3 Vadadustat should be initiated by a physician experienced in the management of anaemia. All other causes of anaemia should be evaluated prior to initiating therapy with Vafseo, and when deciding to increase the dose. Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.
In addition to the presence of symptoms of anaemia, criteria such as rate of fall of haemoglobin (Hb) concentration, prior response to iron therapy, and the risk of needing of red blood cell (RBC) transfusion could be considered in the evaluation of the individual patient’s clinical course and condition.
Posology Evaluation before administration Evaluation of iron stores and nutritional factors Iron status should be evaluated in all patients before and during treatment. Supplemental iron therapy should be administered when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%.
Dose initiation The recommended starting dose is 300 mg once daily. Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Patients converting from an erythropoiesis-stimulating agent (ESA) When converting from an ESA to Vafseo, the recommended starting dose is 300 mg once daily.
1 for course Hb during treatment in individual studies). 4). Patients receiving RBC transfusions are recommended to continue Vafseo treatment during the transfusion period. Vafseo should be paused for those patients receiving temporary ESA rescue treatment and may be resumed when Hb levels are ≥10 g/dL.
Depending on the ESA employed, the pause in Vafseo treatment should be extended to: • 2 days after last dose of epoetin • 7 days after last dose of darbepoetin alfa • 14 days after last dose of methoxy polyethylene glycol-epoetin beta.
Following ESA rescue, Vafseo should be resumed at the prior dose or one dose higher, with subsequent titration according to the dose titration guidelines given below in this section. Dose titration When initiating or adjusting therapy, monitor Hb levels every two weeks until stable, then monitor at least monthly.
Dose adjustment should be done in increments of 150 mg within the range of 150 mg to a maximum recommended daily dose of 600 mg to achieve or maintain Hb levels within 10 to 12 g/dL. Do not increase the dose more frequently than once every 4 weeks.
Decreases in dose can occur more frequently. 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 Vafseo (see Table 1).
Table 1:
Vafseo dose titration 4 Change in Hb Value Less than 10 g/dL 10 to 12 g/dL Greater than 12 g/dL but less than 13 g/dL 13 g/dL or greater No rise in Hb greater than 1 g/dL in 2-week period or more than 2 g/dL in 4 weeks 150 mg increase if no dose increase in past 4 weeks Maintain dose 150 mg reduction Interrupt the dose of Vafseo until Hb is less than or equal to 12 g/dL then resume with dose that is 150 mg less than dose prior to interruption.
If patient was on 150 mg prior to interruption, then resume with 150 mg. Hb rise more than 1 g/dL in any 2-week period or more than 2 g/dL in 4 weeks 150 mg reduction or maintain* dose 150 mg reduction or maintain* dose 150 mg reduction * Dose reduction may not be required in case of a single Hb value.
Monitoring When initiating or adjusting therapy, monitor Hb levels every two weeks until stable, then monitor at least monthly. 4). Missed dose If a dose is missed, patients should take the dose as soon as they remember during the same day and then patients should take the next dose at the usual time the next day.
Patients should not take a double dose. 2). 2). Hepatic impairment No dose adjustment is needed in patients with mild or moderate hepatic impairment. 2). Paediatric population The safety and efficacy of Vafseo in the paediatric population have not been established.
No data are available. Method of administration 5 The film-coated tablet is administered orally with or without food and should be swallowed whole without chewing. Vafseo can be taken at any time before, during, or after dialysis. Vafseo should be administered at least 1 hour before oral iron supplements, products whose primary component consists of iron or iron-containing phosphate binders.
5).