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SORAfenib

Medically reviewed by Drugs.com. Last updated on Sep 14, 2020.

Pronunciation

(sor AF e nib)

Index Terms

  • BAY 43-9006
  • Sorafenib Tosylate

Dosage Forms

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

Tablet, Oral:

NexAVAR: 200 mg

Brand Names: U.S.

  • NexAVAR

Pharmacologic Category

  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
  • Antineoplastic Agent, Vascular Endothelial Growth Factor (VEGF) Inhibitor

Pharmacology

Sorafenib is a multikinase inhibitor that 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%

Special Populations: Race

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

Use: Labeled Indications

Hepatocellular carcinoma: Treatment of unresectable hepatocellular carcinoma (HCC).

Renal cell carcinoma, advanced: Treatment of advanced renal cell carcinoma (RCC).

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

Off Label Uses

Angiosarcoma (recurrent or metastatic)

Data from a phase II sarcoma study which included patients with angiosarcoma support the use of sorafenib in the treatment of angiosarcoma [Maki 2009].

Gastrointestinal stromal tumor (resistant or refractory)

Data from 2 small phase II studies support the use of sorafenib in the treatment of gastrointestinal stromal tumor (GIST), which is resistant to prior therapy with imatinib and sunitinib [Kindler 2011], [Park 2012]. Data from a larger, multicenter, retrospective study also suggest sorafenib may be of benefit in the management of GIST in patients who had failed prior tyrosine kinase therapy, including imatinib and sunitinib, and in some patients who had also failed nilotinib [Montemurro 2013].

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: Adult

Note: Temporarily withhold sorafenib for at least 10 days prior to elective surgery; do not administer sorafenib for at least 2 weeks following major surgery and until adequate wound healing.

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

Off-label dosing: A large, retrospective analysis in patients with HCC determined that a reduced initial dose (<800 mg/day) was associated with a reduced pill burden, reduced cost, and a trend toward reduced discontinuation rates while not associated with inferior overall survival rates. Most patients had Child-Pugh class A or B impairment; the average sorafenib starting dose was 367 mg/day; doses were escalated within 2 months of initiation in less than half of the patients (Reiss 2017).

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

Thyroid carcinoma, differentiated: Oral: 400 mg twice daily; continue until disease progression or until unacceptable toxicity (Brose 2014).

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

Gastrointestinal stromal tumor (off-label use): Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Kindler 2011; Montemurro 2013; Park 2012).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Recommended Sorafenib Dose Reduction Levels for Adverse Reactions

Dose reduction

Hepatocellular carcinoma and renal cell carcinoma

Differentiated thyroid carcinoma

Usual (initial) dose

400 mg twice daily

400 mg twice daily

First dose reduction

400 mg once daily

400 mg (morning) and 200 mg (evening) ~12 hours apart or 200 mg (morning) and 400 mg (evening) ~12 hours apart

Second dose reduction

200 mg once daily or 400 mg every other day

200 mg twice daily

Third dose reduction

None

200 mg once daily

Adverse Reactions Requiring Sorafenib Dosage Adjustment

Adverse reaction

Severity

Sorafenib dosage modification

Cardiac ischemia and/or infarction

Grade 2 or higher

Permanently discontinue sorafenib.

Heart failure

Grade 3

Interrupt treatment until resolves to grade 1 or lower, resume sorafenib with the dose reduced by 1 dose level.

If no resolution after 30 days of treatment interruption, discontinue treatment unless patient is deriving clinical benefit. If more than 2 dose reductions are necessary, permanently discontinue sorafenib.

Grade 4

Permanently discontinue sorafenib.

Hypertension

Grade 2 symptomatic/persistent or grade 2 symptomatic increase by >20 mm Hg (diastolic) or >140/90 mm Hg if previously within normal limits or grade 3

Interrupt sorafenib treatment (and manage with antihypertensive therapy) until symptoms resolve and diastolic BP is <90 mm Hg, then resume with the dose reduced by 1 dose level. If needed, reduce an additional dose level. If more than 2 dose reductions are necessary, permanently discontinue sorafenib.

