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Ativan (Lorazepam) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

ATIVAN Injection, like other injectable benzodiazepines, produces additive depression of the central nervous system when administered with other CNS depressants such as ethyl alcohol, phenothiazines, barbiturates, MAO inhibitors, and other antidepressants.

When scopolamine is used concomitantly with injectable lorazepam, an increased incidence of sedation, hallucinations and irrational behavior has been observed.

There have been rare reports of significant respiratory depression, stupor and/or hypotension with the concomitant use of loxapine and lorazepam.

Marked sedation, excessive salivation, ataxia, and, rarely, death have been reported with the concomitant use of clozapine and lorazepam.

Apnea, coma, bradycardia, arrhythmia, heart arrest, and death have been reported with the concomitant use of haloperidol and lorazepam.

The risk of using lorazepam in combination with scopolamine, loxapine, clozapine, haloperidol, or other CNS-depressant drugs has not been systematically evaluated. Therefore, caution is advised if the concomitant administration of lorazepam and these drugs is required.

Concurrent administration of any of the following drugs with lorazepam had no effect on the pharmacokinetics of lorazepam: metoprolol, cimetidine, ranitidine, disulfiram, propranolol, metronidazole, and propoxyphene. No change in ATIVAN dosage is necessary when concomitantly given with any of these drugs.

Lorazepam-Valproate Interaction

Concurrent administration of lorazepam (2 mg intravenously) with valproate (250 mg twice daily orally for 3 days) to 6 healthy male subjects resulted in decreased total clearance of lorazepam by 40% and decreased formation rate of lorazepam glucuronide by 55%, as compared with lorazepam administered alone. Accordingly, lorazepam plasma concentrations were about two-fold higher for at least 12 hours post-dose administration during valproate treatment. Lorazepam dosage should be reduced to 50% of the normal adult dose when this drug combination is prescribed in patients (see also DOSAGE AND ADMINISTRATION).

OVERDOSAGE

Symptoms

Overdosage of benzodiazepines is usually manifested by varying degrees of central-nervous-system depression, ranging from drowsiness to coma. In mild cases symptoms include drowsiness, mental confusion and lethargy. In more serious examples, symptoms may include ataxia, hypotonia, hypotension, hypnosis, stages one (1) to three (3) coma, and, very rarely, death.

Treatment

Treatment of overdosage is mainly supportive until the drug is eliminated from the body. Vital signs and fluid balance should be carefully monitored in conjunction with close observation of the patient. An adequate airway should be maintained and assisted respiration used as needed. With normally functioning kidneys, forced diuresis with intravenous fluids and electrolytes may accelerate elimination of benzodiazepines from the body. In addition, osmotic diuretics, such as mannitol, may be effective as adjunctive measures. In more critical situations, renal dialysis and exchange blood transfusions may be indicated. Lorazepam does not appear to be removed in significant quantities by dialysis, although lorazepam glucuronide may be highly dialyzable. The value of dialysis has not been adequately determined for lorazepam.

The benzodiazepine antagonist flumazenil may be used in hospitalized patients as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS should be consulted prior to use.

CONTRAINDICATIONS

ATIVAN Injection is contraindicated in patients with a known sensitivity to benzodiazepines or its vehicle (polyethylene glycol, propylene glycol, and benzyl alcohol), in patients with acute narrow-angle glaucoma, or in patients with sleep apnea syndrome. It is also contraindicated in patients with severe respiratory insufficiency, except in those patients requiring relief of anxiety and/or diminished recall of events while being mechanically ventilated. The use of ATIVAN Injection intra-arterially is contraindicated because, as with other injectable benzodiazepines, inadvertent intra-arterial injection may produce arteriospasm resulting in gangrene which may require amputation (see WARNINGS).

DRUG ABUSE AND DEPENDENCE

Controlled Substance Class

Lorazepam is a controlled substance in Schedule IV.

Abuse and Physical and Psychological Dependence

As with other benzodiazepines, ATIVAN Injection has a potential for abuse and may lead to dependence. Physicians should be aware that repeated doses over a prolonged period of time may result in physical and psychological dependence and withdrawal symptoms, following abrupt discontinuance, similar in character to those noted with barbiturates and alcohol.

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