Sorafenib

Indications

Sorafenib is used for: Renal cell carcinoma, Hepatocellular Carcinoma, Thyroid Cancer

Adult Dose

Oral Advanced renal cell carcinoma, Hepatocellular Carcinoma, Thyroid Cancer Adult: 400 mg bid. May continue until patient is no longer responding or unacceptable toxicity occurs. Hepatic Impairment Mild to moderate: Dose adjustment not necessary Severe hepatic impairment: Not studied

Child Dose

Safety and efficacy not established

Renal Dose

Renal Impairment Mild to moderate: Dose adjustment not necessary Severe renal impairment: Not studied

Administration

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, sorafenib should be taken on an empty stomach at least 1 hr before or 2 hr after meals. Swallow whole, do not chew/crush.

Contra Indications

Hypersensitivity

Precautions

Interrupt teatment if patient develops cardiac infarction, ischaemia and/or bleeding fatalities. Regular monitoring of BP, CBC and platelet is recommended. Monitor INR in patients who are on treatment with warfarin. Adequate contraception should be used during and for at least 2 wk after stopping treatment. May need to discontinue treatment if severe or persistent hypertension occurs. Lactation: not known whether distributed in breast milk, discouraged

Pregnancy-Lactation

Interactions

Inducers of isoenzyme CYP3A4 e.g. carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampicin may decrease sorafenib plasma concentration. Coadmin with sorafenib may increase the plasma concentration of doxorubicin and irinotecan.

Adverse Effects

Side effects of Sorafenib : >10% Thrombocytopenia (12-46%),Anemia (44%),Diarrhea (43%),Rash/desquamation (40%),Fatigue (37%),Abd pain (31%),Hand-foot skin reaction (30%),Weight loss (30%),Anorexia (29%),Alopecia (27%),Nausea (24%),Lymphopenia (23%),Neutropenia (18%),Hemorrhage (15-18%),Hypertension (9-17%),Vomiting (16%),Constipation (15%),Neuropathy (13%),Dry skin (11%) 1-10% Headache (10%),Joint pain (10%),Congestive heart failure, MI (1.9%),QT prolonation (rare) <1% Acute renal failure,Angioedema and arrhythmia may occur,Bone pain reported Frequency Not Defined Stevens-Johnson Syndrome,Hyperthyroidism,Interstitial lung disease Potentially Fatal: Bleeding fatalities. Hypertensive crisis.

Mechanism of Action

Sorafenib inhibits cell surface and intracellular kinases to reduce proliferation of tumour cells.