The effect of decontamination procedures on the pharmacodynamics of venlafaxine in overdose

Authors


Mr Venkata V. Pavan Kumar, Postdoctoral Fellow, New Zealand's National School of Pharmacy, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
Tel.: + 64 3 479 5045
Fax: + 64 3 479 7034
E-mail: pavan.kumar@otago.ac.nz

Abstract

WHAT IS ALREADY KNOW ABOUT THIS SUBJECT

• Single dose activated charcoal increases the clearance of venlafaxine in overdose. Combination of single dose activated charcoal and whole bowel irrigation decreases bioavailability of venlafaxine in overdose.

• There is an increased risk of seizures, a potential for cardiac toxicity and a higher rate of fatalities with venlafaxine overdose than other newer antidepressants.

WHAT THIS STUDY ADDS

• Single dose activated charcoal and combination of single dose activated charcoal and whole bowel irrigation decreases the probability of seizures that are caused by overdose of venlafaxine.

AIMS To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination.

METHODS Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t90) of seizure, respectively.

RESULTS A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03–0.08), 0.19 (0.09–0.35) and 0.75 (0.30–0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25–0.89), 0.71 (0.35–1.22) and 0.25 (0.08–0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t90 values for first seizure was 26 h and was not affected by dose or decontamination procedure.

CONCLUSION SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring.

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