Vadadustat

SOURCE: UK SPC (eMC) for Vafseo 150 mg film-coated tablets, section 4.2 (https://www.medicines.org.uk/emc/product/15653/smpc). TARGET AND TITRATION: adjust to achieve or maintain haemoglobin 10 to 12 g/dL. Monitor Hb every two weeks until stable when initiating or adjusting therapy, then at least monthly. If Hb is less than 10 g/dL with no rise greater than 1 g/dL in 2 weeks or 2 g/dL in 4 weeks - increase by 150 mg if there has been no dose increase in the past 4 weeks; Hb 10 to 12 g/dL - maintain dose; Hb greater than 12 but less than 13 g/dL - reduce by 150 mg; Hb 13 g/dL or greater - interrupt until Hb is 12 g/dL or less, then resume at 150 mg less than the dose prior to interruption (if the patient was on 150 mg, resume at 150 mg). If Hb rises by more than 1 g/dL in any 2-week period or more than 2 g/dL in 4 weeks - reduce by 150 mg (dose reduction may not be required for a single Hb value); at Hb greater than 12 g/dL in that situation, reduce by 150 mg. Treatment should not be continued beyond 24 weeks if a clinically meaningful increase in Hb is not achieved - seek and treat alternative explanations before restarting. CONVERSION FROM AN ESA: start at 300 mg once daily; patients converting from a high baseline ESA dose may show an initial decline in Hb before returning to baseline by weeks 16 to 20. Rescue with red blood cell transfusion or ESA may be considered during transition if Hb falls below 9.0 g/dL or the response is not acceptable; patients receiving RBC transfusions are recommended to continue treatment. Pause during temporary ESA rescue and resume when Hb is 10 g/dL or above, extending the pause to 2 days after the last dose of epoetin, 7 days after darbepoetin alfa and 14 days after methoxy polyethylene glycol-epoetin beta; then resume at the prior dose or one dose higher with subsequent titration. MONITORING: ALT, AST and bilirubin must be evaluated before initiation, monthly for three months after initiation and as clinically indicated thereafter. IRON: evaluate iron status before and during treatment and give supplemental iron when serum ferritin is less than 100 mcg/L or transferrin saturation is less than 20%. ADMINISTRATION SPACING: give at least 1 hour before oral iron supplements, iron-containing products or iron-containing phosphate binders, and at least 1 hour before or 2 hours after non-iron-containing phosphate binders or other products whose primary component is a multivalent cation such as calcium, magnesium or aluminium. Assess other causes of anaemia before initiating. MISSED DOSE: take as soon as remembered the same day, then the next dose at the usual time the following day; do not double the dose. POPULATIONS: no dose adjustment for elderly or for renal impairment; no adjustment in mild or moderate hepatic impairment, and not recommended in severe hepatic impairment (Child-Pugh class C). Section 4.4 states the product should not be administered in patients with non-dialysis-dependent CKD, as safety has not been established in that population. PAEDIATRIC: safety and efficacy in the paediatric population have not been established and no data are available.