Nexavar

Nexavar,

a trademark for sorafenib.

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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.