openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings
WARNINGS 1. Effectiveness of the Cytotoxic Regimen Limited data are currently available regarding the preservation of antitumor efficacy when Amifostine is administered prior to cisplatin therapy in settings other than advanced ovarian cancer. Although some animal data suggest interference is possible, in most tumor models the antitumor effects of chemotherapy are not altered by amifostine. Amifostine should not be used in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant survival benefit or cure (e.g., certain malignancies of germ cell origin), except in the context of a clinical study. 2. Hypotension Patients who are hypotensive or in a state of dehydration should not receive Amifostine. Patients receiving Amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of Amifostine. Patients receiving Amifostine at doses recommended for chemotherapy who are taking antihypertensive therapy that cannot be stopped for 24 hours preceding Amifostine treatment, should not receive Amifostine. Prior to Amifostine infusion patients should be adequately hydrated. During Amifostine infusion patients should be kept in a supine position. Blood pressure should be monitored every 5 minutes during the infusion, and thereafter as clinically indicated. It is important that the duration of the 910 mg/m 2 infusion not exceed 15 minutes, as administration of Amifostine as a longer infusion is associated with a higher incidence of side effects. For infusion durations less than 5 minutes, blood pressure should be monitored at least before and immediately after the infusion, and thereafter as clinically indicated. If hypotension occurs, patients should be placed in the Trendelenburg position and be given an infusion of normal saline using a separate i.v. line. During and after Amifostine infusion, care should be taken to monitor the blood pressure of patients whose antihypertensive medication has been interrupted since hypertension may be exacerbated by discontinuation of antihypertensive medication and other causes such as i.v. hydration. Guidelines for interrupting and restarting Amifostine infusion if a decrease in systolic blood pressure should occur are provided in the DOSAGE AND ADMINISTRATION section. Hypotension may occur during or shortly after Amifostine infusion, despite adequate hydration and positioning of the patient (see ADVERSE REACTIONS and PRECAUTIONS). Hypotension has been reported to be associated with dyspnea, apnea, hypoxia, and in rare cases seizures, unconsciousness, respiratory arrest and renal failure. 3. Cutaneous Reactions Serious cutaneous reactions have been associated with Amifostine administration. Serious cutaneous reactions have included erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma and exfoliative dermatitis. These reactions have been reported more frequently when Amifostine is used as a radioprotectant (see ADVERSE REACTIONS). Some of these reactions have been fatal or have required hospitalization and/or discontinuance of therapy . Patients should be carefully monitored prior to, during and after Amifostine administration. Serious cutaneous reactions may develop weeks after initiation of Amifostine administration (see PRECAUTIONS). 4. Hypersensitivity Allergic manifestations including anaphylaxis and severe cutaneous reactions have been associated with Amifostine administration. Nausea and Vomiting Antiemetic medication should be administered prior to and in conjunction with Amifostine (see DOSAGE AND ADMINISTRATION). When Amifostine is administered with highly emetogenic chemotherapy, the fluid balance of the patient should be carefully monitored. 5. Hypocalcemia Serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome or patients receiving multiple doses of Amifostine (see ADVERSE REACTIONS). If necessary, calcium supplements can be administered.
ADVERSE REACTIONS Controlled Trials In the randomized study of patients with ovarian cancer given Amifostine at a dose of 910 mg/m2 prior to chemotherapy, transient hypotension was observed in 62% of patients treated. The mean time of onset was 14 minutes into the 15-minute period of Amifostine infusion, and the mean duration was 6 minutes. In some cases, the infusion had to be prematurely terminated due to a more pronounced drop in systolic blood pressure. In general, the blood pressure returned to normal within 5 to 15 minutes. Fewer than 3% of patients discontinued Amifostine due to blood pressure reductions (see TABLE 4). TABLE 4 Incidence of Common Adverse Events in Patients Receiving Amifostine Phase III Ovarian Cancer Trial (WR-1) 910 mg/m 2 Per Patient Per Infusion Nausea/Vomiting ≥ Grade 3 All Grades 36/122 (30%) 117/122 (96%) 53/592 (9%) 520/592 (88%) Hypotension ≥ Grade 3 According to protocol-defined criteria. WR-1: requiring interruption of infusion; WR-38: drop of >20mm Hg. All Grades 10/122 (8%) 75/122 (61%) 159/592 (27%) Hypotension that requires interruption of the Amifostine infusion should be treated with fluid infusion and postural management of the patient (supine or Trendelenburg position). If the blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be restarted, so that the full dose of Amifostine can be administered. Short term, reversible loss of consciousness has been reported rarely. Nausea and/or vomiting occur frequently after Amifostine infusion and may be severe. In the ovarian cancer randomized study, the incidence of severe nausea/vomiting on day 1 of cyclophosphamide-cisplatin chemotherapy was 10% in patients who did not receive Amifostine, and 19% in patients who did receive Amifostine. Decrease in serum calcium concentrations is a known pharmacological effect of Amifostine. At the recommended doses, clinically significant hypocalcemia was not reported in the ovarian cancer study. Other effects, which have been described during, or following Amifostine infusion are flushing/feeling of warmth, chills/feeling of coldness, malaise, fever, rash, dizziness, somnolence, hiccups and sneezing. These effects have not generally precluded the completion of therapy. Clinical Trials and Pharmacovigilance Reports Allergic reactions characterized by one or more of the following manifestations have been observed during or after Amifostine administration: hypotension, fever, chills/rigors, dyspnea, hypoxia, chest tightness, cutaneous eruptions, pruritus, urticaria and laryngeal edema. Cutaneous eruptions have been commonly reported during clinical trials and were generally non-serious. Serious, sometimes fatal skin reactions including erythema multiforme, and in rare cases, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have also occurred. Rare anaphylactoid reactions and cardiac arrest have also been reported. Hypotension, usually brief systolic and diastolic, has been associated with one or more of the following adverse events: apnea, dyspnea, hypoxia, tachycardia, bradycardia, extrasystoles, chest pain, myocardial ischemia and convulsion. Rare cases of renal failure, myocardial infarction, respiratory and cardiac arrest have been observed during or after hypotension. (See WARNINGS and PRECAUTIONS) Rare cases of arrhythmias such as atrial fibrillation/flutter and supraventricular tachycardia have been reported. These are sometimes associated with hypotension or allergic reactions. Transient hypertension and exacerbations of preexisting hypertension have been observed rarely after Amifostine administration. Seizures and syncope have been reported rarely. (See WARNINGS and PRECAUTIONS)