Vascular Endothelial Growth Factor (VEGF) Inhibitor

Indications: Renal cell carcinoma: Treatment of advanced renal cell carcinoma Soft tissue sarcoma: Treatment of advanced soft tissue sarcoma (in patients who have received prior chemotherapy) Limitations of use: The efficacy of pazopanib for the treatment of adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated.

Cautions: monitor liver function before treatment and at weeks 3, 5, 7, and 9, then at months 3 and 4, and periodically thereafter as clinically indicated if elevated liver enzymes observed control blood pressure before initiating and monitor blood pressure within 1 week of treatment initiation, then frequently throughout treatment (consider dose reduction or interruption if hypertension uncontrolled despite anti-hypertensive therapy. discontinue if blood pressure persistently elevated despite anti-hypertensive therapy and pazopanib dose reduction)

susceptibility to QT-interval prolongation (including electrolyte disturbances, concomitant use of drugs that prolong QT-interval). patients at risk of thrombotic events including myocardial infarction, ischaemic stroke or transient ischaemic attack. cardiac disease (monitor for signs or symptoms of congestive heart failure—monitor left ventricular ejection fraction in patients at risk of heart failure before and during treatment) patients at increased risk of haemorrhage patients at increased risk of gastro- intestinal perforation or fistulas. discontinue treatment 7 days before elective surgery and restart only if adequate wound healing; monitor thyroid function. monitor for proteinuria increased risk of thrombotic microangiopathy—permanently discontinue if symptoms develop. monitor for signs and symptoms of posterior reversible encephalopathy syndrome (including headache, hypertension, seizure, lethargy, confusion, visual and neurological disturbances)—permanently discontinue treatment if symptoms occur.

Contra-indications: cerebral or clinically significant gastro-intestinal haemorrhage or haemoptysis in the past 6 months.

Hepatic impairment: use with caution in mild to moderate impairment (reduce dose to 200 mg once daily in moderate impairment).avoid in severe impairment.

Renal impairment: use with caution if creatinine clearance less than 30 ml/minute (no information available).

Pregnancy: avoid unless potential benefit outweighs risk (toxicity in animal studies) effective contraception advised during treatment.

Side Effects: Most commonly: abdominal pain, abdominal distension, dyspepsia, diarrhoea, weight loss, anorexia, dry mouth, taste disturbance, flatulence, hepatic dysfunction, hyperbilirubinaemia, hypertension, flushing, chest pain, oedema, venous thromboembolic events, dyspnea, cough, pneumothorax, hiccups, epistaxis, voice changes, headache, dizziness, malaise, paraesthesia, insomnia, hypothyroidism, proteinuria (discontinue if grade 4), blood disorders (including thrombocytopenia), hyperalbuminaemia, increased amylase, dehydration, muscle spasm, myalgia, blurred vision, sweating, skin reactions, dry skin, hair and skin discoloration, nail disorders. less commonly: hepatic failure, gastro- intestinal perforation, peritonitis, pancreatitis, fistula, cardiac dysfunction, transient ischaemic attack, stroke, myocardial infarction, myocardial ischaemia, bradycardia, haemorrhage, hypertensive crisis, QT-interval prolongation, pulmonary embolism, peripheral neuropathy, menstrual disturbances, hypomagnesaemia, arthralgia, oropharyngeal pain, photosensitivity reactions. rarely thrombotic microangiopathy.

Dose: adult over 18 years: 800 mg once daily adjust dose in steps of 200 mg according to tolerability (max. 800 mg daily).