Ceritinib

Oral
Metastatic non-small cell lung carcinoma

Patient taking CYP3A inhibitors: Reduce dose by approx ¹/₃, resume to usual dose upon discontinuation of treatment.

Severe: Not recommended.

Severe (Child-Pugh class C): Reduce by approx ¹/₃.

Should be taken with food. Take at the same time each day.

Congenital long QT syndrome. Concomitant use with β-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin, strong CYP3A inducers.

Patient with cardiac diseases, bradycardia, predisposition for QTc prolongation, bradyarrhythmia, electrolyte abnormalities, diabetes mellitus. Severe renal and hepatic impairment. Pregnancy and lactation. Concomitant use with QT prolonging drugs (e.g. pimozide, thioridazine).

Significant: Bradycardia, gastrointestinal toxicity (e.g. diarrhoea, nausea, vomiting, abdominal pain), hyperglycaemia, hepatotoxicity, QTc interval prolongation, increased ALT/AST, blood creatinine, increased serum amylase and lipase.
Blood and lymphatic system disorders: Anemia, neutropenia, thrombocytopenia.
Cardiac disorders: Pericardial effusion, pericarditis.
Eye disorders: Vision impairment, blurred vision, decreased visual acuity, accommodation disorder, presbyopia, photopsia, vitreous floaters.
Gastrointestinal disorders: Constipation, dyspepsia, GERD, dysphagia.
General disorders and administration site conditions: Fatigue, asthenia, pyrexia, fever.
Investigations: Weight loss, hypophosphataemia, increased gamma-glutamyl transferase, decreased serum phosphate, increased serum alkaline phosphatase and bilirubin, increased serum creatinine.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Non-cardiac chest pain, back, limb, musculoskeletal pain.
Nervous system disorders: Headache, dizziness, neuropathy.
Renal and urinary disorders: Azotaemia, renal impairment, injury or failure.
Respiratory, thoracic and mediastinal disorders: Cough, pleural effusion, respiratory tract infection.
Skin and subcutaneous tissue disorders: Rash, maculo-papular rash, dermatitis acneiform, pruritus.
Potentially Fatal: Bradycardia, interstitial lung disease/pneumonitis. Rarely, pancreatitis.

PO: D

This drug may cause fatigue, dizziness or eye disorders, if affected, do not drive or operate machinery.

Establish ALK positivity and correct electrolyte abnormalities prior to initiation of treatment. Monitor renal function and LFT (including ALT, AST, total bilirubin) at baseline and monthly during therapy; fasting blood glucose, serum amylase and lipase levels, blood pressure, cardiac function (e.g. heart rate, QTc interval) periodically; signs and symptoms of pancreatitis, and gastrointestinal and pulmonary toxicities.

Increased risk of QTc prolongation with antiarrhythmics (e.g. quinidine). Enhanced hyperglycaemic effect with corticosteroids. Increased exposure with strong CYP3A inhibitors (e.g. ketoconazole, ritonavir, telithromycin, nefazodone). Decreased exposure with strong CYP3A inducer (e.g. carbamazepine, phenobarbital, rifampicin). May decrease bioavailability with proton pump inhibitors, H₂-receptor antagonists, antacids. May increase serum concentration of CYP3A substrates (e.g. ciclosporin, ergotamine, fentanyl, pimozide), CYP2C9 substrates (e.g. phenytoin, warfarin).
Potentially Fatal: Increased risk of bradycardia with β-blockers, non-dihydropyridine calcium channel blockers (e.g. diltiazem), clonidine, digoxin.

Food increases exposure. Increased exposure with grapefruit or grapefruit juice. Decreased exposure with St. John’s wort.

Description:
Mechanism of Action: Ceritinib is a selective and potent inhibitor of anaplastic lymphoma kinase (ALK), a tyrosine kinase involved in the pathogenesis of non-small cell lung carcinoma. It prevents autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signalling protein and decreases proliferation of ALK-dependent cancer cells.
Pharmacokinetics:
Absorption: Food increases exposure. Time to peak plasma concentration: Approx 4-6 hours.
Distribution: Volume of distribution: 4,230 L. Plasma protein binding: Approx 97%.
Metabolism: Metabolised in the liver by CYP3A via mono-oxygenation, O-dealkylation, N-formylation; further metabolised via glucuronidation and dehydrogenation.
Excretion: Mainly via faeces (approx 92%; 68% as unchanged drug); urine (approx 1%). Elimination half-life: 31-41 hours.

Source: National Center for Biotechnology Information. PubChem Database. Ceritinib, CID=57379345, https://pubchem.ncbi.nlm.nih.gov/compound/Ceritinib (accessed on Jan. 21, 2020)

Store at 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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Anon. Ceritinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/04/2018.

Buckingham R (ed). Ceritinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/04/2018.

Joint Formulary Committee. Ceritinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/04/2018.

Zykadia Capsule (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/04/2018.