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Pharmacologic class: Multikinase inhibitor
Therapeutic class: Antineoplastic
Pregnancy risk category D
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
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
• Bleeding event
• Cardiac ischemia or infarction
• Severe or persistent hypertension
• Skin toxicity
• Major surgery
• Advanced pancreatic cancer
• Recurrent epithelial ovarian cancer
• Hepatocellular, breast, colon, colorectal, non-small-cell lung, and thyroid cancers
• Melanoma and sarcoma
• Hypersensitivity to drug or its components
• Combination with carboplatin and paclitaxel in patients with squamous cell lung cancer
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).
• Administer without food (1 hour before or 2 hours after eating).
CNS: fatigue, sensory neuropathy, headache, asthenia, depression
CV: hypertension, myocardial ischemia, MI, heart failure, hypertensive crisis, prolonged QT/QTc interval
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)
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
• 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.
• 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.
Pharmacologic: kinase inhibitors
Time/action profile ( blood levelss)
|PO||unknown||3 hr||12 hr|
Adverse Reactions/Side Effects
Central nervous system
- depression (most frequent)
- fatigue (most frequent)
- weakness (most frequent)
- interstitial lung disease (life-threatening)
- hoarseness (most frequent)
- torsades de pointes (life-threatening)
- hypertension (most frequent)
- heart failure
- myocardial ischemia
- QT interval prolongation
- hepatotoxicity (life-threatening)
- anorexia (most frequent)
- constipation (most frequent)
- diarrhea (most frequent)
- dyspepsia (most frequent)
- dysphagia (most frequent)
- ↑ lipase/amylase
- mucositis/stomatitis (most frequent)
- nausea (most frequent)
- erectile dysfunction
- nephrotic syndrome
- renal failure
- stevens-johnson syndrome (life-threatening)
- toxic epidermal necrolysis (life-threatening)
- acne (most frequent)
- erythema (most frequent)
- exfoliative dermatitis (most frequent)
- flushing (most frequent)
- hand-foot skin reaction (most frequent)
- (most frequent)
- pruritus (most frequent)
- rash (most frequent)
- dry skin
Fluid and Electrolyte
- hypocalcemia (most frequent)
- hypophosphatemia (most frequent)
- anemia (most frequent)
- bleeding (most frequent)
- leukopenia (most frequent)
- thrombocytopenia (most frequent)
- lymphopenia (most frequent)
- arthralgia (most frequent)
- myalgia (most frequent)
- neuropathy (most frequent)
- angioedema (life-threatening)
- pain (most frequent)
- weight loss
Drug-Drug interactionMay ↑ risk of bleeding with warfarin.Metabolism is ↑ by and blood levels ↓ by inducers of CYP3A4 including rifampin, phenytoin, phenobarbital, carbamazepine, and dexamethasone.↑ blood levels and may ↑ effects of irinotecan, docetaxel, and doxorubicin.Neomycin ↓ blood levels.Metabolism is ↑ by and blood levels ↓ by St. John's wort.
- Monitor BP weekly during first 6 wks and then periodically during therapy. May cause hypertension. If unresponsive to antihypertensives, may require temporary or permanent discontinuation of sorafenib.
- Monitor ECG in patients with HF, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities.
- Assess for dermatologic toxicities. Treat any occurrence of Grade 1 (numbness, dysesthesia, parathesia, tingling, painless swelling, erythema or discomfort of hands or feet which does not disrupt patient's normal activities) with topical symptomatic therapy. Treat the first occurrence of Grade 2 (painful erythema and swelling of hands or feet and/or discomfort affecting patient's normal activities) with topical symptomatic therapy. If no improvement in 7 days or 2nd or 3rd occurrence, interrupt sorafenib therapy until resolves to Grade 0–1. Resume treatment with decreasing dose by one level. If 4th occurrence, discontinue therapy. If Grade 3 toxicity (moist desquamation, ulceration, blistering or severe pain of the hands or feet, or severe discomfort that causes the patient to be unable to work or perform activities of daily living) occurs 1st or 2nd occurrence, interrupt sorafenib therapy until resolves to Grade 0–1. Resume therapy by decreasing dose by one level. If 3rd occurrence, discontinue sorafenib therapy.
- Monitor for bleeding. If any bleeding requires medical intervention, consider permanent discontinuation of sorafenib.
- Assess for chest pain. Consider temporary or permanent discontinuation in patients who develop cardiac ischemia and/or infarction.
- Monitor for signs and symptoms of interstitial lung diseases (dyspnea, cough).
- Lab Test Considerations: Monitor serum magnesium, potassium, calcium periodically in patients with HF, bradyarrhythmias and drugs known to prolong QT interval. May cause hypocalcemia and hypokalemia.
- May ↑ TSH in patients with DTC. Monitor TSH levels monthly.
- Commonly causes hypophosphatemia, ↑ serum lipase and amylase. Pancreatitis rarely occurs.
- Frequently causes lymphopenia, anemia, and thrombocytopenia.
Potential Nursing DiagnosesRisk for impaired skin integrity (Adverse Reactions)
- Do not confuse Nexavar (sorafenib) with Nexium (esomeprazole). Do not confuse sorafenib with sunitinib.
- Oral: Administer 2 tablets (400 mg) twice daily on an empty stomach, at least 1 hr before or 2 hr after eating. Tablets should be swallowed whole and taken with water; do not crush, break or chew.
- If dose reduction is necessary due to adverse reactions, reduce to 400 mg once daily. If additional dose reduction is required, reduce to 400 mg every other day.
- Instruct patient to take sorafenib as directed. If a dose is missed, skip dose and take next dose at regular time; do not double dose. Do not share medication with others; may be harmful.
- Inform patient of risk of hand-foot skin reactions, hypertension and requirement for monitoring, risk of bleeding and cardiac ischemia. Advise patient to notify health care professional promptly if bleeding or chest pain occurs.
- Advise patient to notify health care professional immediately if signs and symptoms of hepatotoxicity (yellow skin or white part of eyes, dark “tea-colored” urine, light-colored bowel movements, worsening nausea, worsening vomiting, abdominal pain), rash, blistering or peeling of skin or inside of mouth, shortness or breath, cough, dizziness, fainting, or fever occur.
- Advise patient to notify health care professional of therapy prior to treatment, dental procedure, or surgery. Sorafenib therapy should be interrupted in patients undergoing major surgery.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Discuss with patient the possibility of hair loss. Explore coping strategies.
- May cause teratogenic effects. Advise both male and female patients to use effective contraception during and for at least 2 wks after stopping therapy. Advise female patients to avoid breastfeeding during therapy.
- Decreased growth and spread of advanced renal cell, hepatocellular, and thyroid carcinoma.