Stivarga

Regorafenib

Monotherapy in adult patients w/ metastatic CRC who have been previously treated w/, or are not considered candidates for, available therapies (including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy & an anti-EGFR therapy); unresectable or metastatic GI stromal tumours (GIST) who progressed on or are intolerant to prior treatment w/ imatinib & sunitinib; hepatocellular carcinoma (HCC) who have been previously treated w/ sorafenib.

160 mg (four 40-mg tab) once daily for 3 wk followed by 1 wk off therapy to comprise a treatment cycle of 4-wk period. Lowest recommended daily dose: 80 mg. Max daily dose: 160 mg.

Should be taken with food: Take at the same time each day. Swallow whole w/ water after a light meal that contains <30% fat.

Hypersensitivity.

Risk of LFT abnormalities. Perform LFTs (ALT, AST & bilirubin) before treatment initiation & closely monitor (at least every 2 wk) during the 1st 2 mth of treatment, then continue periodic monitoring at least mthly thereafter & as clinically indicated. Mild, indirect (unconjugated) hyperbilirubinaemia may occur in patients w/ Gilbert's syndrome. Increased incidence of infection events. Consider treatment interruption in cases of worsening infection events. Increased incidence of haemorrhagic events. Consider permanent treatment discontinuation in the event of severe bleeding necessitating urgent medical intervention. Risk of GI perforation & fistulae. Discontinue treatment if GI perforation or fistula develops. Increased incidence of myocardial ischaemia & infarction. Caution in patients w/ unstable angina or new onset angina (w/in 3 mth of starting Stivarga therapy), recent MI (w/in 6 mth of starting Stivarga therapy) & those w/ cardiac failure NYHA class ≥2. Risk of posterior reversible encephalopathy syndrome (PRES). Discontinue treatment if PRES develops. Increased incidence of arterial HTN. Control BP prior to treatment initiation. Discontinue treatment in case of hypertensive crisis. Carefully consider risk of aneurysms &/or artery dissections before initiating treatment in patients w/ risk factors eg, HTN or history of aneurysm. Risk of thrombotic microangiopathy (TMA), including TTP. Discontinue therapy if TMA develops. May suppress or interfere w/ wound healing. Temporarily interrupt treatment in patients undergoing major surgical procedures. Risk of hand-foot skin reaction (HFSR) or palmar-plantar erythrodysesthesia syndrome. Consider permanent treatment discontinuation in cases of severe or persistent HFSR. Increased incidence of electrolyte abnormalities (including hypophosphatemia, hypocalcaemia, hyponatraemia, hypokalaemia) & metabolic abnormalities (including increased TSH, lipase, amylase). Monitor biochemical & metabolic parameters during treatment. Consider dose interruption/reduction or permanent treatment discontinuation in case of persistent or recurrent significant abnormalities. Each 160-mg daily dose contains 56.06 mg of Na & 1.68 mg of lecithin (derived from soya). Do not drive or use machines if symptoms affecting the ability to conc & react occur during treatment. Closely monitor overall safety in patients w/ mild or moderate hepatic impairment (Child-Pugh A or B). Not recommended in patients w/ severe hepatic impairment (Child-Pugh C). Women of childbearing potential & men should ensure effective contraception during treatment & up to 8 wk after completion of therapy. Should not be used during pregnancy unless clearly necessary & after careful consideration of benefits & risks. Discontinue breast-feeding during treatment. No relevant use in the paed population for the indication of HCC & metastatic CRC. Safety & efficacy have not been established in patients <18 yr for the indication of GIST.

Infection; thrombocytopenia, anaemia; decreased appetite & food intake; haemorrhage, HTN; dysphonia; diarrhoea, stomatitis, vomiting, nausea, constipation; hyperbilirubinaemia, increased transaminases; HFSR, rash; asthenia/fatigue, pain, fever, mucosal inflammation; wt loss. Leucopenia; hypothyroidism; hypokalaemia, hypophosphatemia, hypocalcaemia, hyponatraemia, hypomagnesaemia, hyperuricaemia, dehydration; headache, tremor, peripheral neuropathy; taste disorders, dry mouth, GERD, gastroenteritis; alopecia, dry skin, exfoliative rash; muscle spasms; proteinuria; increased amylase/lipase, abnormal INR.

Increased exposure of regorafenib & decreased exposure of M-2 & M-5 active metabolites if co-administered w/ ketoconazole (strong CYP3A4 inhibitor). Avoid concomitant use w/ strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole); strong UGT1A9 inhibitors (eg, mefenamic acid, diflunisal, niflumic acid). Reduced AUC of regorafenib & increased exposure of M-5 active metabolite if co-administered w/ rifampicin (strong CYP3A4 inducer). Increased metabolism w/ other strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarb, St. John's wort). Increased AUC of irinotecan & SN-38 active metabolite (UGT1A1 substrate). Increased systemic exposure to UGT1A1 & UGT1A9 substrates. Increased AUC & C_max of rosuvastatin (BCRP substrate). Increased plasma conc of other BCRP substrates (eg, MTX, fluvastatin, atorvastatin). Inhibitors & inducers of BCRP & P-gp may interfere w/ exposure of M-2 & M-5 active metabolites. Co-administration w/ neomycin or bile salt-sequestering agents (eg, cholestyramine, cholestagel) may result in decreased regorafenib efficacy.

Targeted Cancer Therapy

L01EX05 - regorafenib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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