Drug Action
Pazopanib is a tyrosine kinase inhibitor.
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Drug reference
Pazopanib is a tyrosine kinase inhibitor.
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First-line treatment of advanced renal cell carcinoma | Treatment of advanced renal cell carcinoma in patients who have had previous treatment with cytokine therapy ▶BY MOUTH ▶Adult: 800 mg daily, adjust dose in steps of 200 mg according to tolerability; maximum 800 mg per day Treatment of selective subtypes of advanced soft-tissue sarcoma ▶BY MOUTH ▶Adult: (consult product literature)
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DUE TO INTERACTIONS ▶Manufacturer advises if concurrent use of potent inhibitors of CYP3A4 is unavoidable, reduce dose to 400 mg daily.
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Cardiac disease. increased risk of gastro- intestinal fistulas. increased risk of gastro-intestinal perforation. increased risk of haemorrhage. increased risk of thrombotic microangiopathy—permanently discontinue if symptoms develop. ischaemic stroke. myocardial infarction. risk of thrombotic events. susceptibility to QT- interval prolongation (including electrolyte disturbances). transient ischaemic attack CAUTIONS, FURTHER INFORMATION ▶Elective surgery Discontinue treatment 7 days before elective surgery and restart only if adequate wound healing. ▶Blood pressure Blood pressure must be controlled before initiating treatment.
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NICE decisions ▶Pazopanib for the first-line treatment of advanced renal cell carcinoma (updated August 2013) NICE TA215 Pazopanib (Votrient ®) is recommended as a first-line treatment option for people with advanced renal cell carcinoma: . who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group performance status of 0 or 1, and . if the manufacturer provides pazopanib at the discounted price agreed under the patient access scheme. People who are currently being treated with pazopanib for advanced metastatic renal cell carcinoma but who do not meet this criteria should have the option to continue their therapy until they and their clinicians consider it appropriate to stop. www.nice.org.uk/guidance/ta215 Scottish Medicines Consortium (SMC) decisions SMC No. 676/11 The Scottish Medicines Consortium has advised (March 2011) that pazopanib (Votrient ®) is accepted for restricted use within NHS Scotland for the first-line treatment of advanced renal cell carcinoma. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland. SMC No. 820/12 The Scottish Medicines Consortium has advised (December 2012) that pazopanib (Votrient ®) is not recommended for use within NHS Scotland for the treatment of selective subtypes of advanced soft tissue sarcoma in patients who have received prior chemotherapy for metastatic disease, or who have progressed within 12 months after neoadjuvant therapy as the economic case was not demonstrated.
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RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938.
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→Appendix 1: pazopanib
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▶Common or very common Alopecia. appetite decreased. arthralgia. asthenia. bradycardia. cancer pain. cardiac disorder. chest pain. chills. cough. dehydration. diarrhoea. dizziness. drowsiness. dry mouth. dysphonia. dyspnoea. electrolyte imbalance. gastrointestinal discomfort. gastrointestinal disorders. haemorrhage. hair colour changes. headache. hepatic disorders. hiccups. hyperbilirubinaemia. hyperhidrosis. hypertension. hypoalbuminaemia. hypothyroidism. increased risk of infection. insomnia. left ventricular dysfunction. leucopenia. mucosal abnormalities. muscle complaints. musculoskeletal pain. nail disorder. nausea. neutropenia. oedema. oral disorders. peripheral neuropathy. proteinuria. respiratory disorders. sensation abnormal. skin reactions. taste altered. thrombocytopenia. vasodilation. venous thromboembolism. vision blurred. vomiting. weight decreased ▶Uncommon Cerebrovascular insufficiency. eye disorders. haemolytic uraemic syndrome. menstrual cycle irregularities. myocardial infarction. myocardial ischaemia. oropharyngeal pain. pancreatitis. photosensitivity reaction. polycythaemia. QT interval prolongation. rhinorrhoea. skin ulcer. thrombotic microangiopathy ▶Rare or very rare Posterior reversible encephalopathy syndrome (PRES)
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Effective contraception advised during treatment.
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Avoid unless potential benefit outweighs risk—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Discontinue breast-feeding.
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Manufacturer advises caution in mild to moderate impairment; avoid in severe impairment. Dose adjustments Manufacturer advises dose reduction to 200 mg daily in moderate impairment.
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Use with caution if creatinine clearance less than 30 mL/minute—no information available.
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▶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—consult product Immune system and malignant disease literature if elevated liver enzymes observed. ▶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— consult product literature). ▶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. ▶Monitor for proteinuria. ▶Monitor thyroid function. ▶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.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 23, 25 ▶Votrient (Novartis Pharmaceuticals UK Ltd) Pazopanib (as Pazopanib hydrochloride) 200 mg Votrient 200mg tablets | 30 tablet P £560.50 Pazopanib (as Pazopanib hydrochloride) 400 mg Votrient 400mg tablets | 30 tablet P £1,121.00
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800 mg daily, adjust dose in steps of 200 mg
First-line fragment. Read the complete Indications and Dose section above.
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(consult product literature)
First-line fragment. Read the complete Indications and Dose section above.
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