Grade 4

Permanently discontinue sorafenib.

QT prolongation

QTc interval >500 msec or ≥60 msec increase from baseline

Interrupt treatment and correct electrolyte (magnesium potassium, calcium) abnormality. Use medical judgment before restarting.

GI perforation

Any grade

Permanently discontinue sorafenib.

Hemorrhage

Grade 2 or higher requiring medical intervention

Permanently discontinue sorafenib.

Other nonhematologic toxicities

Grade 2

Continue treatment with the dose reduced by 1 dose level.

Grade 3 (first occurrence)

Interrupt treatment until resolves to grade 2 or less, then resume with the dose reduced by 1 dose level.

Grade 3 (no improvement within 7 days or second or third occurrence)

Interrupt treatment until resolves to grade 2 or less, then resume with the dose reduced by 2 dose levels.

Grade 3 (fourth occurrence)

Interrupt treatment until resolves to grade 2 or less, then resume with the dose reduced by 2 dose levels (for hepatocellular or renal cell carcinomas) or by 3 levels (for differentiated thyroid carcinoma).

Grade 4

Permanently discontinue sorafenib.

Sorafenib Dosage Modifications for Dermatologic Toxicities

Dermatologic toxicity grade

Occurrence

Sorafenib dosage modificationa

Hepatocellular and renal cell carcinoma

Differentiated thyroid carcinoma

aFollowing improvement of grade 2 or 3 dermatologic toxicity to grade 0 to 1 after at least 28 days of a reduced dose, the sorafenib dose may be increased 1 dose level from the reduced dose. Approximately 50% of patients requiring a dose reduction for dermatologic toxicity are expected to meet these criteria for resumption of the higher dose and roughly 50% of patients resuming the previous dose are expected to tolerate the higher dose (that is, maintain the higher dose level without recurrent grade 2 or higher dermatologic toxicity).

Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting normal activities

First occurrence

Continue sorafenib treatment and consider topical therapy for symptomatic relief. If no improvement within 7 days, see below.

Decrease dose to 600 mg daily. If no improvement within 7 days, see below.

No improvement within 7 days or second or third occurrence

Interrupt sorafenib treatment until resolved or improved to grade 0 to 1. When resuming treatment, decrease dose by 1 dose level.

Interrupt sorafenib treatment until completely resolved or improved to grade 1. When resuming treatment, decrease dose by 1 dose level for second occurrence and by 2 dose levels for third occurrence.

Fourth occurrence

Discontinue sorafenib treatment.

Grade 3: Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living

First occurrence

Interrupt sorafenib treatment until resolved or improved to grade 0 to 1. When resuming treatment, decrease dose by 1 dose level.

Interrupt sorafenib treatment until completely resolved or improved to grade 1. When resuming treatment, decrease dose by 1 dose level.

Second occurrence

Interrupt sorafenib treatment until resolved or improved to grade 0 to 1. When resuming treatment, decrease dose by 1 dose level.

Interrupt sorafenib treatment until completely resolved or improved to grade 1. When resuming treatment, decrease dose by 2 dose levels.

Third occurrence

Discontinue sorafenib treatment.

Suspected Stevens-Johnson syndrome or toxic epidermal necrolysis

Discontinue sorafenib treatment.

Extemporaneously Prepared

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. The suspension is ready for administration after 10 minutes. 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.Lam MS. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy. 2011;31(2):164-192. doi:10.1592/phco.31.2.164[PubMed 21275495]

Administration

Oral: Administer without food (at least 1 hour before or 2 hours after a meal).

