Names and pronunciation
(re′goe-raf′e-nib) Stivarga
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Drug reference
(re′goe-raf′e-nib) Stivarga
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Func. class.: Antineoplastic; multiki- nase inhibitor
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Chem. class.: Signal transduction inhibitor (STI)
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ACTION: Inhibits tyrosine kinase in patients with colorectal cancer
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USES: Metastatic colorectal cancer in those who have received fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, an anti-VEGF therapy; and an anti-EGFR therapy if KRAS wild type
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CONTRAINDICATIONS: Preg nancy Precautions: Breastfeeding, children, geriatric patients, cardiac/renal/hepatic/ dental disease, fistula, GI bleeding or perforation, bone marrow suppression, infection, wound dehiscence, thrombo- cytopenia, neutropenia, immunosup pression
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Black Box Warning: Hepatic disease Black Box Warning: Hepatic disease: fatal hepatotoxicity can occur; obtain LFTs baseline and at least every 2 wk × 2 mo, then monthly • Assess any wounds for wound healing; report wound dehiscence, stop medica- tion, notify prescriber • 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, 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; moni- tor B/P every week × 6 wk, then at start of each cycle or more often if needed; tempo- rarily or permanently discontinue for severe uncontrolled hypertension • Pregnancy/breastfeeding: identify whether patient is pregnant or if preg- nancy is planned; identify contraception type in both men and women; do not use in pregnancy, breastfeeding
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SIDE EFFECTS CNS: Headache, tremor CV: Hypertensive crisis, MI EENT: Blurred vision, conjunctivitis GI: Hepatotoxicity, GI hemorrhage, diar- rhea, GI perforation, xerostomia HEMA: Neutropenia, thrombocytopenia, bleeding INTEG: Rash, alopecia META: Hypokalemia MISC: Fatigue, decreased weight, hand- foot syndrome, hypothyroidism
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INTERACTIONS Increase: regorafenib concentrations— CYP3A4 inhibitors (ketoconazole, itracon- azole, erythromycin, clarithromycin) Increase: plasma concentrations of sim vastatin, calcium channel blockers, ergots Increase: plasma concentration of warfa- rin; avoid use with warfarin; use low- molecular-weight anticoagulants instead Decrease: regorafenib concentrations— CYP3A4 inducers (dexamethasone, phe- nytoin, carBAMazepine, rifAMPin, PHENobarbital) Drug/Food Increase: regorafenib effect—grapefruit juice; avoid use while taking product Drug/Herb Decrease: imatinib concentration—St. John’s wort
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DOSAGE AND ROUTES • Adult: PO 160 mg/day with a low-fat breakfast × 21 days of a 28-day cycle, cycles may be repeated
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Available forms: Tabs 40 mg
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Administer: • Store at 77°F (25°C) • Give at the same time each day with a low-fat breakfast that contains less than 30% fat such as 2 slices of white toast with 1 tbsp of low-fat margarine and 1 tbsp of jelly, and 8 oz of skim milk; or 1 cup of cereal, 8 oz of skim milk, 1 slice of toast with jam, apple juice, and 1 cup of coffee or tea • Swallow tablets whole • If a dose is missed, take as soon as possible that day; do not take 2 doses on the same day • Hand-foot skin reaction: Reduce to 120 mg (grade 2 palmar-plantar erythro- dysesthesia); hold if grade 2 toxicity does not improve in ≤7 days or recurs; hold for ≥7 days in grade 3 toxicity; reduce to 80 mg for recurrent grade 2 toxicity; discon- tinue if 80 mg is not tolerated • Hypertension: Hold in grade 2 hyper- tension Other severe toxicity (except hepato- toxicity) • Hold until toxicity resolves in grade 3 or 4 toxicity; consider the risk/benefits of continuing therapy in grade 4 toxicity, reduce dosage to 120 mg; if grade 3 or 4 toxicity recurs, hold until toxicity resolves, then reduce to 80 mg; discontinue in those who do not tolerate 80-mg dose • Hepatic dose: Baseline mild (Child- Pugh class A) or moderate (Child-Pugh class B): no change; baseline severe he- patic impairment (Child-Pugh class C): use not recommended; AST/ALT eleva- tions during therapy: For grade 3 AST/ALT level elevations, hold dose; if therapy is continued, reduce to 120 mg after levels recover; discontinue in those with AST/ ALT >20 × ULN; AST/ALT >3 × ULN and bilirubin >2 × ULN; recurrence of AST/ALT >5 × ULN despite a reduction to 120 mg
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Assess:
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Evaluate: • Therapeutic response: decrease in spread or size of tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report adverse reactions immedi- ately: bleeding, rash • About reason for treatment, expected results • That effect on male fertility is unknown • To take at the same time of day with low-fat food; not to use grapefruit juice; to take missed dose on same day; not to take multiple doses on the same day; to keep original container • To report immediately hepatic effect (yellowing skin, eyes, nausea, vomiting, dark urine), increased B/P (severe head- ache), GI perforation/fistula (dyspepsia, flatulence, fever, chills, epigastric pain) • Pregnancy/breastfeeding: not to use in pregnancy; to report if pregnancy is suspected or if breastfeeding; for men and women to use contraception during and for 2 mo after termination of treatment
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PHARMACOKINETICS Protein binding 99%, metabolized by CYP3A4, UGT1A0, half-life 14-58 hr
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• Adult: PO 160 mg/day with a low-fat breakfast × 21 days of a 28-day cycle, cycles may be repeated
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