Evrenzo Special Precautions

Hemoglobin level monitoring: In CKD patients, hemoglobin levels should not exceed the upper limit of the target value recommended for use. Excessively high hemoglobin levels and a rapid increase in hemoglobin may increase the risks of deep vein thrombosis and vascular access thrombosis. During the treatment with this product, the dose of roxadustat should be adjusted based on the Hb level to maintain the Hb level within the range of 100-120 g/L. After starting treatment or adjusting the dose, monitor the Hb level every 2 weeks until it reaches and stabilizes within the target range, after which monitoring can be done every 4 weeks. If the Hb level increases by more than 20 g/L within 4 weeks, necessary actions should be taken, such as reducing the dose or suspending the treatment (see Dose Adjustment under Dosage & Administration for details).
Blood pressure monitoring: Hypertension was observed as an adverse event in clinical trials, though these may be influenced by factors such as underlying disease and dialysis, and the relationship to the drug is not yet clear. The possibility of blood pressure increases during roxadustat treatment for anemia cannot be ruled out. Therefore, blood pressure should be monitored before starting, at the start, and during treatment with roxadustat. Patients with poorly controlled hypertension were excluded from clinical trials, so those with uncontrolled hypertension should use this product with caution.
Patients with moderate to severe hepatic impairment: The efficacy and safety of this product have not been established in patients with moderate and severe hepatic impairment (Child Pugh Class B and C). For these patients, treatment should only be initiated after a thorough assessment of the patient's risk-benefit. Patients should be closely monitored during dose adjustments, and the starting dose of roxadustat should be appropriately reduced (see Dose Adjustment under Dosage & Administration for details).
Serious infection: Serious infections, including fatal ones, have been reported in both DD and NDD CKD patients with anemia treated with roxadustat. The causal relationship between roxadustat and serious infections has not been established. In the study of DD CKD patients with anemia, the incidence of serious infections was similar in patients treated with roxadustat compared to those treated with epoetin alfa (24.4% and 14.3/100 PY with roxadustat versus 24.6% and 12.8/100 PY with epoetin alfa); the most commonly reported serious infections were pneumonia, sepsis, and peritonitis. In the study of NDD CKD patient with anemia, serious infections occurred more frequently but at similar exposure-adjusted rates in patients treated with roxadustat (18.9%, 12.4 patients with events per 100 patient years of exposure [PY]) compared to placebo (12.9%, 10.6 patients with events per 100 PY), with the most common serious infections being pneumonia, sepsis, and urinary tract infection. In DD patients, the incidence of fatal infections was similar between treatment groups (2.4%, 1.4/100 PY with roxadustat versus 2.4%, 1.2/100 PY with epoetin alfa). However, there was a numerical imbalance in the subgroup of patients who started roxadustat within 4 months of beginning dialysis (2.5%, 1.7/100 PY with roxadustat versus 1.4%, 0.9/100 PY with epoetin alfa). In NDD studies, the incidence of fatal infections was higher in the roxadustat group (3.6%, 2.0/100 PY) compared to the placebo group (2.1%, 1.2/100 PY). Fatal infections were most pronounced in severe NDD CKD patients with anemia (e.g. eGFR < 10 mL/min/1.73 m²) who were just started roxadustat treatment and in NDD CKD patients with anemia who started dialysis while on roxadustat. Risk-benefit profile should be assessed carefully before starting roxadustat treatment in patients with active severe or serious infections. It is recommended to monitor patients for symptoms and signs of infection during treatment with roxadustat and advise them to contact their doctors if signs or symptoms of infection appear. Suspected infections should be promptly assessed and treated.
Sepsis: Sepsis was one of the most commonly reported serious infections and included fatal events. Patients with signs and symptoms of sepsis (e.g., an infection that spreads throughout the body with low blood pressure and the potential for organ failure) should be promptly evaluated and treated according to standard of care.
Deep Vein Thrombosis: In clinical trials involving DD and NDD CKD patients with anemia, those treated with roxadustat had a higher incidence of deep vein thrombosis (DVT) compared to patients receiving placebo or epoetin alfa. Treatment with roxadustat should be considered after a thorough assessment of the patient's risk-benefit profile. Patients should be advised to contact their doctors if they experience signs or symptoms of DVT. DVT should be promptly assessed and treated.
Vascular Access Thrombosis: In clinical trials involving DD and NDD CKD patients with anemia, those treated with roxadustat had an increased incidence of vascular access thrombosis (VAT) compared to those receiving placebo or epoetin alfa. In studies involving DD CKD patients with anemia, the highest incidence of VAT in roxadustat-treated patients occurred within the first 12 weeks of treatment and when hemoglobin levels increased by more than 20 g/L over 4 weeks. Hemoglobin levels should be closely monitored for the first 12 weeks of treatment. Dose adjustments or discontinuation should be made as needed, following the dose adjustment guidelines (Table 7). Treatment should be started after careful assessment of patient's risk-benefit profile. Patients with VAT should be promptly assessed and treated.
Seizures: In clinical trials involving DD and NDD CKD patient with anemia, those treated with roxadustat had a higher incidence of seizures compared to those receiving placebo or epoetin alfa. During the initial months of roxadustat treatment, patients should be closely monitored for any premonitory neurologic symptoms. Treatment should be started after careful assessment of patient's risk-benefit profile. Patients should be advised to promptly contact their doctors if they experience new-onset seizures, premonitory symptoms, or an increase in the frequency or severity of seizures.
Secondary hypothyroidism: Cases of secondary hypothyroidism have been reported with the use of roxadustat. These reactions were reversible upon roxadustat withdrawal. Monitoring of thyroid function is recommended as clinically indicated.
Roxadustat should not be co-administered with ESAs.
Athletes should use this medication with caution.
Use in Children: The safety and efficacy of roxadustat in pediatric patients under 18 years of age have not been established.
Use in the Elderly: No dose adjustment based on age is required for patients over 65 years old. Analyses of hemoglobin levels and roxadustat doses in subjects aged ≥ 65 and < 65 years from Studies FGCL-4592-806 and FGCL-4592-808 showed no significant differences in hemoglobin levels or roxadustat doses between the two age groups.