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Acetaminophen: May enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and sorafenib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Consider therapy modification

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: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw 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

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cholic Acid: BSEP/ABCB11 Inhibitors may decrease the excretion of Cholic Acid. Management: Avoid the use of bile salt efflux pump inhibitors with cholic acid. If such a combination cannot be avoided, monitor serum transaminases (eg, AST, ALT) and bilirubin closely. Consider therapy modification

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

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

GlyBURIDE: SORAfenib may enhance the hypoglycemic effect of GlyBURIDE. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Irinotecan Products: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Avoid combination

Neomycin: May decrease the serum concentration of SORAfenib. Avoid combination

Obeticholic Acid: BSEP/ABCB11 Inhibitors may increase serum concentrations of the active metabolite(s) of Obeticholic Acid. Management: Avoid concomitant use of obeticholic acid and bile salt efflux pump (BSEP) inhibitors if possible. If concomitant therapy is necessary, monitor patients for elevated liver transaminases and elevated bilirubin. 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

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

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

Proton Pump Inhibitors: May decrease the absorption of SORAfenib. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Avoid combination

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypertension (9% to 41%)

Dermatologic: Alopecia (14% to 67%), palmar-plantar erythrodysesthesia (21% to 69%), pruritus (14% to 20%), skin rash (including desquamation; 19% to 40%), xeroderma (10% to 13%)

Endocrine & metabolic: Hypoalbuminemia (59%), hypocalcemia (12% to 36%), hypophosphatemia (35% to 45%), increased amylase (30% to 34%), increased thyroid stimulating hormone level (>0.5 mU/L: 41%), weight loss (10% to 49%)

Gastrointestinal: Abdominal pain (11% to 31%), anorexia (16% to 29%), constipation (14% to 16%), decreased appetite (30%), diarrhea (43% to 68%), gastrointestinal hemorrhage, increased serum lipase (40% to 41%), nausea (21% to 24%), stomatitis (24%; grades 3/4: 2%), vomiting (11% to 16%)

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

Hepatic: Hepatic insufficiency (11%), increased serum alanine aminotransferase (59%), increased serum aspartate aminotransferase (54%)

Infection: Infection

Nervous system: Fatigue (37% to 46%), headache (10% to 17%), mouth pain (14%), pain (including tumor pain), peripheral sensory neuropathy (13%), voice disorder (13%)

Neuromuscular & skeletal: Asthenia (12%), limb pain (15%), ostealgia

Respiratory: Dyspnea (14%), respiratory tract hemorrhage

Miscellaneous: Fever (11%)

1% to 10%:

Cardiovascular: Cardiac failure (2%), flushing, ischemic heart disease (including myocardial infarction: 2% to 3%)

Dermatologic: Acne vulgaris, erythema of skin (10%), exfoliative dermatitis, folliculitis, hyperkeratosis (7%)

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

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

Genitourinary: Erectile dysfunction, proteinuria

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

Nervous system: Depression

Neuromuscular & skeletal: Arthralgia (10%), muscle spasm (10%), myalgia

Renal: Renal failure syndrome

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

<1%:

Cardiovascular: Cardiac arrhythmia, hypertensive crisis, prolonged QT interval on ECG, thromboembolism, transient ischemic attacks

Dermatologic: Eczema, erythema multiforme

Endocrine & metabolic: Dehydration, gynecomastia, hyperthyroidism

Gastrointestinal: Cholangitis, cholecystitis, gastritis, gastrointestinal perforation, pancreatitis

Genitourinary: Nephrotic syndrome

Hepatic: Hepatic failure, hepatic injury, increased serum alkaline phosphatase (transient), increased serum bilirubin, jaundice

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Nervous system: Cerebral hemorrhage, reversible posterior leukoencephalopathy syndrome

Otic: Tinnitus

Respiratory: Interstitial pulmonary disease (acute respiratory distress, interstitial pneumonitis, pneumonitis, radiation pneumonitis)

Frequency not defined: Hepatic: Hepatitis

Postmarketing:

Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis

Hematologic & oncologic: Thrombotic microangiopathy

Hypersensitivity: Angioedema

Neuromuscular & skeletal: Osteonecrosis of the jaw, rhabdomyolysis

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Increased risk of bleeding may occur; consider permanently discontinuing sorafenib 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.

• Cardiovascular events: Sorafenib may cause cardiac ischemia or infarction; heart failure has been reported in multiple clinical studies. Depending on the severity, cardiovascular events may require treatment interruption, dose reduction, and/or discontinuation. Patients with unstable coronary artery disease or recent myocardial infarction were excluded from some studies. In a scientific statement from the American Heart Association, sorafenib has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: minor) (AHA [Page 2016]).

