watching for [5:<100 20 100 119 25 120 139 30 140 179 40 180 50 Resume infusion, if BP returns to normal within 5 minutes and patient is asymptomatic. a Reconstitution Reconstitute vial containing 500 mg of amifostine powder with 9.7 mL of 0.9% sodium chloride for injection, to provide a solution containing 50 mg/mL. a Dilution May be diluted with 0.9% sodium chloride for injection in a PVC container to a final concentration of 5 40 mg/mL. a Rate of Administration Prophylaxis of cisplatin-induced nephrotoxicity: Administer over 15 minutes. 1 Infusions over> 15 minutes are associated with increased side effects a (see Hypotension under Cautions) and more rapid infusions have not been studied systematically. 1 Prophylaxis of radiation therapy-induced xerostomia: Administer over 3 minutes. 1 Dosage Available as the trihydrate form of amifostine; dosage expressed in terms of amifostine. a Adults Prophylaxis of Cisplatin-induced Nephrotoxicity IV Initially, 910 mg/m 2 once daily over 15 minutes, starting 30 minutes prior to cisplatin administration. a If full initial dose is tolerated, repeat the full dose during subsequent courses of chemotherapy as tolerated. 1 If the full dose cannot be administered, reduce dosage to 740 mg/m 2 during subsequent chemotherapy cycles. a Prophylaxis of Radiation Therapy-induced Xerostomia IV 200 mg/m 2 once daily over 3 minutes; initiate infusion 15 30 minutes prior to standard fractionated radiation therapy (1.8 2 Gy). a Special Populations Hepatic Impairment No specific dosage recommendations at this time. a Renal Impairment No specific dosage recommendations at this time. a Geriatric Patients Careful dosage selection recommended due to possible age-related decreases in hepatic, renal, or cardiac function and concomitant diseases or drug therapies. a Cautions for Amifostine Contraindications Known sensitivity to aminothiol compounds. a Warnings/Precautions Warnings Effectiveness of Cytotoxic Regimen Possible interference in antitumor effect of chemotherapy; however, most tumor models suggest amifostine does not alter antitumor effect. a Limited data available regarding preservation of antitumor efficacy when amifostine administered prior to cisplatin in malignancies other than advanced ovarian cancer. a Effectiveness of Radiotherapy Insufficient data available to exclude the possibility that amifostine might interfere with the efficacy of high-dose (definitive) radiation therapy; use not recommended in patients receiving such therapy, except in clinical trials. a Hypotension Hypotension occurs frequently during or shortly after infusion, despite hydration and positioning. a May be associated with dyspnea, apnea, hypoxia, and rarely seizures, unconsciousness, respiratory arrest, and renal failure. 1 Administer IV infusions over 15 minutes to minimize the risk of hypotensive reactions. a If hypotension occurs, interrupt infusion, place patient in Trendelenburg's position and initiate IV infusion of 0.9% sodium chloride in a separate line. a (See Guideline for Interrupting Infusion due to Decreases in SBP under Dosage and Administration.) Use not recommended in hypotensive or dehydrated patients or in patients concurrently receiving antihypertensive agents. a (See Specific Drugs under Interactions.) Hypertension Withdrawal of antihypertensive therapy and IV hydration may exacerbate hypertension in patients whose antihypertensive therapy has been interrupted for amifostine therapy; carefully monitor BP during and after IV infusion in such patients. 1 GI Effects Nausea and/or vomiting occurs frequently and may be severe. 1 Administer effective antiemetic therapy (e.g., an IV corticosteroid such as dexamethasone and a type 3 serotonin [5-HT 3 ] receptor antagonist) prior to and in conjunction with amifostine therapy. 1 Carefully monitor patient s fluid balance in those receiving highly emetogenic chemotherapy. 1 Hypocalcemia Hypocalcemia occurs rarely. a Monitor serum calcium concentrations in patients at risk of hypocalcemia (e.g., those with nephrotic syndrome, those receiving multiple doses of amifostine); initiate calcium supplementation as necessary. 