Nexavar

Sorafenib

Treatment of hepatocellular carcinoma (HCC). Treatment of patients w/ advanced renal cell carcinoma (RCC) who have failed prior interferon-α or interleukin-2 based therapy or are considered unsuitable for such therapy. Treatment of patients w/ progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine.

400 mg bd (total daily dose of 800 mg). When necessary, reduce dose to 2 tab of 200 mg once daily for HCC & RCC, & to 600 mg daily in divided doses (two 200-mg tab & one 200-mg tab 12 hr apart) for DTC. If additional dose reduction is necessary, reduce to 400 mg daily in divided doses (two 200-mg tab 12 hr apart), & if necessary further reduce to one 200-mg tab once daily. Dose may be increased after improvement of non-haematological adverse reactions.

Should be taken on an empty stomach: Take on an empty stomach or w/ a low or moderate fat meal. If the patient intends to have a high fat meal, take at least 1 hr before or 2 hr after meals.

Hypersensitivity.

Risk of dermatological toxicities; arterial HTN; formation of aneurysms &/or artery dissections; decreases in blood glucose; haemorrhage; treatment-emergent cardiac ischaemia/infarction events; QT interval prolongation; GI perforation (uncommon). Patients taking concomitant warfarin or phenprocoumon should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes. Temporary interrupt therapy in patients undergoing major surgical procedures. Caution when co-administered w/ compd that are metabolised/eliminated predominantly by UGT1A1 (eg, irinotecan) or UGT1A9 pathways; docetaxel; neomycin or other antibiotics. Reports of higher mortality in patients w/ squamous cell carcinoma of the lung treated w/ sorafenib + platinum-based chemotherapies. Monitoring of fluid balance & electrolytes in patients at risk of renal dysfunction is advised. No data available in patients requiring dialysis & in patients w/ Child Pugh C (severe) hepatic impairment. Do not use during pregnancy unless clearly necessary. Women of childbearing potential must use effective contraception during treatment. Do not breast-feed during treatment. Safety & efficacy in childn & adolescents <18 yr have not yet been established. Reports of renal failure in elderly; consider monitoring of renal function. RCC: Benefit-risk in high-risk patients has not been evaluated. DTC: Management of suspected adverse drug reactions may require temporary interruption or dose reduction of sorafenib therapy. Treat tracheal, bronchial & oesophageal infiltration w/ localized therapy prior to administering sorafenib. Close monitoring of blood Ca & TSH levels are recommended.

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

Decreased conc w/ CYP3A4 inducers (eg, rifampicin, St. John's wort, phenytoin, carbamazepine, phenobarb, dexamethasone). Potential increase in plasma conc of P-gp substrates eg, digoxin. Modest increases in capecitabine & 5-FU exposure when co-administered w/ sorafenib. 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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