Names and pronunciation
Inlyta
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Drug reference
Inlyta
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Func. class.: Antineoplastics, biologic response modifiers, signal transduc- tion inhibitors (STIs)
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Chem. class.: Tyrosine kinase inhibitor
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ACTION: Inhibits receptor tyrosine kinases including vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR- 2, and VEGFR-3; inhibits tumor growth and phosphorylation of VEGFR-2 and VEGF- mediated endothelial cell proliferation
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USES: Treatment of advanced renal cell cancer after failure of 1 prior sys- temic therapy
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CONTRAINDICATIONS: Preg- nancy, breastfeeding Precautions: Risk for or history of thromboembolic disease, recent bleeding, untreated brain metastasis, recent GI bleeding, GI perforation, fistula, surgery, moderate hepatic disease, uncontrolled hypertension, hyper/hypothyroidism, pro- teinuria, infertility, end-stage renal disease (CrCl <15 mL/min); not intended for use in adolescents, children, infants, neonates
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SIDE EFFECTS CNS: Dizziness, headache, reversible posterior leukoencephalopathy syndrome (RPLS), fatigue CV: Hypertension, arterial thromboem- bolic events (ATE), venous thromboem- bolic events (VTE) ENDO: Hypothyroidism, hyperthyroidism GI: Lower GI bleeding/perforation/fistula, abdominal pain, constipation, diarrhea, dysgeusia, dyspepsia, dysphonia, hemor- rhoids, nausea, mucosal inflammation, stomatitis, vomiting, increased ALT/AST GU: Proteinuria HEMA: Bleeding, intracranial bleed- ing, anemia, polycythemia, decreased/ increased hemoglobin, lymphopenia, thrombocytopenia, neutropenia INTEG: Palmar-plantar erythrodysesthe- sia (hand and foot syndrome), rash, dry skin, pruritus, alopecia, erythema MISC: Weight loss, dehydration, metabolic and electrolyte laboratory abnormalities MS: Asthenia, arthralgia, musculoskele- tal pain, myalgia RESP: Cough, dyspnea
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INTERACTIONS Increase: effect of axitinib—CYP3A4/5 inhibitors, strong/moderate (ketoconazole, boceprevir, chloramphenicol, conivaptan, delavirdine, fosamprenavir, imatinib, indin avir, isoniazid, itraconazole, dalfopristin, quinupristin, posaconazole, ritonavir, telithromycin, tipranavir [boosted with rito- navir], darunavir [boosted with ritonavir], aldesleukin [IL-2], amiodarone, aprepi- tant, fosaprepitant, atazanavir, bromocrip- tine, clarithromycin, crizotinib, danazol, diltiaZEM, dronedarone, erythromycin, flu- voxaMINE, lanreotide, lapatinib, micon- azole, miFEPRIStone, nefazodone, nelfina- vir, niCARdipine, octreotide, pantoprazole, saquinavir, tamoxifen, verapamil, voricon- azole, grapefruit juice); avoid using together, or reduce axitinib Decrease: effect of axitinib—CYP3A4/5 inducers, strong/moderate (rifAMPin, carBAMazepine, dexamethasone, phenytoin, PHENobarbital, rifabutin, rifapentine, St. John’s wort, ethanol, bexarotene, bosen- tan, efavirenz, etravirine, griseofulvin, metyr- aPONE, modafinil, nafcillin, nevirapine, OXcarbazepine, vemurafenib, pioglitazone, topiramate); avoid using together Increase or decrease: effect of axitinib— CYP3A4/5 inhibitors and inducers (quiNINE) Drug/Lab Test Increase: creatinine, lipase, amylase, potassium Decrease: bicarbonate, calcium, albu- min, glucose, phosphate, sodium Increase or decrease: sodium, glucose Drug/Food Increase: drug effect—grapefruit or grapefruit juice Drug/Herb Decrease: effect of axitinib—St. John’s wort NURSING CONSIDERATIONS
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DOSAGE AND ROUTES Advanced renal cell carcinoma after failure of 1 systemic therapy • Adult: PO 5 mg bid (at 12-hr intervals), may increase to 7 mg bid and then to 10 mg bid in intervals of 6 wk First-line treatment of advanced renal cell cancer, with pembrolizumab • Adults: PO 5 mg bid with pembroli- zumab 200 mg IV on day 1 q3wk or 400 mg IV on day 1 q6wk. The axitinib dosage may be increased to 7 mg bid and then to 10 mg bid q6wk or longer in normoten- sive patients First-line treatment of advanced renal cell cancer, with avelumab • Adults: PO 5 mg bid with avelumab 800 mg IV over 1 hr q2wk until disease progression or unacceptable toxicity. The axitinib dosage may be increased to 7 mg bid and then to 10 mg bid in normo- tensive patients • Adult receiving a strong CYP3A4/5 in- hibitor: Reduce dose by ½, adjust as needed
