Ceritinib (Zykadia) — Clinical FAQs

Question 1

What is Ceritinib FDA-approved to treat?

Accepted Answer

Ceritinib is FDA-approved for the following oncology indications: 1. Metastatic ALK-positive NSCLC — 1st-line treatment (2017, ASCEND-4 trial) 2. Metastatic ALK-positive NSCLC previously treated with crizotinib (2014 accelerated approval, confirmed 2017; ASCEND-5 trial).

Question 2

How does Ceritinib work (mechanism of action)?

Accepted Answer

Ceritinib is a second-generation, orally bioavailable ALK tyrosine kinase inhibitor approximately 20-fold more potent than crizotinib in biochemical assays. It competitively inhibits ATP binding at the ALK kinase domain, blocking autophosphorylation and downstream signaling through RAS/ERK, PI3K/AKT, and JAK/STAT3 pathways. Ceritinib retains activity against the majority of crizotinib-resistant ALK mutations (e.g., L1196M, G1269A, S1206Y, I1171T) arising within the ALK kinase domain, though it has limited activity against the G1202R solvent-front mutation. It also inhibits IGF-1R and ROS1, contributing to its broader kinase profile.

Question 3

How is Ceritinib administered?

Accepted Answer

Ceritinib is administered Oral (PO). Recommended dose is 450 mg PO once daily with food (revised from original 750 mg fasted; food-effect study showed comparable exposure with improved GI tolerability at 450 mg with food).

Question 4

What are the most common side effects of Ceritinib?

Accepted Answer

The most commonly reported side effects of Ceritinib (≥10% incidence) include: Diarrhea (up to 86%), Nausea (up to 80%), Vomiting (up to 60%), Abdominal pain, Elevated ALT/AST and others (11 total). Consult your oncologist for complete prescribing information.

Question 5

Does Ceritinib have a black box warning?

Accepted Answer

Yes. Ceritinib carries FDA black box warning(s) regarding: 1. Severe or life-threatening hepatotoxicity: Drug-induced hepatotoxicity including fatal cases reported; monitor ALT, AST, and total bilirubin every 2 weeks during first 9 months then monthly; withhold, dose reduce, or permanently discontinue based on severity 2. Severe ILD/pneumonitis: Fatal and life-threatening cases reported; permanently discontinue for Grade 3–4 ILD/pneumonitis 3. QT interval prolongation: Avoid in patients with congenital long QT syndrome; monitor ECG and electrolytes; withhold for QTc >500 ms 4. Severe or life-threatening gastrointestinal toxicity: Diarrhea, nausea, vomiting can be severe; dose modification or discontinuation may be required

Question 6

Is Ceritinib safe during pregnancy?

Accepted Answer

Ceritinib pregnancy safety: Can cause fetal harm based on mechanism of action. Women of reproductive potential should use effective contraception during treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential should use contraception during treatment and for 3 months after the last dose. Breastfeeding not recommended during treatment and for 2 weeks after the final dose.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

ceritinib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms