crizotinib (kriz-oh-ti-nib) Xalkori

 Indications

Metastatic non-small cell lung cancer (NSCLC) that is

positive for anaplastic lymphoma kinase (ALK).

Metastatic NSCLC that is positive for ROS1.

Action

Inhibits receptor tyrosine kinases including anaplastic

lymphoma kinase (ALK), Hepatocyte Growth Factor Receptor

(HGFR, c-Met), ROS1, and Recepteur d’Origine

Nantais (RON). Therapeutic Effects: Decreased

spread of lung cancer and improved survival.

Pharmacokinetics

Absorption: 43% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism and Excretion: Mostly metabolized

by the liver (CYP3A4/5 enzyme system) also acts as a

inhibitor of CYP3A. 53% excreted in feces unchanged,

2.3% eliminated unchanged in urine.

Half-life: 42 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 4–6 hr unknown

Contraindications/Precautions

Contraindicated in: Concurrent use of strong inhibitors/

inducers of the CYP3A enzyme system; Congenital

long QT syndrome; OB: May cause fetal harm; Lactation:

Breast feeding should be avoided.

Use Cautiously in: Heart failure, bradyarrhythmias,

electrolyte abnormalities, concurrent medications that

prolong QT interval (qrisk of arrhythmias); Asian

patients (qblood levels); Hepatic impairment; Severe

renal impairment; Rep: Women of reproductive potential

and men with female sexual partners of reproductive

potential (use effective contraception); Pedi: Safety

and effectiveness not established.

Adverse Reactions/Side Effects

CNS: fatigue, headache, insomnia. EENT: visual disturbances.

Resp: PNEUMONITIS. CV: QT INTERVAL PROLONGATION,

bradycardia, edema, chest pain. Derm:

rash. Endo:ptestosterone. GI: HEPATOTOXICITY, constipation,

diarrhea, nausea, vomiting, abdominal pain,

dysgeusia, esophagitis,pappetite, stomatitis. GU:p

fertility. Neuro: neuropathy. Misc: fever.

Interactions

Drug-Drug: Strong CYP3A inhibitors including

atazanavir, clarithromycin, indinavir, itraconazole,

ketoconazole, nefazodone, nelfinavir, ritonavir,

saquinavir, and voriconazole mayqlevels;

concurrent use should be avoided. Strong CYP3A inducers

including carbamazepine, phenobarbital,

phenytoin, rifabutin, and rifampin mayplevels and

effectiveness; concurrent use should be avoided. May

qlevels of alfentanil, cyclosporine, dihydroergotamine,

ergotamine, fentanyl, pimozide, quinidine,

sirolimus, and tacrolimus; avoid concurrent

use. Beta-blockers, verapamil, diltiazem, digoxin,

and clonidine mayqrisk of bradycardia; avoid concurrent

use, if possible.

Drug-Natural Products: Concurrent use of St.

John’s wort mayplevels and effectiveness and should

be avoided.

Drug-Food: Grapefruit or grapefruit juice mayq

levels and should be avoided.

Route/Dosage

PO (Adults): 250 mg twice daily until disease progression

or no longer tolerated by patient.

Renal Impairment

PO (Adults): CCr 30 mL/min (not on dialysis)—

250 mg once daily.

Availability

Capsules: 200 mg, 250 mg.