Daprodustat: Difference between revisions
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|useInPregnancyFDA=There is insufficient available data to establish a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with CKD. | |useInPregnancyFDA=There is insufficient available data to establish a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with CKD. | ||
|useInNursing=We advise patients not to breastfeed during treatment with JESDUVROQ, and for one week after the final dose because JESDUVROQ was found in rat milk which means it will also be present in human milk , and high possiblity the infant being exposed during lactation process | |useInNursing=We advise patients not to breastfeed during treatment with JESDUVROQ, and for one week after the final dose because JESDUVROQ was found in rat milk which means it will also be present in human milk , and high possiblity the infant being exposed during lactation process | ||
|useInGeri=No overall differences in safety or effectiveness were observed between older patients of age 65 or more and younger patients. | |||
|useInHepaticImpair=mild hepatic impairment -no dose adjustment is required | |||
moderate hepatic impairment - reduce the starting dose of JESDUVROQ by half except in those whose initial dose is 1mg. | |||
severe hepatic impairment (Child-Pugh Class C)- | |||
|administration=for adults treated for CKD with atleast 4 months of dialysis and not on an ESA, the initial dosage depends on the hemoglobin level: | |||
hemoglobin <9- 4mg once daily Dose of JESDUVROQ | |||
hemoglobin 9 to 10mg- 2mg once daily Dose of JESDUVROQ | |||
hemoglobin >10mg- 1mg once daily Dose of JESDUVROQ | |||
|monitoring=Doses of JESDUVROQ is adjusted considering the hemoglobin rate of rise, rate of decline and hemoglobin variability. | |||
Dose of JESDUVROQ is reduced 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. | |||
Treatment with JESDUVROQ is immedetly interrupted if hemoglobin >12g/dl. | |||
Treatment with JESDUVROQ should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in hemoglobin level is not achieved. | |||
|overdose=Headache and gastrointestinal adverse reactions (e.g., nausea) has been associated with JESDUVROQ overdose. | |||
there is no specific antidote and hemodialysis doesn't remover JESDUVROQ as it is protein bound. | |||
|mechAction=It is a reversible inhibitor of HIF-PH1, PH2 and PH3 which results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin. | |||
|structure=the molecular formula of daprodustat is C19H27N3O6, and its molecular mass is 393.43. | |||
|PD=Daprodustat increases endogenous production of erythropoietin in a dose-dependent manner within 6 to 8 hours after administration. With repeat doses, there was a peak increase in reticulocyte counts occuring between 7 and 15 days, with subsequent increases in red blood cell production. | |||
Daprodustat also increases the transferrin, and total iron binding capacity and decrease of iron, transferrin saturation and hepcidin after administering it for 52 weeks in patients with CKD on dialysis. | |||
|PK=Following oral administration, daprodustat is readily absorbed with median time to peak concentration (Tmax) in healthy patients ranging from 1 hour to 4 hours. | |||
Following intravenous dosing, the volume of distribution at steady-state in healthy subjects is 14.3 L. | |||
The terminal elimination half-life of daprodustat is approximately 1 hour to 4 hours. | |||
|howSupplied=JESDUVROQ tablets are available as 1 mg, 2 mg, 4 mg, 6 mg or 8 mg of daprodustat. | |||
1 mg, gray, biconvex, round film-coated tablets debossed with “GS KF” on one face. | |||
2 mg, yellow, biconvex, round film-coated tablets debossed with “GS V7” on one face. | |||
4 mg, white, biconvex, round film-coated tablets debossed with “GS 13” on one face. | |||
6 mg, pink, biconvex, round film-coated tablets debossed with “GS IM” on one face. | |||
8 mg, orange, biconvex, round film-coated tablets debossed with “GS 5E” on one face. | |||
|storage=Stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). | |||
}} | }} | ||
Latest revision as of 04:27, 26 April 2024
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alen Antony Pathil, M.D.[2]
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Black Box Warning
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JESDUVROQ increases the risk of thrombotic vascular events like MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, AND THROMBOSIS OF VASCULAR ACCESS
See full prescribing information for complete Boxed Warning.
