Usage
- Desidustat is prescribed for the treatment of anemia in adult patients with chronic kidney disease (CKD), both on dialysis and not on dialysis.
- Pharmacological classification: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. Erythropoiesis-stimulating agent.
- Mechanism of Action: Desidustat inhibits HIF-PH, leading to the stabilization of hypoxia-inducible factors (HIFs). This results in increased production of erythropoietin (EPO), improved iron metabolism, and ultimately, enhanced erythropoiesis (red blood cell production).
Alternate Names
How It Works
- Pharmacodynamics: Desidustat increases hemoglobin levels by stimulating erythropoietin production. It also improves iron utilization.
- Pharmacokinetics: Administered orally. Peak plasma concentration is reached in a dose-dependent manner. It doesn’t show significant drug accumulation after multiple doses. Mean elimination half-life ranges from 6 to 14 hours. Not a substrate of P-gp or BCRP at gastrointestinal pH 5.5. No significant interaction with transporters such as OATP1B1, OATP1B3, OAT1, and OCT2 at clinically relevant doses. Shows interaction with OAT3 with IC50 of 1.7 μM.
- Mode of Action: Binds to and inhibits prolyl hydroxylase domain (PHD) enzymes, which normally degrade HIF-α. By inhibiting PHD, Desidustat allows HIF-α to accumulate and dimerize with HIF-β, translocate to the nucleus, and initiate transcription of genes involved in erythropoiesis, iron metabolism, and angiogenesis.
- Elimination Pathways: Renal and Hepatic
Dosage
Standard Dosage
Adults:
- Non-Dialysis Patients: Starting dose is 100 mg orally three times a week (e.g., Monday, Wednesday, Friday, or Tuesday, Thursday, Saturday, two days apart, not four days apart).
- Dialysis Patients:
- ESA-naive: 100 mg orally three times a week (administered after dialysis session).
- ESA-experienced: 100 mg, 125 mg, or 150 mg orally three times a week, depending on prior ESA dose.
- It is recommended that desidustat is to be taken after completion of the dialysis session.
- Maximum Dose: 150 mg three times per week for both dialysis and non-dialysis patients.
- Dose Adjustments: According to hemoglobin levels assessed every four weeks as follows:
| Change in Hb g% level every 4 weeks | Hb <10 g% | Hb 10 to <11 g% | Hb 11 to <12 g% | Hb ≥12 g% |
|---|
| <1.0 increase | Increase the dose | Increase the dose | Maintain the dose | Stop treatment for 14 days, initiate one lower dose if Hb <11.5 g% |
| ≥1.0 increase to ≤2.0 increase | Maintain the dose | Maintain the dose | Decrease the dose | Decrease the dose |
| >2.0 increase | Maintain the dose | Decrease the dose | Decrease the dose | Decrease the dose |
Children:
- Safety and efficacy not established in pediatric patients.
Special Cases:
- Elderly Patients: Use with caution due to potential comorbidities and concomitant medications.
- Patients with Renal Impairment: Dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustments may be necessary.
- Patients with Comorbid Conditions: Close monitoring is recommended, especially for patients with cardiovascular disease, hypertension, diabetes, or history of thromboembolic events.
Clinical Use Cases
The provided sources focus solely on Desidustat’s use in treating anemia related to CKD and do not offer dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments are based on hemoglobin levels (assessed every 4 weeks), concomitant medications, and liver function.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea
- Abdominal pain
- Headache
- Peripheral edema
- Pyrexia (Fever)
- Hypertension
- Dizziness, fatigue
- Upper respiratory tract infection
Rare but Serious Side Effects
- Thromboembolic events
- Hyperkalemia
- Elevated liver enzymes
- Allergic reactions (including rash, itching, angioedema)
- Seizures
Long-Term Effects
- Increased risk of cardiovascular events with prolonged use at higher doses.
Adverse Drug Reactions (ADR)
- Any signs of thrombosis or stroke.
- Severe allergic reactions.
- Severe hyperkalemia.
- Significant liver dysfunction.
Contraindications
- Hypersensitivity to Desidustat or any of its components.
- Uncontrolled hypertension.
- History of cardiovascular disease, stroke or thrombosis
- Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil).
Drug Interactions
- CYP450 Interactions: No significant inhibition or induction of major CYP enzymes (1A2, 2C8, 2C9, 2C19, 2D6, 3A4/5). Minimal potential for CYP-mediated drug interactions.
- Other Interactions:
- Anticoagulants (warfarin, dabigatran): Close monitoring required.
