vadadustat

Absorption: Extent of absorption following oral administration unknown.

Distribution: Unknown.

Protein Binding: 99.5%.

Metabolism/Excretion: Primarily metabolized in the liver via UDP-glucuronosyltransferase. 59% excreted in urine (as metabolites); 27% excreted in feces (9% as unchanged drug).

Half-Life: 9.2 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–3 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Uncontrolled hypertension;
Acute coronary syndrome, stroke, or TIA within past 3 mo;
Active, acute liver disease or cirrhosis;
Active malignancy;
Lactation: Lactation.

Use Cautiously in:

Cardiovascular or cerebrovascular disease;
History of GI erosion, peptic ulcer disease, concurrent use of medications that ↑ risk of GI erosion, and current tobacco smokers and alcohol drinkers;
OB: Safety not established in pregnancy;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, abdominal pain, DEEP VEIN THROMBOSIS (DVT) (ESPECIALLY WITH HGB >11 G/DL) , MI (ESPECIALLY WITH HGB >11 G/DL) , VASCULAR ACCESS THROMBOSIS (ESPECIALLY WITH HGB >11 G/DL)

GI: diarrhea, ↑liver enzymes, dyspepsia, gastroesophageal erosion, HEPATOTOXICITY, nausea, vomiting

Neuro: dizziness, fatigue, headache, PULMONARY EMBOLISM (PE) (ESPECIALLY WITH HGB >11 G/DL) , SEIZURES, STROKE (ESPECIALLY WITH HGB >11 G/DL)

Misc: DEATH (ESPECIALLY WITH HGB >11 G/DL) , MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Organic anion transporter (OAT) 1 inhibitors, including probenecid and rifampin, and OAT3 inhibitors, including gemfibrozil, probenecid, and teriflunomide, may ↑ levels and risk of toxicity.
NSAIDs, oral potassium, corticosteroids, or alcohol may ↑ risk of gastroesophageal erosions; avoid concurrent use.
Oral iron preparations and phosphate binders may ↓ levels and effectiveness. Administer ≥1 hr before oral iron preparations or iron-containing phosphate binders; administer ≥1 hr or ≥2 hr after non-iron-containing phosphate binders.
May ↑ levels and risk of toxicity of breast cancer resistance protein substrates, including sulfasalazine.
May ↑ levels and risk of toxicity of simvastatin and simvastatin; starting dose of simvastatin should be 5 mg/day and dose should not exceed 20 mg/day; rosuvastatin dose should not exceed 5 mg/day.
May ↑ levels and risk of toxicity of OAT3 substrates, including cefaclor, famotidine, furosemide, oseltamivir, penicillin G, or sitagliptin.

Route/Dosage ⬆ ⬇

Not Being Treated With Erythropoietin-Stimulating Agent (ESA)
PO (Adults ): 300 mg once daily.
Being Switched From ESA
PO (Adults ): 300 mg once daily. During transition phase, if Hgb ↓ to <9 g/dL or if Hgb response is unacceptable, may consider RBC transfusions or ESA treatment. If patient receives RBC transfusions, continue vadadustat treatment. If patient receives ESA rescue treatment, hold vadadustat treatment until Hgb ≥10 g/dL. Hold vadadustat until 2 days after last epoetin dose, 7 days after last darbepoetin dose, or 14 days after last methoxy polyethylene glycol-epoetin beta dose. When reinitiating vadadustat, resume at previous dose or ↑ previous dose by 150 mg.

Availability ⬆ ⬇

Tablets: 150 mg; 300 mg; 450 mg

Assessment ⬆ ⬇

Assess for arterial and venous thrombotic events (MI, stroke, DVT, PE).
Assess BP for hypertension periodically during therapy. Adjust or start antihypertensive therapy as needed.
Monitor for premonitory neurologic symptoms and seizure activity. Implement seizure precautions if indicated.
Assess for gastric and esophageal erosions and GI bleeding.
Assess for possible malignancy or tumor growth (unexplained weight loss, new masses or lymphadenopathy, persistent pain or fatigue).

Lab Test Considerations:

Evaluate iron status before and during treatment. Administer supplemental iron therapy if serum ferritin <100 mcg/L or serum transferrin saturation <20%.
Perform Hgb at baseline, during therapy, and after each dose adjustment. Monitor Hgb every 2 wk until stable and then monthly. If Hgb ↑ >1 g/dL in any 2-wk period or >2 g/dL in 4 wk, hold or ↓ dose. If Hgb >11 g/dL, hold vadadustat until Hgb ≤11 g/dL; then resume by ↓ dose by 150 mg/day. Treatment should not be continued >24 wk if an ↑ in Hgb level is not achieved.
Monitor ALT, AST, and bilirubin before starting, monthly for the 1st 6 mo, and then as clinically indicated. If ALT or AST ↑ >3 times upper limit of normal (ULN) or if ALT or AST ↑ >3 times ULN with a bilirubin ↑ >2 times ULN, discontinue vadadustat.

Implementation ⬆ ⬇

Use the lowest dose sufficient to ↓ the need for RBC transfusions.
PO: Administer with or without food. DNC: Swallow tablets whole. Do not cut, crush, or chew. Administer without regard to timing or type of dialysis.
Administer >1 hr before oral iron supplements, products containing iron, or iron-containing phosphate binders. Administer >1 hr before or 2 hr after non-iron-containing phosphate binders.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. If dose is missed, advise to take as soon as possible. If dose is missed the same day as the next dose, skip the dose, and take the next dose at usual time. Do not double doses.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient to seek immediate medical attention if signs or symptoms of MI, stroke, DVT, or PE occur.
Advise patient of the signs/symptoms of gastric and esophageal erosions and of GI bleeding, and to seek prompt medical care if these occur.
Advise patient to contact health care provider immediately for hypertension, hepatotoxicity, new-onset seizures, premonitory symptoms, or change in seizure frequency.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes ⬆ ⬇

Increased hemoglobin.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

59922- Akebia Therapeutics, Inc.
- 59922-641- VAFSEO
  - 59922-641-60- 1 BOTTLE in 1 CARTON (59922-641-60) / 60 TABLET, FILM COATED in 1 BOTTLE

59922- Akebia Therapeutics, Inc.
- 59922-642- VAFSEO
  - 59922-642-60- 1 BOTTLE in 1 CARTON (59922-642-60) / 60 TABLET, FILM COATED in 1 BOTTLE

59922- Akebia Therapeutics, Inc.
- 59922-643- VAFSEO
  - 59922-643-60- 1 BOTTLE in 1 CARTON (59922-643-60) / 60 TABLET, FILM COATED in 1 BOTTLE

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