Sorafenat 200

Sorafenib

Hepatocellular carcinoma (HCC) in those unable to undergo surgery & whom local chemotherapy is unsuitable. Advanced renal cell carcinoma (RCC). Locally advanced or metastatic, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine.

400 mg (2 tab) bid. Total daily dose: 800 mg. Continue until observed clinical benefit or unacceptable toxicity. Dose reduction: HCC, advanced RCC 2 tab once daily. DTC 600 mg daily in divided doses (two 200 mg-tab & one 200 mg-tab 12 hr apart). May further reduce to 200 mg bid, followed by 200 mg once daily. May be increased after improvement of non-hematological adverse reactions.

Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meal.

Hypersensitivity.

Permanently discontinue treatment in severe or persistent cases of hand foot skin reaction (palmar-plantar erythrodysaesthesia) & rash; in cases of severe or persistent HTN or hypertensive crisis despite institution of antihypertensives; if any bleeding event necessitates medical intervention. Interrupt treatment temporarily, modify dose &/or apply topical therapy in case of rash & hand foot skin reaction that appear during the 1st 6 wk of treatment; reduce dose in managing suspected adverse drug reactions; in case of symptomatic hypoglycemia; in patients undergoing major surgical procedures. Consider temporary or permanent discontinuation in patients who develop cardiac ischaemia &/or infarction. Discontinue in case of GI perforation. Increased incidence of arterial HTN, risk of bleeding; decreased blood glucose due to loss of consciousness; QT/QTc interval prolongation leading to increased risk for ventricular arrhythmias; GI perforation; treatment-emergent cardiac ischaemia/infarction; grade 3 & 4 hypocalcemia in patients w/ DTC. Patients who have or may develop QTc prolongation eg, w/ congenital long QT syndrome, treated w/ high cumulative dose of anthracycline therapy, taking certain anti-arrhythmics or other medicinal products that lead to QT prolongation, & those w/ electrolyte disturbances (eg, hypokalaemia, hypocalcaemia or hypomagnesaemia). High risk patients w/ RCC. Carefully evaluate prognosis of individual patient considering max lesion size, symptoms related to disease & progression rate before initiating treatment. Treat tracheal, bronchial, & esophageal infiltration w/ localized therapy prior to administration in patients w/ DTC. Regularly monitor BP & treat in accordance w/ standard medical practice if required; check blood glucose levels in diabetic patients to assess if anti-diabetic medicinal product dosage needs to be adjusted. Consider periodic monitoring w/ on-treatment electrocardiograms & electrolytes (Mg, K, & Ca). Closely monitor TSH & blood Ca level in DTC patients. Correct severe hypocalcaemia to prevent QT-prolongation or torsade de pointes complications. Regularly monitor changes in prothrombin time, INR or clinical bleeding episodes in patients taking concomitant warfarin or phenprocoumon. Infrequent bleeding events or INR elevations w/ concomitant warfarin therapy. Concomitant treatment w/ compounds metabolised/eliminated predominantly by UGT1A1 (eg, irinotecan) or UGT1A9 pathways; docetaxel; neomycin or other antibiotics. Consider risk of reduced plasma conc before concomitant use w/ antibiotics. Higher incidence of resp failure, hemorrhages & infectious adverse events in patients treated w/ add-on platinum-based chemotherapies. Patients requiring dialysis. Monitor fluid balance & electrolytes in patients at risk of renal dysfunction. Severe hepatic impairment (Child-Pugh C). Women of childbearing potential must use effective contraception during treatment & for at least 2 wk after completion. May impair male & female fertility. Not to be used during pregnancy. Discontinue breastfeeding during treatment. Childn. Consider monitoring renal function in elderly.

Infection; lymphopenia; anorexia, hypophosphataemia; HTN, haemorrhage including GI, resp tract, & cerebral haemorrhage; diarrhoea, nausea, vomiting, constipation; dry skin, rash, alopecia, hand foot skin reaction, erythema, pruritus; arthralgia; fatigue, fever, pain including mouth, abdominal, bone, tumour pain & headache; decreased wt, increased amylase & lipase. Folliculitis; leucopenia, neutropenia, anaemia, thrombocytopenia; hypothyroidism; hypocalcaemia, hypokalaemia, hyponatraemia, hypoglycaemia; depression; peripheral sensory neuropathy, dysgeusia; tinnitus; CHF, myocardial ischaemia & infarction; flushing; rhinorrhoea, dysphonia; dyspepsia, dysphagia, GERD, stomatitis including dry mouth & glossodynia; keratoacanthoma/squamous cell cancer of skin, dermatitis, exfoliative acne, skin desquamation, hyperkeratosis; myalgia, muscle spasms; renal failure, proteinuria; erectile dysfunction; asthenia, flu-like illness, mucosal inflammation; transient increase in transaminases. SJS, TEN.

Reduced AUC w/ rifampicin. Decreased conc w/ other inducers of CYP3A4 activity &/or glucuronidation eg, Hypericum perforatum (St. John's wort), phenytoin, carbamazepine, phenobarb & dexamethasone. Concomitant use w/ warfarin or phenprocoumon; other antibiotics. Inhibited glucuronidation via UGT1A1 & UGT1A9. Increased plasma conc of P-gp substrates eg, digoxin. Increased exposure of paclitaxel; capecitabine & 5-FU. Increased AUC of doxorubicin; irinotecan. Increased AUC & C_max of docetaxel. Decreased exposure w/ neomycin.

Targeted Cancer Therapy

L01EX02 - sorafenib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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