactose; it is unsuitable for specified rare hereditary disorders of galactose metabolism or absorption.
- Severe renal impairment has not been studied; severe hepatic impairment requires close monitoring.
- The orange capsule contains sunset yellow FCF, which may cause allergic reactions.
Monitoring
- ECG and electrolytes at baseline, early after starting treatment and periodically according to clinical risk.
- Serum uric acid before treatment and periodically thereafter.
- Assess left ventricular ejection fraction before treatment in patients with symptoms or risk factors for heart failure.
- Monitor for cognitive change, dizziness, ataxia, syncope, neuropathy and visual disturbance.
- Promptly investigate bone pain, altered gait, reduced mobility or deformity.
- Monitor hepatic function and adverse effects closely in severe hepatic impairment; check haematology and biochemical tests according to toxicity and clinical status.
Clinical pharmacology
Entrectinib inhibits TRKA, TRKB, TRKC, ROS1 and ALK kinases. CYP3A4 is its principal metabolic pathway and produces the active metabolite M5; entrectinib and M5 are highly protein-bound.
Formulation and product differences
- The selected products are hard capsules that must be swallowed intact.
- Both capsule presentations contain lactose.
- The orange capsule contains sunset yellow FCF; the yellow capsule does not.
- Store in the original package with the bottle tightly closed to protect from moisture.
entrectinib preparations and strengths
Capsule
Route: Oral
Strengths: 100 mg, 200 mg
entrectinib interactions
The oncology team should review prescription, over-the-counter and herbal products before treatment and whenever they change.
Strong or moderate CYP3A inhibitors, including itraconazole, voriconazole, posaconazole, ketoconazole and some antiviral medicines
These can substantially increase entrectinib exposure and adverse effects, so combined use should usually be avoided.
CYP3A or P-glycoprotein inducers, including rifampicin, carbamazepine, phenytoin, phenobarbital and St John's wort
These can lower entrectinib exposure and reduce its anticancer effect, so combined use should be avoided.
Grapefruit products and Seville oranges
These may raise entrectinib concentrations and should be avoided.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.