Skip to Content
How to talk to a doctor about advanced ovarian cancer >>

Amifostine

Pronunciation

(am i FOS teen)

Index Terms

  • Ethiofos
  • Gammaphos
  • WR-2721
  • YM-08310

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Ethyol: 500 mg (1 ea)

Generic: 500 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 500 mg (1 ea)

Brand Names: U.S.

  • Ethyol

Pharmacologic Category

  • Antidote
  • Chemoprotective Agent

Pharmacology

Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated (by cisplatin or radiation therapy) in tissues.

Distribution

Vd: 3.5 L; unmetabolized prodrug is largely confined to the intravascular compartment; active metabolite is distributed into normal tissues with high concentrations in bone marrow, GI mucosa, skin, liver, and salivary glands

Metabolism

Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)

Excretion

Urine (as metabolites)

Clearance, plasma: 2.17 L/minute

Half-Life Elimination

Children: 9.3 minutes (Fouladi 2001); Adults: ~8 to 9 minutes

Protein Binding

4%

Use: Labeled Indications

Reduce the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands; reduce the cumulative renal toxicity associated with repeated administration of cisplatin

Use: Unlabeled

Prevention of radiation proctitis in patients with rectal cancer

Contraindications

Hypersensitivity to aminothiol compounds or any component of the formulation

Dosing: Adult

Note: Amifostine doses >300 mg/m2 are associated with a moderate emetic potential. Antiemetic medication, including dexamethasone 20 mg IV and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.

Cisplatin-induced renal toxicity, reduction: IV: 910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy

For 910 mg/m2 doses, the manufacturer suggests the following blood pressure-based adjustment schedule:

The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from baseline, as defined below:

Decrease of 20 mm Hg if baseline systolic blood pressure <100

Decrease of 25 mm Hg if baseline systolic blood pressure 100-119

Decrease of 30 mm Hg if baseline systolic blood pressure 120-139

Decrease of 40 mm Hg if baseline systolic blood pressure 140-179

Decrease of 50 mm Hg if baseline systolic blood pressure ≥180

If blood pressure returns to normal within 5 minutes (assisted by fluid administration and postural management) and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m2.

Xerostomia from head and neck cancer, reduction:

IV: 200 mg/m2 over 3 minutes once daily 15-30 minutes prior to radiation therapy or

SubQ (off-label route): 500 mg once daily prior to radiation therapy

Prevention of radiation proctitis in rectal cancer (off-label use): IV: 340 mg/m2 once daily prior to radiation therapy (Keefe, 2007; Peterson, 2008)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Reconstitution

For IV infusion, reconstitute intact vials with 9.7 mL 0.9% sodium chloride injection and dilute in 0.9% sodium chloride to a final concentration of 5-40 mg/mL. For SubQ administration, reconstitute with 2.5 mL NS or SWFI.

Administration

Amifostine doses >300 mg/m2 are associated with a moderate emetic potential; antiemetics are recommended to prevent nausea/vomiting (Dupuis, 2011)

IV: Administer over 3 minutes (prior to radiation therapy) or 15 minutes (prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be kept in supine position during infusion. Note: SubQ administration (off-label) has been used.

Compatibility

Stable in NS.

Y-site administration: Incompatible with acyclovir, amphotericin B, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine edisylate.

Compatibility in syringe: Incompatible with ceftriaxone.

Storage

Store intact vials of lyophilized powder at room temperature of 20°C to 25°C (68°F to 77°F). Reconstituted solutions (500 mg/10 mL) and solutions for infusion are chemically stable for up to 5 hours at room temperature (25°C) or up to 24 hours under refrigeration (2°C to 8°C).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Hypotension (15% to 61%; grades 3/4: 3% to 8%; dose dependent)

Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)

1% to 10%: Endocrine & metabolic: Hypocalcemia (clinically significant: 1%)

<1% (Limited to important or life-threatening): Apnea, anaphylactoid reactions, anaphylaxis, arrhythmia, atrial fibrillation, atrial flutter, back pain, bradycardia, cardiac arrest, chest pain, chest tightness, chills, cutaneous eruptions, dizziness, erythema multiforme, exfoliative dermatitis, extrasystoles, dyspnea, fever, flushing, hiccups, hypersensitivity reactions (fever, rash, hypoxia, dyspnea, laryngeal edema), hypertension (transient), hypoxia, malaise, MI, myocardial ischemia, pruritus, rash (mild), renal failure, respiratory arrest, rigors, seizure, sneezing, somnolence, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, tachycardia, toxic epidermal necrolysis, toxoderma, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Cutaneous reactions: Serious cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported with amifostine. May be delayed, developing up to weeks after treatment initiation. Cutaneous reactions have been reported more frequently when used as a radioprotectant. Discontinue treatment for severe/serious cutaneous reaction, or with fever. Withhold treatment and obtain dermatologic consultation for rash involving lips or mucosa (of unknown etiology outside of radiation port) and for bullous, edematous or erythematous lesions on hands, feet or trunk; reinitiate only after careful evaluation.

• Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if allergic reaction occurs; do not rechallenge. Medications for the treatment of hypersensitivity reactions should be available.

• Hypocalcemia: Reports of clinically-relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome, or patients receiving multiple amifostine doses. May require calcium supplementation.

• Hypotension: Hypotension may occur during or shortly after infusion. Patients who are hypotensive or dehydrated should not receive amifostine. Adequately hydrate prior to treatment and keep in a supine position during the infusion. Monitor blood pressure every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate IV line; subsequent infusions may require a dose reduction. Infusions >15 minutes are associated with a higher incidence of adverse effects.

• Nausea/vomiting: Amifostine doses >300 mg/m2 are associated with a moderate emetic potential (Dupuis, 2011). The incidence of nausea and vomiting is higher in patients receiving amifostine, compared to chemotherapy alone. Antiemetic medications, including dexamethasone 20 mg IV and a serotonin 5-HT3 receptor antagonist, should be administered prior to and in conjunction with amifostine. Use with caution in patients whom the adverse effects of nausea/vomiting may have serious adverse events.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events.

• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.

Concurrent drug therapy issues:

• Antihypertensive therapy: Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.

Other warnings/precautions:

• Appropriate use: Should not be used (in patients receiving chemotherapy for malignancies other than ovarian cancer) where chemotherapy is expected to provide significant survival benefit or in patients receiving definitive radiotherapy, unless within the context of a clinical trial.

Monitoring Parameters

Blood pressure should be monitored every 5 minutes during the infusion and after administration if clinically indicated; serum calcium levels (in patients at risk for hypocalcemia). Evaluate for cutaneous reactions prior to each dose.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber shortness of breath, angina, bradycardia, tachycardia, arrhythmia, severe dizziness, passing out, urinary retention, change in amount of urine passed, severe nausea, severe vomiting, signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures), redness or irritation of palms or soles of feet, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide