The use of Anexate (Ro 15-1788) in acute self-poisoning with benzodiazepines alone or combined with other drugs — Preliminary results

Rouzioux, J. M.; Baud, Frédéric J.; Bismuth, C; Cailar, J. du; Ducluzeau, R; Durocher, A.; Flesch, F.; Bikpi-Benissan, G.; Jaeger, Albert; Jean, P.; Jouglard, J; Manfrendi, R.; Passeron, D.; Saulnier, F.; Sockel, F.

doi:10.1016/0300-9572(88)90011-1

Cited by 7 publications

(7 citation statements)

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“…The present meta‐analyses included 13 trials with a total of 994 randomised (990 treated and evaluable) patients . All trials were randomised, double‐blind, placebo‐controlled, prospective trials.…”

Section: Resultsmentioning

confidence: 99%

“…Three trials had exclusion criteria related to the use of benzodiazepines: known or suspected benzodiazepine overdose , known therapeutic use of benzodiazepines and known hypersensitivity to benzodiazepines . One trial excluded patients with the evidence of alcohol or tricyclic antidepressants (TCAs) ingestion , and four trials excluded patients with (severe) organic injury and/or liver or renal impairment . Another four trials excluded patients with known or suspected brain trauma, new neurological findings or epilepsy .…”

Section: Resultsmentioning

confidence: 99%

“…One trial excluded patients with the evidence of alcohol or tricyclic antidepressants (TCAs) ingestion , and four trials excluded patients with (severe) organic injury and/or liver or renal impairment . Another four trials excluded patients with known or suspected brain trauma, new neurological findings or epilepsy . Four trials did not inform about exclusion criteria .…”

Section: Resultsmentioning

confidence: 99%

“…In all included trials, a total of 720 patients (72.4%) were intoxicated with benzodiazepines. Ten studies provided information about single‐ versus multi‐drug intoxication with benzodiazepine on total 596 patients, and of these, 205 patients suffered from a single‐drug intoxication with benzodiazepines and 391 patients suffered from a multi‐drug intoxication with the most common other drugs being: ethanol, anxiolytics (including barbiturates), opioids and TCAs . Three studies did not provide information about co‐ingested drugs .…”

Section: Resultsmentioning

confidence: 99%

“…All included trials administered flumazenil intravenously and initial dose of flumazenil varied from 0.1 mg to 2.5 mg. Total flumazenil dose varied from 1.0 to 10.0 mg (table ). Nine studies informed about average used flumazenil dose, which varied from 0.77 to 7.13 mg (table ) .…”

Section: Resultsmentioning

confidence: 99%

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Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials

Penninga

Graudal

Ladekarl

et al. 2015

Basic Clin Pharma Tox

127

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Flumazenil is used for the reversal of benzodiazepine overdose. Serious adverse events (SAEs) including seizures and cardiac arrhythmias have been reported in patients treated with flumazenil, and the clinical advantage of flumazenil treatment has been questioned. The objective was to assess the risk of (S)AEs associated with the use of flumazenil in patients with impaired consciousness due to known or suspected benzodiazepine overdose. Studies included in the meta-analyses were identified by literature search in Medline, Cochrane Library and Embase using combinations of the words flumazenil, benzodiazepines, antianxiety agents, poisoning, toxicity and overdose. Randomised clinical trials (RCTs) in verified or suspected benzodiazepine overdose patients comparing treatment with flumazenil versus placebo were included. Pre-defined outcome measures were AEs, SAEs and mortality. Thirteen trials with a total of 994 randomised (990 evaluable) patients were included. AEs were significantly more common in the flumazenil group (138/498) compared with the placebo group (47/492) (risk ratio: 2.85; 95% confidence interval: 2.11-3.84; p < 0.00001). SAEs were also significantly more common in the flumazenil group compared with the placebo group (12/498 versus 2/492; risk ratio: 3.81; 95% CI: 1.28-11.39; p = 0.02). The most common AEs in the flumazenil group were agitation and gastrointestinal symptoms, whereas the most common SAEs were supraventricular arrhythmia and convulsions. No patients died during the blinded phase of the RCTs. The use of flumazenil in a population admitted at the emergency department with known or suspected benzodiazepine intoxication is associated with a significantly increased risk of (S)AEs compared with placebo. Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials

Penninga

Graudal

Ladekarl

et al. 2015

Basic Clin Pharma Tox

127

View full text Add to dashboard Cite

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The use of flumazenil in the management of acute drug poisoning — a review

1991

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The popularity and widespread availability of benzodiazepines (BZD) has led to their frequent abuse in intentional drug poisoning. Although mortality from pure BZD overdose is usually small, in elderly, debilitated patients, or when BZD are combined with other CNS depressant drugs, morbidity increases significantly and outcome may be fatal. Drug overdose is therefore a medical emergency necessitating close observation and support of vital functions. Recently, the specific BZD antagonist flumazenil (Anexate) has become clinically available and much experience in its usefulness has accumulated. The present review summarizes a total of 30 studies and reports published to date, involving approximately 760 intoxicated patients. Flumazenil was evaluated both in prehospital use as well as in emergency rooms or in intensive care units. The age of patients ranged from 4-90 years and doses of flumazenil varied between 0.3-10 mg, approximately 1 mg being the most frequently used. All patients intoxicated with only BZD returned to full consciousness within minutes after the injection of flumazenil. When a mixture of BZD and other CNS depressants was abused, a range of effects was observed. This varied from no change to a return to full orientation, depending on the contribution of the BZD to the state of unconsciousness. Re-sedation occurred in about 65% of flumazenil treated patients, usually within 0.5-3 h after the first dose, the shorter interval being associated with mixed-drug poisoning. Repeated doses of the antagonist (0.2-2 mg), sometimes followed by continuous infusion (0.1-0.5 mg/h), were effective in maintaining patients fully oriented.(ABSTRACT TRUNCATED AT 250 WORDS)

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