Names and pronunciation
(paz-oh′pa-nib) Votrient
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Drug reference
(paz-oh′pa-nib) Votrient
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Func. class.: Antineoplastic biologic response modifiers/multikinase angio- genesis inhibitor
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Chem. class.: Kinase inhibitor
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ACTION: Targets vascular endothelial growth factor receptors; a multikinase angiogenesis inhibitor
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USES: Advanced renal cell carcinoma; soft-tissue sarcoma patients who have received prior chemotherapy
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Unlabeled uses: GI stromal tumors (GISTs)
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CONTRAINDICATIONS: Preg nancy, hypothyroidism, QT prolongation, MI, wound dehiscence, hypertension Precautions: Breastfeeding, children, cardiac/renal/hepatic/dental disease, GI bleeding
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Black Box Warning: Hepatic disease (fatalities) Black Box Warning: Hepatic disease: fatal hepatotoxicity can occur; obtain LFTs baseline and at least every 2 wk × 2 mo, then monthly • Fatal bleeding: from GI, respiratory, GU tracts, permanently discontinue in those with severe bleeding • Palmar-plantar erythrodysesthesia (hand-foot syndrome): more common in those previously treated; reddening, swelling, numbness, desquamation on palms and soles • GI perforation/fistula: discontinue if this occurs, assess for pain in epigastric area, dyspepsia, flatulence, fever, chills • Hypertension/hypertensive crisis: hy- pertension usually occurs in the first cycle; in those with preexisting hypertension, do not start treatment until B/P is controlled; monitor B/P every wk × 6 wk, then at start of each cycle or more often if needed, tem- porarily or permanently discontinue for severe uncontrolled hypertension • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding
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SIDE EFFECTS CNS: Intracranial bleeding, headache CV: Heart failure, hypertension, hyperten- sive crisis, chest pain, MI, QT prolonga- tion, torsades de pointes GI: Nausea, hepatotoxicity, vomiting, dys- pepsia, GI hemorrhage, anorexia, abdom- inal pain, GI perforation, pancreatitis, diarrhea; hepatotoxicity (geriatric) HEMA: Neutropenia, thrombocytopenia, bleeding INTEG: Rash, alopecia MISC: Fatigue, epistaxis, pyrexia, hot sweats, increased weight, flulike symp- toms, hypothyroidism, hand-foot syn- drome, retinal tear/detachment
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INTERACTIONS Increase: QT prolongation—class IA/III antidysrhythmics, some phenothiazines, β-agonists, local anesthetics, tricyclics, haloperidol, chloroquine, droperidol, pentamidine; CYP3A4 inhibitors (amiod- arone, clarithromycin, erythromycin, telithromycin, troleandomycin), arsenic trioxide; CYP3A4 substrates (methadone, pimozide, QUEtiapine, quiNIDine, ris- periDONE, ziprasidone) Increase: pazopanib concentrations— CYP3A4 inhibitors (ketoconazole, itra- conazole, erythromycin, clarithromycin) Increase: plasma concentrations of simvastatin, calcium-channel blockers, ergots Increase: plasma concentration of warfa- rin; avoid use with warfarin; use low- molecular-weight anticoagulants instead Decrease: PAZOPanib concentrations— CYP3A4 inducers (dexamethasone, phe- nytoin, carBAMazepine, rifampin, PHENobarbital) Drug/Food Increase: PAZOPanib effect—grapefruit juice; avoid use while taking product Drug/Herb Decrease: PAZOPanib concentration— St. John’s wort
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DOSAGE AND ROUTES • Adult: PO 800 mg/day without food (1 hr before, 2 hr after a meal), may decrease to 400 mg/day if not tolerated (renal cell can- cer); or adjust in 200-mg increments based on toxicity (soft-tissue sarcoma); use with strong CYP3A4 inhibitors 400 mg daily Hepatic dose Adult: PO 200 mg daily (moderate hepatic disease)
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Available forms: Tabs 200 mg
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Administer: • Give on an empty stomach (1 hr before or 2 hr after a meal); separate doses by ∼24 hr • Do not crush tablets may affect rate of absorption and systemic exposure; only intact, whole tablets should be used • If a dose is missed, it should not be taken if it is <12 hr until the next dose • Store at room temperature 77°F (25°C)
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Assess:
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Evaluate: • Therapeutic response: decrease in size, spread of tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report adverse reactions immedi- ately: heart attack, stroke • About reason for treatment, expected results • That effect on male fertility is unknown • Not to crush or chew tabs; to take on an empty stomach 1 hr before or 2 hr after meals; to avoid grapefruit juice • Blood clots: Pain in legs, chest pain, swelling in legs, arms, notify provider im- mediately • Hepatotoxicity: To notify provider im- mediately of yellow skin, eyes, clay-color- ed stools, dark urine, monitor LFTs before and at 3, 5, 7, 9 wk, then 3 mo, 4 mo if symptoms are present HIGH ALERT
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PHARMACOKINETICS Protein binding 99%, peak 2-4 hr, dura- tion 24 hr, half-life 31 hr
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• Adult: PO 800 mg/day without food (1 hr before, 2 hr after a meal), may decrease to 400 mg/day if not tolerated (renal cell can- cer); or adjust in 200-mg increments based on toxicity (soft-tissue sarcoma); use with strong CYP3A4 inhibitors 400 mg daily Hepatic dose Adult: PO 200 mg daily (moderate hepatic disease)
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