1 Sensitivity Reactions Hypersensitivity Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis and severe cutaneous reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, exfoliative dermatitis) reported. a Serious cutaneous reactions reported more frequently when used as a radioprotectant. a Withhold amifostine and consider dermatologic consultation and biopsy if cutaneous reactions or mucosal lesions of unknown etiology occur. a Careful monitoring during and after administration is recommended. a If acute hypersensitivity reactions occur, immediately and permanently discontinue infusion and institute appropriate therapy as indicated (e.g., epinephrine and other appropriate measures). a General Precautions Safety not established in patients with preexisting cardiovascular or cerebrovascular disease (e.g., ischemic heart disease, arrhythmias, CHF, history of stroke or TIAs; use with caution in such patients. Specific Populations Pregnancy Category C. a Lactation Not known whether amifostine is distributed into milk. a Use not recommended. a Geriatric Use Response in patients 65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased renal, hepatic, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. a Common Adverse Effects Hypotension, nausea, vomiting. a Interactions for Amifostine Specific Drugs Drug Interaction Comments Antihypertensive agents Additive hypotensive effects a Temporarily discontinue antihypertensive therapy 24 hours prior to amifostine administration; concurrent administration is not recommended a Dexamethasone Pharmacokinetic interaction unlikely a Metoclopramide Pharmacokinetic interaction unlikely. a Amifostine Pharmacokinetics Distribution Extent Following IV administration, rapidly distributed into tissues; <10% of amifostine remains in plasma 6 minutes after administration. a Not known whether amifostine is distributed into milk. a Measurable levels of metabolites have been found in bone marrow cells. a Elimination Metabolism Rapidly and extensively metabolized, principally via alkaline phosphatase, to the active free sulfhydryl (thiol) metabolite (WR-1065) 1 2 9 11 15 22 and subsequently, to a less active disulfide metabolite. a Elimination Route Minimal renal excretion, averaging 0.69, 2.64, and 2.22% for amifostine, thiol metabolite, and disulfide metabolite respectively. a Half-life Biphasic; terminal half-life is approximately 8 minutes. a Stability Storage Parenteral Powder for Injection 20 25 C. a Reconstituted solution is stable for 5 hours at room temperature (approximately 25 C) or 24 hours under refrigeration (2 8 C). a Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Compatibility with solutions other than 0.9% sodium chloride for injection without additives has not been examined. a Use of other solutions is not recommended. a Actions Pharmacologically active free sulfhydryl binds to and detoxifies cytotoxic platinum-containing metabolites of cisplatin and scavenges free radicals induced by the drug. 1 2 9 11 16 Cytoprotection against cisplatin-induced toxicity appears to result from prevention and/or, to a lesser extent, reversal of DNA platination by the drug (cisplatin-DNA adducts). 2 Radioprotectant effect appears to be mediated at least in part by removal of oxygen from tissues 2 15 20 and by scavenging hydroxyl radicals and repairing radiation-induced DNA radicals through donation of hydrogen. 2 11 12 15 20 Preferentially protects healthy cells because of increased cellular uptake of amifostine and more rapid generation of the active free sulfhydryl metabolite in these cells compared with malignant cells. 1 2 9 12 16 Advice to Patients Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., antihypertensive medications), as well as any concomitant illnesses. a Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. a Importance of informing patients of other important precautionary information. a (See Cautions) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Amifostine Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV infusion 500 mg (of anhydrous amifostine) Ethyol MedImmune AHFS DI Essentials. Copyright 2017, Selected Revisions March 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. MedImmune Oncology, Inc. Ethyol (amifostine) for injection prescribing information. Gaithersburg, MD; 2001 Oct. 2. Spencer CM, Goa KL. Amifostine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs . 1995; 50:1001-31. [PubMed 8612469] 3. Anon. U.S. Bioscience Ethyol to be marketed in U.S. by Alza via $35 mil. deal. F-D-C Rep . 1995; Dec 18: T&G-2 3. 4. Rose P, Kemp G, Glick J. Ethyol (amifostine) protects against cumulative cisplatin toxicities. Paper presented at the 1996 Annual Meeting of the American Society of Clinical Oncology (ASCO). Philadelphia, PA: 1996 May 18-21. Abstract. 5. Budd GT, Bukowski RM, Adelstein D et al. Mature results of a randomized trial of carboplatin (C) and amifostine (A) vs. C alone in patients (pts) with advanced malignancies. Paper presented at the 1996 Annual Meeting of the American Society of Clinical Oncology (ASCO). Philadelphia, PA: 1996 May 18-21. Abstract. 