Amifostine

ETHYOL is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues.

• ETHYOL is a cytoprotective agent indicated for: – reduction of cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. ( 1.1 ) – reduction of the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.ICD-10: C56.9

• ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds. ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.contraindicated

– For reduction of cumulative renal toxicity with chemotherapy, the recommended starting dose is 910 mg/m 2 administered once daily as a 15-minute intravenous infusion, starting 30 minutes prior to chemotherapy. ( 2.1 ) – For reduction of moderate to severe xerostomia from radiation of the head and neck, the recommended dose is 200 mg/m 2 administered once daily as a 3-minute intravenous infusion, starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy). ( 2.2 ) 2.1 Important Administration Instructions Hydration and Premedication Prior to ETHYOL infusion, verify that patients are adequately hydrated and correct existing dehydration if clinically indicated. When administering ETHYOL at the 910 mg/m 2 dose, antiemetic medications, including intravenous dexamethasone 20 mg and a serotonin 5HT 3 receptor antagonist, are recommended prior to ETHYOL administration. Additional antiemetics may be required based on the chemotherapy drugs administered. When administering ETHYOL at the 200 mg/m 2 dose, it is recommended that antiemetic medication be administered prior to ETHYOL administration. Oral 5HT 3 receptor antagonists, alone or in combination with other antiemetics are recommended in the radiotherapy setting. Supine Position and Blood Pressure Monitoring Patients should be kept in a supine position during the ETHYOL infusion. When administering ETHYOL at the 910 mg/m 2 dose, monitor blood pressure before, at least every 5 minutes during the infusion, at the end of the infusion, and thereafter as clinically indicated.

– Hypotension and Cardiovascular Events: Patients who are hypotensive or dehydrated should not receive ETHYOL. If interruption of antihypertensive therapy is possible, interrupt antihypertensive therapy 24 hours prior to ETHYOL administration. Monitor blood pressure during infusion; interrupt and restart infusion if decrease in systolic blood pressure is observed. Do not administer ETHYOL to hypotensive patients who are taking antihypertensive therapy that cannot be stopped for 24 hours prior to ETHYOL administration. ( 5.3 ) – Severe Cutaneous Reactions: Monitor patients prior to, during, and weeks after administration for severe cutaneous reactions. Discontinue for cutaneous reactions or lesions appearing outside of the injection site/radiation port or on the palms or soles. ( 5.4 ) – Hypersensitivity: Discontinue for severe acute allergic reactions. Administer treatment for serious allergic events. ( 5.5 ) – Nausea and Vomiting: Administer antiemetic medication prior to and in conjunction with ETHYOL. Monitor fluid balance when administered with highly emetogenic chemotherapy. ( 5.6 ) – Hypocalcemia: Monitor serum calcium levels in patients at risk of hypocalcemia. If necessary, administer calcium supplements. ( 5.7 ) – Embryo-Fetal Toxicity: ETHYOL can cause fetal harm. Advise patients of the potential risk to a fetus ( 5.8 , 8.1 , 8.3 ). Also, refer to the cisplatin full prescribing information for pregnancy and contraception information. 5.1 Effectiveness of the Chemotherapy Regimen ETHYOL may interfere with the antitumor activity of chemotherapy regimens.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: – Hypotension and Cardiovascular Events [see Warnings and Precautions (5.3) ] – Severe Cutaneous Reactions [see Warnings and Precautions (5.4) ] – Hypersensitivity [see Warnings and Precautions (5.5) ] – Nausea and Vomiting [see Warnings and Precautions (5.6) ] – Hypocalcemia [see Warnings and Precautions (5.7) ] Most common adverse reactions are hypotension, nausea and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Legacy Pharma Inc. at 1-800-727-7151 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. ETHYOL was administered to patients receiving chemotherapeutic agents for advanced ovarian cancer (WR-1 study) or who were receiving standard fractionated radiotherapy for head and neck cancer (WR-38 study) [see Clinical Studies (14) ] . In the WR-38 study of patients with head and neck cancer, 17% (26/150) discontinued ETHYOL due to adverse reactions. All but one of these patients continued to receive radiation treatment until completion. Table 2 summarizes adverse reactions reported in patients from the WR-1 and WR-38 clinical trials.

