Home

helps physicians and healthcare professionals

Erectile Dysfunction

helps physicians and healthcare professionals

Doctor123.org

helps physicians and healthcare professionals

SORAfenib


General


Pronunciation

(sor AF e nib)


Brand Names: U.S.

  • NexAVAR

Indications


Use: Labeled Indications

Hepatocellular cancer: Treatment of unresectable hepatocellular cancer (HCC)

Renal cell cancer, advanced: Treatment of advanced renal cell cancer (RCC)

Thyroid cancer, differentiated: Treatment of locally recurrent or metastatic, progressive, differentiated thyroid cancer (refractory to radioactive iodine treatment)


Contraindications


Known severe hypersensitivity to sorafenib or any component of the formulation; use in combination with carboplatin and paclitaxel in patients with squamous cell lung cancer


Dosing and Administration


Dosing: Adult

Note: Interrupt treatment (temporarily) in patients undergoing major surgical procedures.

Hepatocellular cancer (HCC): Oral: 400 mg twice daily; continue until no longer clinically benefiting or until unacceptable toxicity occurs (Llovet 2008)

Renal cell cancer (RCC), advanced: Oral: 400 mg twice daily; continue until no longer clinically benefiting or until unacceptable toxicity occurs (Escudier 2007; Escudier 2009)

Thyroid cancer, differentiated: Oral: 400 mg twice daily; continue until no longer clinically benefiting or until unacceptable toxicity occurs (Brose 2013)

Angiosarcoma (off-label use): Oral: 400 mg twice daily (Maki 2009)

Gastrointestinal stromal tumor (GIST) (off-label use): Oral: 400 mg twice daily (Wiebe 2008)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

Manufacturer 's labeling: No dosage adjustment is necessary for mild, moderate, or severe impairment (not dependent on dialysis); has not been studied in dialysis patients.

The following adjustments have also been reported: Safety and pharmacokinetics were studied in varying degrees of renal dysfunction with the following empiric dose levels recommended based on patient tolerance (Miller, 2009):

CrCl 40 to 59 mL/minute: 400 mg twice daily

CrCl 20 to 39 mL/minute: 200 mg twice daily

CrCl <20 mL/minute: Data inadequate to define dose

Hemodialysis (any CrCl): 200 mg once daily


Dosing: Hepatic Impairment

Hepatic impairment at baseline:

Manufacturers labeling:

Mild to moderate (Child-Pugh class A and B) impairment: No dosage adjustment is necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

The following adjustments have also been reported: Safety and pharmacokinetics were studied in varying degrees of hepatic dysfunction with the following empiric dose levels recommended based on patient tolerance (Miller, 2009):

Mild hepatic dysfunction (bilirubin >1 to ≤1.5 times ULN and/or AST >ULN): 400 mg twice daily

Moderate hepatic dysfunction (bilirubin >1.5 to ≤3 times ULN; any AST): 200 mg twice daily

Severe hepatic dysfunction:

Bilirubin >3 to 10 x ULN (any AST): 200 mg every 3 days was not tolerated

Albumin <2.5 g/dL (any bilirubin and any AST): 200 mg once daily

Drug-induced liver injury during treatment: Unexplained (eg, not due to viral hepatitis or progressive underlying malignancy) significantly increased transaminases: Discontinue treatment.


Administration

Administer on an empty stomach (1 hour before or 2 hours after eating).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). NIOSH recommends single gloving for administration of an intact tablet. If it is necessary to manipulate the tablets (eg, to prepare an oral suspension), it is recommended to double glove, wear a protective gown, and prepare in a controlled device (NIOSH 2014).


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F). Protect from moisture.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

NexAVAR: 200 mg


Extemporaneously Prepared

Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). When manipulating tablets, NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye protection as well as ventilated engineering controls are recommended (NIOSH 2014).

An oral suspension may be prepared with tablets. Place two 200 mg tablets into a glass containing 60 mL (2 oz) water; let stand 5 minutes before stirring. Stir until tablets are completely disintegrated, forming a uniform suspension. Administer within 1 hour after preparation. Stir suspension again immediately before administration. To ensure the full dose is administered, rinse glass several times with a total of 180 mL (6 oz) water and administer residue. Note: Brown tablet coating may initially form a thin film but has no effect on the dosing accuracy.

Nexavar data on file, Bayer Healthcare Pharmaceuticals.

