Read Mosby's 2014 Nursing Drug Reference Online
Authors: Linda Skidmore-Roth
Mosby's 2014 Nursing Drug Reference (108 page)
Canada only Side effects:
italics
= common;
bold
= life-threatening 
Nurse Alert
HIGH ALERTcrizotinib
(kriz-oh′ti-nib)
XALKORI
Func. class.:
Antineoplastic; biologic response modifiers
Chem. class.:
Signal transduction inhibitors (STIs)
Inhibits receptor tyrosine kinases (anaplastic lymphoma kinase (ALK), Hepatocyte Growth Factor Receptor (HGFR, c-Met), Recepteur d’Origine Nantais (RON)
Locally advanced or metastatic non–small-cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test
Pregnancy (D), breastfeeding, hypersensitivity
Precautions:
Neonates, infants, children, adolescents, pneumonitis, severe hepatic disease, congenital long QT syndrome, severe renal impairment, end-stage renal disease, vision disorders
Calculator
• Adult:
PO
250 mg bid, continue as long beneficial
Dose adjustments for hematologic toxicities
•
For Grade 1-2:
no dosage adjustment needed;
Grade 3:
interrupt treatment until toxicity resolves to grade ≤2, then continue with the same dosage schedule. In case of recurrence after a grade 4 event with dose reduction, interrupt treatment until toxicity resolves to grade ≤2; when resuming treatment, reduce dosage to 250 mg PO daily;
Grade 4:
interrupt treatment until toxicity resolves to grade ≤2; when resuming treatment, reduce dosage to 200 mg PO bid. In case of grade 4 recurrence, permanently discontinue treatment
Dose adjustments for hepatic laboratory abnormalities
•
For Grade 1:
No dosage adjustment necessary;
Grade 2 ALT/AST elevations with grade ≤1 total bilirubin elevations:
no dosage adjustment necessary;
Grade 3-4 ALT/AST elevations with grade ≤1 total bilirubin elevations:
interrupt treatment until toxicity resolves to grade ≤1 or baseline; when resuming treatment, reduce dosage to 200 mg PO bid; in case of recurrence, interrupt treatment until toxicity resolves to grade ≤1, and when resuming treatment, reduce dosage to 250 mg PO daily; permanently discontinue treatment in case of further recurrence;
Grade 2-4 ALT/AST elevations with concurrent Grade 2-4 total bilirubin elevations (in the absence of cholestasis or hemolysis):
permanently discontinue treatment
Dose adjustments for pneumonitis not attributable to NSCLC progression, other pulmonary disease, infection, or radiation effect
•
For any grade pneumonitis:
permanently discontinue
Dose adjustment for QTc prolongation:
•
For Grade 1-2 QTc prolongation:
no dosage adjustment necessary;
For Grade 3 QTc prolongation:
interrupt treatment until toxicity resolves to grade ≤1; when resuming treatment, reduce dosage to 200 mg PO bid; in case of recurrence, interrupt treatment until toxicity resolves to grade ≤1 and when resuming treatment, reduce dosage to 250 mg PO daily; permanently discontinue in case of further recurrence;
For Grade 4 QTc prolongation:
permanently discontinue
Available forms:
Cap 200, 250 mg
•
May be taken orally with or without food
•
Have the patient swallow capsule whole; do not crush or chew
•
If a dose is missed, it can be taken up to 6 hr before the next dose is due to maintain the twice daily regimen. Do not take both doses at the same time
CNS:
Dizziness, balance disorder, presyncope, neuropathy (motor and sensory), burning sensation, dysesthesia, hyperesthesia, hypoesthesia, neuralgia, paresthesias, peripheral neuropathy (motor and sensory), headache, insomnia
CV:
QT prolongation, disseminated intravascular coagulation (DIC), septic shock, bradycardia
EENT:
Diplopia, photopsia
, photophobia,
blurred vision
, visual field defect,
vitreous floaters
, visual brightness, reduced
visual acuity;
esophageal disorders
GI:
Nausea, diarrhea, vomiting, constipation
, decreased appetite, dysgeusia, abdominal pain, abdominal discomfort/pain, stomatitis, oral ulceration, glossodynia, glossitis, cheilitis, mucosal inflammation, oropharyngeal pain/discomfort, oral pain, esophageal disorder, elevated hepatic enzymes and hyperbilirubinemia,
hepatotoxicity,
dyspepsia, dysphagia, epigastric discomfort/pain, burning, esophagitis, esophageal obstruction/pain/spasm, esophageal ulceration, gastroesophageal reflux, odynophagia, and reflux esophagitis
HEMA:
Grade 3/4 neutropenia, thrombocytopenia,
lymphopenia
MISC:
Fatigue, fever,
edema
, localized/peripheral edema, chest pain (unspecified), chest discomfort, musculoskeletal chest pain, arthralgia, back pain,
rash
RESP:
Severe, life-threatening pneumonitis, pneumonia, hypoxia, acute respiratory distress syndrome (ARDS),
dyspnea, empyema, pulmonary hemorrhage,
pulmonary embolism,
