Overview

1. Name of the medicinal product

• XALKORI® (Crizotinib) hard capsules, 200 mg and 250 mg

2. Qualitative and quantitative composition

• Each capsule contains 200 mg or 250 mg of crizotinib

3. Pharmaceutical form

• Hard capsule, for oral use

4. Clinical particulars

• Therapeutic indications

  • Treatment of adults with advanced non-small cell lung cancer (NSCLC) that is ALK-positive or ROS1-positive

  • Treatment of paediatric patients (≥6 years) and adolescents with relapsed/refractory ALK-positive anaplastic large cell lymphoma (ALCL)

  • Treatment of paediatric patients and adolescents with relapsed/refractory ALK-positive inflammatory myofibroblastic tumour (IMT). keytruda-infusion

• Posology and method of administration

  • Adults: 250 mg twice daily orally, with or without food

  • Children: dose based on body surface area (BSA), according to paediatric dosing guidelines

  • Dose modifications may be required for toxicity, hepatic or renal impairment

• Contraindications

  • Hypersensitivity to crizotinib or any excipient

• Special warnings and precautions

  • Hepatotoxicity (monitor liver function tests)

  • Interstitial lung disease/pneumonitis

  • QT interval prolongation and bradycardia

  • Visual disturbances

  • Risk of embryo-foetal toxicity; contraception required

5. Pharmacological properties

• Mechanism of action

  • Crizotinib is a selective, ATP-competitive small-molecule inhibitor of the receptor tyrosine kinases ALK, ROS1, and MET

  • In ALK- or ROS1-positive tumours, inhibition leads to decreased proliferation and survival of cancer cells

• Pharmacokinetics

  • Oral bioavailability: ~43%

  • Protein binding: ~90%

  • Metabolism: primarily CYP3A4/5

  • Half-life: ~42 hours

  • Elimination: mainly via faeces (63%), urine (22%)

6. Undesirable effects

• Very common: visual disorders, nausea, vomiting, diarrhoea, constipation, oedema, elevated transaminases, fatigue, decreased appetite

• Common: neutropenia, anaemia, dizziness, neuropathy, interstitial lung disease

7. Drug interactions

• CYP3A inhibitors increase crizotinib exposure

• CYP3A inducers decrease crizotinib levels

• Caution with CYP3A substrates with narrow therapeutic range

This is the official-style SmPC description in English, summarised from the EMA/UK MHRA documents.tramadol-uk