6. Planting AST, Vermorken JB, Catimel G et al. Randomized phase II study of weekly cisplatin with or without amifostine in patients with advanced head and neck cancer. Paper presented at the 1996 Annual Meeting of the American Society of Clinical Oncology (ASCO). Philadelphia, PA: 1996 May 18-21. Abstract. 7. Schiller JH, Larson ML, Larson MH et al. Amifostine (A), cisplatin (C), vinblastine (V): a highly active regimen for non small cell lung cancer (NSCLC). Eur J Cancer . 1995; 31A(Suppl 5):S230. 8. Schiller JH, Berry W, Storer B et al. Phase II trial of amifostine, cisplatin and vinblastine for metastatic nonsmall cell lung cancer. Proc Am Soc Clin Oncol . 1995; 14:356. 9. Treskes M, Holwerda U, Nijtmans LGJ et al. The reversal of cisplatin-protein interactions by the modulating agent WR2721 and its metabolites WR1065 and WR33278. Cancer Chemother Pharmacol . 1992; 29:467-70. [PubMed 1314713] 10. Glick J, Kemp G, Rose P et al. A randomized trial of cyclophosphamide and cisplatin amifostine in the treatment of advanced epithelial ovarian cancer. Proc Am Soc Clin Oncol . 1994; 13:432. 11. Peters GJ, van der Vijgh WJF. Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): preclinical aspects. Eur J Cancer . 1995; 31A(Suppl 1):S1-7. 12. Turrisi AT, Glover DJ, Hurwitz S et al. Final report of the phase I trial of single-dose WR-2721 [ S -2-(3-Aminopropyl-amino)ethylphosphorothioic acid]. Cancer Treat Rep . 1986; 70:1389-93. [PubMed 2431774] 13. Perry DJ, Krasnow SH, Reilly JG et al. Phase II study of cisplatin and etoposide with WR-2721 for advanced non-small cell lung cancer. Paper presented at the 1994 Annual Meeting of the American Society of Clinical Oncology (ASCO). Abstract. 14. Facchini T, Belpomme D, Kemp G et al. Amifostine (AMI) selectively protects against cumulative toxicities of cyclophosphamide (C) and cisplatin (P). Eur J Cancer . 1995; 31A(Suppl 5):Abstract No. 15. Liu T, Liu Y, He S et al. Use of radiation with or without WR-2721 in advanced rectal cancer. Cancer . 1992; 69:2820-25. [PubMed 1315211] 16. Anand AJ, Bashey B. Newer insights into cisplatin nephrotoxicity. Ann Pharmacother . 1993; 27:1519-25. [PubMed 8305788] 17. Bilezikian JP. Management of acute hypercalcemia. N Engl J Med . 1992; 326:1196-203. [PubMed 1532633] 18. Glover D, Riley L, Carmichael K et al. Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent). N Engl J Med . 1983; 309:1137-41. [PubMed 6312315] 19. Glover DJ, Shaw L, Glick JH et al. Treatment of hypercalcemia in parathyroid cancer with WR-2721, S -2-(3-aminopropylamino) ethyl-phosphorothioic acid. Ann Intern Med . 1985; 103:55-7. [PubMed 2988391] 20. Smoluk GD, Fahey RC, Calabro-Jones PM et al. Radioprotection of cells in culture by WR-2721 and derivatives: form of the drug responsible for protection. Cancer Res . 1988; 48:3641-7. [PubMed 2837320] 21. Brown JM. Sensitizers and protectors in radiotherapy. Cancer . 1985; 55:2222-8. [PubMed 2983876] 22. Ryan SV, Carrithers SL, Parkinson SJ et al. Hypotensive mechanisms of amifostine. J Clin Pharmacol . 1996; 36:365-73. [PubMed 8728352] 23. Gandara DR, Perez EA, Wiebe V et al. Cisplatin chemoprotection and rescue: pharmacologic modulation of toxicity. Semin Oncol . 1991; 18(Suppl 3):49-55. 24. Yuhas JM. Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S -2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res . 1980; 40:1519-24. [PubMed 6245795] 25. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul. 26. Pameijer FA, Mancuso AA, Mendenhall WM et al. Evaluation of pretreatment computed tomography as a predictor of local control in T1/T2 pyriform sinus carcinoma treated with definitive radiotherapy. Head Neck . 1998; 20:159-68. [PubMed 9484948] 27. Murakami M, Kuroda Y, Okamoto Y et al. Neoadjuvant concurrent chemoradiotherapy followed by definitive radiotherapy or surgery for operable thoracic esophageal carcinoma. Int J Radiat Oncol Biol Phys . 1998; 40:1049-59. [PubMed 9539559] a. MedImmune Oncology, Inc. Ethyol (amifostine) for injection prescribing information. Gaithersburg, MD; 2005 Sept. Next Interactions Print this page Add to My Med List More about amifostine Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Drug class: antineoplastic detoxifying agents Consumer resources Amifostine Amifostine Intravenous (Advanced Reading) Professional resources Amifostine (FDA) Amifostine (Wolters Kluwer) Other brands: Ethyol Related treatment guides Cancer Non-Small Cell Lung Cancer Ovarian Cancer> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer West-Ward Pharmaceuticals Drug Class Antineoplastic detoxifying agents Related Drugs Cancer carboplatin , fluorouracil , cyclophosphamide , Cytoxan , etoposide , Adriamycin , doxorubicin , vincristine , More... 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