JESDUVROQ Film coated tablet Ref.[50977] Active ingredients: Daprodustat

2.1 Pre-Treatment and On-Treatment Evaluations of Anemia, Iron Stores, and Liver Tests

Evaluation of Anemia and Iron Stores

Correct and exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) before initiating JESDUVROQ. Evaluate the iron status in all patients before and during treatment with JESDUVROQ. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/mL or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of therapy.

Liver Testing

Assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin prior to initiation of JESDUVROQ. Repeat the liver tests if the patient develops signs or symptoms that could be consistent with liver disease during treatment with JESDUVROQ.

2.2 Important Dosing Information

Individualize dosing and use the lowest dose of JESDUVROQ sufficient to reduce the need for red blood cell transfusions. Do not target a hemoglobin higher than 11 g/dL.

JESDUVROQ can be taken with or without food, and without regard to concomitant administration of iron or phosphate binders [see Clinical Pharmacology (12.3)].

JESDUVROQ should be swallowed whole. Tablets should not be cut, crushed, or chewed.

JESDUVROQ can be administered without regard to the timing or type of dialysis [see Clinical Pharmacology (12.3)].

If a dose of JESDUVROQ is missed, it should be taken as soon as possible, unless it is the same day as the next dose. In this case, the missed dose should be skipped, and the next dose taken at the usual time. Double-doses should not be taken to make-up for a missed dose.

2.3 Recommended Starting Dose of JESDUVROQ

Adults with Anemia Due to Chronic Kidney Disease Receiving Dialysis for at Least 4 Months

Adults Not Being Treated with an ESA: For adults not being treated with an ESA, the starting dose of JESDUVROQ is based on the hemoglobin level (see Table 1). Dose modifications are needed for patients receiving concomitant treatment with a moderate CYP2C8 inhibitor or moderate hepatic impairment [see Dosage and Administration (2.5, 2.6), Drug Interactions (7.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Table 1. Starting Dose of JESDUVROQ for Adults on Dialysis not Receiving an Erythropoiesis-Stimulating Agent:

^a See dosing modifications in Section 2.5 if the patient has moderate hepatic impairment and Section 2.6 if the patient is on a moderate CYP2C8 inhibitor.

Adults Being Switched from an ESA: For adults being switched from an ESA to JESDUVROQ, the starting dose of JESDUVROQ is based on the dose regimen of the ESA at the time of substitution (see Table 2). Dose modifications are needed for patients receiving concomitant treatment with a moderate CYP2C8 inhibitor or moderate hepatic impairment [see Dosage and Administration (2.5, 2.6), Drug Interactions (7.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Table 2. Starting Dose of JESDUVROQ for Adults on Dialysis Switching from an Erythropoiesis-Stimulating Agent:

ESA = Erythropoiesis stimulating agent.

^a See dosing modifications in Section 2.5 if the patient has moderate hepatic impairment and Section 2.6 if the patient is on a moderate CYP2C8 inhibitor.
^b For patients on subcutaneous epoetin alfa, convert the epoetin alfa subcutaneous dose to intravenous dose equivalent by multiplying the subcutaneous dose received per week by 1.42 to obtain the weekly intravenous dose.

2.4 Monitoring Response to Therapy and Dose Adjustment

Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks for the first month and then every 4 weeks thereafter.

When adjusting doses of JESDUVROQ, consider hemoglobin rate of rise, rate of decline and hemoglobin variability. Do not increase the dose of JESDUVROQ more frequently than once every 4 weeks.

• If the dose of JESDUVROQ needs to be adjusted, increase or decrease by one dose level at a time (see Table 3).
• Decrease the dose of JESDUVROQ if hemoglobin increases rapidly (e.g., greater than 1 g/dL over 2 weeks or greater than 2 g/dL over 4 weeks) or if the hemoglobin exceeds 11 g/dL.
• If hemoglobin exceeds 12 g/dL, interrupt treatment with JESDUVROQ. When the hemoglobin is within the target range, treatment may be restarted at one dose level lower (see Table 3).
• Treatment with JESDUVROQ should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in hemoglobin level is not achieved. Alternative explanations for an inadequate response should be sought and treated before re-starting therapy.

Table 3. Dose Levels of JESDUVROQ:

^a 24 mg is the maximum recommended once daily dose.

2.5 Dosage Modification for Hepatic Impairment

Reduce the starting dose of JESDUVROQ by half (see Tables 1 and 2) in patients with moderate hepatic impairment (Child-Pugh Class B) except in patients whose starting dose is already 1 mg.

Use of JESDUVROQ in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.6 Dosage Modification for Concomitant Treatment with Moderate CYP2C8 Inhibitors

Reduce the starting dose of JESDUVROQ by half (see Tables 1 and 2) in patients who are on clopidogrel or a moderate CYP2C8 inhibitor except in patients whose starting dose is already 1 mg [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Monitor hemoglobin and adjust the dose of JESDUVROQ when initiating or stopping therapy with clopidogrel or a moderate CYP2C8 inhibitor during treatment with JESDUVROQ.

Headache and gastrointestinal adverse reactions (e.g., nausea) may be seen with acute overdose with JESDUVROQ. There is no specific antidote. Hemodialysis will not substantially remove daprodustat because it is highly protein bound.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). [See USP Controlled Room Temperature].