Loading…
Sorafenib is a brand name for Sorafenib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Sorafenib tablets are a kinase inhibitor indicated for the treatment of Unresectable hepatocellular carcinoma(1.1) Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment (1.3) 1.1 Hepatocellular Carcinoma Sorafenib tablets are indicated for the…
Verbatim from this product's FDA label. Tap a section to expand.
•The recommended dosage is 400 mg orally twice daily without food. 1 Recommended Dosage The recommended dosage of sorafenib tablets is 400 mg orallytwice daily without food (at least 1 hourbefore or 2 hours after a meal) until the patient is no longer clinically benfiting from therapy or untilunacceptable toxicity.
2 Dose Modifications for Adverse Reactions Recommended Dosage Modifications The recommended dosage modifications for adverse reactions are provided in Tables 1, 2, and 3. 1)] Cardiac Ischemia and/or Infarction Grade 2 and above Permanently discontinue.
3 Grade 4 Permanently discontinue. 2)] Grade 2 and above requiring medical intervention Permanently discontinue. 3 Grade 4 Permanently discontinue. 5)] Any grade Permanently discontinue. 9)] Greater than 500 milliseconds OR Increase from baseline of 60 milliseconds or greater Interrupt and correct electrolyte abnormalities (magnesium, potassium, calcium).
Use medical judgement before restarting. 10)] Grade 3 ALT or higher in the absence of another cause4 OR AST/ALT greater than 3 × upper limit normal (ULN) with bilirubin greater than 2 × ULN in the absence of another cause4 Permanently discontinue.
1)] Grade 2 Continue treatment at reduced dose by 1 dose level. Grade 3 1st occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 1 dose level. No improvement within 7 days OR 2nd or 3rd occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels.
4th occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels for HCC or 3 dose levels for DTC. Grade 4 Permanently discontinue. 0). 2 If no recovery after 30 day interruption, discontinue treatment unless the patient is deriving clinical benefit.
3 If more than 2 dose reductions are required, permanently discontinue treatment. 5 or greater, ascites and/or encephalopathy in the absence of underlying cirrhosis or other organ failure considered to be due to drug-induced liver injury.
Table 3:
Recommended Dosage Modifications for Dermatologic Toxicities Dermatologic Toxicity Grade Occurrence Sorafenib T ablets Dosage Modification Hepatocellular Differentiated Thyroid Carcinoma Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities 1st occurrence Continue sorafenib tablets and consider topical therapy for symptomatic relief.
The most common adverse reactions (≥20%) are diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, hypertension, and hemorrhage. , Ltd. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described reflect exposure to sorafenib tablets in 504 patients who participated in placebo-controlled studies in hepatocellular carcinoma N=297), or differentiated thyroid carcinoma (N = 207). The most common adverse reactions (≥20%), which were considered to be related to sorafenib tablets, in patients with HCC or DTC are diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, hypertension, and hemorrhage.
Hepatocellular Carcinoma Table 4 shows the percentage of patients in the SHARP (HCC) study experiencing adverse reactions that were reported in at least 10% of patients and at a higher rate in the Sorafenib Tablets -treated group than in those eceiving placebo.
0). Hypertension was reported in 9% of patients treated with sorafenib tablets and 4% of those receiving placebo. Grade 3 hypertension was reported in 4% of sorafenib tablets -treated patients and 1% of those receiving placebo. Hemorrhage/bleeding was reported in 18% of those receiving sorafenib tablets and 20% of patients receiving placebo.
The rates of Grade 3 and 4 bleeding were also higher in patients receiving placebo (Grade 3 – 3% sorafenib tablets and 5% placebo and Grade 4 – 2% sorafenib tablets and 4% placebo). 4% in sorafenib tablets -treated patients and 4% of patients receiving placebo.
1) Hemorrhage: Discontinue sorafenib tablets if needed. 2) Hypertension: Monitor blood pressure weekly during the first 6 weeks and periodically thereafter. 3) Dermatologic Toxicities: Interrupt and/or decrease dose. 4) Gastrointestinal Perforation: Discontinue sorafenib tablets.
