sorafenib
Pharmacologic class: Multikinase inhibitor
Therapeutic class: Antineoplastic
Pregnancy risk category D
Action
Decreases tumor cell proliferation in vitro and inhibits tumor growth of murine renal cell carcinoma; interacts with multiple intracellular and cell-surface kinases, several of which are involved with angiogenesis
Availability
Tablets: 200 mg
Indications and dosages
➣ Advanced renal cell carcinoma; unresectable hepatocellular carcinoma
Adults: 400 mg P.O. twice daily, continued until patient no longer benefits from therapy or experiences unacceptable toxicity
Dosage adjustment
• Bleeding event
• Cardiac ischemia or infarction
• Severe or persistent hypertension
• Skin toxicity
• Major surgery
Off-label uses
• Advanced pancreatic cancer
• Recurrent epithelial ovarian cancer
• Hepatocellular, breast, colon, colorectal, non-small-cell lung, and thyroid cancers
• Melanoma and sarcoma
Contraindications
• Hypersensitivity to drug or its components
• Combination with carboplatin and paclitaxel in patients with squamous cell lung cancer
Precautions
Use cautiously in:
• skin toxicities, hypertension, bleeding, cardiac ischemia, myocardial infarction (MI), congestive heart failure (CHF), bradyarrhythmias, or electrolyte abnormalities
• congenital long QT syndrome (avoid use)
• concurrent use of gemcitabine/cisplatin in patients with squamous cell lung cancer (not recommended)
• concurrent use of drugs known to prolong QT interval (including Class Ia and III antiarrhythmics), CYP3A4 inducers, or CYP2B6 and CYP2C8 substrates
• patients undergoing surgery
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
Administration
• Administer without food (1 hour before or 2 hours after eating).
Adverse reactions
CNS: fatigue, sensory neuropathy, headache, asthenia, depression
CV: hypertension, myocardial ischemia, MI, heart failure, hypertensive crisis, prolonged QT/QTc interval
EENT: hoarseness
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, mouth pain, mucositis, stomatitis, dyspepsia, dysphagia, anorexia, GI perforation (uncommon)
GU: erectile dysfunction
Hepatic: drug-induced hepatitis
Hematologic: lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, hemorrhage
Musculoskeletal: arthralgia, myalgia
Respiratory: cough, dyspnea
Skin: rash, desquamation, palmar-plantar erythrodysesthesia (PPE), alopecia, pruritus, dry skin, erythema, acne, flushing, exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
Other: decreased appetite, weight loss, flulike syndrome, fever, hypersensitivity (including angioedema, anaphylactic reaction)
Interactions
Drug-drug. CYP3A4 inducers (such as carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin): increased sorafenib metabolism and decreased blood level
Docetaxel: increased docetaxel area under the curve (AUC) and plasma concentration
Neomycin: decreased sorafenib mean area under the curve
Warfarin: increased risk of bleeding, elevated INR
Drug-diagnostic tests. Amylase, bilirubin, lipase: increased
Hemoglobin, platelets, serum phosphates, WBCs: decreased
Liver enzymes: increased
Drug-food. High-fat meal: reduced drug bioavailability
Drug-herbs. St. John's wort: decreased sorafenib blood level
Patient monitoring
• Monitor CBC with differential, platelets, serum phosphate, INR, amylase, lipase, and liver enzyme levels.
• Watch closely for PPE.
• Measure blood pressure weekly during first 6 weeks of therapy and thereafter as needed.
☞ Monitor for cardiac symptoms, especially prolonged QT interval, in patients with CHF, bradyarrhythmias, electrolyte abnormalities, and concurrent use of drugs known to prolong QT interval. If cardiac ischemia or infarction occurs, consider temporarily or permanently discontinuing drug.
☞ If GI perforation occurs, discontinue drug and initiate appropriate measures.
☞ Be aware that drug-induced hepatitis may result in hepatic failure and death. Discontinue drug if there is no alternative explanation for significant transaminase elevations (such as viral hepatitis or progressing, underlying malignancy).
☞ Monitor patient for SJS and TEN; discontinue drug if either of these conditions, which may be life-threatening, occur.
☞ Watch for bleeding. If bleeding necessitates medical intervention, consider discontinuing drug.
Patient teaching
• Instruct patient to take drug 1 hour before or 2 hours after eating.
☞ Urge patient to immediately report irregular heartbeats or signs and symptoms of liver disorder or hypersensitivity, including rash, bleeding, or chest pain.
• Advise patient to report symptoms of PPE (redness, pain, swelling, or blisters on hands and soles). Mention that these symptoms may warrant dosage decrease.
• Stress importance of weekly blood pressure checks during first 6 weeks of therapy.
• Instruct males and females to use effective birth control during therapy.
• Tell female with childbearing potential to avoid pregnancy during therapy and for at least 2 weeks after.
• Advise breastfeeding patient to stop breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.