ceritinib(redirected from Zykadia)
Pregnancy Category: D
Pharmacologic: kinase inhibitors
Pharmacologic: kinase inhibitors
Treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) that has progressed despite treatment with or intolerance to crizotinib.
Acts as a tyrosine kinase inhibitor, inhibiting anaplastic lymphoma kinase as well as other kinases, resulting in decreased growth of certain malignant cell lines.
Slowed progression of metastatic NSCLC.
Absorption: Absorption follows oral administration; food significantly ↑ absorption and may ↑ risk of adverse reactions.
Distribution: Slight preference to distribute from plasma into red blood cells.
Metabolism and Excretion: Metabolized in the liver (mostly by CYP3A) and is a substrate of P-glucoprotein (P-gp); 68% eliminated unchanged in feces, 1.3% in urine.
Half-life: 41 hr.
Time/action profile (clinical response)
|PO||unknown||4–6 hr (blood level)||7.1–7.4 mos|
Contraindicated in: Obstetric: Pregnancy (may cause fetal harm); Lactation: Discontinue ceritinib or discontinue breastfeeding.
Use Cautiously in: Females with reproductive potential (effective contraception required); Moderate to severe hepatic impairment/severe renal impairment (CCr <30 mL/min; Pediatric: Safe and effective use in children has not been established.
Adverse Reactions/Side Effects
Central nervous system
- fatigue (most frequent)
- interstitial lung disease/pneumonitis (life-threatening)
- Qtc prolongation (life-threatening)
- bradycardia (life-threatening)
- GI toxicity (life-threatening)
- hepatotoxicity (life-threatening)
- abdominal pain (most frequent)
- ↓ appetite (most frequent)
- constipation (most frequent)
- diarrhea (most frequent)
- esophagitis/reflux/dysphagia (most frequent)
- ↑ liver enzymes (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- rash (most frequent)
- hyperglycemia (life-threatening)
Fluid and Electrolyte
- hypophosphatemia (most frequent)
- ↑ creatinine (most frequent)
- anemia (most frequent)
- ↑ lipase (most frequent)
Drug-Drug interactionConcurrent use of strong inhibitors of CYP3A including ketoconazole, nefazodone, and telithromycin ↑ blood levels and the risk of toxicities (if unavoidable, dose reduction is necessary). Strong inducers of CYP3A including carbamazepine, phenytoin, and rifampin may ↓ blood levels and effectiveness; concurrent use should be avoided.Ceritinib inhibits CYP3A and CYP2C9 enzymes and may ↑ blood levels and the risk of toxicity from alfentanil, cyclosporine, dihyroergotamine, ergotamine, fentanyl, phenytoin, pimozide, quinidine, sirolimus, tacrolimus, and warfarin ; dose of these medications may need to be decreased/adjusted.Grapefruit/grapefruit juice ↑ blood levels and the risk of toxicity; concurrent ingestion should be avoided.St. John's wort ↓ blood levels and effectiveness; concurrent use should be avoided.
Oral (Adults) 750 mg once daily; dose reduction/modifcation/discontinuation required for GI toxicity, ↑ liver enzymes, hyperglycemia, QT prolongation or bradycardia; Concurrent use of strong CYP3A inhibitors—↓ dose by 1/3 rounded to the nearest 150 mg strength.
Capsules: 150 mg
- Assess for signs and symptoms of interstitial lung disease or pneumonitis (trouble breathing, shortness of breath, fever, cough with or without mucus, chest pain). If these symptoms occur, discontinue therapy permanently.
- Monitor ECG periodically during therapy. If QTc interval is >500 msec on at least 2 separate ECGs, withhold ceritinib until QTc interval <481 msec or recovery to baseline if QTc ≥481 msec, resume ceritinib with a 150 mg dose reduction. If QTc interval prolongation in combination Torsades de pointes or polymorphic ventricular tachycardia or signs and symptoms of serious arrhythmia, discontinue ceritinib permanently.
- If symptomatic bradycardia that is not life-threatening occurs, withhold ceritinib until recovery to asymptomatic bradycardia or a heart rate ≥ 60 bpm, evaluate concurrent medications causing bradycardia, and adjust dose of ceritinib. If clinically significant bradycardia requiring intervention or life-threatening bradycardia in patients taking concurrent medication known to cause bradycardia or a medication known to cause hypotension occurs withhold ceritinib until asymptomatic bradycardia recovers to ≥60 bpm. If concurrent medication can be adjusted or discontinued, resume ceritinib with a 150 mg dose reduction and frequent monitoring. If life-threatening bradycardia occurs in patients not taking medications known to cause bradycardia or hypotension, discontinue ceritinib permanently.
- Assess for nausea, vomiting, diarrhea. If severe or intolerable nausea, vomiting, or diarrhea continue despite optimal antiemetic or antidiarrheal therapy, withhold ceritinib until improved; then resume with a 150 mg dose reduction.
- Lab Test Considerations: Monitor liver function tests at least monthly. If ALT or AST >5 times the upper limit of normal and total bilirubin is ≤2 times the upper limit of normal, withhold ceritinib until recovery to baseline or less than or equal to 3 times the upper limit of normal, then resume ceritinib with a 150 mg dose reduction. If ALT or AST >3 times the upper limit of normal and total bilirubin is >2 times the upper limit of normal in the absence of cholestasis or hemolysis, permanently discontinue ceritinib.
- Monitor blood glucose periodically during therapy. If persistent hyperglycemia >250 mg/dL despite anti-hyperglycemic therapy, withhold ceritinib until hyperglycemia is adequately controlled, then resume with a 150 mg dose reduction. If adequate hyperglycemic control cannot be achieved, discontinue therapy.
- May cause decreased hemoglobin and serum phosphate; increased creatinine, glucose, lipase, and total bilirubin.
Potential Nursing DiagnosesIneffective airway clearance (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)
- Oral: Administer on an empty stomach, at least 2 hr before or after meals.
- Instruct patient to take ceritinib as directed. Take missed doses as soon as remembered unless within 12 hrs of next dose. Instruct patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
- Inform patient to avoid consuming grapefruit and grapefruit juice during therapy.
- Advise patient to notify health care professional if nausea, vomiting, and diarrhea is severe or persistent; if signs and symptoms of hepatotoxicity (feeling tired, itchy skin, skin or whites of eyes turn yellow, nausea and vomiting, decreased appetite, pain on right side of stomach, dark or brown, tea-colored urine, bleed or bruise easily); pneumonitis; QTc interval prolongation or bradycardia (new chest pain, changes in heartbeat, palpitations, dizziness, fainting, or changes in or use of a new heart or blood pressure medication); hyperglycemia (increased thirst, increased hunger, headaches, trouble thinking or concentration, urinating often, blurred vision, tiredness, breath smells like fruit)
- Advise female patient to use effective contraceptives during and for at least 2 wks following completion of therapy and to notify health care provider if pregnancy is planned or suspected or if breastfeeding.
- Slowed progression of metastatic NSCLC.