5) Risk of Impaired Wound Healing: Withhold sorafenib tablets for at least 10 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of sorafenib tablets after resolution of wound healing complications has not been established.
7) QT Prolongation: Monitor electrocardiograms and electrolytes in patients at increased risk for ventricular arrhythmias. Correct electrolytes. 2) Drug-Induced Liver Injury: Monitor liver function tests regularly; discontinue for unexplained transaminase elevations.
10) Embryo-Fetal Toxicity: Sorafenib tablets may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. 3) Impairment of Thyroid Stimulating Hormone Suppression (TSH) in DTC: Monitor TSH monthly and adjust thyroid replacement therapy in patients with thyroid cancer.
9% in the sorafenib tablets -treated group compared with 0% in patients receiving placebo. Patients with unstable coronary artery disease or recent myocardial infarction were excluded from this study. 2)]. 2)]. 2 Hemorrhage An increased risk of bleeding may occur following sorafenib tablets administration.
4% and 4%) were similar in sorafenib tablets -treated patients and those receiving placebo, respectively. 4%) in sorafenib tablets -treated patients and in those receiving placebo. 2)]. Due to the potential risk of bleeding, treat tracheal, bronchial, and esophageal infiltration with local therapy prior to administering sorafenib tablets in patients with DTC.
3% of patients receiving placebo. 4% of patients receiving placebo. Hypertension was usually mild to moderate, occurred early in the course of treatment, and was managed with standard antihypertensive therapy. Permanent discontinuation due to hypertension occurred in 1 of 297 sorafenib tablets -treated patients in the SHARP (HCC) study, and 1 of 207 sorafenib tablets -treated patients in the DECISION (DTC) study.
Sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. (4) Sorafenib tablets in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer.
(4) 4 CONTRAINDICATIONS Sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. 8)].
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in United States of America? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
If no improvement within 7 days, see below. Decrease sorafenib tablets to 600 mg daily If no improvement within 7 days, see below. No improvement within 7 days at reduced dose OR 2nd and 3rd occurrence Interrupt sorafenib tablets until resolved or improved to Grade 0 to 1.
Interrupt sorafenib tablets until completely resolved or improved to Grade 1. When resuming treatment, decrease dose by 1 dose level. When resuming treatment, decrease dose by 1 dose level for 2nd occurrence and 2 dose levels for 3rd occurrence.
4th occurrence Discontinue sorafenib tablets 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 1st occurrence Interrupt sorafenib tablets until resolved or improved to Grade 0 to 1.
Interrupt sorafenib tablets until completely resolved or improved to Grade 1. When resuming treatment, decrease dose by 1 dose level. When resuming treatment, decrease dose by 1 dose level. 2nd occurrence Interrupt sorafenib tablets until resolved or improved to Grade 0 to 1.
Interrupt sorafenib tablets until completely resolved or improved to Grade 1. When resuming treatment, decrease dose by 1 dose level. When resuming treatment, decrease dose by 2 dose levels. 3rd occurrence Discontinue sorafenib tablets treatment.
Following improvement of Grade 2 or 3 dermatologic toxicity to Grade 0 or 1 for at least 28 days on a reduced dose of sorafenib tablets, the dose of sorafenib tablets 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).
Renal failure was reported in <1% of patients treated with sorafenib tablets and 3% of patients receiving placebo. Clinical pancreatitis was reported in 1 of 297 sorafenib tablets -treated patients (Grade 2). The rate of adverse reactions (including those associated with progressive disease) resulting in permanent discontinuation was similar in both the sorafenib tablets -treated patients and those receiving placebo (32% of sorafenib tablets -treated patients and 35% of patients receiving placebo).
Laboratory test abnormalities reported in SHARP are presented in Table 5. 0). 3)]. 3 to 135). The population exposed to sorafenib tablets was 50% male, and had a median age of 63 years. Dose interruptions for adverse reactions were required in 66% of patients receiving sorafenib tablets and dose reductions were required in 64% of patients.