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Available forms: Tablets 1, 5 mg
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Administer: • Premedicate with antihistamine and ac- etaminophen 30-60 min prior to each dose • Use safe handling precautions • Give with or without food; swallow tablet whole with a glass of water • If patient vomits or misses a dose, an additional dose should not be taken; the next dose should be taken at the usual time • Store at room temperature
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Assess: • Bleeding: monitor for GI bleeding or perforation; temporarily discontinue ther- apy if any bleeding that requires treatment • Surgery: discontinue ≥24 hr before surgery; may be resumed after adequate wound healing • Hepatic/renal disease: dosage should be reduced in patients with moderate (Child-Pugh Class B) hepatic disease; monitor liver function tests (ALT, AST, bili- rubin) before and periodically during therapy; monitor CCr before and during treatment • Hypertension: B/P should be well con- trolled before starting treatment; monitor for hypertension and administer antihy- pertensive therapy as needed before and during therapy; dose should be reduced for persistent hypertension; therapy should be discontinued if B/P remains elevated after a dosage reduction or if there is evidence of hypertensive crisis; after discontinuation, monitor B/P for hypotension in those receiving antihyper- tensives • Hyper/hypothyroidism: monitor thy- roid function tests before and periodically during therapy; thyroid disease should be treated with thyroid medications • Monitor for proteinuria before and periodically during therapy; product may need to be decreased or discontin- ued if moderate to severe proteinuria occurs • RPLS: monitor for headache, seizures, visual changes, confusion, drowsiness, hemiplegia, discontinue product if these occur • Pregnancy/breastfeeding: determine if the patient is pregnant or breastfeeding before using this product; may also cause infertility; do not use in pregnancy and for 1 wk after last dose or breastfeeding; obtain pregnancy test in women of child- bearing potential before starting therapy
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Evaluate: • Therapeutic response: decreased spread of malignancy
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Patient and caregiver information: • That product will be discontinued ≥24 hr before surgery; may be resumed after adequate wound healing • To notify prescriber of bleeding that is severe or that requires treatment • That laboratory testing will be re- A quired before and periodically during product use • How to monitor B/P and that B/P products should be continued as di- rected by prescriber • That product may be taken without regard to meals • To report all adverse reactions, in- cluding neurologic, GI bleeding • To avoid use with grapefruit/grapefruit juice, St. John’s wort • Pregnancy/breastfeeding: to use con- traception during treatment, and for 1 wk after last dose or to avoid use of this product; to notify prescriber if pregnancy is planned or suspected; not to breastfeed HIGH ALERT
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PHARMACOKINETICS Absorption: bioavailability 58%; distribu- tion: protein binding >99%; metabolized in liver by CYP3A4/5, CYP1A2, CYP2C19, and UGT1A1; metabolites are carboxylic acid, sulfoxide, and N-glucuronide; excretion 41% in feces and 23% in urine, 12% unchanged; half-life: 2.5-6.1 hr; steady state 2-3 days; onset unknown, peak 2.5-4.1 hr, increased in moderate hepatic disease; duration unknown
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• Adult: PO 5 mg bid (at 12-hr intervals), may increase to 7 mg bid and then to 10 mg bid in intervals of 6 wk First-line treatment of advanced renal cell cancer, with pembrolizumab
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• Adults: PO 5 mg bid with pembroli- zumab 200 mg IV on day 1 q3wk or 400 mg IV on day 1 q6wk. The axitinib dosage may be increased to 7 mg bid and then to 10 mg bid q6wk or longer in normoten- sive patients First-line treatment of advanced renal cell cancer, with avelumab
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• Adults: PO 5 mg bid with avelumab 800 mg IV over 1 hr q2wk until disease progression or unacceptable toxicity. The axitinib dosage may be increased to 7 mg bid and then to 10 mg bid in normo- tensive patients
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• Adult receiving a strong CYP3A4/5 in- hibitor: Reduce dose by ½, adjust as needed
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