Amifostine

U.S. BRAND NAMES — Ethyol®
PHARMACOLOGIC CATEGORY Adjuvant, Chemoprotective Agent (Cytoprotective)Antidote
DOSING: ADULTS — Note: Antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist, is recommended prior to and in conjunction with amifostine.
Cisplatin-induced renal toxicity, reduction: I.V.: 740-910 mg/m2 once daily over 15 minutes 30 minutes prior to cytotoxic therapy Note: Doses >740 mg/m2 are associated with a higher incidence of hypotension and may require interruption of therapy or dose modification for subsequent cycles. 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: I.V.: 200 mg/m2/day over 3 minutes 15-30 minutes prior to radiation therapy or SubQ (unlabeled route): 500 mg/day prior to radiation therapy
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: Ethyol®: 500 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Ethyol®: 500 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.V.: Administer over 3-15 minutes; 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 has been used.
COMPATIBILITY — Stable in NS.
Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin, doxycycline, droperidol, enalaprilat, etoposide, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, netilmicin, ondansetron, piperacillin, plicamycin, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, trimetrexate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Acyclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine edisylate.
USE — 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
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Hypotension (15% to 62%; grades 3/4: 3% to 8%; dose dependent) Gastrointestinal: Nausea/vomiting (53% to 96%; grades 3/4: 8% to 30%; dose dependent)
<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), hypocalcemia, hypoxia, 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
CONTRAINDICATIONS — Hypersensitivity to amifostine, aminothiol compounds, or any component of the formulation
WARNINGS / PRECAUTIONS — Patients who are hypotensive or dehydrated should not receive amifostine. Interrupt antihypertensive therapy for 24 hours before amifostine. Patients who cannot safely stop their antihypertensives 24 hours before amifostine should not receive it. Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored 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 I.V. line; subsequent infusions may require a dose reduction. Use caution in patients with cardiovascular and cerebrovascular disease and any other patients in whom the adverse effects of hypotension and nausea/vomiting may have serious adverse events.
It is recommended that antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT3 receptor antagonist be administered prior to and in conjunction with amifostine. Rare hypersensitivity reactions, including anaphylaxis and severe cutaneous reaction, have been reported with a higher frequency in patients receiving amifostine as a radioprotectant. Discontinue if allergic reaction occurs; do not rechallenge.
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. Safety and efficacy in children have not been established.
DRUG INTERACTIONS — Antihypertensives: May potentiate the hypotensive effects of amifostine.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have demonstrated embryotoxicity. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions in the nursing infant, breast-feeding should be discontinued.
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)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypotension, nausea, vomiting, anxiety and reversible urinary retention. Treatment includes infusion of normal saline for hypotension and supportive measures as clinically indicated.
CANADIAN BRAND NAMES — Ethyol®
INTERNATIONAL BRAND NAMES — Amiphos (IN); Cytofos (TH); Erifostine (AR); Ethyol (AR, AT, AU, BE, BG, BR, CA, CL, CR, CZ, DE, DK, DO, EC, ES, FR, GB, GT, HK, HN, IE, IL, IT, MX, NI, NL, NZ, PA, PE, PH, PL, SG, SV, TH, UY, VE); Ethyol 500 (ZA)
MECHANISM OF ACTION — 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 in tissues.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (active-free thiol and disulfide)
Half-life elimination: 8-9 minutes
Excretion: Urine Clearance, plasma: 2.17 L/minute
PATIENT INFORMATION — This medication is given to help reduce side effects of your cancer therapy. Report immediately lightheadedness, dizziness, fainting, or any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups.