FDA label db378ec8-3c0a-468e-8dd8-b538ecd8d125

WARNINGS Rapid Decrease of Blood Pressure Caution must be observed when reducing severely elevated blood pressure. Diazoxide should only be administered utilizing the new 150-mg minibolus dosage. The use of a 300-mg intravenous dose of diazoxide has been associated with angina and with myocardial and cerebral infarction. One instance of optic nerve infarction was reported when a 100-mmHg reduction in diastolic pressure occurred over ten minutes following a single 300-mg bolus. In one prospective trial conducted in patients with severe hypertension and coexistent coronary artery disease, a 50% incidence of ischemic changes in the electrocardiogram was observed following single 300-mg bolus injections of diazoxide. The desired blood pressure lowering should therefore be achieved over as long a period of time as is compatible with the patient's status. At least several hours and preferably 1 or 2 days is tentatively recommended. Improved safety with equal efficacy can be achieved by administering HYPERSTAT I.V. Injection as a minibolus dose (1 to 3 mg/kg every 5 to 15 minutes up to a maximum of 150 mg in a single injection) until a diastolic blood pressure below 100 mmHg is achieved. HYPERSTAT I.V. Injection should not be administered in a bolus dose of 300 mg since this mode of administration is less predictable and less controllable than the minibolus dosage. If hypotension severe enough to require therapy results from the reduction in blood pressure, it will usually respond to the Trendelenberg maneuver. If necessary, sympathomimetic agents such as dopamine or norepinephrine may be administered. Special attention is required for patients with diabetes mellitus and those in whom retention of salt and water may present serious problems. Myocardial Lesions in Animals Intravenous administration of diazoxide in dogs has induced subendocardial necrosis and necrosis of papillary muscles. These lesions, which are also produced by other vasodilator drugs (ie, hydralazine, minoxidil) and by catecholamines, are presumed to be related to anoxia resulting from a combination of reflex tachycardia and decreased perfusion.

ADVERSE REACTIONS It is reasonable to speculate that the currently recommended minibolus dosing regimen, which has replaced the 300-mg bolus dose in clinical practice, will result in adverse effects which are of similar character but of lesser frequency and severity. In clinical experience with the rapid bolus administration of 300 mg, the most common adverse reactions reported were: hypotension (7%); nausea and vomiting (4%); dizziness and weakness (2%). Additional adverse reactions reported with bolus administration of 300 mg were as follows: Cardiovascular: sodium and water retention after repeated injections, especially important in patients with impaired cardiac reserve; hypotension to shock levels; myocardial ischemia, usually transient and manifested by angina, atrial and ventricular arrhythmias, and marked electrocardiographic changes, but occasionally leading to myocardial infarction; optic nerve infarction following too rapid decrease in severely elevated blood pressure; supraventricular tachycardia and palpitation; bradycardia; chest discomfort or nonanginal "tightness in the chest." Central Nervous System: cerebral ischemia, usually transient but occasionally leading to infarction and manifested by unconsciousness, convulsions, paralysis, confusion, or focal neurological deficit such as numbness of the hands; vasodilative phenomena, such as orthostatic hypotension, sweating, flushing, and generalized or localized sensations of warmth; various transient neurological findings secondary to alteration in regional blood flow to brain, such as headache (sometimes throbbing), dizziness, lightheadedness, sleepiness (also reported as lethargy, somnolence or drowsiness), euphoria or "funny feeling," ringing in the ears and momentary hearing loss, and weakness of short duration; apprehension or anxiety. Gastrointestinal: rarely, acute pancreatitis; nausea, vomiting and/or abdominal discomfort; anorexia; alteration in taste; parotid swelling; salivation; dry mouth; lacrimation; ileus; constipation and diarrhea. Other: hyperglycemia in diabetic patients, especially after repeated injections; hyperosmolar coma in an infant; transient hyperglycemia in nondiabetic patients; transient retention of nitrogenous wastes; various respiratory finding secondary to the relaxation of smooth muscle, such as dyspnea, cough and choking sensation; warmth or pain along the injected vein; cellulitis without sloughing and/or phlebitis at the injection site of extravasation; back pain and increased nocturia; hypersensitivity reactions, such as rash, leukopenia and fever; papilledema induced by plasma volume expansion secondary to the administration of diazoxide reported in a patient who had received eleven injections (300 mg/dose) over a 22-day period; malaise and blurred vision; transient cataract in an infant; hirsutism, and decreased libido.