- – Advise not to breastfeed. ( 8.2 ) See 17 for PATIENT COUNSELING INFORMAITON. 8.1 Pregnancy Risk Summary When ETHYOL is used in combination with cisplatin, refer to the cisplatin full prescribing information for pregnancy information. Based on findings in animals, ETHYOL can cause fetal harm when administered to a pregnant woman. There are no available data on ETHYOL use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, intravenous administration of ETHYOL to pregnant rabbits during organogenesis was embryotoxic at doses approximately sixty percent of the recommended dose in humans based on body surface area (see Data) . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the estimated background risk of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data ETHYOL has been shown to be embryotoxic in rabbits at intravenous doses of 50 mg/kg, approximately sixty percent of the recommended dose in humans on a body surface area basis.

Metabolism

Clinical pharmacokinetic studies show that ETHYOL is rapidly cleared from the plasma with a distribution half-life of < 1 minute and an elimination half-life of approximately 8 minutes. Less than 10% of ETHYOL remains in the plasma 6 minutes after drug administration.

In clinical trials, the maximum single dose of ETHYOL was 1300 mg/m 2 . No information is available on single doses higher than this in adults. At the higher doses, anxiety and reversible urinary retention occurred. The most likely symptom of overdosage is hypotension, which should be managed by infusion of normal saline and other supportive measures, as clinically indicated [see Warnings and Precautions (5.3) ] .

• Dec 8, 1995NDANDA020221Legacy Pharma

1. 1Pyrexia15920%
2. 2Nausea14218%
3. 3Vomiting11514%
4. 4Hypotension11014%
5. 5Mucosal Inflammation9111%
6. 6Chills698.6%
7. 7Dehydration698.6%
8. 8Rash668.2%
9. 9Pruritus577.1%
10. 10Rash Generalised516.3%
11. 11Thrombocytopenia516.3%
12. 12Dyspnoea506.2%
13. 13Malaise465.7%
14. 14Injection Site Erythema445.5%
15. 15Diarrhoea435.3%

Recent PubMed references pinned to Amifostine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Amifostine-Iron Nanoparacrystalline for Tumor-Selective Immunogenic Ferroptosis.
  Nano letters · 2026 · Huang Z, Zhou H, Huang S, et al.
  PMID 41448721DOI 10.1021/acs.nanolett.5c05065
• Amifostine and melatonin attenuate radiation-induced oxidative stress, inflammation, and fibrotic remodeling in the vocal folds and subglottic glands of rats.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025 · Kim JM, Park GC, Lee HW, et al.
  PMID 41110366DOI 10.1016/j.biopha.2025.118658
• Melatonin may be an alternative to amifostine in salivary gland protection in irradiated rats.
  BMC oral health · 2025 · Yorgancilar N, Kose O, Rakici SY, et al.
  PMID 41039419DOI 10.1186/s12903-025-06859-6
• Analysis of the Metabolomic Profile in Serum of Mice Treated with RadioDefender, a Novel Radiation Medical Countermeasure.
  Radiation research · 2025 · Carpenter AD, Brink MW, Li X, et al.
  PMID 40991958DOI 10.1667/RADE-25-00072.1
• An alternative approach to replacing the synthetic radioprotective drug amifostine with natural compounds in a piscine model exposed to (60)Co gamma radiation.
  Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine · 2025 · Darul Raiyaan GI, Kantha Deivi A, Sankari D, et al.
  PMID 40849986DOI 10.1016/j.apradiso.2025.112133
• Oral administration amifostine-grafted chitosan nanodrug for intestinal radioprotection.
  International journal of biological macromolecules · 2025 · Qian Z, Wang Z, Liu C, et al.
  PMID 40669615DOI 10.1016/j.ijbiomac.2025.146046
• Local amifostine administration mitigates chemotherapy-induced esophageal mucosal damage: A novel approach for targeted treatment in a rabbit model.
  Histology and histopathology · 2026 · Li Y, Zhang J, Wang B, et al.
  PMID 40641419DOI 10.14670/HH-18-957
• Amifostine-loaded Prussian blue nanoparticles for simultaneous efficient radioprotection and deep decorporation of radiocesium.
  Colloids and surfaces. B, Biointerfaces · 2025 · Wang B, Liu Y, Li C, et al.
  PMID 40381289DOI 10.1016/j.colsurfb.2025.114788

