Version May 2024
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: Oral: 400 mg twice daily; continue until no longer clinically benefiting or until unacceptable toxicity occurs (Ref).
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 (Ref).
Thyroid carcinoma, differentiated: Oral: 400 mg twice daily; continue until disease progression or until unacceptable toxicity (Ref).
Angiosarcoma (off-label use): Oral: 400 mg twice daily (Ref).
Gastrointestinal stromal tumor (off-label use): Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
A pharmacokinetic study evaluated sorafenib dosing to determine an initial tolerable dose in patients with varying degrees of renal dysfunction. The following empiric starting doses were identified based on patient tolerance (Ref):
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
Hepatic impairment at baseline:
Manufacturer's 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).
A pharmacokinetic study evaluated sorafenib dosing to determine an initial tolerable dose in patients with varying degrees of hepatic dysfunction. The following empiric starting doses were identified based on patient tolerance (Ref):
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:
Albumin <2.5 g/dL (any bilirubin and any AST): 200 mg once daily
Bilirubin >3 to 10 x ULN (any AST): A dose of 200 mg every 3 days was not tolerated, therefore no dosage was identified in this pharmacokinetic study for patients meeting these parameters.
Drug-induced liver injury during treatment:
ALT elevation, grade 3 or higher (in the absence of another cause): Permanently discontinue sorafenib.
ALT, AST >3 times ULN with bilirubin >2 times ULN (in the absence of another cause): Permanently discontinue sorafenib.
Alkaline phosphatase increase (any grade) in the absence of known bone pathology and bilirubin increase (grade 2 or higher): Permanently discontinue sorafenib.
INR ≥1.5 considered to be due to drug-induced liver injury: Permanently discontinue sorafenib.
Ascites and/or encephalopathy (in the absence of underlying cirrhosis or other organ failure) considered to be due to drug-induced liver injury: Permanently discontinue sorafenib.
|
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 reaction |
Severity |
Sorafenib dosage modification |
|---|---|---|
|
a If sorafenib is discontinued, a drop in BP is expected and antihypertensive therapy should be reduced and/or interrupted as clinically appropriate (ESC [Lyon 2022]). | ||
|
b ASCO (Armenian 2017); ESC (Lyon 2022). | ||
|
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 |
If indicated, initiate appropriate antihypertensive therapya to reduce the risk for cardiovascular complicationsb. | |
|
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. | |
|
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. | ||
Refer to adult dosing.
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
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.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
NexAVAR: 200 mg
Generic: 200 mg
Yes
Tablets (NexAVAR Oral)
200 mg (per each): $255.13
Tablets (SORAfenib Tosylate Oral)
200 mg (per each): $210.83 - $216.74
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
NexAVAR: 200 mg
Available from specialty pharmacies. Further information may be obtained at 1-866-639-2827 or www.nexavar-us.com.
Oral: Administer without food (at least 1 hour before or 2 hours after a meal).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Hepatocellular carcinoma: Treatment of unresectable hepatocellular carcinoma (HCC).
According to guidelines from the American Society of Clinical Oncology for systemic therapy for advanced HCC, sorafenib is a first-line option for select patients with advanced HCC with Child Pugh class A hepatic impairment, performance status of 0 or 1, and with contraindications to atezolizumab and/or bevacizumab therapy. Sorafenib is a second-line therapy option in patients who received first-line therapy with atezolizumab and bevacizumab (ASCO [Gordan 2020]).
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).
Angiosarcoma (recurrent or metastatic); Gastrointestinal stromal tumor (resistant or refractory)
NexAVAR may be confused with NexIUM.
SORAfenib may be confused with axitinib, gefitinib, imatinib, lenvatinib, regorafenib, selumetinib, sonidegib, SUNItinib, tivozanib, vandetanib, vemurafenib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (major), UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP/ABCB11, UGT1A1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: 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. Risk D: Consider therapy modification
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Belinostat: UGT1A1 Inhibitors may increase the serum concentration of Belinostat. Risk X: Avoid combination
Bevacizumab: May enhance the adverse/toxic effect of SORAfenib. Specifically, the risk for hand-foot skin reaction may be increased. Risk C: 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. Risk C: Monitor therapy
CARBOplatin: SORAfenib may enhance the adverse/toxic effect of CARBOplatin. CARBOplatin may increase the serum concentration of SORAfenib. 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. Risk D: Consider therapy modification
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
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. Risk D: Consider therapy modification
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of SORAfenib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of SORAfenib. Risk X: Avoid combination
Dacarbazine: SORAfenib may enhance the adverse/toxic effect of Dacarbazine. SORAfenib may increase serum concentrations of the active metabolite(s) of Dacarbazine. Risk C: 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. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOCEtaxel: SORAfenib may increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
GlyBURIDE: SORAfenib may enhance the hypoglycemic effect of GlyBURIDE. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the absorption of SORAfenib. Risk C: 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. Risk X: Avoid combination
Neomycin (Systemic): May decrease the serum concentration of SORAfenib. Risk X: 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. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
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. Risk X: Avoid combination
PACLitaxel (Protein Bound): SORAfenib may enhance the adverse/toxic effect of PACLitaxel (Protein Bound). 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. Risk X: Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: 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. Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Taurursodiol: BSEP/ABCB11 Inhibitors may enhance the adverse/toxic effect of Taurursodiol. Specifically, the risk for liver dysfunction may be increased. Management: Avoid coadministration of sodium phenylbutyrate and taurursodiol with BSEP inhibitors when possible. If concomitant use is necessary, monitoring of serum transaminases and bilirubin is recommended. Risk D: Consider therapy modification
Warfarin: SORAfenib may enhance the anticoagulant effect of Warfarin. SORAfenib may increase the serum concentration of Warfarin. Risk C: Monitor therapy
Bioavailability is decreased 29% with a high-fat meal containing 900 calories, 50% from fat (bioavailability is similar to fasting state when administered with a moderate-fat meal). Management: Administer without food, at least 1 hour before or 2 hours after a meal.
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.
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.
It is not known if sorafenib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during sorafenib treatment and for 2 weeks after the final sorafenib dose.
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). Monitor BP (baseline, weekly for the first 6 weeks, then as indicated). Monitor ECG in patients at risk for prolonged QT interval. Monitor for signs/symptoms of bleeding, GI perforation, hand-foot skin reaction and other dermatologic toxicities, heart failure, and/or 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.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment, including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). BP at each clinical visit (as well as daily home monitoring for first cycle, after dose increases, and every 2 to 3 weeks thereafter); ECG and QTc assessment in patients at moderate- or high-risk of QTc prolongation (assess QTc monthly during the first 3 months and every 3 to 6 months thereafter); baseline echocardiography in high- and very high-risk patients (repeat every 3 months during the first year and every 6 to 12 months thereafter); consider baseline echocardiography in low- and moderate-risk patients (consider repeating every 4 months during the first year for moderate-risk patients and every 6 to 12 months thereafter) (ESC [Lyon 2022]).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
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)
Protein binding: 99.5%.
Metabolism: Hepatic, via CYP3A4 (primarily oxidated to the pyridine N-oxide; active, minor) and UGT1A9 (glucuronidation).
Bioavailability: 38% to 49%; reduced by 29% when administered with a high-fat (900 calories; 50% from fat) meal.
Half-life elimination: 25 to 48 hours.
Time to peak, plasma: ~3 hours.
Excretion: Feces (77%, 51% of dose as unchanged drug); urine (19%, as metabolites).
Race/ethnicity: Mean AUC in Asians is 30% lower than in white patients.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
