ZYKADIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYKADIA (ZYKADIA).
ZYKADIA (ceritinib) is a tyrosine kinase inhibitor that targets ALK, IGF-1R, insulin receptor, and ROS1. It inhibits ALK phosphorylation and downstream signaling pathways, leading to reduced tumor cell proliferation.
| Metabolism | Primarily metabolized by CYP3A4. |
| Excretion | Primarily fecal (91%) as unchanged drug; renal excretion is minimal (<1%). |
| Half-life | Terminal elimination half-life is approximately 18.2 hours (range 13.5-22.3 h), supporting once-daily dosing. |
| Protein binding | 99.5% bound to human plasma proteins, predominantly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 24.1 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 30-50% under fasting conditions; increased with high-fat meal (70-100 mg/day). |
| Onset of Action | No rapid clinical effect; time to steady-state concentration is approximately 3 days with once-daily dosing. |
| Duration of Action | Duration of action is continuous with daily dosing; drug levels remain above therapeutic threshold over 24-hour interval. |
150 mg orally once daily, taken with food, until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). Not studied in end-stage renal disease (CrCl <15 mL/min) or on dialysis. |
| Liver impairment | Mild (Child-Pugh A): 150 mg once daily. Moderate (Child-Pugh B): 100 mg once daily. Severe (Child-Pugh C): 50 mg once daily. |
| Pediatric use | Safety and efficacy not established in patients <18 years; no recommended pediatric dose. |
| Geriatric use | No specific dose adjustment based on age; monitor renal function and manage toxicities as in younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYKADIA (ZYKADIA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions (e.g., hepatotoxicity, pneumonitis) in breastfed infants, advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | ZYKADIA (ceritinib) is embryotoxic and fetotoxic in animal studies. There are no adequate human data. Based on its mechanism of action (ALK inhibitor) and animal findings, it is expected to cause fetal harm if administered during pregnancy. Avoid use in pregnant women unless benefit outweighs risk. If used, advise patient of potential risk to fetus. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
None known.
| Precautions | ["Hepatotoxicity: ALT, AST, and bilirubin elevations; monitor liver function tests.","Interstitial lung disease/pneumonitis: Monitor pulmonary symptoms.","QT interval prolongation: Monitor ECG in patients at risk.","Hyperglycemia: Monitor glucose levels.","Bradycardia: Monitor heart rate.","Pancreatitis: Monitor lipase and amylase."] |
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| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) at baseline and monthly or as clinically indicated. Monitor for pulmonary symptoms (cough, dyspnea) and consider prompt evaluation for interstitial lung disease/pneumonitis. Monitor cardiac function (ECG, electrolytes) for QTc prolongation. In pregnant women, perform fetal ultrasound monitoring for growth and development, especially if exposed during organogenesis. |
| Fertility Effects | Based on animal studies, ceritinib may impair male and female fertility. In female rats, ovarian atrophy and reduced corpora lutea observed. In male rats, testicular degeneration and reduced sperm count. Potential for reversible or irreversible impairment. Advise patients of potential fertility effects. |