The 10 most recently updated of 86 ClinicalTrials.gov registrations naming Amifostine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Phase 1 Study to Evaluate Safety and Efficacy of XER-001 (Amifostine for Nasoduodenal Delivery) in Combination With Sterotactic Body Radiotherapy for Treatment in Patients With Locally Advanced Pancreatic Cancer.
  Recruiting · Phase 1 · Phase 2 · Interventional · 36 enrolled · Xerient Pharma
  NCT07157033updated 2026-05-01
• A Study of GR1014 Cutaneous Gel for the Prevention of Skin Reactions Caused by Radiation Therapy for Breast Cancer
  Active not recruiting · Phase 2 · Interventional · 273 enrolled · Graegis Pharmaceuticals Ltd
  NCT07192588updated 2025-09-25
• Study of Cytoreductive Surgery and Hyperthermic Intrathoracic Pleural Chemotherapy (HITC) With Escalating Doses for Children and Adolescents With Unilateral Pleural Malignancy
  Completed · Phase 1 · Interventional · 7 enrolled · M.D. Anderson Cancer Center
  NCT01998529updated 2023-09-14
• A Study of Amifostine (Ethyol) in Patients With Colorectal Cancer
  Terminated · Phase 2 · Interventional · 4 enrolled · University of Cincinnati
  NCT00601198updated 2023-08-01
• Combination Chemotherapy, Amifostine, and Peripheral Stem Cell Transplantation in Treating Patients With Stage II, Stage III, or Stage IV Breast Cancer
  Completed · Phase 1 · Interventional · 15 enrolled · City of Hope Medical Center
  NCT00003927updated 2023-07-05
• Amifostine and Melphalan in Treating Patients With Primary Systemic Amyloidosis Who Are Undergoing Peripheral Stem Cell Transplantation
  Terminated · Phase 1 · Interventional · 8 enrolled · Eastern Cooperative Oncology Group
  NCT00052884updated 2023-06-18
• AminoMedixTM for Kidney Protection During Radionuclide Therapy
  Completed · Observational · 28 enrolled · Excel Diagnostics and Nuclear Oncology Center
  NCT05785663updated 2023-03-27
• Amifostine & High-Dose Combination Chemotherapy in Treating Patients With Acute ML or CML
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Rush University Medical Center
  NCT00003407updated 2023-02-02
• Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer
  Completed · Phase 3 · Interventional · 111 enrolled · Children's Oncology Group
  NCT00274937updated 2022-10-25
• Surgery, Radiation Therapy, and Combination Chemotherapy in Treating Patients With Recurrent Head and Neck Cancer
  Terminated · Phase 2 · Interventional · 35 enrolled · Abramson Cancer Center at Penn Medicine
  NCT00003777updated 2022-01-26

Frequently asked questions

How does Amifostine work?

ETHYOL is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues.

What is Amifostine used for?

According to FDA labeling, Amifostine carries indications including: ETHYOL is a cytoprotective agent indicated for: – reduction of cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. ( 1.1 ) – reduction of the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Amifostine?

Amifostine is classified as Detoxifying agents for antineoplastic treatment, Free Radical Scavenging Activity, Parathyroid Gland Activity Alteration.

What are the brand names for Amifostine?

Amifostine is marketed under brand names including Ethyol.

What are the contraindications for Amifostine?

Amifostine labeling lists contraindications including: ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds. ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.. Always consult the full prescribing information and a clinician.