upper respiratory tract infection (nasopharyngitis, pharyngitis, rhinitis), cough
Protein binding 91%; distribution into the tissues and plasma; metabolized by the CYP3A4/5; primary metabolic pathways are oxidation to metabolites; terminal half-life 42 hr; excreted 63% feces, 22% urine; unchanged drug 53% feces, 2.3% urine; absolute bioavailability is 43%; peak is 4-6 hr; steady state is reached within 15 days; dosage adjustments may need to be made in hepatic/renal disease and Asian patients
Increase:
CYP3A4 inhibitors (ketoconazole, atazanavir, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, voriconazole, boceprevir, delavirdine, isoniazid, dalfopristin; quinupristin, tipranavir)
Decrease:
CYP3A4 inducers (rifampin, carBAMazepine, PHENobarbital, phenytoin, rifabutin); antacids, H2-blockers, proton pump inhibitors (PPIs)
Increase:
action of—midazolam
Avoid use with CYP3A4 substrates (alfentanil, cycloSPORINE, ergotamine, dihydroergotamine fentaNYL, sirolimus, colchicine)
Increase:
QT prolongation, torsades de pointes—arsenic trioxide, certain phenothiazines (chlorproMAZINE, mesoridazine, thioridazine), grepafloxacin, levomethadyl, pentamidine, probucol, sparfloxacin, troleandomycin, class IA antiarrhythmics (disopyramide, procainamide, quiNIDine), class III antiarrhythmics (amiodarone, dofetilide, ibutilide, sotalol), clarithromycin, ziprasidone, pimozide, haloperidol, halofantrine, quiNIDine, chloroquine, dronedarone, droperidol, erythromycin, methadone, posaconazole, propafenone, saquinavir, abarelix, amoxapine, apomorphine, asenapine, β-agonists, ofloxacin, eribulin, ezogabine, flecainide, gatifloxacin, gemifloxacin, halogenated anesthetics, iloperidone, levofloxacin, local anesthetics, magnesium sulfate, potassium sulfate, sodium, maprotiline, moxifloxacin, nilotinib, norfloxacin, ciprofloxacin, olanzapine, paliperidone, some phenothiazines (fluPHENAZine, perphenazine, prochlorperazine, trifluoperazine), telavancin, tetrabenazine, tricyclic antidepressants, venlafaxine, vorinostat, citalopram, alfuzosin, cloZAPine, cyclobenzaprine, dolasetron, palonosetron, QUEtiapine, rilpivirine, SUNItinib, tacrolimus, tacrolimus, vardenafil, indacaterol, dasatinib, fluconazole, lapatinib, lopinavir/ritonavir, mefloquine, octreotide, ondansetron, ranolazine,
risperiDONE, telithromycin, vemurafenib
Do not use with St. John’s wor
Do not use with grapefruit juic
•
Severe, life-threatening, or fatal treatment-related
pneumonitis: all cases occurred within 2 mo of treatment initiation; monitor for pulmonary symptoms that may indicate pneumonitis, other causes of pneumonitis should be excluded; permanently discontinue in patients with treatment-related pneumonitis l
•
Hepatic disease:
liver function test (LFT) abnormalities, altered bilirubin levels may occur during treatment; monitor LFTs and bilirubin levels prior to treatment, then monthly; more frequent testing is needed in those presenting with grade 2 or greater toxicities; laboratory alterations should be managed with dose reduction, treatment interruption, or discontinuation
•
QT prolongation
has been reported with use of product; therefore, avoid crizotinib use in those patients; monitor ECG and electrolytes in patients with congestive heart failure, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), or in patients taking concomitant medications known to prolong the QT interval; treatment interruption, dosage adjustment, treatment discontinuation may be needed in patients who develop QT prolongation
•
Vision disorders,
generally start within 2 wk of the start of therapy; ophthalmological evaluation should be considered, particularly if patients experience photopsia or new or increased vitreous floaters; caution should be used when driving or operating machinery by patients who experience vision disorders
•
Pregnancy/breastfeeding:
identify if pregnancy is planned or suspected (pregnancy category D), do not breastfeed
•
CBC with differential; BUN/creatinine
•
Storage of capsules at room temperature
•
Decreasing spread of malignancy
•
That missed doses can be taken up to 6 hr before the next dose is due to maintain the twice daily regimen
•
To use reliable contraception; both women and men of childbearing age should use adequate contraceptive methods during therapy and for at least 90 days after completing treatment, pregnancy category D
•
To report immediately shortness of breath, cough, fatigue, visual changes
•
Not to take with grapefruit juice
•
To avoid activities requiring mental alertness until effects are known
•
To report signs of QT prolongation (abnormal heartbeats, dizziness, syncope)
•
To swallow caps whole and avoid contact with broken cap