Avoid the use of JESDUVROQ in patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting JESDUVROQ.
An increase of more than 1 g/dL over 2 weeks may contribute to these risks, also targeting hemoglobin greater than 11g/dl is further expected to increase the risk of above mentioned thrombotic events just like other Erythropoietin Stimulating Agents.
|
Overview
Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3. that is FDA approved for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Hypertension, Abdominal pain, Dizzines, Hypersensitivity, and thrombotic vascular events like Myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis and vascular access thrombosis..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
daprodustat is indicated for the treatment of anemia due to chronic kidney disease who has been receiving dialysis for last 4 months
Limitations: 1. It is not used as a substitute for blood transfusion for immediate correction of anemia 2. It is not used in patients with CKD with no history of dialysis.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Daprodustat FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
1.Contraindicated in patients receiving a strong CYP2C8 inhibitor such as gemfibrozil
2.contraindicated in patients with uncontrolled hypertension
Warnings
|
JESDUVROQ increases the risk of thrombotic vascular events like MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, AND THROMBOSIS OF VASCULAR ACCESS
See full prescribing information for complete Boxed Warning.
Avoid the use of JESDUVROQ in patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting JESDUVROQ.
An increase of more than 1 g/dL over 2 weeks may contribute to these risks, also targeting hemoglobin greater than 11g/dl is further expected to increase the risk of above mentioned thrombotic events just like other Erythropoietin Stimulating Agents.
|
1. Increased risk of thrombotic vascular events JESDUVROQ increseas the risk of Myicardial infatcion, Stroke, Pulmonary embolism and thus is avoided in patients with prior history of cardiovascular events. Furthermore, we also avoid rapid rise of hemoglobin greater than 1g/dl over 2weeks. Also targeting a hemoglobin more than 11 g/dl using this medication can also further the risk of vascular thrombotic events
2. Risk of hospitalization due to heart failure Patients with prior history of heart failure are advised to not use JESDUVROQ as it further increases the risk of heart failure
3. Hypertention JESDUVROQ is contraindicated in patients with uncontrolled hypertension. As cases of hypertensive crisis due to Hypertensive encephalopathy and seizures have been reported, therefore periodic monitoring of blood pressure and usage of antihypertensive to control the blood pressure maybe required.
4. Gastrointestinal erosion This drug has cases of gastric and esophageal erosion been reported. Thus this with increased risk for gastrointestinal erosions, such as history of gastrointestinal erosion, peptic ulcer disease, use of concomitant medications that increase the risk of gastrointestinal erosion, and current tobacco smokers and alcohol drinkers are recommended to avoid this medication.
5. Adverse events in patients with CKD and not on dialysis- In a large cardiovascular outcomes trial in adults with anemia of CKD who were not on dialysis, an increased risk of cardiovascular mortality, stroke, thromboembolism, serious acute kidney injury, hospitalization for heart failure, and serious gastrointestinal erosions was observed in patients treated with JESDUVROQ compared to recombinant EPO.
6. Malignancy Since JESDUVROQ increases hypoxia inducible factor (HIF)-1 levels which is associated with unfavourable effects of cancer growth. This it is not indicated with patients with history of malignancy.
Adverse Reactions
Clinical Trials Experience
In the clinical train Hypertention, Thrombotic vascular events and Abdominal pain as are the most common adverse effects
Other adverse effects include dizziness and hypersensitivity presenting as rash, urticaria and dermatitis.
Postmarketing Experience
There is limited information regarding Daprodustat Postmarketing Experience in the drug label.
Drug Interactions
1. Concomitant administration of strong CYP2C8 inhibitors (e.g., gemfibrozil) with JESDUVROQ is contraindicated due to a marked increase in daprodustat exposure.
2.Concomitent administration of CYP2C8 inducers (e.g., rifampin) may decrease daprodustat exposure, which may result in loss of efficacy.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C
There is insufficient available data to establish a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with CKD.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Daprodustat in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Daprodustat during labor and delivery.
