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No data are available with regard to overdosage with TIMOLIDE (timolol maleate-hydrochlorothiazide) in humans.
Pretreatment of mice with hydrochlorothiazide (5 mg/kg) did not alter the LD50 of timolol (1320 mg/kg compared to 1300 mg/kg without pretreatment).
No specific information is available on the treatment of over-dosage with TIMOLIDE (timolol maleate-hydrochlorothiazide) , and no specific antidote is available. Treatment is symptomatic and supportive. Therapy with TIMOLIDE (timolol maleate-hydrochlorothiazide) should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage, and correction of dehydration, electrolyte imbalance, and hypotension by established procedures.
Overdosage has been reported with Tablets BLOCADREN* (timolol maleate). A 30-year-old female ingested 650 mg of BLOCADREN (maximum recommended daily dose _ 60 mg) and experienced second and third degree heart block. She recovered without treatment but approximately two months later developed irregular heartbeat, hypertension, dizziness, tinnitus, faintness, increased pulse rate and borderline first degree heart block.
The oral LD50 of the drug is 1190 and 900 mg/kg in female mice and female rats, respectively.
An in vitro hemodialysis study, using 14C timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily.
The most common signs and symptoms to be expected with overdosage with a beta-adrenergic receptor blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. If overdosage occurs the following therapeutic measures should be considered:
(1) Gastric lavage.
(2) Symptomatic bradycardia: Use atropine sulfate intravenously in a dosage of 0.25 mg to 2 mg to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride should be administered cautiously. In refractory cases the use of a transvenous cardiac pacemaker may be considered.
(4) Bronchospasm: Use isoproterenol hydrochloride. Additional therapy with aminophylline may be considered.
(5) Acute cardiac failure: Conventional therapy with digitalis, diuretics, and oxygen should be instituted immediately. In refractory cases the use of intravenous aminophylline is suggested. This may be followed, if necessary, by glucagon hydrochloride which has been reported to be useful.
(6) Heart block (second or third degree): Use isoproterenol hydrochloride or a transvenous cardiac pacemaker.
The most common signs and symptoms observed with hydrochlorothiazide overdosage are those caused by electrolyte depletion (hypokalemia, hypochloremia, hypona-tremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
TIMOLIDE (timolol maleate-hydrochlorothiazide) is contraindicated in patients with bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease (see WARNINGS); sinus bradycardia; second and third degree atrioventricular block; overt cardiac failure (see WARNINGS); cardiogenic shock; anuria; hypersensitivity to this product or to sulfonamide-derived drugs.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/28/2005
Additional Timolide Information
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