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Amifostine

Pronunciation: A-mi-FOS-teen
Class: Cytoprotective agent

Trade Names

Ethyol
- Injection, lyophilized powder for solution 500 mg

Pharmacology

Amifostine is an organic thiophosphate cytoprotective agent that can reduce the toxicity of cisplatin or radiation. It binds to, and thereby detoxifies, reactive metabolites of cisplatin. It scavenges reactive oxygen species generated by exposure to cisplatin or radiation.

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Pharmacokinetics

Distribution

Distribution half-life is less than 1 min.

Metabolism

Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to the active free thiol metabolite. A disulfide metabolite is then subsequently produced.

Elimination

Rapidly cleared from plasma; elimination half-life is approximately 8 min. Renal excretion is 0.69% to 2.64% (parent compound and metabolites).

Indications and Usage

Prevent or reduce renal damage in patients receiving repeated cisplatin doses for advanced ovarian cancer; reduce incidence of moderate to severe xerostomia in patients undergoing radiation of the parotid gland for head and neck cancer.

Unlabeled Uses

Prevention of antineoplastic-induced bone marrow toxicity; radiation- and/or chemotherapy-induced mucositis; prevent or reduce cisplatin-induced neurotoxicity and cyclophosphamide-induced granulocytopenia; prevent or reduce toxicity of radiation therapy to other areas; reduce toxicity of paclitaxel.

Contraindications

Hypersensitivity to aminothiol compounds.

Dosage and Administration

Reduction of Cumulative Renal Toxicity With Chemotherapy
Adults

IV 910 mg/m 2 once daily as a 15-min IV infusion, 30 min before chemotherapy.

Reduction of Moderate to Severe Xerostomia From Radiation of the Head and Neck
Adults

IV 200 mg/m 2 once daily as a 3-min IV infusion, 15 to 30 min prior to standard fraction radiation therapy (1.8 to 2 gray).

General Advice

  • Reconstitute powder with 9.7 mL of sodium chloride 0.9%. Prior to infusion, dilute amifostine in sodium chloride 0.9% to a final concentration of 5 to 40 mg/mL.
  • Do not mix with other IV medications or IV fluids.
  • Do not administer if cloudiness or particulate matter is noted.
  • Follow manufacturer's guidelines for interrupting and restarting amifostine if a decrease in systolic BP is noted. Stop the infusion for significant decreases in systolic BP. If systolic BP returns to normal and the patient is asymptomatic within 5 min, restart the infusion and continue to monitor BP. If the full dose cannot be administered, administer amifostine 740 mg/m 2 for subsequent chemotherapy cycles.
  • Ensure patients are adequately hydrated before amifostine administration.
  • Keep patient in a supine position during administration.
  • Administer antiemetic medication prior to and in conjunction with amifostine administration.

Storage/Stability

Store vials at 68° to 77°F. Reconstituted and diluted solutions are stable for up to 5 h at controlled room temperature or for up to 24 h if refrigerated (36° to 46°F).

Drug Interactions

Antihypertensives

Coadministration of drugs with similar pharmacologic effects may potentiate hypotension or cause additive side effects, including toxicity. Interrupt antihypertensive therapy 24 h preceding administration of amifostine. Amifostine should not be administered if antihypertensive therapy cannot be stopped for 24 hours preceding amifostine treatment.

Adverse Reactions

Cardiovascular

Hypotension (all grades) (62%); arrhythmias (including atrial fibrillation/flutter and supraventricular tachycardia), cardiac arrest, exacerbation of preexisting hypertension, hypotension (associated with apnea, bradycardia, cardiac arrest, chest pain, dyspnea, extrasystoles, hypoxia, MI, myocardial ischemia, tachycardia), syncope, transient hypertension.

CNS

Dizziness, malaise, seizures, somnolence.

Dermatologic

Erythema multiforme, exfoliative dermatitis, rash, Stevens-Johnson syndrome, TEN.

GI

Nausea, vomiting (all grades) (96%).

Hypersensitivity

Allergic reactions (including chest tightness, chills, cutaneous eruption, dyspnea, fever, hypotension, hypoxia, laryngeal edema, pruritus, rigors, urticaria), anaphylactoid reactions.

Respiratory

Respiratory arrest; hiccups, sneezing.

Miscellaneous

Hypocalcemia (1%); chills, feeling of coldness, feeling of warmth, fever, flushing; renal failure (rare).

Precautions

Monitor

Monitor BP every 5 min during the 15-min infusion and as clinically indicated thereafter. Monitor BP at least before and immediately after the 3-min infusion, and as clinically indicated thereafter. Monitor patient carefully before, during, and after amifostine administration for cutaneous reactions. Monitor the fluid balance of patients administered highly emetogenic chemotherapy. Monitor serum calcium levels in patients at risk of hypocalcemia.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Hypersensitivity

Allergic manifestations, including anaphylaxis and severe cutaneous reactions, have occurred.

Special Risk Patients

Use cautiously in patients with preexisting cardiovascular or cerebrovascular conditions, such as ischemic heart disease, arrhythmias, CHF, or history of stroke or transient ischemic attack. Use with caution in patients in whom the common amifostine adverse effects of nausea/vomiting and hypotension may be more likely to have serious consequences.

Cutaneous reactions

Severe cutaneous reactions have been associated with amifostine. Serious cutaneous reactions have included erythema multiforme, Stevens-Johnson syndrome, TEN, toxoderma, and exfoliative dermatitis. These reactions have been more frequent when amifostine is used as a radioprotectant.

Effectiveness of the cytotoxic regimen

Do not use in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant survival benefit or cure.

Effectiveness of radiotherapy

Do not administer in patients receiving definitive radiotherapy.

Hypotension

Do not give to patients who are hypotensive or dehydrated. If symptomatic hypotension develops, discontinue the infusion, place the patient in the Trendelenburg position, and administer normal saline via a separate IV line.

Overdosage

Symptoms

Anxiety, hypotension, reversible urinary retention.

Patient Information

  • Advise patient that medication will be prepared and administered by health care provider in a health care setting just before chemotherapy or radiation therapy.
  • Advise patient to remain supine for 15 min after completion of infusion and to use caution when standing up.
  • Instruct patient to inform health care provider if noting any of the following during the administration of drug: anxiety, itching, rapid heart beat, rash, shortness of breath or difficulty breathing, sweating, swelling of the throat.

Copyright © 2009 Wolters Kluwer Health.

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