ure. 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 *
According to protocol-defined criteria. WR-1: requiring interruption of infusion; WR-38: drop of >20mm Hg.
Phase III Ovarian Cancer
Trial (WR-1)
910 mg/m2 _____________________________
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*
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 h |
