sorafenib

sorafenib,

a miscellaneous antineoplastic.

indications This drug is used to treat advanced and metastatic murine renal cell carcinoma.

contraindications Pregnancy and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects of this drug include fatigue, weight loss, headache, anorexia, mouth ulceration, abdominal pain, constipation, pruritus, erythema, hand-foot rash, acne, flushing, and alopecia. Life-threatening side effects include hypertension, cardiac ischemia, infarction, pancreatitis, hemorrhage, leukopenia, lymphopenia, anemia, neutropenia, thrombocytopenia, and exfoliative dermatitis. Common side effects include nausea, diarrhea, vomiting, dry skin, hypophosphatemia, arthralgia, myalgia, and hoarseness.

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sorafenib Warning - High-alert drug!

Nexavar

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

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

Precautions

Use cautiously in:
• skin toxicities, hypertension, bleeding, cardiac ischemia, myocardial infarction (MI)
• concurrent use of CYP3A4 inducers, doxorubicin, irinotecan, 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).

Route	Onset	Peak	Duration
P.O.	Unknown	3 hr	Unknown

Adverse reactions

CNS: fatigue, sensory neuropathy, headache, asthenia, depression

CV: hypertension, myocardial ischemia, MI , heart failure, hypertensive crisis

EENT: hoarseness

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, mouth pain, mucositis, stomatitis, dyspepsia, dysphagia, anorexia

GU: erectile dysfunction

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

Other: decreased appetite, weight loss, flulike syndrome, fever

Interactions

Drug-drug. CYP3A4 inducers (such as carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin): increased sorafenib metabolism and decreased blood level

Doxorubicin, irinotecan: increased absorption of these drugs

Warfarin: increased risk of bleeding, elevated INR

Drug-diagnostic tests. Amylase, lipase: increased

Hemoglobin, platelets, serum phosphates, WBCs: decreased

Liver enzymes: transient increases

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.

Patient education

• Instruct patient to take drug 1 hour before or 2 hours after eating.
☞ Urge patient to immediately report 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.