In the randomized study of patients with ovarian cancer given ETHYOL® 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 ETHYOL 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 5-15 minutes. Fewer than 3% of patients discontinued ETHYOL due to blood pressure reductions. In the randomized study of patients with head and neck cancer given ETHYOL at a dose of 200 mg/m2 prior to radiotherapy, hypotension was observed in 15% of patients treated.
In the randomized study of patients with head and neck cancer, 17% (26/150) discontinued ETHYOL due to adverse events. All but one of these patients continued to receive radiation treatment until completion.
Hypotension that requires interruption of the ETHYOL 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 ETHYOL can be administered. Short term, reversible syncope (loss of consciousness) has been reported rarely.
Nausea and/or vomiting occur frequently after ETHYOL 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 ETHYOL, and 19% in patients who did receive ETHYOL. In the randomized study of patients with head and neck cancer, the incidence of severe nausea/vomiting was 8% in patients who received ETHYOL and 1% in patients who did not receive ETHYOL.
Decrease in serum calcium concentrations is a known pharmacological effect of ETHYOL. At the recommended doses, clinically significant hypocalcemia was reported in 1% of patients in the randomized head and neck cancer study (see WARNINGS).
Other effects, which have been described during or following ETHYOL infusion are flushing/feeling of warmth, chills/feeling of coldness, malaise, pyrexia, rash, dizziness, somnolence, hiccups, diarrhea, sneezing, diplopia and blurred vision. These effects have not generally precluded the completion of therapy.
Injection site reactions (including rash/erythema, pruritus, urticaria, pain, inflammation, bruising and local swelling) were also observed.
Indication: ETHYOL (amifostine) is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer.
ETHYOL is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.
IMPORTANT DOSAGE AND ADMINISTRATION INSTRUCTIONS
Patients should be adequately hydrated prior to ETHYOL infusion. Blood pressure should be monitored prior to, during and immediately after infusion. Antiemetic medication should be administered prior to and in conjunction with ETHYOL.
IMPORTANT SAFETY INFORMATION
ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.
WARNINGS AND PRECAUTIONS
ETHYOL should not be administered in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant survival benefit or cure. ETHYOL should not be administered in patients receiving definitive radiotherapy, since there are at present insufficient data to exclude a tumor-protective effect in this setting.
Patients who are hypotensive or in a state of dehydration should not receive ETHYOL. Patients should have antihypertensive therapy interrupted 24 hours preceding administration of ETHYOL. Patients should not receive ETHYOL where therapy cannot be stopped for 24 hours preceding treatment.
The fluid balance of the patient should be carefully monitored when ETHYOL is administered with highly emetogenic chemotherapy.
Fatal and serious cutaneous reactions such as Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxicoderma, exfoliative dermatitis and drug reaction with biopsy-confirmed eosinophilia and systemic symptoms (DRESS) have been reported with ETHYOL treatment. These reactions is higher in patients receiving ETHYOL as a radioprotectant. Serious cutaneous reactions may develop weeks after initiation of ETHYOL administration. Discontinue Ethyol for cutaneous reactions or mucosal lesions appearing outside the injection site or radiation port and for erythematous, edematous or bullous lesions on the palms or soles. Monitor patients carefully prior to, during and after ETHYOL administration. In case of severe acute allergic reactions ETHYOL should be immediately and permanently discontinued. Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis.
In a randomized study of patients with ovarian cancer given ETHYOL, the most common adverse events included transient hypotension, nausea, vomiting, and a decrease in serum calcium concentrations. Other adverse events reported in clinical studies involving patients with ovarian or head and neck cancers include hypersensitivity and anaphylactic reactions, flushing, chills, malaise, pyrexia, diplopia, blurred vision, rash, dizziness, somnolence, hiccups, diarrhea, and sneezing. Injection site reactions including pruritus and urticaria were also observed.
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