Roxadustat

Source: UK SPC (eMC) for Evrenzo 100 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/101441/smpc). Treatment should be INITIATED BY A PHYSICIAN EXPERIENCED IN THE MANAGEMENT OF ANAEMIA; all other causes of anaemia should be evaluated before initiating therapy and when deciding to increase the dose, and adequate IRON STORES should be ensured prior to initiating treatment. Treatment should NOT be continued beyond 24 weeks of therapy if a clinically meaningful increase in Hb is not achieved — seek and treat alternative explanations for inadequate response before restarting. CONVERSION FROM AN ESA: the starting dose is based on the average prescribed ESA dose in the 4 weeks before conversion, and the first roxadustat dose replaces the next scheduled ESA dose. §4.2 Table 1 (three times per week): darbepoetin alfa IV/SC less than 25 micrograms/week, OR epoetin IV/SC less than 5,000 IU/week, OR methoxy polyethylene glycol-epoetin beta IV/SC less than 80 micrograms/month = roxadustat 70 mg; darbepoetin alfa 25 to less than 40 micrograms/week, OR epoetin 5,000 up to 8,000 IU/week, OR methoxy PEG-epoetin beta 80 up to and including 120 micrograms/month = 100 mg; darbepoetin alfa 40 up to and including 80 micrograms/week, OR epoetin more than 8,000 up to and including 16,000 IU/week, OR methoxy PEG-epoetin beta more than 120 up to and including 200 micrograms/month = 150 mg; darbepoetin alfa more than 80 micrograms/week, OR epoetin more than 16,000 IU/week, OR methoxy PEG-epoetin beta more than 200 micrograms/month = 200 mg. Conversion of DIALYSIS patients otherwise stable on ESA treatment is only to be considered when there is a valid clinical reason; conversion of NON-DIALYSIS patients otherwise stable on ESA has not been investigated and any such decision must be based on individual benefit-risk. DOSE ADJUSTMENT AND Hb MONITORING: monitor Hb every two weeks until the desired 10 to 12 g/dL is achieved and stabilised, then every 4 weeks or as clinically indicated. The dose may be adjusted stepwise up or down from the starting dose 4 weeks after treatment start and every 4 weeks thereafter — EXCEPT that if Hb increases by more than 2 g/dL at any time within a 4-week period the dose must be reduced by one step immediately. Steps follow the sequence 20 mg - 40 mg - 50 mg - 70 mg - 100 mg - 150 mg - 200 mg - 250 mg - 300 mg - 400 mg (400 mg only for CKD patients on dialysis). §4.2 Table 2 rules, by change in Hb over the previous 4 weeks against current Hb: change of MORE THAN +1.0 g/dL — Hb below 10.5 no change, Hb 10.5 to 11.9 reduce by one step, Hb 12.0 to 12.9 reduce by one step, Hb 13.0 or higher withhold dosing, monitor Hb and resume when Hb is less than 12.0 g/dL at a dose reduced by TWO steps; change BETWEEN -1.0 and +1.0 g/dL — Hb below 10.5 increase by one step, Hb 10.5 to 11.9 no change, Hb 12.0 to 12.9 reduce by one step, Hb 13.0 or higher withhold as above; change of LESS THAN -1.0 g/dL — Hb below 10.5 increase by one step, Hb 10.5 to 11.9 increase by one step, Hb 12.0 to 12.9 no change, Hb 13.0 or higher withhold as above. If additional dose reduction is required for a patient already on the lowest dose (20 mg three times per week), do NOT break the tablet — reduce the frequency to twice per week, and if further reduction is needed, to once weekly. MISSED DOSE: if more than 1 day remains until the next scheduled dose, take the missed dose as soon as possible; if one day or less remains, skip it and take the next dose on the next scheduled day, resuming the regular schedule thereafter. ELDERLY: no adjustment of the starting dose is required. HEPATIC IMPAIRMENT: no adjustment of the starting dose level in mild impairment (Child-Pugh A); in MODERATE impairment (Child-Pugh B) the starting dose is to be reduced BY HALF, or to the dose level closest to half the starting dose, with caution recommended; NOT recommended in severe impairment (Child-Pugh C) as safety and efficacy have not been evaluated. PAEDIATRIC: safety and efficacy in patients under 18 years have NOT been established and no data are available, so paedDose is null — verify any under-18 use against a children's formulary. ADMINISTRATION TIMING: tablets should be taken at least 1 HOUR AFTER administration of phosphate binders (except lanthanum) or other medicinal products containing multivalent cations such as calcium, iron, magnesium or aluminium. KEY SAFETY (§4.4): cardiovascular and mortality risk is estimated to be comparable to that of ESA therapy; thrombotic vascular events (DVT, pulmonary embolism, cerebral infarction — majority serious, fatal cerebral infarction reported) must be weighed against benefit, particularly with pre-existing risk factors including obesity and prior TVE; vascular access thrombosis was very common in dialysis patients, with rates highest in the first 12 weeks and particularly at Hb above 12 g/dL and with an Hb rise of more than 2 g/dL over 4 weeks; seizures were common — use with caution in patients with a history of seizures, epilepsy or conditions predisposing to seizure. NOTE ON SOURCES: no US (openFDA) label was retrieved for this bundle, so all content is UK SPC. eMC §4.5 was NOT captured — the interaction entries below come from §4.2 only and must be verified against the full SPC. §4.4 and §4.8 were truncated at the source-fetch limit.