Class: Multikinase inhibitor
- Tablets 200 mg
Decreases tumor cell proliferation in vitro.
Bioavailability is 38% to 49%. T max is 3 h. Steady state plasma levels occur within 7 days. Administration with high-fat meals reduced sorafenib bioavailability 29%.
In vitro protein binding is 99.5%.
Metabolism occurs primarily in the liver by CYP3A4 and UGT1A9-mediated glucuronidation. Eight metabolites have been identified, of which pyridine N-oxide has shown in vitro potency similar to the parent drug.
Mean elimination t ½ is about 25 to 48 h. After oral administration of a sorafenib 100 mg oral solution, 96% was recovered within 14 days (77% in the feces and 19% in the urine).
Special PopulationsRenal Function Impairment
No dose adjustments are necessary for mild, moderate, or severe renal function impairment in patients not undergoing dialysis.Hepatic Function Impairment
Mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic function impairment decreased AUC by 23% and 65%, respectively. Not studied in severe (Child-Pugh class C) hepatic function impairment.Gender
No dose adjustments are necessary for gender.Race
Mean AUC in Asians is 30% lower than in white patients.Age
No dose adjustments are necessary for age.
Indications and Usage
Treatment of advanced renal cell carcinoma; treatment of unresectable hepatocellular carcinoma.
Dosage and AdministrationAdults
PO 400 mg (two 200 mg tablets) twice daily. Continue treatment until patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.Dosage Adjustment
Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction. When dose reduction is necessary, sorafenib dosage may be reduced to 400 mg once daily; if additional dose reduction is required, dosage may be reduced to 400 mg every other day.Skin toxicity grade 1
Continue treatment and consider topical therapy for symptomatic relief.Skin toxicity grade 2 First occurrence
Continue treatment and consider topical therapy for symptomatic relief. If no relief occurs in 7 days, interrupt treatment until toxicity resolves to grade 0 to 1. When resuming treatment, decrease dosage by one dose level (400 mg twice daily to 400 mg once daily; 400 mg once daily to 400 mg every other day).Second or third occurrence
Interrupt treatment until toxicity resolves to grade 0 to 1. When resuming treatment, decrease dosage by one dose level (400 mg once daily to 400 mg every other day).Fourth occurrence
Discontinue sorafenib.Skin toxicity grade 3 First or second occurrence
Interrupt treatment until toxicity resolves to grade 0 to 1. When resuming treatment, decrease dosage by one dose level (400 mg twice daily to 400 mg once daily; 400 mg once daily to 400 mg every other day).Third occurrence
- Administer each dose with a full glass of water on an empty stomach, at least 1 h before or 2 h after eating.
- Caution patient not to chew, crush, or break tablets.
- If a dose is missed, skip that dose and administer the next dose at the regularly scheduled time. Never administer 2 doses at the same time to catch up.
Store tablets at controlled room temperature (59° to 86°F). Keep in a dry place.
Drug InteractionsCYP2B6 and CYP2C8 substrates (eg, bupropion, rosiglitazone)
Plasma levels of drugs metabolized by these isozymes are expected to be elevated by sorafenib.CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, rifampin, St. John's wort)
Sorafenib plasma levels may be reduced.Docetaxel
Use with caution; docetaxel plasma levels may be increased.Doxorubicin
Use with caution; a 21% increase in doxorubicin AUC has been reported.Drugs metabolized by UGT1A1 (eg, irinotecan)
Use with caution.Fluorouracil
Use with caution; increases and decreases in fluorouracil AUC have been reported.Warfarin
Infrequent bleeding events and elevated INR have been reported.
Laboratory Test Interactions
None well documented.
Fatigue (46%); sensory neuropathy (13%); asthenia (at least 10%); headache (10%); depression (1% to less than 10%).
Rash/desquamation (40%); hand-foot reaction (30%); alopecia (27%); pruritus (19%); dry skin (11%); erythema (at least 10%); acne, exfoliative dermatitis, flushing (1% to less than 10%).
Diarrhea (55%); anorexia (29%); nausea (24%); vomiting (16%); constipation (15%); decreased appetite, dyspepsia, dysphagia, mucositis, stomatitis (1% to less than 10%).
Erectile dysfunction (1% to less than 10%).
Thrombocytopenia, lymphopenia (47%); anemia (44%); neutropenia (18%); hemorrhage (15%); leukopenia (at least 10%).
Liver dysfunction (11%).
Hypoalbuminemia (59%); hypophosphatemia (45%); elevated INR (42%); elevated lipase (41%); elevated amylase (34%).
Weight loss (30%); transient increases in transaminases (1% to less than 10%).
Joint pain (10%); arthralgia, myalgia (1% to less than 10%).
Dyspnea (14%); hoarseness (1% to less than 10%).
Abdominal pain (30%); pain (at least 10%); influenza-like illness, pyrexia (1% to less than 10%).
Monitor BP weekly during first 6 wk of therapy and monitor and treat thereafter if necessary.
Category D .
Safety and efficacy not established.
No dose adjustment necessary in patients with Child-Pugh class A and B hepatic function impairment. Sorafenib has not been studied in patients with Child-Pugh class C hepatic function impairment.
Treatment-emergent cardiac ischemia/infarction has been reported. Consider temporary or permanent discontinuation of sorafenib in patients who develop cardiac ischemia and/or infarction.
Hand-foot skin reactions and rash are the most common adverse reactions.
An uncommon adverse reaction, which warrants discontinuation of therapy.
May increase risk of bleeding. If any bleeding event necessitates medical intervention, consider permanent discontinuation of sorafenib.
Treatment-emergent mild to moderate hypertension has been reported, usually early in the course of therapy.
Temporarily interrupt therapy in patients undergoing major surgical procedures.
No data available. Diarrhea and dermatologic events have been associated with dosages of 800 mg twice daily.
- Advise patient or caregiver to read patient information leaflet carefully before starting therapy, and to read and check for new information each time the medication is refilled.
- Advise patient that usual dosage is 2 tablets taken twice daily but that the dose may be reduced, or the medication temporarily withheld, if bothersome adverse reactions develop.
- Advise patient to take each dose with a full glass of water on an empty stomach, 1 h before or 2 h after eating. Caution patient to swallow tablets whole and not to chew, crush, or break.
- Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient not to take 2 doses at the same time to catch up.
- Advise patient that sorafenib can cause BP to become elevated and to check BP at least once a week for the first 6 wk of therapy and periodically thereafter. Advise patient that medications may be needed to control elevated BP.
- Instruct patient to immediately notify health care provider if any of the following occur: chest pain, chest pressure, or unexplained shortness of breath on exertion or with activity; redness, pain, swelling, or blistering of palms of hands or soles of feet; unexplained bleeding.
- Advise patient to notify health care provider if rash; persistent diarrhea; persistent nausea and/or vomiting; weakness; mouth sores; or numbness, tingling, or pain in hands or feet develops.
- Advise patient to use effective contraception during treatment and for 2 wk after stopping therapy.
- Caution women of childbearing potential to avoid becoming pregnant while using sorafenib and for 2 wk after stopping therapy.
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