Nexavar

sorafenib

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; 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.

SORAfenib

(so-ra-fe-nib) ,

NexAVAR

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Advanced renal cell carcinoma.Unresectable hepatocellular carcinoma.Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine therapy.

Action

Inhibits tumor growth by inhibiting multikinase enzyme, some of which are involved in angiogenesis.

Therapeutic effects

Decreased growth and spread of advanced renal cell carcinoma, hepatocellular carcinoma and DTC.

Pharmacokinetics

Absorption: 38–49% absorbed following oral administration; absorption decreased by high fat meals.
Distribution: Unknown.
Protein Binding: 995% bound to plasma proteins.
Metabolism and Excretion: Mostly metabolized by the liver (CYP3A4 and UGT1A9 systems), some metabolites are pharmacologically active. Absorbed drug is eliminated in feces (51%); of absorbed drug, 77% is excreted in feces and 19% is renally eliminated.
Half-life: 25–48 hr.

Time/action profile ( blood levelss)

ROUTEONSETPEAKDURATION
POunknown3 hr12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use with carboplatin and paclitaxel in patients with squamous cell lung cancer; Congenital long QT syndrome; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: History of cardiovascular disease; Drugs that affect the CYP3A4 or UGT1A9 systems; may result in significant interactions; Heart failure, bradycardia, concurrent use of QT-interval prolonging drugs, or electrolyte abnormalities (↑ risk of QT interval prolongation); Obstetric: Childbearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • depression (most frequent)
  • fatigue (most frequent)
  • weakness (most frequent)

Respiratory

  • interstitial lung disease (life-threatening)
  • hoarseness (most frequent)

Cardiovascular

  • torsades de pointes (life-threatening)
  • hypertension (most frequent)
  • heart failure
  • myocardial ischemia
  • QT interval prolongation

Gastrointestinal

  • 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)
  • vomiting

Genitourinary

  • erectile dysfunction
  • nephrotic syndrome
  • proteinuria
  • renal failure

Dermatologic

  • 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)
  • hypokalemia

Hematologic

  • anemia (most frequent)
  • bleeding (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)
  • lymphopenia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • myalgia (most frequent)

Neurologic

  • neuropathy (most frequent)

Miscellaneous

  • angioedema (life-threatening)
  • pain (most frequent)
  • weight loss

Interactions

Drug-Drug interaction

May ↑ 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.

Route/Dosage

Oral (Adults) 400 mg twice daily; dose ↓ recommended for skin toxicity and/or neuropathy.

Availability

Tablets: 200 mg

Nursing implications

Nursing assessment

  • 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 Diagnoses

Risk for impaired skin integrity (Adverse Reactions)

Implementation

  • 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.

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • Decreased growth and spread of advanced renal cell, hepatocellular, and thyroid carcinoma.

Nexavar

a trademark for sorafenib.
Mentioned in ?
References in periodicals archive ?
NEXAVAR is thought to inhibit both the tumor cell and tumor vasculature.
Natco Pharma could continue to manufacuture and mkt the cancer drug in India at a price that is over 30 times lesser than Bayer s to produce and sell a generic of its kidney cancer drug Nexavar in India.
It comes after the National Institute for Health and Clinical Excellence (Nice) rejected an appeal by manufacturer Bayer over the drug Nexavar (sorafenib).
She said: "Whilst the policy pledge is due in April 2011, today we are asking the Government to bring this date forward for the 400 liver cancer patients who will benefit from Nexavar.
Evidence seen by Nice suggests Nexavar can increase survival by an extra 2.
Support groups claim Nexavar can prolong life and said the ruling discriminates against the terminally ill.
Bayer AG (Leverkusen, Germany) has started testing a contested sister compound to its potential blockbuster Nexavar in the third and last phase, raising the stakes in a legal tussle with development partner Onyx Pharmaceuticals Inc.
The National Institute for Health and Clinical Excellence said the price being charged by pharmaceutical firm Bayer for the medicine Nexavar was "simply too high".
Drug-Eluting Beads to be combined with Nexavar in Phase II Study
Emeryville, CA, announced the US Food and Drug Administration (FDA) has granted Nexavar orphan drug status to treatment patients with liver cancer.
Comment: In preclinical studies, Nexavar was found to target two classes of kinases involved in tumor cell proliferation and tumor angiogenesis.
com/research/xkwg7g/liver_cancer) has announced the addition of the "Liver Cancer Therapeutics Market to 2018 - Nexavar, the Only Approved Targeted Therapy for Advanced Disease, Continues to Dominate as Other Late Stage Trials Fail" report to their offering.