Ceritinib

Patients taking strong CYP3A inhibitors: Reduce dose by approx ¹/₃ (rounded to the nearest multiple of the 150 mg dosage strength); may increase dose gradually based on patient's response and tolerability. Resume ceritinib to its original dose once the strong CYP3A inhibitor is discontinued. Refer to specific product guidelines.

Severe (Child-Pugh class C): Reduce dose by approx ¹/₃ (rounded to the nearest multiple of the 150 mg dosage strength).

Ceritinib Should be taken with food.

Patient with pre-existing bradycardia, history of or predisposition for QT prolongation, electrolyte disturbances or diabetes mellitus. Avoid in patients with congenital long QT syndrome. Severe renal and hepatic impairment. Pregnancy and lactation. Concomitant use with strong CYP3A inhibitors.

Significant: Bradycardia; severe gastrointestinal toxicity (e.g. diarrhoea, vomiting, nausea); hepatotoxicity, hyperglycaemia, photosensitivity, increased lipase and/or amylase.
Blood and lymphatic system disorders: Anaemia.
Cardiac disorders: Pericarditis.
Eye disorders: Vision disorders.
Gastrointestinal disorders: Constipation, oesophageal disorder, abdominal pain.
General disorders and administration site conditions: Fatigue.
Investigations: Decreased weight, increased blood creatinine; abnormal LFTs.
Metabolism and nutrition disorders: Decreased appetite, hypophosphataemia.
Renal and urinary disorders: Renal failure or impairment.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Pancreatitis, interstitial lung disease, pneumonitis; QT prolongation leading to increased risk of ventricular tachyarrhythmias (e.g. torsades de pointes).

PO: Z (Generally not recommended.)

This drug may cause fatigue and visual disturbances, if affected, do not drive or operate machinery. Avoid prolonged exposure to sunlight; wear sunscreen or protective clothing when going outdoors. Women of childbearing potential and men with partners who could become pregnant must use effective birth control methods during therapy and for 6 months (in women) or for 3 months (in men) after stopping the treatment.

Obtain pregnancy test prior to treatment initiation. Confirm ALK-positive status before therapy. Monitor renal function, liver function (e.g. ALT, AST, total bilirubin), lipase, amylase, fasting blood glucose, electrolytes, blood pressure and heart rate. Perform cardiac monitoring (e.g. ECG). Assess for signs and symptoms of gastrointestinal or pulmonary toxicity and pancreatitis.

Increased risk of bradycardia with β-blockers, non-dihydropyridine calcium channel blockers, clonidine and digoxin. Increased serum concentration with strong CYP3A inhibitors (e.g. ketoconazole, ritonavir, telithromycin, itraconazole, nefazodone) and P-gp inhibitors. Decreased serum concentration with strong CYP3A inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin). May decrease bioavailability with acid-reducing agents (e.g. PPIs, H₂-receptor antagonists, antacids) and P-gp inducers. May increase serum concentration of CYP3A substrates (e.g. alfuzosin, amiodarone, cisapride, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quetiapine, quinidine, lovastatin, simvastatin, sildenafil, midazolam, triazolam, tacrolimus, alfentanil, sirolimus), CYP2C9 substrates (e.g. warfarin), BCRP substrates (e.g. rosuvastatin, topotecan, sulfasalazine) and P-gp substrates (e.g. digoxin, dabigatran, colchicine, pravastatin). Increased risk of QT prolongation with class I antiarrhythmics (e.g. quinidine, procainamide, disopyramide), class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide) or other drugs that have QT prolongation effects (e.g. domperidone, droperidol, chloroquine, clarithromycin, haloperidol, methadone, cisapride, moxifloxacin).

Increased systemic exposure with food. Increased serum concentration with grapefruit and grapefruit juice. Decreased serum concentration with St. John's wort.

Description:
Overview: Ceritinib, an antineoplastic agent, is a tyrosine kinase inhibitor which targets anaplastic lymphoma kinase (ALK), insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR) and c-ros oncogene 1 (ROS1). Among these, it is most active against ALK, acting as a highly selective and potent inhibitor of this kinase.
Mechanism of Action: Ceritinib inhibits ALK, a tyrosine kinase involved in the pathogenesis of non-small cell lung carcinoma. It prevents ALK autophosphorylation, ALK-mediated phosphorylation of the downstream signalling protein signal transducer and activator of transcription 3 (STAT3), and proliferation of ALK-dependent cancer cells.
Pharmacodynamics: In vitro studies have shown that ceritinib suppressed the proliferation of cell lines that expressed echinoderm microtubule-associated protein-like 4 (EML4)-ALK and nucleophosmin (NPM)-ALK fusion proteins.

In cardiac electrophysiology, the pharmacokinetic/pharmacodynamic analysis has demonstrated a concentration-dependent QT interval prolongation.
Pharmacokinetics:
Absorption: Increased systemic exposure with food. Time to peak plasma concentration: Approx 4-6 hours.
Distribution: Plasma protein binding: Approx 97%.
Metabolism: Metabolised mainly in the liver by CYP3A isoenzymes.
Excretion: Via faeces (approx 92%; 68% as unchanged drug); urine (approx 1%). Elimination half-life: 41 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 57379345, Ceritinib. https://pubchem.ncbi.nlm.nih.gov/compound/Ceritinib. Accessed Oct. 27, 2025.

Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01ED02 - ceritinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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Zykadia 150 mg Hard Capsules (Novartis Pharmaceuticals UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/10/2025.

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