Sorafenat 200 Adverse Reactions

The most important serious adverse reactions were myocardial infarction/ischaemia, gastrointestinal perforation, drug induced hepatitis, haemorrhage, and hypertension/hypertensive crisis.
The most common adverse reactions were diarrhoea, fatigue, alopecia, infection, hand foot skin reaction (corresponds to palmar plantar erythrodysaesthesia syndrome in MedDRA) and rash. Adverse reactions reported in multiple clinical trials or through post-marketing use are listed as follows in Table 2, by system organ class (in MedDRA) and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 2.)

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Further information on selected adverse drug reactions: Congestive heart failure: In company sponsored clinical trials congestive heart failure was reported as an adverse event in 1.9% of patients treated with sorafenib (N=2276). In study 11213 (RCC) adverse events consistent with congestive heart failure were reported in 1.7% of patients treated with sorafenib and 0.7% receiving placebo. In study 100554 (HCC), 0.99% of those treated with sorafenib and 1.1% receiving placebo were reported with these events.
Additional information on special populations: In clinical trials, certain adverse drug reactions such as hand foot skin reaction, diarrhoea, alopecia, weight decrease, hypertension, hypocalcaemia, and keratoacanthoma/squamous cell carcinoma of skin occurred at a substantially higher frequency in patients with differentiated thyroid compared to patients in the renal cell or hepatocellular carcinoma studies.
Laboratory test abnormalities in HCC (study 3) and RCC (study 1) patients: Increased lipase and amylase were very commonly reported. CTCAE Grade 3 or 4 lipase elevations occurred in 11% and 9% of patients in the sorafenib group in study 1 (RCC) and study 3 (HCC), respectively, compared to 7% and 9% of patients in the placebo group. CTCAE Grade 3 or 4 amylase elevations were reported in 1% and 2% of patients in the sorafenib group in study 1 and study 3, respectively, compared to 3% of patients in each placebo group. Clinical pancreatitis was reported in 2 of 451 sorafenib treated patients (CTCAE Grade 4) in study 1, 1 of 297 sorafenib treated patients in study 3 (CTCAE Grade 2), and 1 of 451 patients (CTCAE Grade 2) in the placebo group in study 1.
Hypophosphataemia was a very common laboratory finding, observed in 45% and 35% of sorafenib treated patients compared to 12% and 11% of placebo patients in study 1 and study 3, respectively. CTCAE Grade 3 hypophosphataemia (1-2 mg/dl) in study 1 occurred in 13% of sorafenib treated patients and 3% of patients in the placebo group, in study 3 in 11% of sorafenib treated patients and 2% of patients in the placebo group. There were no cases of CTCAE Grade 4 hypophosphataemia (<1 mg/dl) reported in either sorafenib or placebo patients in study 1, and 1 case in the placebo group in study 3. The aetiology of hypophosphataemia associated with sorafenib is not known CTCAE Grade 3 or 4 laboratory abnormalities occurring in ≥5% of sorafenib treated patients included lymphopenia and neutropenia.
Hypocalcaemia was reported in 12% and 26.5% of sorafenib treated patients compared to 7.5% and 14.8% of placebo patients in study 1 and study 3, respectively. Most reports of hypocalcaemia were low grade (CTCAE Grade 1 and 2). CTCAE grade 3 hypocalcaemia (6.0-7.0 mg/dL) occurred in 1.1% and 1.8% of sorafenib treated patients and 0.2% and 1.1% of patients in the placebo group, and CTCAE grade 4 hypocalcaemia (<6.0 mg/dL) occurred in 1.1% and 0.4% of sorafenib treated patients and 0.5% and 0% of patients in the placebo group in study 1 and 3, respectively. The aetiology of hypocalcaemia associated with sorafenib is not known.
In studies 1 and 3 decreased potassium was observed in 5.4% and 9.5% of sorafenib-treated patients compared to 0.7% and 5.9% of placebo patients, respectively. Most reports of hypokalaemia were low grade (CTCAE Grade 1). In these studies CTCAE Grade 3 hypokalaemia occurred in 1.1% and 0.4% of sorafenib treated patients and 0.2% and 0.7% of patients in the placebo group. There were no reports of hypokalaemia CTCAE grade 4.
Laboratory test abnormalities in DTC patients (study 5): Hypocalcaemia was reported in 35.7% of sorafenib treated patients compared to 11.0% of placebo patients. Most reports of hypocalcaemia were low grade. CTCAE grade 3 hypocalcaemia occurred in 6.8% of sorafenib treated patients and 1.9% of patients in the placebo group, and CTCAE grade 4 hypocalcaemia occurred in 3.4% of sorafenib treated patients and 1.0% of patients in the placebo group.
Other clinically relevant laboratory abnormalities observed in the study 5 are shown in Table 3. (See Table 3.)

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