Amifostine

Amifostine Brand Name- Ethyol

What is Amifostine

Amifostine (WR-2721, ethiofos) is a phosphorylated sulfhydryl-containing prodrug that protects tissues from the cytotoxic actions of radiation and chemotherapy.

It was originally developed by the military for use as a radioprotectant in the event of nuclear warfare.

Amifostine has selective cytoprotective effects for normal tissues. In the pivotal US trial, amifostine reduced the incidence and severity of myelosuppression, nephrotoxicity and peripheral neuropathies seen with cisplatin and cyclophosphamide combination therapy.

Studies examining the myeloprotective effects of amifostine show a higher white blood cell nadir, shorter duration of neutropenia, and a decreased incidence of neutropenia-related adverse events as compared to controls. These chemoprotective effects seem to be additive with repeated cycles and do not affect antitumor efficacy.

Preliminary trials indicate enhanced response rates but no effect on survival in patients treated with radiation and amifostine.

In head and neck cancer patients, amifostine administered prior to radiation therapy significantly reduced the incidence of acute- and late-onset xerostomia as compared to patients who received radiation alone.

Amifostine is being studied to see if it is efficacious at preventing toxicities due to paclitaxel, melphalan and mitomycin-C in pediatric patients. Initial studies have shown that treatment with amifostine may increase platelet, red blood cell, and neutrophil counts and decrease transfusion requirements in patients with myelodysplastic syndromes.

Amifostine has been in use in Europe since 1994. Amifostine was FDA-approved on December 8, 1995 for prevention of cisplatin-induced nephrotoxicity in ovarian cancer patients and in March 1996 was given FDA approval for use in patients with non-small cell lung cancer receiving cisplatin based chemotherapy; this indication was removed in April 2006.

In June 1998, the FDA designated Ethyol as an orphan drug for reducing the incidence and severity of radiation-induced xerostomia.

In June 1999, the FDA approved Ethyol for this use.

Indications

  1. bone marrow suppression prophylaxis
  2. myelodysplastic syndrome (MDS)
  3. nephrotoxicity prophylaxis
  4. neurotoxicity prophylaxis
  5. xerostomia prophylaxis

For nephrotoxicity prophylaxis in patients receiving cisplatin for advanced ovarian cancer

Side Effects

  1. anaphylactoid reactions
  2. angina
  3. apnea
  4. atrial fibrillation
  5. atrial flutter
  6. blurred vision
  7. bradycardia
  8. cardiac arrest
  9. chest pain (unspecified)
  10. chest pressure syndrome
  11. chills
  12. diarrhea
  13. diplopia
  14. dizziness
  15. drowsiness
  16. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  17. dyspnea
  18. erythema
  19. erythema multiforme
  20. exfoliative dermatitis
  21. fever
  22. flushing
  23. hiccups
  24. hypertension
  25. hypocalcemia
  26. hypotension
  27. hypotension
  28. hypoxia
  29. injection site reaction
  30. laryngeal edema
  31. malaise
  32. myocardial infarction
  33. nausea
  34. pruritus
  35. rash
  36. renal failure (unspecified)
  37. respiratory arrest
  38. seizures
  39. sinus tachycardia
  40. sneezing
  41. Stevens-Johnson syndrome
  42. supraventricular tachycardia (SVT)
  43. syncope
  44. toxic epidermal necrolysis
  45. urticaria
  46. vomiting

Monitoring Parameters

  • blood pressure
  • pregnancy testing
  • serum calcium

Contraindications

  • angina
  • breast-feeding
  • cardiac arrhythmias
  • cardiac disease
  • cerebrovascular disease
  • chemotherapy
  • children
  • dehydration
  • exfoliative dermatitis
  • geriatric
  • heart failure
  • hypocalcemia
  • hypotension
  • infants
  • myocardial infarction
  • neonates
  • pregnancy
  • pregnancy testing
  • radiation therapy
  • renal disease
  • serious rash
  • stroke

Interactions

  • Acebutolol
  • Aliskiren; Amlodipine
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Aliskiren; Hydrochlorothiazide, HCTZ
  • Aliskiren; Valsartan
  • Alpha-blockers
  • Amiloride
  • Amiloride; Hydrochlorothiazide, HCTZ
  • Amlodipine
  • Amlodipine; Atorvastatin
  • Amlodipine; Benazepril
  • Amlodipine; Celecoxib
  • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
  • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
  • Amlodipine; Olmesartan
  • Amlodipine; Telmisartan
  • Amlodipine; Valsartan
  • Angiotensin II receptor antagonists
  • Angiotensin-converting enzyme inhibitors
  • Atenolol
  • Atenolol; Chlorthalidone
  • Azilsartan
  • Azilsartan; Chlorthalidone
  • Benazepril
  • Benazepril; Hydrochlorothiazide, HCTZ
  • Bendroflumethiazide; Nadolol
  • Beta-blockers
  • Betaxolol
  • Bisoprolol
  • Bisoprolol; Hydrochlorothiazide, HCTZ
  • Brimonidine; Timolol
  • Calcium-channel blockers
  • Candesartan
  • Candesartan; Hydrochlorothiazide, HCTZ
  • Captopril
  • Captopril; Hydrochlorothiazide, HCTZ
  • Carteolol
  • Carvedilol
  • Central-acting adrenergic agents
  • Chlorothiazide
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Clevidipine
  • Diazoxide
  • Diltiazem
  • Dorzolamide; Timolol
  • Doxazosin
  • Enalapril, Enalaprilat
  • Enalapril; Felodipine
  • Enalapril; Hydrochlorothiazide, HCTZ
  • Eplerenone
  • Epoprostenol
  • Eprosartan
  • Eprosartan; Hydrochlorothiazide, HCTZ
  • Esmolol
  • Felodipine
  • Fenoldopam
  • Fosinopril
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Hydralazine
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydralazine; Isosorbide Dinitrate, ISDN
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Irbesartan
  • Hydrochlorothiazide, HCTZ; Lisinopril
  • Hydrochlorothiazide, HCTZ; Losartan
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Metoprolol
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrochlorothiazide, HCTZ; Olmesartan
  • Hydrochlorothiazide, HCTZ; Propranolol
  • Hydrochlorothiazide, HCTZ; Quinapril
  • Hydrochlorothiazide, HCTZ; Spironolactone
  • Hydrochlorothiazide, HCTZ; Telmisartan
  • Hydrochlorothiazide, HCTZ; Triamterene
  • Hydrochlorothiazide, HCTZ; Valsartan
  • Iloprost
  • Irbesartan
  • Isradipine
  • Labetalol
  • Levobetaxolol
  • Levobunolol
  • Lisinopril
  • Losartan
  • Mecamylamine
  • Methyclothiazide
  • Metolazone
  • Metoprolol
  • Minoxidil
  • Moexipril
  • Nadolol
  • Nebivolol
  • Nebivolol; Valsartan
  • Nicardipine
  • Nifedipine
  • Nimodipine
  • Nisoldipine
  • Nitroprusside
  • Olmesartan
  • Penbutolol
  • Perindopril
  • Perindopril; Amlodipine
  • Phenoxybenzamine
  • Phentolamine
  • Pindolol
  • Potassium-sparing diuretics
  • Prazosin
  • Propranolol
  • Quinapril
  • Ramipril
  • Reserpine
  • Sacubitril; Valsartan
  • Sotalol
  • Spironolactone
  • Telmisartan
  • Terazosin
  • Thiazide diuretics
  • Timolol
  • Trandolapril
  • Trandolapril; Verapamil
  • Treprostinil
  • Triamterene
  • Valsartan
  • Vasodilators
  • Verapamil
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