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.
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