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
Pregnancy
There are no available data in pregnant women to inform a drug associated risk
Animal data
Based on findings from animal studies and mechanism of action, therapy may cause fetal harm when administered to a pregnant woman; in animal reproduction studies, oral administration to pregnant rats and rabbits during period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at recommended dose of 400 mg twice daily; apprise pregnant women and females of reproductive potential of potential risk to fetus
Pregnancy testing
Verify pregnancy status of females of reproductive potential prior to initiation of therapy
Contraception
Females: Therapy may cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 6 months following last dose of drug
Males: Based on genotoxicity and findings in animal reproduction studies, advise male patients with female partners of reproductive potential and pregnant partners to use effective contraception during treatment and for 3 months after the last dose
Infertility
Males: Based on findings in animal studies, therapy may impair fertility in males of reproductive potential
Lactation
There are no data on presence of drug or its metabolites in human milk, or its effects on breast-fed child or on milk production; drug was present in milk of lactating rats; because of potential for serious adverse reactions in breastfed child from drug, advise lactating women not to breastfeed during treatment and for 2 weeks after last dose
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.