Vadadustat is used for anemia in chronic kidney disease patients on dialysis, but it may cause serious adverse reactions such as thrombosis, liver injury, and increased blood pressure, requiring close monitoring. The following is explained in three aspects.

I. Serious Adverse Reactions

1.Thrombosis and Cardiovascular Events

It may increase the risk of death, myocardial infarction, stroke, venous thromboembolism, and vascular access thrombosis.

If hemoglobin rises too quickly or the target exceeds 11 g/dL, the above risks are further amplified.

Patients with cardiovascular or cerebrovascular disease are at higher risk; those with recent myocardial infarction, cerebrovascular events, or acute coronary syndrome should avoid use.

If chest pain, difficulty breathing, hemiplegia, slurred speech, sudden vision changes, lower limb swelling and pain, or dialysis access abnormalities occur, seek medical attention immediately.

2.Hepatotoxicity

It may cause hepatocellular injury, mostly occurring within the first 3 months of treatment.

It presents as elevated ALT, AST, and bilirubin, mostly asymptomatic, and may recover after discontinuation.

If ALT or AST persistently exceeds 3 times the upper limit of normal, or is accompanied by bilirubin exceeding 2 times the upper limit of normal, the drug should be discontinued.

It is not recommended for patients with cirrhosis or active acute liver disease.

3.Worsening Blood Pressure

It may lead to worsening hypertension, and even hypertensive crisis, hypertensive encephalopathy, and seizures.

It is contraindicated in patients with uncontrolled hypertension.

Blood pressure should be monitored regularly during medication, and antihypertensive treatment should be adjusted or initiated when necessary.

4.Seizures

Seizures may occur during treatment.

Attention should be paid to new-onset seizures, aura symptoms, or changes in seizure frequency.

If headache, irritability, fear, confusion, or abnormal sensations occur, inform the doctor promptly.

5.Gastrointestinal Erosion and Bleeding

Gastric or esophageal erosion and gastrointestinal bleeding may occur.

Patients with a history of gastrointestinal erosion, peptic ulcer, concomitant use of drugs that increase erosion risk, smoking, or alcohol consumption are at higher risk.

If abdominal pain, black stools, hematemesis, difficulty swallowing, or retrosternal pain occurs, seek medical attention immediately.

6.Malignancy Risk

It may adversely affect cancer growth.

It is not recommended for patients with active malignancy.

During medication, attention should be paid to cancer-related symptoms, and a doctor should be consulted if there are concerns.

II. Other Common Adverse Reactions

1.Digestive System

Diarrhea is relatively common, and nausea, vomiting, and abdominal pain may also occur.

Some patients require permanent discontinuation due to gastrointestinal symptoms.

2.Nervous System

Headache and dizziness may occur.

Dizziness may present as vertigo, balance disturbance, or presyncope.

3.Other

Fatigue, weakness, and malaise.

Difficulty breathing and shortness of breath.

Arteriovenous fistula thrombosis.

Dialysis-related complications.

III. Special Populations and Medication Precautions

1.Pregnancy and Lactation

It may harm the fetus during pregnancy, and should be used only when the benefits outweigh the risks.

It is not recommended during lactation, and breastfeeding should not occur within 2 days after discontinuation.

2.Pediatric and Elderly

Safety and effectiveness in pediatric patients have not been established.

Elderly patients do not need dose adjustment based on age alone, but overall condition should be monitored.

3.Patients With Liver Injury

It is not recommended for patients with cirrhosis or active acute liver disease.

4.Adverse Reactions Related to Drug Interactions

Concomitant use with oral iron supplements, iron-containing products, and phosphate binders reduces vadadustat exposure and affects efficacy, so administration should be staggered.

Concomitant use with BCRP substrates, statins, and OAT3 substrates may increase the exposure and adverse reaction risk of these drugs, requiring monitoring and dose adjustment as appropriate.

5.Overdose

Overdose can cause excessive elevation of hemoglobin.

The dose should be reduced or the drug discontinued, and management should be based on clinical needs; dialysis can remove about 16% of the drug, and there is no specific antidote.