4% of patients receiving placebo. Table 8 shows the percentage of DTC patients experiencing adverse reactions at a higher rate in sorafenib tablets -treated patients than in patients receiving placebo in the double-blind phase of the DECISION study.
Grade 3 adverse reactions occurred in 53% of sorafenib tablets -treated patients compared to 23% of patients receiving placebo. Grade 4 adverse reactions occurred in 12% of sorafenib tablets-treated patients compared to 7% of patients receiving placebo.
0 2 Includes the following terms: abdominal pain, abdominal discomfort, hepatic pain, esophageal pain, esophageal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness, abdominal rigidity 3 Includes the following terms: stomatitis, aphthous stomatitis, mouth ulceration, mucosal inflammation 4 Includes the following terms: oral pain, oropharyngeal discomfort, glossitis, burning mouth syndrome, glossodynia 5 Palmar-plantar erythrodysesthesia syndrome (Hand-foot skin reaction) 6 Includes the following terms: hypertension, blood pressure increased, blood pressure systolic increased The relative increase for the following laboratory abnormalities observed in sorafenib-treated patients as compared to patients receiving placebo in the DECISION study is similar to that observed in the RCC and HCC studies: lipase, amylase, hypokalemia, hypophosphatemia, neutropenia, lymphopenia, anemia, and thrombocytopenia.
Hypocalcemia was more frequent and more severe in patients with DTC, especially those with a history of hypoparathyroidism, compared to patients with RCC or HCC. Other laboratory test abnormalities reported in DECISION are presented in Table 9.
0). 1 %): Cardiovascular:Common: congestive heart failure*†, myocardial ischemia and/or infarction Uncommon: hypertensive crisis* Rare: QT prolongation* Dermatologic:Very common: erythema Common: exfoliative dermatitis, acne, flushing, folliculitis, hyperkeratosis Uncommon: eczema, erythema multiforme Digestive:Very common: increased lipase, increased amylase Common: mucositis, stomatitis (including dry mouth and glossodynia), dyspepsia, dysphagia, gastrointestinal reflux Uncommon: pancreatitis, gastritis, gastrointestinal perforations*, cholecystitis, cholangitis Note that elevations in lipase are very common (41%, see below); a diagnosis of pancreatitis should not be made solely on the basis of abnormal laboratory values General Disorders:Very common: infection, hemorrhage (including gastrointestinal* and respiratory tract* and uncommon cases of cerebral hemorrhage*), asthenia, pain (including mouth, bone, and tumor pain), pyrexia, decreased appetite Common: influenza-like illness Hematologic:Very common: leukopenia, lymphopenia Common: anemia, neutropenia, thrombocytopenia Uncommon: INR abnormal Hepatobiliary disorders:Rare: drug-induced hepatitis (including hepatic failure and death) Hypersensitivity:Uncommon: hypersensitivity reactions (including skin reactions and urticaria), anaphylactic reaction Metabolic and Nutritional:Very common: hypophosphatemia Common: transient increases in transaminases, hypocalcemia, hypokalemia, hyponatremia, hypothyroidism Uncommon: dehydration, transient increases in alkaline phosphatase, increased bilirubin (including jaundice), hyperthyroidism Musculoskeletal:Very common: arthralgia Common: myalgia, muscle spasms Nervous System and Psychiatric:Common: depression, dysgeusia Uncommon: tinnitus, reversible posterior leukoencephalopathy* Renal and Genitourinary:Common: renal failure, proteinuria Rare: nephrotic syndrome Reproductive:Common: erectile dysfunction Uncommon: gynecomastia Respiratory:Common: rhinorrhea Uncommon: interstitial lung disease-like events (includes reports of pneumonitis, radiation pneumonitis, acute respiratory distress, interstitial pneumonia, pulmonitis and lung inflammation) In addition, the following medically significant adverse reactions were uncommon during clinical trials of sorafenib tablets: transient ischemic attack, arrhythmia, and thromboembolism.
