Roxadustat oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of roxadustat.
Drugs List
Therapeutic Indications
Uses
Symptomatic anaemia - due to chronic renal failure
Dosage
Treatment should be initiated by a physician experienced in the management of anaemia.
Adults
Patients not currently receiving an erythropoiesis-stimulating agent (ESA)
Body weight less than 100kg: 70mg three times per week.
Body weight 100kg and over: 100mg three times per week.
Patients converting from an ESA
The recommended starting dose of roxadustat is based on the average prescribed ESA dose in the 4 weeks before conversion. The first roxadustat dose should replace the next scheduled dose of the current ESA as below:
Darbepoetin alfa intravenous or subcutaneous
Less than 25micrograms per week: 70mg three times per week.
25micrograms per week to less than 40micrograms per week: 100mg three times per week.
40micrograms per week to 80micrograms per week: 150mg three times per week.
More than 80micrograms per week: 200mg three times per week.
Epoetin intravenous or subcutaneous
Less than 5000IU per week: 70mg three times per week.
5000IU per week to 8000IU per week: 100mg three times per week.
More than 8000IU per week to 16,000IU per week: 150mg three times per week.
More than 16,000IU per week: 200mg three times per week.
Methoxy polyethylene glycol-epoetin beta intravenous or subcutaneous
Less than 80micrograms per month: 70mg three times per week.
80micrograms per month to 120micrograms per month: 100mg three times per week.
More than 120micrograms per month to 200micrograms per month: 150mg three times per week.
More than 200micrograms per month: 200mg three times per week.
Patients with Hepatic Impairment
Moderate hepatic impairment (Child-Pugh class B)
Reduce starting dose by half or to the dose level that is closest to half the starting dose when starting treatment in patients with moderate hepatic impairment (Child-Pugh class B).
Additional Dosage Information
Maintenance dose
Maintenance dose ranges from 20mg to 400mg three times per week. Haemoglobin (Hb) levels should be monitored every 2 weeks until the desired Hb level of 10 to 12g/dL is achieved and stabilised, and every 4 weeks thereafter, or as clinically needed.
Dose adjustment
See product literature for dose adjustment algorithm. If dose reduction is required for a patient already on the lowest dose of 20mg three times per week, the dose frequency should be reduced to twice per week. If further dose reduction is needed, the dose frequency may be further reduced to once weekly.
Maximum recommended dose
Patients not on dialysis - maximum dose of 3mg/kg bodyweight or 300mg three times per week, whichever is lower.
Patients on dialysis - maximum dose of 3mg/kg bodyweight or 400mg 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. The regular dosing schedule should be resumed thereafter.
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Severe hepatic impairment
Third trimester of pregnancy
Uncontrolled hypertension
Precautions and Warnings
Infection
Obesity
Predisposition to thromboembolic disease
Cardiovascular disorder
Epileptic disorder
First trimester of pregnancy
Glucose-galactose malabsorption syndrome
History of seizures
History of thrombosis
Lactose intolerance
Moderate hepatic impairment
Second trimester of pregnancy
Reduce dose in moderate hepatic impairment (Child-Pugh Class B)
Advise ability to drive/operate machinery may be affected by side effects
Ensure adequate iron stores before initiating treatment
Exclude other causes of anaemia before treatment
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Contains lactose
Contains soya or soya derivative
Take 1 hour after phosphate binders or multivalent cations
Avoid haemoglobin level >12g/dl
Haemoglobin should not increase by more than 2g/dl per month
Increased risk of thrombotic events if haemoglobin >13g/dl
Investigate patients developing a sudden lack of response to treatment
Monitor blood pressure especially at the start of treatment
Monitor haemoglobin levels
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report symptoms of infection immediately
Consider discontinuing if seizures occur
Consider discontinuing if thromboembolism occurs
Advise patient to seek advice at first indications of pregnancy
Discontinue if no response to treatment within 24 weeks
Female: Contraception required during and for 1 week after treatment
Advise patient to follow dosage instructions closely
Pneumonia, urinary tract infections and sepsis are the most commonly reported serious infections with roxadustat and patients with signs and symptoms of an infection should be evaluated promptly.
Misuse can lead to an increase in blood cells which can consequently thicken the blood and cause life-threatening problems with the cardiovascular system.
Investigate an inadequate response to therapy. Correct any nutrient deficiencies. The erythropoietic response may be compromised by intercurrent infections, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases or bone marrow fibrosis. Consider a reticulocyte count as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, consider an examination of the bone marrow.
The risk of thrombotic vascular events (TVEs) should be carefully weighed against the benefits from treatment with roxadustat, particularly in patients with pre-existing risk factors for TVE, including obesity and prior history of TVEs such as deep vein thrombosis and pulmonary embolism.
Conversion of dialysis patients otherwise stable on ESA treatment should only be considered when there is a valid clinical reason. A decision to treat stable ESA patients with anaemia associated with chronic kidney failure and not on dialysis should be based on a benefit risk consideration.
Roxadustat must be taken at least 1 hour after phosphate binders or multivalent cations (medicines or supplements that contain calcium, iron, magnesium or aluminium such as sevelamer carbonate or calcium acetate).
Pregnancy and Lactation
Pregnancy
Roxadustat is contraindicated during the third trimester of pregnancy but may be used with caution during the first and second trimester.
The manufacturer recommends that roxadustat should not be used in women planning on becoming pregnant, during pregnancy or when anaemia associated with chronic kidney disease is diagnosed during pregnancy. In such cases, roxadustat should be discontinued and alternative therapy started if appropriate. Women of childbearing potential must use highly effective contraception during treatment and for at least one week after the last dose of roxadustat. At the time of writing there are no data on the use of roxadustat in pregnant women but animal studies have shown reproductive toxicity. The potential risk is unknown.
Lactation
Roxadustat is contraindicated during breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking roxadustat. It is unknown if roxadustat is excreted in human milk. Animal data have shown excretion of roxadustat in milk. A risk to the neonate cannot be excluded.
Side Effects
Constipation
Deep vein thrombosis (DVT)
Diarrhoea
Headache
Hyperbilirubinaemia
Hyperkalaemia
Hypertension
Insomnia
Nausea
Peripheral oedema
Pulmonary embolism
Seizures
Sepsis
Thrombosis of vascular access sites
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2021
Reference Sources
Summary of Product Characteristics: Evrenzo (roxadustat) film coated tablets. Astellas Pharma Ltd. Revised August 2021.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 November 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.