Drug Interactions

Acetaminophen: May enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Consider therapy modification

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bevacizumab: May enhance the adverse/toxic effect of SORAfenib. Specifically, the risk for hand-foot skin reaction may be increased. Monitor therapy

Bisphosphonate Derivatives: Systemic Angiogenesis Inhibitors may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

CARBOplatin: SORAfenib may enhance the adverse/toxic effect of CARBOplatin. Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Avoid combination

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cholic Acid: BSEP/ABCB11 Inhibitors (Clinically Relevant) may decrease the excretion of Cholic Acid. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of SORAfenib. Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of SORAfenib. Monitor therapy

Dacarbazine: SORAfenib may decrease the serum concentration of Dacarbazine. Sorafenib may also increase the concentration of dacarbazines active metabolite. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

DOCEtaxel: SORAfenib may increase the serum concentration of DOCEtaxel. Monitor therapy

DOXOrubicin (Conventional): SORAfenib may increase the serum concentration of DOXOrubicin (Conventional). Monitor therapy

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fluorouracil (Systemic): SORAfenib may decrease the serum concentration of Fluorouracil (Systemic). SORAfenib may increase the serum concentration of Fluorouracil (Systemic). Monitor therapy

Fluorouracil (Topical): SORAfenib may decrease the serum concentration of Fluorouracil (Topical). SORAfenib may increase the serum concentration of Fluorouracil (Topical). Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Irinotecan Products: SORAfenib may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. SORAfenib may increase the serum concentration of Irinotecan Products. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Neomycin: May decrease the serum concentration of SORAfenib. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

PACLitaxel (Conventional): SORAfenib may enhance the adverse/toxic effect of PACLitaxel (Conventional). Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Avoid combination

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Propacetamol: SORAfenib may enhance the hepatotoxic effect of Propacetamol. SORAfenib may increase serum concentrations of the active metabolite(s) of Propacetamol. Specifically, acetaminophen exposure may be increased. Management: Consider less frequent and/or lower daily doses of propacetamol in patients who are also taking sorafenib. Monitor for liver toxicity, particularly with higher propacetamol doses. Consider therapy modification

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of SORAfenib. Avoid combination

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Warfarin: SORAfenib may enhance the anticoagulant effect of Warfarin. SORAfenib may increase the serum concentration of Warfarin. Management: Warfarin dose adjustment will likely be necessary. Increase frequency of INR monitoring during sorafenib therapy (particularly when starting or stopping therapy), and increase monitoring for signs and symptoms of bleeding. Consider therapy modification


Monitoring Parameters

CBC with differential, electrolytes (magnesium, potassium, calcium), phosphorus, lipase and amylase levels; liver function tests; blood pressure (baseline, weekly for the first 6 weeks, then periodic); monitor for hand-foot skin reaction and other dermatologic toxicities; monitor ECG in patients at risk for prolonged QT interval; signs/symptoms of bleeding; signs/symptoms of GI perforation. Additionally the Canadian labeling recommends considering monitoring of left ventricular ejection fraction at baseline and periodically during treatment.

Thyroid function testing:

Patients with differentiated thyroid cancer: Monitor TSH monthly.

Patients with RCC and HCC (Hamnvik 2011):

Pre-existing levothyroxine therapy: Obtain baseline TSH levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months

Without pre-existing thyroid hormone replacement: TSH at baseline, then every 4 weeks for 4 months, then every 2 to 3 months


Adverse Reactions


>10%:

Cardiovascular: Hypertension (9% to 41%; grade 3: 3% to 4%; grade 4: <1%; grades 3/4: 10%, onset: ~3 weeks)

Central nervous system: Fatigue (37% to 46%), headache ( ≤10% to 17%), mouth pain (14%), voice disorder (13%), peripheral sensory neuropathy ( ≤13%), pain (11%)

Dermatologic: Palmar-plantar erythrodysesthesia (21% to 69%; grade 3: 6% to 8%; grades 3/4: 19%), alopecia (14% to 67%), skin rash (including desquamation; 19% to 40%; grade 3: ≤1%; grades 3/4: 5%), pruritus (14% to 20%), xeroderma (10% to 13%), erythema ( ≥10%)

Endocrine & metabolic: Hypoalbuminemia ( ≤59%), weight loss (10% to 49%), hypophosphatemia (35% to 45%; grade 3: 11% to 13%; grade 4: <1%), increased thyroid stimulating hormone level (>0.5 mU/L: 41%; due to impairment of exogenous thyroid suppression), hypocalcemia (12% to 36%), increased amylase (30% to 34% [usually transient])

Gastrointestinal: Diarrhea (43% to 68%; grade 3: 2% to 10%; grade 4: <1%), increased serum lipase (40% to 41% [usually transient]), abdominal pain (11% to 31%), decreased appetite (30%), anorexia (16% to 29%), stomatitis (24%), nausea (21% to 24%), constipation (14% to 16%), vomiting (11% to 16%)

