Ceritinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ceritinib.
Drugs List
Therapeutic Indications
Uses
Anaplastic lymphoma kinase (ALK)+ve advanced non-small cell lung cancer
First-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer.
Treatment of adult patients with anaplastic lymphoma kinase (ALK)- positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
450mg once daily with food at the same time each day.
Patients with concurrent medical condition and unable to take dose with food
No food should be eaten for at least 2 hours before and for 1 hour after dose.
If daily dose with food is 450mg, dose should be increased to 750mg, taken on an empty stomach.
If daily dose with food is 300mg, dose should be increased to 450mg, taken on an empty stomach.
If daily dose with food is 150mg, treatment should be discontinued.
Patients with Hepatic Impairment
Severe hepatic impairment
Reduce dose by one third to nearest 150mg dose regimen.
Additional Dosage Information
Missed doses
A missed dose may be taken unless the next dose is due within 12 hours. If vomiting occurs the next dose should be taken at the next scheduled time.
Severe or intolerable nausea, vomiting or diarrhoea despite treatment
Suspend treatment until improvement seen. Reinitiate at a dose reduced by 150mg.
ALT/AST elevations greater than 5 times the upper limit of normal (ULN) and total bilirubin less than or equal to 2 times ULN
Suspend treatment until recovery to baseline ALT/AST levels of less than or equal to 3 times ULN. Reinitiate at a dose reduced by 150mg.
ALT/AST elevations greater than 3 times ULN and total bilirubin greater than 2 times ULN (in the absence of cholestasis or haemolysis).
Discontinue ceritinib permanently.
QT corrected for heart rate (QTc) greater than 500msec on at least 2 separate ECGs
Suspend treatment until recovery to baseline or QTc is less than or equal to 480msec. Check and correct electrolytes. Reinitiate at a dose reduced by 150mg.
QTc greater than 500msec or QTc change of greater than 60 msec from baseline and torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia
Discontinue ceritinib permanently.
Persistent hyperglycaemia greater than 250mg/dl despite treatment
Suspend treatment until hyperglycaemia is well controlled, then reinitiate at a dose reduced by 150mg. If glucose control cannot be obtained, discontinue treatment with ceritinib permanently.
Grade 3 or greater elevations in lipase or amylase
Suspend treatment until lipase or amylase recovers to grade 1 or less. Reinitiate at a dose reduced by 150mg.
Treatment related interstitial lung disease (ILD)/pneumonitis
Discontinue ceritinib permanently.
Bradycardia
Symptomatic, may be severe and medically significant
Suspend treatment and evaluate concomitant medicinal products known to cause bradycardia and anti-hypertensive products.
If concomitant products are identified and dose adjusted or discontinued, resume treatment of ceritinib once symptoms have resolved to grade 1 or baseline or heart rate 60bpm or above.
If no concomitant products are identified or concomitant products are not discontinued or their doses not modified, resume treatment with dose reduced by 150mg once symptoms have resolved to grade 1 or baseline or heart rate of 60bpm or above.
Life threatening consequences, urgent intervention required
Discontinue permanently if no contributing concomitant medicinal products are identified.
If concomitant products are identified and dose adjusted or discontinued, resume treatment of ceritinib once symptoms have resolved to grade 1 or baseline or heart rate 60bpm or above with dose reduced by 150mg.
Contraindications
Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Elevated serum transaminases - greater than 5 times upper limit of normal
Family history of long QT syndrome
Bradycardia
Diabetes mellitus
Electrolyte imbalance
History of torsade de pointes
Hyperglycaemia
QTc interval greater than or equal to 500 msec
Severe hepatic impairment
Severe renal impairment
Correct electrolyte disorders before treatment
Reduce dose in patients with severe hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Avoid H2 antagonists 10 hours before or 2 hours after dose
Confirm ALK-positive status prior to treatment
Treatment to be initiated and supervised by a specialist
Capsules should not be opened or crushed
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor fasting serum glucose prior to and periodically during treatment
Monitor serum amylase and lipase before and regularly during treatment
Diabetic control may need adjustment
Monitor ECG in patients at risk of QT prolongation
Monitor for gastrointestinal toxicity
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Monitor heart rate and blood pressure regularly
Monitor liver function before, every 2 weeks for 3 months & then monthly
Monitor serum electrolytes
Reduce dose if bradycardia develops
Discontinue treatment if interstitial lung disease develops
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if blood glucose levels cannot be controlled
Discontinue if severe bradycardia occurs
Discontinue if treatment related pneumonitis is diagnosed
Discontinue permanently if QTc > 500 msec and is > 60 msec above baseline
Interrupt treatment if heart rate less than 60 bpm
Suspend if AST/ALT >5 x ULN and bilirubin less than or equal to 2 x ULN
Suspend if glucose levels persistently above 250mg/dl despite treatment
Suspend if grade 3/ intolerable gastrointestinal toxicity despite treatment
Suspend treatment if grade 3 or greater elevations in lipase or amylase
Dose adjustment may be required if food intake changes
Advise patient not to take St John's wort concurrently
Avoid antacids within 2 hours of dose
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 3 months after treatment
Avoid concurrent use of proton pump inhibitors
Pregnancy and Lactation
Pregnancy
The use of ceritinib is contraindicated during pregnancy.
The manufacturer does not recommend using ceritinib during pregnancy unless the clinical condition requires treatment with ceritinib.
At the time of writing, there is limited data on the use of ceritinib in human pregnancy.
Lactation
The use of ceritinib is contraindicated during breastfeeding.
The manufacturer does not recommend using ceritinib during breastfeeding. The manufacturer states a decision must be made whether to discontinue breastfeeding or discontinue ceritinib. The benefit of breastfeeding of the child and the benefit of therapy to the patient should be taken into consideration.
At the time of writing, it is unknown whether ceritinib is excreted in human breast milk, a risk to neonates cannot be excluded.
Side Effects
Abdominal discomfort
Abdominal pain
Abnormal liver function tests
Acute hepatic injury
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Asthenia
Azotaemia
Blurred vision
Bradycardia
Cholestatic hepatitis
Constipation
Decreased appetite
Dermatitis acneiform
Diarrhoea
Disturbances in accommodation
Dyspepsia
Dysphagia
Elevated amylase levels
Elevated serum lipase
Epigastric discomfort
Fatigue
Floaters
Gamma glutamyl transferase (GGT) increased
Gastroesophageal reflux disease
Hepatic impairment
Hepatocellular damage
Hepatotoxicity
Hyperbilirubinaemia
Hyperglycaemia
Hypophosphataemia
Impaired vision
Increase in alkaline phosphatase
Increases in hepatic enzymes
Interstitial lung disease
Maculopapular rash
Nausea
Pancreatitis
Pericardial effusion
Pericarditis
Photopsia
Pneumonitis
Presbyopia
Prolongation of QT interval
Rash
Reduced visual acuity
Renal failure
Renal impairment
Serum bilirubin increased
Serum creatinine increased
Sinus bradycardia
Upper abdominal pain
Vomiting
Weight loss
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 2019
Reference Sources
Summary of Product Characteristics: Zykadia 150mg hard capsules. Novartis Pharmaceuticals UK Ltd. Revised April 2019.
Summary of Product Characteristics: Zykadia 150mg film-coated tablets. Novartis Pharmaceuticals UK Ltd.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.