Sorafenib Accord

Sorafenib Accord treatment should be supervised by a physician experienced in the use of anticancer therapies. Posology The recommended dose of Sorafenib Accord in adults is 400 mg sorafenib (two tablets of 200 mg) twice daily (equivalent to a total daily dose of 800 mg).

Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. 3 Posology adjustments Management of suspected adverse drug reactions may require temporary interruption or dose reduction of sorafenib therapy.

4). When dose reduction is necessary during the treatment of differentiated thyroid carcinoma (DTC), the Sorafenib Accord dose should be reduced to 600 mg sorafenib daily in divided doses (two tablets of 200 mg and one tablet of 200 mg twelve hours apart).

If additional dose reduction is necessary, Sorafenib Accord may be reduced to 400 mg sorafenib daily in divided doses (two tablets of 200 mg twelve hours apart), and if necessary further reduced to one tablet of 200 mg once daily. After improvement of non-haematological adverse reactions, the dose of Sorafenib Accord may be increased.

Paediatric population The safety and efficacy of Sorafenib Accord in children and adolescents aged <18 years have not yet been established. No data are available. Elderly population No dose adjustment is required in the elderly (patients above 65 years of age).

Renal impairment No dose adjustment is required in patients with mild, moderate or severe renal impairment. 2). Monitoring of fluid balance and electrolytes in patients at risk of renal dysfunction is advised. Hepatic impairment No dose adjustment is required in patients with Child Pugh A or B (mild to moderate) hepatic impairment.

2). Method of administration For oral use. It is recommended that sorafenib should be administered without food or with a low or moderate fat meal. If the patient intends to have a high-fat meal, sorafenib tablets should be taken at least 1 hour before or 2 hours after the meal.

The tablets should be swallowed with a glass of water.

Summary of the safety profile 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.

Tabulated list of adverse reactions Adverse reactions reported in multiple clinical trials or through post-marketing use are listed below in table 1, 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.

Table 1:

All adverse reactions reported in patients in multiple clinical trials or through post- marketing use System organ class Very common Common Uncommon Rare Not known Infections and infestations infection folliculitis Blood and lymphatic system disorders lymphopenia leucopenia neutropenia anaemia thrombocytopenia Immune system disorders hypersensitivity reactions (including skin reactions and urticaria) anaphylactic reaction angioedema Endocrine disorders hypothyroidism hyperthyroidism Metabolism and nutrition disorders anorexia hypo- phosphataemia hypocalcaemia hypokalaemia hyponatraemia hypoglycaemia dehydration tumour lysis syndrome Psychiatric disorders depression Nervous system disorders peripheral sensory neuropathy dysgeusia reversible posterior leukoencephalo- pathy* encephalo- pathy° 10 System organ class Very common Common Uncommon Rare Not known Ear and labyrinth disorders tinnitus Cardiac disorders congestive heart failure* myocardial ischaemia and infarction* QT prolongation Vascular disorders haemorrhage (inc.

Dermatological toxicities Hand foot skin reaction (palmar-plantar erythrodysaesthesia) and rash represent the most common adverse drug reactions with sorafenib. Rash and hand foot skin reaction are usually CTC (Common Toxicity Criteria) Grade 1 and 2 and generally appear during the first six weeks of treatment with sorafenib.

8). 4 Hypertension An increased incidence of arterial hypertension was observed in sorafenib-treated patients. Hypertension was usually mild to moderate, occurred early in the course of treatment, and was amenable to management with standard antihypertensive therapy.

Blood pressure should be monitored regularly and treated, if required, in accordance with standard medical practice. 8). Aneurysms and artery dissections The use of vascular endothelial growth factor (VEGF) pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections.

Before initiating Sorafenib Accord, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm. Hypoglycaemia Decreases in blood glucose, in some cases clinically symptomatic and requiring hospitalization due to loss of consciousness, have been reported during sorafenib treatment.

In case of symptomatic hypoglycaemia, sorafenib should be temporarily interrupted. Blood glucose levels in diabetic patients should be checked regularly in order to assess if anti-diabetic medicinal product's dosage needs to be adjusted.

Haemorrhage An increased risk of bleeding may occur following sorafenib administration. 8). 4%). 3% in the placebo group. Patients with unstable coronary artery disease or recent myocardial infarction were excluded from these studies. 8).

1), which may lead to an increased risk for ventricular arrhythmias. Use sorafenib with caution in patients who have, or may develop prolongation of QTc, such as patients with a congenital long QT syndrome, patients treated with a high cumulative dose of anthracycline therapy, patients taking certain anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and those with electrolyte disturbances such as hypokalaemia, hypocalcaemia, or hypomagnesaemia.

1.