Nursing Mothers
We advise patients not to breastfeed during treatment with JESDUVROQ, and for one week after the final dose because JESDUVROQ was found in rat milk which means it will also be present in human milk , and high possiblity the infant being exposed during lactation process
Pediatric Use
There is no FDA guidance on the use of Daprodustat in pediatric settings.
Geriatic Use
No overall differences in safety or effectiveness were observed between older patients of age 65 or more and younger patients.
Gender
There is no FDA guidance on the use of Daprodustat with respect to specific gender populations.
Race
There is no FDA guidance on the use of Daprodustat with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Daprodustat in patients with renal impairment.
Hepatic Impairment
mild hepatic impairment -no dose adjustment is required
moderate hepatic impairment - reduce the starting dose of JESDUVROQ by half except in those whose initial dose is 1mg.
severe hepatic impairment (Child-Pugh Class C)-
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Daprodustat in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Daprodustat in patients who are immunocompromised.
Administration and Monitoring
Administration
for adults treated for CKD with atleast 4 months of dialysis and not on an ESA, the initial dosage depends on the hemoglobin level: hemoglobin <9- 4mg once daily Dose of JESDUVROQ hemoglobin 9 to 10mg- 2mg once daily Dose of JESDUVROQ hemoglobin >10mg- 1mg once daily Dose of JESDUVROQ
Monitoring
Doses of JESDUVROQ is adjusted considering the hemoglobin rate of rise, rate of decline and hemoglobin variability.
Dose of JESDUVROQ is reduced 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.
Treatment with JESDUVROQ is immedetly interrupted if hemoglobin >12g/dl.
Treatment with JESDUVROQ should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in hemoglobin level is not achieved.
IV Compatibility
There is limited information regarding the compatibility of Daprodustat and IV administrations.
Overdosage
Headache and gastrointestinal adverse reactions (e.g., nausea) has been associated with JESDUVROQ overdose.
there is no specific antidote and hemodialysis doesn't remover JESDUVROQ as it is protein bound.
Pharmacology
There is limited information regarding Daprodustat Pharmacology in the drug label.
Mechanism of Action
It is a reversible inhibitor of HIF-PH1, PH2 and PH3 which results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin.
Structure
the molecular formula of daprodustat is C19H27N3O6, and its molecular mass is 393.43.
Pharmacodynamics
Daprodustat increases endogenous production of erythropoietin in a dose-dependent manner within 6 to 8 hours after administration. With repeat doses, there was a peak increase in reticulocyte counts occuring between 7 and 15 days, with subsequent increases in red blood cell production.
Daprodustat also increases the transferrin, and total iron binding capacity and decrease of iron, transferrin saturation and hepcidin after administering it for 52 weeks in patients with CKD on dialysis.
Pharmacokinetics
Following oral administration, daprodustat is readily absorbed with median time to peak concentration (Tmax) in healthy patients ranging from 1 hour to 4 hours.
Following intravenous dosing, the volume of distribution at steady-state in healthy subjects is 14.3 L.
The terminal elimination half-life of daprodustat is approximately 1 hour to 4 hours.
Nonclinical Toxicology
There is limited information regarding Daprodustat Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Daprodustat Clinical Studies in the drug label.
How Supplied
JESDUVROQ tablets are available as 1 mg, 2 mg, 4 mg, 6 mg or 8 mg of daprodustat.
1 mg, gray, biconvex, round film-coated tablets debossed with “GS KF” on one face. 2 mg, yellow, biconvex, round film-coated tablets debossed with “GS V7” on one face. 4 mg, white, biconvex, round film-coated tablets debossed with “GS 13” on one face. 6 mg, pink, biconvex, round film-coated tablets debossed with “GS IM” on one face. 8 mg, orange, biconvex, round film-coated tablets debossed with “GS 5E” on one face.
Storage
Stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F).
Images
Drug Images
{{#ask: Page Name::Daprodustat |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Daprodustat |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Daprodustat Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Daprodustat interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Daprodustat Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Daprodustat Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.