Axitinib Accord

Treatment with Axitinib Accord should be conducted by a physician experienced in the use of anticancer therapies. Posology The recommended dose of axitinib is 5 mg twice daily. Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs that cannot be managed by concomitant medicinal products or dose adjustments.

If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. Dose adjustments Dose increase or reduction is recommended based on individual safety and tolerability.

e. 0) for two consecutive weeks may have their dose increased to 7 mg twice daily unless the patient’s blood pressure is > 150/90 mmHg or the patient is receiving antihypertensive treatment. Subsequently, using the same criteria, patients who tolerate an axitinib dose of 7 mg twice daily may have their dose increased to a maximum of 10 mg twice daily.

Other products are available for the increased dose of 7 mg. 4). When dose reduction is necessary, the axitinib dose may be reduced to 3 mg twice daily and further to 2 mg twice daily. Dose adjustment is not required on the basis of patient age, race, gender, or body weight.

5). Selection of an alternate concomitant medicinal product with no or minimal CYP3A4/5 inhibition potential is recommended. g. the starting dose should be reduced from 5 mg twice daily to 2 mg twice daily) is recommended. 4). 5). 5). Selection of an alternate concomitant medicinal product with no or minimal CYP3A4/5 induction potential is recommended.

Although axitinib dose adjustment has not been studied in patients receiving strong CYP3A4/5 inducers, if a strong CYP3A4/5 inducer must be co-administered, a gradual dose increase of axitinib is recommended. Maximal induction with high-dose strong CYP3A4/5 inducers has been reported to occur within one week of treatment with the inducer.

If the dose of axitinib is increased, the patient should be monitored carefully for toxicity. 4). 5). 2). 2). Virtually no data are available regarding axitinib treatment in patients with a creatinine clearance of < 15 mL/min. Hepatic impairment No dose adjustment is required when administering axitinib to patients with mild hepatic impairment (Child-Pugh class A).

g. the starting dose should be reduced from 5 mg twice daily to 2 mg twice daily). 2). Paediatric population The safety and efficacy of Axitinib Accord in children and adolescents < 18 years have not been established. No data are available.

4: cardiac failure events, hypertension, thyroid dysfunction, arterial thromboembolic events, venous thromboembolic events, elevation of haemoglobin or haematocrit, haemorrhage, gastrointestinal perforation and fistula formation, wound healing complications, PRES, proteinuria, and elevation of liver enzymes.

9 The most common (≥ 20 %) adverse reactions observed following treatment with axitinib were diarrhoea, hypertension, fatigue, decreased appetite, nausea, weight decreased, dysphonia, palmar- plantar erythrodysaesthesia (hand-foot) syndrome, haemorrhage, hypothyroidism, vomiting, proteinuria, cough, and constipation.

1). Post-marketing adverse reactions identified in clinical studies are also included. The adverse reactions are listed by system organ class, frequency category and grade of severity. Frequency categories 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), very rare (< 1/10,000), and not known (cannot be estimated from the available data).

The current safety database for axitinib is too small to detect rare and very rare adverse reactions. Categories have been assigned based on absolute frequencies in the pooled clinical studies data. Within each system organ class, adverse reactions with the same frequency are presented in order of decreasing seriousness.

Table 1. 9 0 0 11 a Adverse reactions are according to treatment-emergent, all causality frequency. 0 c See Description of selected adverse reactions section. d Fatal (Grade 5) cases were reported. e Including Leukoencephalopathy. f Including cardiac failure, cardiac failure congestive, cardiopulmonary failure, ejection fraction decreased, left ventricular dysfunction and right ventricular failure.

g Including accelerated hypertension, blood pressure increased, hypertension and hypertensive crisis. h Including activated partial thromboplastin time prolonged, anal haemorrhage, arterial haemorrhage, blood urine present, central nervous system haemorrhage, cerebral haemorrhage, coagulation time prolonged, conjunctival haemorrhage, contusion, diarrhea haemorrhagic, dysfunctional uterine bleeding, epistaxis, gastric haemorrhage, gastrointestinal haemorrhage, gingival bleeding, haematemesis, haematochezia, haematocrit decreased, haematoma, haematuria, haemoglobin decreased, haemoptysis, haemorrhage, haemorrhage coronary artery, haemorrhage urinary tract, haemorrhoidal haemorrhage, haemostasis, increased tendency to bruise, international normalized ratio increased, lower gastrointestinal haemorrhage, melaena, petechiae, pharyngeal haemorrhage, prothrombin time prolonged, pulmonary haemorrhage, purpura, rectal haemorrhage, red blood cell count decreased, renal haemorrhage, scleral haemorrhage, scrotal […]

Specific safety events should be monitored before initiation of, and periodically throughout, treatment with axitinib as described below. 8). Signs or symptoms of cardiac failure should periodically be monitored throughout treatment with axitinib.

Management of cardiac failure events may require temporary interruption or permanent discontinuation and/or dose reduction of axitinib therapy. 8). In a controlled clinical study, the median onset time for hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg) was within the first month of the start of axitinib treatment and blood pressure increases have been observed as early as 4 days after starting axitinib.

5 Blood pressure should be well-controlled prior to initiating axitinib. Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. In the case of persistent hypertension, despite use of antihypertensive medicinal products, the axitinib dose should be reduced.

For patients who develop severe hypertension, temporarily interrupt axitinib and restart at a lower dose once the patient is normotensive. 2). In case of severe or persistent arterial hypertension and symptoms suggestive of posterior reversible encephalopathy syndrome (PRES) (see below), a diagnostic brain magnetic resonance image (MRI) should be considered.

8). Thyroid function should be monitored before initiation of, and periodically throughout, treatment with axitinib. Hypothyroidism or hyperthyroidism should be treated according to standard medical practice to maintain euthyroid state.

8). Axitinib should be used with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had an arterial embolic or thrombotic event within the previous 12 months.

8). Axitinib should be used with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had a venous embolic or thrombotic event within the previous 6 months. 8, polycythaemia).

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