Drug information of Ceritinib
AUC and Cmax increased 73% and 41%, respectively, when a single ceritinib 500 mg was administered with a high-fat meal, and 58% and 43%, respectively when taken with a low-fat meal (when compared to fasting). A dose optimization study (comparing ceritinib 450 mg or 600 mg daily with food to ceritinib 750 mg [fasted]) found no clinically meaningful difference in the systemic steady-state exposure of ceritinib 450 mg (with food) compared to the 750 mg fasted arm (Cho 2017).
4,230 L (following a single 750 mg fasted dose), with a small preferential distribution to red blood cells versus plasma
Primarily hepatic via CYP3A
Feces (~92% with 68% as unchanged drug); urine (~1%)
Time to Peak
~4 to 6 hours
41 hours (following a single 750 mg fasted dose)
97% to human plasma proteins
Non-small cell lung cancer (ALK-positive), metastatic: Oral: 450 mg once daily (with food); continue until disease progression or unacceptable toxicity.
Missed doses: If a dose is missed, take the missed dose unless the next dose is due within 12 hours. If vomiting occurs, do not administer an additional dose, patients should continue with the next scheduled dose.
- Blurred vision
- burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
- clay-colored stools
- dark urine
- decreased appetite
- dry mouth
- flushed, dry skin
- fruit-like breath odor
- increased hunger
- increased thirst
- increased urination
- itching, skin rash
- loss of appetite
- stomach pain or tenderness
- swelling of the feet or lower legs
- troubled breathing
- unexplained weight loss
- unsteadiness or awkwardness
- unusual tiredness or weakness
- weakness in the arms, hands, legs, or feet
- yellow eyes or skin
InteractionsAmlodipine/Atorvastatine , Propranolol , Triamcinolone NN , Carbamazepine , Dorzolamide and timolol , fentanyl , Dolasetron , Palonosetron , vandetanib , sparfloxacin , Dofetilide , Goserelin , Promazine , Vasopressin , Efavirenz , Tipranavir , Etravirine , Dabrafenib , Halofantrine , Grepafloxacin , Mibefradil , Nicardipine , cobicistat , Delavirdine , Terfenadine , Abarelix , Alfuzosin , Perflutren , trabectedine , Duvelisib , Apalutamide , Flibanserin , Entrectinib , Risankizumab , Levomilnacipran , ELBASVIR/GRAZOPREVIR , Larotrectinib , Clevidipine , gilteritinib , glasdegib , Eliglustat , Romidepsin , oleandomycin , Bepridil , Pasireotide , bedaquiline , Gefitinib , Dasatinib , Gemtuzumab , Remdesivir , Cannabidiol , Sarecycline , voxelotor , Avapritinib , Capmatinib , Dienestrol , Nicotine
Points of recommendation
Bradycardia: Symptomatic bradycardia has been reported; heart rate <50 beats/minute has occurred. If possible, avoid concurrent use with other agents known to cause bradycardia (eg, beta blockers, nondihydropyridine calcium channel blockers, clonidine, digoxin). Monitor heart rate and blood pressure regularly. If symptomatic bradycardia (not life-threatening) occurs, withhold treatment until recovery to asymptomatic bradycardia or to a heart rate of ≥60 beats/minute, evaluate concurrent medications, and adjust ceritinib dose. Permanently discontinue for life-threatening bradycardia due to ceritinib; if life-threatening bradycardia occurs and concurrent medications associated with bradycardia can be discontinued or dose adjusted, restart ceritinib at a reduced dose (with frequent monitoring).
- Gastrointestinal toxicity: Severe and/or persistent gastrointestinal toxicity has occurred with ceritinib (at a dose of 750 mg in a fasted state). Diarrhea, nausea, vomiting, or abdominal pain occurred in the majority of patients in clinical trials using ceritinib 750 mg daily fasted (including some grade 3 and 4 events); over one-third of patients required treatment interruptions or dose reductions due to severe or persistent gastrointestinal toxicity. The incidence and severity of gastrointestinal toxicity were reduced in a clinical study utilizing ceritinib 450 mg daily with food (Cho 2017); most events were grade 1. Manage symptoms medically with appropriate therapy (eg, antidiarrheals, antiemetics, fluid replacement) as indicated. May require therapy interruption and/or dosage reduction. Ceritinib is associated with a moderate emetic potential (Hesketh 2017; Roila 2016); antiemetics may be needed to prevent nausea and vomiting. If vomiting occurs, do not administer an additional dose; continue with the next scheduled dose.
- Hepatotoxicity: Hepatotoxicity has been observed in patients treated with ceritinib in clinical trials, including ALT levels >5 times ULN in over one-quarter of patients and AST elevations in nearly one-fifth of patients. Concurrent ALT elevations >3 times ULN with total bilirubin >2 times ULN (with normal alkaline phosphatase) occurred rarely. Monitor liver function tests (eg, ALT, AST, total bilirubin) monthly and as clinically necessary, more frequently in patients who develop transaminase abnormalities. May require therapy interruption, dosage reduction, and/or permanent discontinuation.
- Hyperglycemia: Hyperglycemia, including grade 3 and 4 toxicity, has been observed in ceritinib-treated patients. Monitor fasting blood glucose levels at baseline and as clinically necessary. May require initiation or optimization of antihyperglycemic therapy. Temporarily interrupt therapy for hyperglycemia until adequately controlled; reduce dose upon recovery. If adequate glycemic control is not possible with medical management, permanently discontinue ceritinib.
- Pancreatitis: Although rare, pancreatitis (with fatality) has been reported. Grade 3 to 4 lipase and amylase elevations occurred in clinical trials. Monitor lipase and amylase prior to treatment and periodically during treatment as clinically necessary. May require treatment interruption and dose reduction.
- Pulmonary toxicity: Severe and life-threatening interstitial lung disease (ILD)/pneumonitis have been reported, including grade 3 or 4 events and fatalities. Monitor for signs/symptoms of pulmonary toxicity; permanently discontinue in patients diagnosed with treatment-related ILD/pneumonitis.
- QTc prolongation: QTc interval prolongation has occurred in clinical studies, and may be concentration-dependent. Based on post-baseline ECG assessment, a QTc interval increase of >60 msec over baseline was observed in a small percentage of patients; some patients experienced a QTc >500 msec (when taking ceritinib 750 mg daily fasted). QT prolongation may lead to an increased risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death. Avoid use in patients with congenital long QTc syndrome. Correct electrolyte abnormalities prior to initiating therapy. Periodically monitor ECG and electrolytes in patients with heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications known to prolong the QTc interval. QT prolongation may require treatment interruption, dosage reduction, or discontinuation. Permanently discontinue in patients who develop QTc interval prolongation in combination with torsades de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia.
Based on findings in animal reproduction studies and its mechanism of action, ceritinib may cause fetal harm if administered to a pregnant woman.