ethyol

Important safety information

Hypotension and Cardiovascular Events: Patients who are hypotensive or dehydrated should not receive ETHYOL. If interruption of antihypertensive therapy is possible, interrupt antihypertensive therapy 24 hours prior to ETHYOL administration. Monitor blood pressure during infusion; interrupt and restart infusion if decrease in systolic blood pressure is observed. Do not administer ETHYOL to hypotensive patients who are taking antihypertensive therapy that cannot be stopped for 24 hours prior to ETHYOL administration. ( 5.3 ) – Severe Cutaneous Reactions: Monitor patients prior to, during, and weeks after administration for severe cutaneous reactions. Discontinue for cutaneous reactions or lesions appearing outside of the injection site/radiation port or on the palms or soles. ( 5.4 ) – Hypersensitivity: Discontinue for severe acute allergic reactions. Administer treatment for serious allergic events. ( 5.5 ) – Nausea and Vomiting: Administer antiemetic medication prior to and in conjunction with ETHYOL. Monitor fluid balance when administered with highly emetogenic chemotherapy. ( 5.6 ) – Hypocalcemia: Monitor serum calcium levels in patients at risk of hypocalcemia. If necessary, administer calcium supplements. ( 5.7 ) – Embryo-Fetal Toxicity: ETHYOL can cause fetal harm. Advise patients of the potential risk to a fetus ( 5.8 , 8.1 , 8.3 ). Also, refer to the cisplatin full prescribing information for pregnancy and contraception information. 5.1 Effectiveness of the Chemotherapy Regimen ETHYOL may interfere with the antitumor activity of chemotherapy regimens. Do not use ETHYOL 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. Limited data are currently available regarding interference with antitumor efficacy when ETHYOL is administered prior to cisplatin therapy in settings other than advanced ovarian cancer. 5.2 Effectiveness of Radiotherapy ETHYOL may interfere with the antitumor activity of the radiotherapy regimens. Do not use ETHYOL in patients receiving definitive radiotherapy, except in the context of a clinical trial, since there are insufficient data to exclude a tumor-protective effect in this setting. ETHYOL was studied with standard fractionated radiotherapy and when ≥75% of both parotid glands were exposed to radiation. The safety and efficacy of ETHYOL on the incidence of xerostomia in the setting of combined chemotherapy and radiotherapy, and in the setting of accelerated or hyperfractionated therapy, have not been established. 5.3 Hypotension and Cardiovascular Events Severe hypotension with serious sequelae have been reported in clinical studies and post-marketing experience in patients treated with ETHYOL. Severe hypotension events included apnea, dyspnea, hypoxia, chest pain, tachycardia, bradycardia, extrasystoles, supraventricular tachycardia, atrial fibrillation/flutter, myocardial ischemia, myocardial infarction, unconsciousness, syncope, seizure, renal failure, and respiratory and cardiac arrest. In the WR-1 study of patients with ovarian cancer dosing ETHYOL at 910 mg/m 2 , transient hypotension was observed in 62% of the patients treated, with 8% of the patients experiencing ≥ Grade 3 hypotension. The mean time of onset was 14 minutes after initiation of the ETHYOL infusion, the mean duration of hypotension was 6 minutes, and blood pressure returned to normal within 15 minutes after the onset of hypotension in most cases. Approximately 3% of patients permanently discontinued ETHYOL due to severe hypotension. In the WR-38 study of patients with head and neck cancer administering ETHYOL at a dose of 200 mg/m 2 prior to radiotherapy, hypotension was observed in 15% of patients treated, with 3% of the patients experiencing ≥ Grade 3 hypotension. Before administration of ETHYOL, verify that patients are not hypotensive or dehydrated. Adequately hydrate patients prior to initiating ETHYOL infusion. Patients receiving ETHYOL at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of ETHYOL. Patients receiving ETHYOL at doses recommended for chemotherapy who are taking antihypertensive therapy that cannot be stopped for 24 hours preceding ETHYOL treatment should avoid treatment with ETHYOL. During and after ETHYOL infusion, closely monitor the blood pressure of patients whose antihypertensive medication has been interrupted since hypertension may be exacerbated by discontinuation of antihypertensive medication or other causes such as intravenous hydration. During ETHYOL infusion, keep patients in a supine position and monitor blood pressure every 5 minutes during the infusion, and thereafter as clinically indicated. 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. It is important that the duration of the 910 mg/m 2 infusion does not exceed 15 minutes, as administration of ETHYOL as a longer infusion is associated with a higher incidence of adverse reactions. If hypotension occurs, place patients in the Trendelenburg position and give an infusion of normal saline using a separate intravenous line. 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. Guidelines for interrupting and restarting ETHYOL infusion if a decrease in systolic blood pressure should occur are provided [see Dosage and Administration (2.1) ] . 5.4 Severe Cutaneous Reactions Fatal and severe cutaneous reactions have been reported in clinical studies and post-marketing experience in patients treated with ETHYOL. Severe cutaneous reactions include erythema multiforme, Stevens- Johnson syndrome, toxic epidermal necrolysis, toxicoderma, exfoliative dermatitis and drug reaction with biopsy-confirmed eosinophilia and systemic symptoms (DRESS). These reactions have been reported more frequently when ETHYOL is used as a radioprotectant [see Adverse Reactions (6) ] . Severe cutaneous reactions may develop weeks after initiation of ETHYOL administration. Monitor patients carefully prior to, during, and after ETHYOL administration. Discontinue ETHYOL for cutaneous reactions or mucosal lesions appearing outside of the injection site or radiation port and for erythematous, edematous or bullous lesions on the palms or soles. 5.5 Hypersensitivity Hypersensitivity reactions, including anaphylaxis, have been reported in clinical studies and post-marketing experience with ETHYOL administration. Hypersensitivity and anaphylactic reactions observed during or after ETHYOL administration have included pyrexia, chills, dyspnea, hypoxia, chest discomfort, cutaneous eruptions, pruritus, urticaria, and laryngeal edema. Epinephrine and other appropriate measures should be available for treatment of serious infusion-related reactions when administering ETHYOL. When severe allergic reactions occur, immediately and permanently discontinue ETHYOL. 5.6 Nausea and Vomiting Nausea and/or vomiting occur frequently after ETHYOL infusion and may be severe. In the WR-1 study of patients with ovarian cancer dosing ETHYOL at 910 mg/m 2 , vomiting was observed in 96% of the patients treated, with severe nausea/vomiting on day 1 of cyclophosphamide-cisplatin chemotherapy in 19% of patients. In the WR-38 study of patients with head and neck cancer administering ETHYOL at a dose of 200 mg/m 2 prior to radiotherapy, vomiting was observed in 53% of patients treated, with severe nausea/vomiting in 8% of patients. Administer antiemetic medication(s) prior to and in conjunction with ETHYOL [see Dosage and Administration (2.1) ] . When ETHYOL is administered with highly emetogenic chemotherapy, closely monitor the fluid balance of the…