- Antiplatelet agents (aspirin, clopidogrel): Close monitoring required.
- Medications affecting liver enzymes (ketoconazole, rifampin): Dosage adjustments may be necessary.
- Antihypertensive medications: May require adjustment.
- Erythropoiesis-stimulating agents: Avoid concomitant use.
- Iron supplements: No significant interaction expected.
- Phosphate binders: No significant interaction expected.
- Food and Lifestyle Factors: Limit or avoid alcohol consumption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Fetal Risks: Potential risks to the fetus are unknown. Use only if potential benefit outweighs risk. Animal studies show adverse effects at high doses.
- Breastfeeding: Not known if Desidustat is excreted in breast milk. Breastfeeding is contraindicated due to potential ADR.
Drug Profile Summary
- Mechanism of Action: HIF-PH inhibitor, stimulates erythropoietin production.
- Side Effects: Nausea, vomiting, diarrhea, headache, hypertension, peripheral edema. Serious side effects: thromboembolic events, hyperkalemia.
- Contraindications: Hypersensitivity, uncontrolled hypertension, strong CYP2C8 inhibitors. History of cardiovascular disease.
- Drug Interactions: Anticoagulants, antiplatelet agents, drugs metabolized by CYP enzymes.
- Pregnancy & Breastfeeding: Category C; contraindicated during breastfeeding. Not recommended during pregnancy unless the potential benefits justify the risks.
- Dosage: Starting dose: 100mg thrice weekly. Maximum dose: 150 mg thrice weekly. Dose adjusted according to hemoglobin levels and ESA experience if applicable.
- Monitoring Parameters: Hemoglobin levels, blood pressure, liver function tests, kidney function tests, signs of thrombosis.
Popular Combinations
Information on popular drug combinations is not available in the provided sources.
Precautions
- General Precautions: Assess for allergies, organ dysfunction (renal/hepatic), and cardiovascular history. Monitor blood pressure and hemoglobin levels.
- Specific Populations:
- Pregnant Women: Avoid unless benefits clearly outweigh risks.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Safety and efficacy not established in children; use with caution in elderly.
- Menstruating Individuals: No specific information available.
- Lifestyle Considerations: Limit or avoid alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Desidustat?
A: The starting dose is 100 mg orally three times a week for both dialysis and non-dialysis patients. For patients switching from an ESA, the initial dose may be 100 mg, 125 mg, or 150 mg based on prior ESA dose. Dosage is titrated based on hemoglobin response, not exceeding a maximum of 150 mg three times weekly.
Q2: How does Desidustat work?
A: Desidustat inhibits HIF-PH, stabilizing HIFs, increasing EPO production, and stimulating erythropoiesis.
Q3: What are the common side effects of Desidustat?
A: Common side effects include nausea, vomiting, diarrhea, headache, peripheral edema, and hypertension.
Q4: Is Desidustat safe during pregnancy and breastfeeding?
A: Desidustat is Pregnancy Category C and should be avoided during pregnancy unless potential benefits justify the risks to the fetus. Desidustat is contraindicated while breastfeeding.
Q5: What are the contraindications for Desidustat?
A: Contraindications include hypersensitivity to Desidustat, uncontrolled hypertension, and concomitant use of strong CYP2C8 inhibitors. History of cardiovascular disease.
Q6: Does Desidustat interact with other medications?
A: Desidustat may interact with anticoagulants, antiplatelet agents, medications affecting liver enzymes, and other drugs. Close monitoring is necessary when co-administering these medications.
Q7: How should Desidustat be administered?
A: Desidustat is administered orally as an immediate-release tablet, three times per week, with dosing two days apart but not four days apart. For patients on dialysis, it should be taken after the dialysis session.
Q8: How often should hemoglobin levels be monitored in patients taking Desidustat?
A: Hemoglobin levels should be monitored every four weeks to guide dose adjustments.
Q9: What is the difference between Desidustat’s use in dialysis and non-dialysis patients?
A: The main difference lies in the starting dose for ESA-experienced patients. Non-dialysis ESA-experienced patients start at 100 mg while those on dialysis have a starting dose determined by previous ESA dosage (100mg, 125mg, or 150mg). ESA-naive patients, both dialysis and non-dialysis, start with 100 mg. In patients on dialysis, the medication is taken after the dialysis session.
Q10: What are the key monitoring parameters while a patient is under Desidustat treatment?
A: Key parameters to monitor include hemoglobin, blood pressure, liver function tests (LFTs), and kidney function tests (KFTs). Regularly assess for any signs of thrombosis and other potential side effects.