• 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 sorafenib treatment. Dermatologic toxicity is usually managed with topical treatment, treatment delays, dose reductions, and/or (in severe or persistent cases), permanent discontinuation. The risk for hand-foot skin reaction increased with cumulative doses of sorafenib; in addition, 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). 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.

• GI perforation: GI perforation has been reported (rare); monitor patients for signs/symptoms (abdominal pain, constipation, or vomiting); permanently discontinue sorafenib treatment if GI perforation occurs.

• Hepatotoxicity: Sorafenib-induced hepatitis (characterized by a hepatocellular pattern of liver damage with significant increases of transaminases) may result in hepatic failure and death. Bilirubin elevations and INR increases may also occur. Severe drug-induced liver injury (transaminase elevations >20 times ULN or with significant clinical sequelae [eg, elevated INR, ascites, transplantation or fatality]) occurred rarely. Monitor LFTs regularly. Discontinue sorafenib if significantly increased transaminases occur without alternative explanation (eg, viral hepatitis, progressing underlying malignancy).

• Hypertension: Sorafenib may cause hypertension (generally mild to moderate), especially in the early course of sorafenib treatment. Monitor BP weekly during first 6 weeks of treatment; thereafter, monitor and manage as appropriate. 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 with sorafenib; may increase the risk for ventricular arrhythmia. Avoid sorafenib 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 carcinoma study; monitor TSH levels monthly and as clinically necessary, and adjust thyroid replacement as needed.

• Wound healing complications: Vascular endothelial growth factor receptor inhibitors are associated with impaired wound healing; therefore, sorafenib may affect wound healing. Withhold sorafenib treatment for at least 10 days prior to elective surgery; do not administer sorafenib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming sorafenib treatment after resolution of wound healing complications has not been established.

Monitoring Parameters

CBC with differential, electrolytes (magnesium, potassium, calcium), phosphorus, lipase and amylase levels; LFTs; evaluate pregnancy status prior to treatment initiation (in females of reproductive potential); BP (baseline, weekly for the first 6 weeks, then as indicated); monitor for hand-foot skin reaction and other dermatologic toxicities; monitor ECG in patients at risk for prolonged QT interval; signs/symptoms of bleeding, GI perforation, heart failure, impaired wound healing. Monitor adherence.

Thyroid function testing:

Patients with differentiated thyroid cancer: Monitor TSH monthly.

Patients with RCC and HCC (Hamnvik 2011):

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

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

Reproductive Considerations

Evaluate pregnancy status in females of reproductive potential prior to initiating sorafenib treatment. Females of reproductive potential should use effective contraception during treatment and for 6 months after the final sorafenib dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last sorafenib dose.

Pregnancy Considerations

Information related to sorafenib use in pregnancy is limited (Mahdi 2018). Based on the mechanism of action and findings from animal reproduction studies, in utero exposure to sorafenib may cause fetal harm. Sorafenib inhibits angiogenesis, which is a critical component of fetal development.

Patient Education

What is this drug used for?

• It is used to treat cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Constipation

• Abdominal pain

• Nausea

• Vomiting

• Loss of strength and energy

• Dry skin

• Hair loss

• Lack of appetite

• Itching

• Weight loss

• Muscle spasm

• Muscle pain

• Mouth irritation

• Change in taste

• Mouth sores

• Acne

• Flushing

• Runny nose

• Joint pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Bleeding like 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 severe or persistent bleeding

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Thyroid problems like change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, trouble focusing, inability handling heat or cold, menstrual changes, tremors, or sweating

• Depression

• Sexual dysfunction

• Shortness of breath

• Excessive weight gain

• Sweating a lot

• Vision changes

• Fast heartbeat

• Severe dizziness

• Passing out

• Chest pain

• Severe headache

• Abnormal heartbeat

• Swelling of arms or legs

• Painful extremities

• Burning or numbness feeling

• Redness or irritation of palms of hands or soles of feet

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.