ceritinib, Zykadia

 Indications

Anaplastic lymphoma kinase (ALK)-positive, metastatic

non-small cell lung cancer (NSCLC).

Action

Acts as a tyrosine kinase inhibitor, inhibiting anaplastic

lymphoma kinase as well as other kinases, resulting in

decreased growth of certain malignant cell lines.

Therapeutic Effects: Slowed progression of metastatic

NSCLC.

Pharmacokinetics

Absorption: Absorption follows oral administration;

food significantlyqabsorption and mayqrisk 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)

ROUTE ONSET PEAK DURATION

PO unknown 4–6 hr

(blood

level)

7.1–7.4 mos Contraindications/Precautions

Contraindicated in: OB: Pregnancy (may cause fetal

harm); Lactation: Discontinue ceritinib or discontinue

breast feeding; Congenital long QT syndrome.

Use Cautiously in: Moderate to severe hepatic impairment/

severe renal impairment (CCr 30 mL/min);

HF, bradycardia, electrolyte abnormalities, or concurrent

use of QT prolonging medications; Concurrent use

of strong CYP3A4 inhibitors; Rep: Women of reproductive

potential and men with female partners of reproductive

potential; Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: fatigue. Resp: INTERSTITIAL LUNG DISEASE/PNEUMONITIS.

CV: BRADYCARDIA, TORSADE DE POINTES, QT interval

prolongation. GI: HEPATOTOXICITY, PANCREATITIS,

abdominal pain,pappetite, constipation, diarrhea,

esophagitis/reflux/dysphagia,qliver enzymes, nausea,

vomiting. Derm: rash. Endo: hyperglycemia. F and

E: hypophosphatemia. GU:qcreatinine. Hemat:

anemia.Metab:qlipase.

Interactions

Drug-Drug: Concurrent use of strong CYP3A inhibitors

including ketoconazole, and nefazodoneq

blood levels and the risk of toxicities; avoid concurrent

use; if unavoidable,pceritinib dose. Strong CYP3A inducers

including carbamazepine, phenytoin, and

rifampin maypblood levels and effectiveness; avoid

concurrent use. Mayqblood levels and the risk of toxicity

of CYP3A4 and CYP2C9 substrates, including alfentanil,

cyclosporine, dihyroergotamine, ergotamine,

fentanyl, phenytoin, pimozide, quinidine,

sirolimus, tacrolimus, and warfarin; dose of these

medications may need to bep. Beta-blockers, diltiazem,

verapamil, digoxin, and clonidine mayq

risk of bradycardia; avoid concurrent use, if possible.

Concurrent use of QT interval prolonging medications

mayqrisk of QT interval prolongation and torsade

de pointes.

Drug-Food: Grapefruit/grapefruit juiceqblood

levels and the risk of toxicity; concurrent ingestion

should be avoided. St. John’s wortpblood levels and

effectiveness; concurrent use should be avoided.

Route/Dosage

PO (Adults): 750 mg once daily; continue until disease

progression or unacceptable toxicity; Concurrent

use of strong CYP3A inhibitors—pdose by 1⁄3

rounded to the nearest 150-mg strength.

Availability

Capsules: 150 mg.