(am i FOS teen)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Ethyol: 500 mg (1 ea)
Generic: 500 mg (1 ea [DSC])
Solution Reconstituted, Intravenous [preservative free]:
Generic: 500 mg (1 ea [DSC])
Brand Names: U.S.
- Chemoprotective Agent
Amifostine is a 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.
Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Urine (minimal; as amifostine and metabolites)
Children: 9.3 minutes (Fouladi 2001); Adults: ~8 minutes
Use: Labeled Indications
Renal toxicity (cisplatin-induced): Reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer.
Xerostomia due to radiation therapy for head and neck cancer: 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.
Limitations of use: The clinical data do not suggest the efficacy of cisplatin-based chemotherapy or radiation therapy for the approved indications is altered by amifostine. Data on the effects of amifostine on the efficacy of chemotherapy or radiotherapy in other settings is limited. Do not administer amifostine in other settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy, unless within the context of a clinical study.
Off Label Uses
Radiation proctitis in patients with rectal cancer (prevention)
Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the Management of Mucositis Secondary to Cancer Therapy and the European Society for Medical Oncology (ESMO) Clinical Recommendations for the management of oral and gastrointestinal mucositis, intravenous amifostine given for prevention of radiation proctitis in patients receiving radiation for rectal cancer is effective and recommended for the prevention of this condition.
Hypersensitivity to amifostine, aminothiol compounds, or any component of the formulation
Note: Amifostine doses >300 mg/m2 are associated with a moderate emetic potential. Antiemetic medication, including dexamethasone (20 mg IV when used for cisplatin-induced renal toxicity) and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Renal toxicity (cisplatin-induced): 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 to 119
Decrease of 30 mm Hg if baseline systolic blood pressure 120 to 139
Decrease of 40 mm Hg if baseline systolic blood pressure 140 to 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 due to radiation therapy for head and neck cancer: IV: 200 mg/m2 over 3 minutes once daily 15 to 30 minutes prior to radiation therapy
Radiation proctitis in rectal cancer, prevention (off-label use): IV: 340 mg/m2 once daily prior to radiation therapy (Lalla 2014; Peterson 2015)
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Adjustment for Toxicity
Cutaneous reactions or mucosal lesions appearing outside of the injection site or radiation port: Discontinue.
Bullous, edematous or erythematous lesions on the palms or soles: Discontinue.
Severe acute allergic reaction: Discontinue permanently.
For IV infusion, reconstitute intact vials with 9.7 mL NS injection and dilute in NS to a final concentration of 5 mg/mL to 40 mg/mL.
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 (15 to 30 minutes prior to radiation therapy) or over 15 minutes (30 minutes prior to cisplatin); administration as a longer infusion is associated with a higher incidence of side effects. Patients should be adequately hydrated and kept in supine position during infusion.
Store intact vials at 20°C to 25°C (68°F to 77°F). Reconstituted solutions (500 mg/10 mL) and solutions diluted in NS (in polyvinyl chloride [PVC] bags) for infusion are chemically stable for up to 5 hours at room temperature (~25°C [~77°F]) or up to 24 hours under refrigeration (2°C to 8°C [36°F to 46°F]).
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
Benperidol: 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
Lormetazepam: 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
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. 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
Cardiovascular: Hypotension (ovarian cancer: 61% to 62%; head and neck cancer: 15%; generally transient)
Gastrointestinal: Nausea and vomiting (ovarian cancer: 96%; head and neck cancer: 53%), severe nausea and vomiting (ovarian cancer: 19%; head and neck cancer: 8%)
1% to 10%: Endocrine & metabolic: Hypocalcemia (head and neck cancer: 1%; clinically significant)
Frequency not defined:
Cardiovascular: Bradycardia, chest pain, extrasystoles, flushing, ischemic heart disease, tachycardia
Central nervous system: Chills, dizziness, drowsiness, malaise, sensation of cold
Dermatologic: Erythema multiforme, skin rash
Gastrointestinal: Diarrhea, hiccups
Local: Injection site reaction (includes bruising at injection site, erythema at injection site, inflammation at injection site, injection site pruritus, pain at injection site, rash at injection site, swelling at injection site, urticaria at injection site)
Ophthalmic: Blurred vision, diplopia
Respiratory: Apnea, dyspnea, hypoxia, sneezing
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, atrial fibrillation, atrial flutter, cardiac arrhythmia, DRESS syndrome, hypersensitivity reaction (includes chest discomfort, laryngeal edema, pruritus, rigors, urticaria), myocardial infarction, renal failure, seizure, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, toxic epidermal necrolysis, transient hypertension
Concerns related to adverse effects:
• Cutaneous reactions: Serious cutaneous reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxicoderma, exfoliative dermatitis, and drug reaction with biopsy-proven eosinophilia and system symptoms (DRESS) 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. Evaluate for dermatologic reactions prior to each dose, during therapy and after treatment discontinuation. Discontinue treatment for severe/serious cutaneous reactions or mucosal lesions that appear outside of the radiation port and for bullous, edematous, or erythematous lesions on the palms or soles.
• Hypersensitivity: Rare hypersensitivity reactions, including anaphylaxis and allergic reaction, have been reported. Discontinue if severe acute 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. Short term (reversible) syncope (loss of consciousness) has been rarely reported. 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. Interrupt antihypertensive therapy for 24 hours before treatment; patients who cannot safely stop their antihypertensives 24 hours before should not receive amifostine.
• 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 for whom the adverse effects of nausea/vomiting may have serious adverse events.
• 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:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Appropriate use: According to the manufacturer, amifostine 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. The American Society of Clinical Oncology (ASCO) has published guidelines for the use of protectants for chemotherapy and radiation (Hensley 2009). According to the ASCO guidelines, amifostine may be considered for prevention of nephrotoxicity in patients receiving cisplatin-based therapy. While amifostine may be considered to reduce the incidence of grade 3 or 4 neutropenia associated with chemotherapy, the guidelines suggest that alternative strategies (eg, growth factors) may be utilized in this situation. The guidelines recommend against the use of amifostine to reduce the incidence of thrombocytopenia associated with chemotherapy or radiation therapy. Data is insufficient to recommend amifostine for prevention of neurotoxicity or ototoxicity associated with platinum-based chemotherapy, for prevention of neurotoxicity associated with paclitaxel, for prevention of radiation therapy-induced mucositis associated with head and neck cancer, or for prevention of esophagitis due to chemotherapy in patients with non-small cell lung cancer. Additionally, amifostine may be considered to decrease the incidence of acute and late xerostomia in patients undergoing radiation therapy alone (for head and neck cancer); however, the guidelines do not support the use of amifostine in patients with head and neck cancer receiving concurrent platinum-based chemotherapy.
Blood pressure (monitor 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, during therapy, and after treatment discontinuation. Monitor hydration status.
Adverse events have been observed in animal reproduction studies.
• 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, abnormal heartbeat, severe dizziness, passing out, severe nausea, vomiting, swollen glands, redness or irritation of palms or soles of feet, severe injection site irritation, seizures, signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures), 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 health care 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.
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- Drug class: antineoplastic detoxifying agents
Other brands: Ethyol