Hematologic & oncologic: Lymphocytopenia (23% to 47%; grades 3/4: ≤13%), thrombocytopenia (12% to 46%; grades 3/4: 1% to 4%), increased INR ( ≤42%), neutropenia ( ≤18%; grades 3/4: ≤5%), hemorrhage (15% to 17%; grade 3: 2%), leukopenia

Hepatic: Increased serum ALT (59%; grades 3/4: 4%), increased serum AST (54%; grades 3/4: 2%), hepatic insufficiency ( ≤11%; grade 3: 2%; grade 4: 1%)

Infection: Infection

Neuromuscular & skeletal: Limb pain (15%), weakness (12%), myalgia

Respiratory: Dyspnea ( ≤14%), cough ( ≤13%)

Miscellaneous: Fever (11%)

1% to 10%:

Cardiovascular: Ischemic heart disease (including myocardial infarction; ≤3%), cardiac failure (2%, congestive), flushing

Central nervous system: Depression, glossalgia

Dermatologic: Hyperkeratosis (7%), acne vulgaris, exfoliative dermatitis, folliculitis

Endocrine & metabolic: Hypokalemia (5% to 10%), hyponatremia, hypothyroidism

Gastrointestinal: Dysgeusia (6%), dyspepsia, dysphagia, gastroesophageal reflux disease, mucositis, xerostomia

Genitourinary: Erectile dysfunction, proteinuria

Hematologic & oncologic: Squamous cell carcinoma of skin (3%; grades 3/4: 3%), anemia

Hepatic: Increased serum transaminases (transient)

Neuromuscular & skeletal: Muscle spasm (10%), arthralgia ( ≤10%), myalgia

Renal: Renal failure

Respiratory: Epistaxis (7%), flu-like symptoms, hoarseness, rhinorrhea

<1% (Limited to important or life-threatening): Acute renal failure, amyotrophy, anaphylaxis, angioedema, aortic dissection, cardiac arrhythmia, cardiac failure, cerebral hemorrhage, cholangitis, cholecystitis, dehydration, eczema, erythema multiforme, gastritis, gastrointestinal hemorrhage, gastrointestinal perforation, gynecomastia, hepatic failure, hepatitis, hypersensitivity reaction (skin reaction, urticaria), hypertensive crisis, hyperthyroidism, increased serum alkaline phosphatase, increased serum bilirubin, interstitial pulmonary disease (acute respiratory distress, interstitial pneumonia, lung inflammation, pneumonitis, pulmonitis, radiation pneumonitis), malignant neoplasm of skin (keratoacanthomas), nephrotic syndrome, ostealgia, osteonecrosis (jaw), pancreatitis, pleural effusion, prolonged QT interval on ECG, respiratory tract hemorrhage, reversible posterior leukoencephalopathy syndrome (RPLS), rhabdomyolysis, Stevens-Johnson syndrome, thromboembolism, toxic epidermal necrolysis (TEN), transient ischemic attacks, tumor lysis syndrome, tumor pain


Warnings/Precautions


Special Populations: Race

Mean AUC in Asians is 30% lower than in white patients.


Warnings/Precautions

Concerns related to adverse effects:

- Bleeding: Increased risk of bleeding may occur; consider permanently discontinuing with serious bleeding events (eg, requires medical intervention). Fatal bleeding events have been reported. Thyroid cancer patients with tracheal, bronchial, and esophageal infiltration should be treated with local therapy prior to administering sorafenib due to the potential bleeding risk.

- Cardiac ischemia/infarction: May cause cardiac ischemia or infarction; consider discontinuation (temporary or permanent) in patients who develop these conditions. Use in patients with unstable coronary artery disease or recent myocardial infarction has not been studied.

- Dermatologic toxicity: Hand-foot skin reaction and rash (generally grades 1 or 2) are the most common drug-related adverse events, and typically appear within the first 6 weeks of treatment; usually managed with topical treatment, treatment delays, and/or dose reductions. Consider permanently discontinuing with severe or persistent dermatological toxicities. The risk for hand-foot skin reaction increased with cumulative doses of sorafenib (Azad 2009). Severe dermatologic toxicities, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported; may be life-threatening. Discontinue sorafenib for suspected SJS or TEN.

