Pazopanib (Specialist drug)

INDICATIONS: the recommended dose for the treatment of renal cell carcinoma (RCC) or soft tissue sarcoma (STS) is 800 mg once daily. Treatment should only be initiated by a physician experienced in the administration of anti-cancer medicinal products. DOSE MODIFICATION: dose modification (decrease or increase) should be in 200 mg decrements or increments in a stepwise fashion based on individual tolerability in order to manage adverse reactions; the dose should not exceed 800 mg. HEPATIC IMPAIRMENT: all patients should have liver function tests before starting and during therapy. 800 mg once daily remains the recommended dose in patients with mild abnormalities in serum liver tests (normal bilirubin with any degree of ALT elevation, or bilirubin elevation >35% direct up to 1.5 x ULN regardless of ALT). A reduced dose of 200 mg once daily is recommended in moderate hepatic impairment (bilirubin >1.5 to 3 x ULN regardless of ALT). Pazopanib is not recommended in severe hepatic impairment (total bilirubin >3 x ULN regardless of ALT). Administration in mild or moderate hepatic impairment should be undertaken with caution and close monitoring of tolerability. DRUG-INDUCED HEPATOTOXICITY (SPC Table 1): transaminase elevation 3-8 x ULN — continue with weekly liver function monitoring until return to Grade 1 or baseline; transaminase elevation >8 x ULN — interrupt until return to Grade 1 or baseline, and if the benefit of reinitiating outweighs the hepatotoxicity risk, reintroduce at a reduced dose of 400 mg daily with weekly serum liver tests for 8 weeks (permanently discontinue if transaminase elevations >3 x ULN recur); transaminase elevations >3 x ULN concurrent with bilirubin >2 x ULN — permanently discontinue. Serum liver tests should be performed before initiation, at weeks 3, 5, 7 and 9, then at months 3 and 4, with periodic testing continuing after month 4. ELDERLY: limited data in patients aged 65 years and older; no clinically significant differences in safety were observed in the RCC studies, but greater sensitivity of some elderly patients cannot be ruled out. PAEDIATRIC: pazopanib should not be used in children younger than 2 years of age because of safety concerns regarding organ growth and maturation; safety and efficacy in children aged 2 to 18 years have not been established and no posology recommendation can be made. SOURCE LIMITS: the fetched eMC sections were truncated (§4.4 and §4.8 incomplete) and eMC §4.5 was not fetched — the interactions listed in this draft come from section 7 of the US prescribing information contained in the same bundle and must be checked against the UK SPC §4.5. US labelling additionally advises reducing the pazopanib dose to 400 mg if a strong CYP3A4 inhibitor cannot be avoided, and avoiding gastric acid-reducing agents.