Symptomatic anaemia associated with chronic kidney disease (CKD)

The appropriate dose of roxadustat must be taken orally three times per week and not on consecutive days.

The dose should be individualised to achieve and maintain target Hb levels of 10 to 12 g/dL as described below.

Roxadustat treatment should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in Hb levels is not achieved. Alternative explanations for an inadequate response should be sought and treated before re-starting roxadustat.

Starting dose at treatment initiation

Adequate iron stores should be ensured prior to initiating treatment.

Patients not currently treated with an erythropoiesis-stimulating agent (ESA)

For patients initiating anaemia treatment not previously treated with ESA the recommended starting dose of roxadustat is 70 mg three times per week in patients weighing less than 100 kg and 100 mg three times per week in patients weighing 100 kg and over.

Patients converting from an ESA

Patients currently treated with an ESA can be converted to roxadustat, however, 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 treatment has not been investigated. A decision to treat these patients with roxadustat should be based on a benefit-risk consideration for the individual patient.

The recommended starting dose of roxadustat is based on the average prescribed ESA dose in the 4 weeks before conversion (see Table 1). The first roxadustat dose should replace the next scheduled dose of the current ESA.

Table 1. Starting doses of roxadustat to be taken three times per week in patients converting from an ESA:

ESA: erythropoiesis-stimulating agent

Dose adjustment and Hb monitoring

The individualised maintenance dose ranges from 20 mg to 400 mg three times per week (see section maximum recommended dose). Hb levels should be monitored every two weeks until the desired Hb level of 10 to 12 g/dL is achieved and stabilised, and every 4 weeks thereafter, or as clinically indicated.

The dose of roxadustat can be adjusted stepwise up or down from the starting dose 4 weeks after treatment start, and every 4 weeks thereafter except if the Hb increases by more than 2 g/dL, in which case the dose should be reduced by one step immediately. When adjusting the dose of roxadustat, consider the current Hb level and the recent rate of change in Hb level over the past 4 weeks, and follow the dose adjustment steps according to the dose adjustment algorithm described in Table 2.

The stepwise dose adjustments up or down should follow the sequence of the available doses: 20 mg-40 mg-50 mg-70 mg-100 mg-150 mg-200 mg-250 mg-300 mg-400 mg (only for CKD patients on dialysis).

Table 2. Dose adjustment rules:

The dose of roxadustat should not be adjusted more frequently than once every 4 weeks, except if Hb increases by more than 2 g/dL at any time within a 4-week period, in which case the dose should be reduced by one step immediately.
¹ Change in haemoglobin (Hb) over the previous 4 weeks = (present Hb value) - (previous Hb value drawn 4 weeks ago).

If additional dose reduction is required for a patient already on the lowest dose (20 mg three times per week), do not reduce the 20 mg dose by breaking the tablet, but reduce the dose frequency to twice per week. If further dose reduction is needed, the dose frequency may be further reduced to once weekly.

Maintenance dose

After stabilisation to target Hb levels between 10 to 12 g/dL, the Hb levels should continue to be monitored regularly and the dose adjustment rules followed (see Table 2).

Patients starting dialysis while on roxadustat treatment

No specific dose adjustment is required for CKD patients who start dialysis while on treatment with roxadustat. Normal dose adjustment rules (see Table 2) should be followed.

Concomitant roxadustat treatment with inducers or inhibitors

When initiating or discontinuing concomitant treatment with strong inhibitors (e.g. gemfibrozil) or inducers (e.g. rifampicin) of CYP2C8, or inhibitors (e.g. probenecid) of UGT1A9: the Hb levels should be monitored routinely and the dose adjustment rules followed (see Table 2).

Maximum recommended dose

Patients not on dialysis do not exceed a roxadustat dose of 3 mg/kg body weight or 300 mg three times per week, whichever is lower.

Patients on dialysis do not exceed a roxadustat dose of 3 mg/kg body weight or 400 mg three times per week, whichever is lower.

Missed dose

If a dose is missed, and there is more than 1 day until the next scheduled dose, the missed dose must be taken as soon as possible. If one day or less remains before the next scheduled dose, the missed dose must be skipped, and the next dose must be taken on the next scheduled day. In each case, the regular dosing schedule should be resumed thereafter.

Roxadustat film-coated tablets are to be taken orally with or without food. Tablets are to be swallowed whole and not chewed, broken or crushed due to the absence of clinical data under these conditions, and to protect the light-sensitive tablet core from photodegradation.

The 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.