The following treatments may be used to manage hand-foot skin reaction in addition to the recommended dosage modifications (Lacouture 2008): Prior to treatment initiation, a pedicure is recommended to remove hyperkeratotic areas/calluses, which may predispose to HFSR; avoid vigorous exercise/activities which may stress hands or feet. During therapy, patients should reduce exposure to hot water (may exacerbate hand-foot symptoms); avoid constrictive footwear and excessive skin friction. Patients may also wear thick cotton gloves or socks and should wear shoes with padded insoles. Grade 1 HFSR may be relieved with moisturizing creams, cotton gloves and socks (at night) and/or keratolytic creams such as urea (20% to 40%) or salicylic acid (6%). Apply topical steroid (eg, clobetasol ointment) twice daily to erythematous areas of grade 2 HFSR; topical anesthetics (eg, lidocaine 2%) and then systemic analgesics (if appropriate) may be used for pain control. Resolution of acute erythema may result in keratotic areas which may be softened with keratolytic agents.

- Gastrointestinal perforation: Gastrointestinal perforation has been reported (rare); monitor patients for signs/symptoms (abdominal pain, constipation, or vomiting); discontinue treatment if gastrointestinal perforation occurs.

- Hypertension: May cause hypertension (generally mild-to-moderate), especially in the first 6 weeks of treatment; monitor. Use caution in patients with underlying or poorly-controlled hypertension. Consider discontinuing (temporary or permanent) in patients who develop severe or persistent hypertension while on appropriate antihypertensive therapy.

- QT prolongation: QT prolongation has been observed; may increase the risk for ventricular arrhythmia. Avoid use in patients with congenital long QT syndrome. Monitor electrolytes and ECG in patients with heart failure, bradyarrhythmias, and concurrent medications know to prolong the QT interval. Correct electrolyte (calcium, magnesium, potassium) imbalances. Interrupt treatment for QTc interval >500 msec or for ≥60 msec increase from baseline.

- Thyroid impairment: Sorafenib impairs exogenous thyroid suppression. TSH level elevations were commonly observed in the thyroid cancer study; monitor TSH levels monthly and as clinically necessary, and adjust thyroid replacement as needed.

- Wound healing complications: May complicate wound healing; temporarily withhold treatment for patients undergoing major surgical procedures. The appropriate timing to resume sorafenib after major surgery has not been determined.

Disease-related concerns:

- Hepatic impairment: Sorafenib levels in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B) were similar to levels observed in patients without hepatic impairment. Not studied in patients with severe hepatic impairment (Child-Pugh class C). In a small study of Asian patients with advanced HCC, sorafenib demonstrated efficacy with adequate tolerability in a hepatitis B-endemic area (Yau, 2009). There have been reports of sorafenib-induced hepatitis (including hepatic failure and death) which is characterized by hepatocellular liver damage and transaminase increases (significant); increased bilirubin and INR may also occur. Monitor hepatic function regularly; discontinue sorafenib for unexplained significant transaminase increases.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Avoid concurrent use with strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, St John 's wort); may decrease sorafenib levels/effects. Use caution when administering sorafenib with compounds that are metabolized predominantly via UGT1A1 (eg, irinotecan). The incidence of hand-foot skin reaction is increased in patients treated with sorafenib plus bevacizumab in comparison to those treated with sorafenib monotherapy (Azad, 2009). Use in combination with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Monitor PT/INR in patients on warfarin therapy due to potential for bleeding events to occur.

Special handling:

- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).


Pregnancy Risk Factor

D


Pregnancy Considerations

Animal reproduction studies have demonstrated teratogenicity and fetal loss. Based on its mechanism of action and because sorafenib inhibits angiogenesis, a critical component of fetal development, adverse effects on pregnancy would be expected. Women of childbearing potential should be advised to avoid pregnancy. Men and women of reproductive potential should use effective birth control during treatment and for at least 2 weeks after treatment is discontinued.


Actions


Pharmacology

Multikinase inhibitor; inhibits tumor growth and angiogenesis by inhibiting intracellular Raf kinases (CRAF, BRAF, and mutant BRAF), and cell surface kinase receptors (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-beta, cKIT, FLT-3, RET, and RET/PTC)


Metabolism

Hepatic, via CYP3A4 (primarily oxidated to the pyridine N-oxide; active, minor) and UGT1A9 (glucuronidation)


Excretion

Feces (77%, 51% of dose as unchanged drug); urine (19%, as metabolites)


Time to Peak

~3 hours


Half-Life Elimination

25 to 48 hours


Protein Binding

99.5%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience constipation, dry skin, hair loss, lack of appetite, itching, weight loss, muscle pain, or joint pain. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of bleeding (vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), shortness of breath, sweating a lot, confusion, vision changes, tachycardia, severe dizziness, passing out, angina, severe headache, severe abdominal pain, severe nausea, severe vomiting, severe diarrhea, swelling of arms or legs, painful extremities, severe loss of strength and energy, burning or numbness feeling, redness or irritation of palms of hands or soles of feet, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Copyright © 2016 - 2017
Doctor123.org | Disclaimer