For these adverse reactions, the causal relationship to sorafenib tablets has not been established. *adverse reactions may have a life-threatening or fatal outcome. 9% of patients treated with sorafenib tablets (N= 2276). 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of sorafenib tablets.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic disorders:
Thrombotic microangiopathy (TMA) Dermatologic:Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) Hypersensitivity: Angioedema Musculoskeletal: Rhabdomyolysis, osteonecrosis of the jaw Respiratory: Interstitial lung disease-like events (which may have a life-threatening or fatal outcome) Vascular: Arterial (including aortic) aneurysms, dissections, and rupture
Monitor blood pressure weekly during the first 6 weeks of sorafenib tablets. Thereafter, monitor blood pressure and treat hypertension, if required, in accordance with standard medical practice. 2)]. 4 Dermatologic Toxicities Hand-foot skin reaction and rash represent the most common adverse reactions attributed to sorafenib tablets.
Rash and hand-foot skin reaction are usually Grade 1 and 2 and generally appear during the first six weeks of treatment with sorafenib tablets. 3%) of 207 sorafenib tablets -treated patients with DTC. 2)]. There have been reports of severe dermatologic toxicities, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
These cases may be life-threatening. Discontinue sorafenib tablets if SJS or TEN are suspected. 5 Gastrointestinal Perforation Gastrointestinal perforation has been reported in less than 1% of patients taking sorafenib tablets. In some cases this was not associated with apparent intra-abdominal tumor.
In the event of a gastrointestinal perforation, permanently discontinue sorafenib tablets. 6 Increased Risk of Bleeding with Concomitant Us e of Warfarin Infrequent bleeding or elevations in the International Normalized Ratio (INR) have been reported in some patients taking warfarin while on sorafenib tablets.
Monitor patients taking concomitant warfarin regularly for changes in prothrombin time (PT), INR or clinical bleeding episodes. 7 Risk of Impaired Wound Healing Impaired wound healing can occur in patients who receive drugs that inhibit the VEGF signaling pathway.
Therefore, sorafenib tablets has the potential to adversely affect wound healing. Withhold sorafenib tablets for at least 10 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
The safety of resumption of sorafenib tablets after resolution of wound healing complications has not been established. 81; 95% CI 1. 80). The use of sorafenib tablets in combination with carboplatin/paclitaxel is contraindicated in patients with squamous cell lung cancer.
Sorafenib tablets in combination with gemcitabine/cisplatin are not recommended in patients with squamous cell lung cancer. The safety and effectiveness of sorafenib tablets has not been established in patients with non-small cell lung cancer.
9 QT Interval Prolongation Sorafenib tablets can prolong the QT/QTc interval. QT/QTc interval prolongation increases the risk for ventricular arrhythmias. Avoid sorafenib tablets in patients with congenital long QT syndrome. Monitor electrolytes and electrocardiograms in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics.
Correct electrolyte abnormalities (magnesium, potassium, calcium). 2)]. 10 Drug-Induced Liver Injury Sorafenib-induced hepatitis is characterized by a hepatocellular pattern of liver damage with significant increases of transaminases which may result in hepatic failure and death.
Increases in bilirubin and INR may also occur. 06%) in a global monotherapy database. Monitor liver function tests regularly. 2)]. 11 Embryo-Fetal Toxicity Based on its mechanism of action and findings in animals, sorafenib tablets may cause fetal harm when administered to a pregnant woman.
Sorafenib caused embryo-fetal toxicities in animals at maternal exposures that were significantly lower than the human exposures at the recommended dose of 400 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of sorafenib tablets. 3)]. 12 Impairment of Thyroid Stimulating Hormone Suppression in Differentiated Thyroid Carcinoma Sorafenib tablets impairs exogenous thyroid suppression.
5 mU/L. 5 mU/L was observed in 41% of sorafenib tablets -treated patients as compared with 16% of those receiving placebo patients. 4 mU/L. Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC.