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. |
| Molecular Weight | 558.61 |
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 | Based on animal studies and mechanism of action (ALK inhibitor), there is potential for teratogenicity and embryo-fetal harm. Avoid use in first trimester unless no alternative. |
| 2nd trimester | Limited human data; animal studies show adverse effects. Use only if maternal benefit outweighs risk. May cause fetal harm. |
| 3rd trimester | Same as second trimester; potential risk of fetal toxicity. Consider alternative therapy if possible. |
Clinical note
Comprehensive clinical and safety monograph for ZYKADIA (ZYKADIA).
| Placental transfer | Ceritinib molecular weight (558.61 Da) suggests likely placental transfer. Animal studies demonstrate transfer across placenta. |
| Breastfeeding | No human data on presence in breast milk or effects on infant. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 1 month after last dose. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to ceritinib or any excipients
| 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. |
| Food/Dietary | Take ZYKADIA with food (preferably at same meal each day) to enhance absorption and reduce GI side effects. Avoid grapefruit and grapefruit juice as they inhibit CYP3A metabolism, increasing ceritinib levels and risk of toxicity. |
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| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
| Clinical Pearls |
| ZYKADIA (ceritinib) is a second-generation ALK inhibitor for ALK-positive metastatic NSCLC. Monitor for GI toxicities (diarrhea, nausea, vomiting) and hepatotoxicity. Drug-induced bradycardia and hyperglycemia may occur. Dose reduction recommended if on strong CYP3A inhibitors. Administer with food to increase absorption but reduce GI side effects; avoid grapefruit. |
| Patient Advice | Take ZYKADIA exactly as prescribed once daily with food to reduce nausea and diarrhea. · Do not take with grapefruit or grapefruit juice as it may affect drug levels. · Report severe or persistent diarrhea, nausea, vomiting, or abdominal pain to your doctor immediately. · Monitor for signs of liver problems: yellowing skin/eyes, dark urine, fatigue, or easy bruising. · Avoid becoming pregnant; use effective contraception during treatment and for at least 2 weeks after last dose. · Do not drive or operate heavy machinery if you experience dizziness, fatigue, or slow heart rate. |