6/8/2023 0 Comments Diazepam antidoteLonger half-lives in infants may be due to incomplete maturation of metabolic pathways.Įlimination half-life increases by approximately 1 hour for each year of age beginning with a half-life of 20 hours at 20 years of age. In both premature and full term infants the active metabolite desmethyldiazepam shows evidence of continued accumulation compared to children. In full term infants, elimination half-lives around 30 hours have been reported, with a longer average half-life of 54 hours reported in premature infants of 28 to 34 weeks gestational age and 8 to 81 days post-partum. ![]() In children 3 to 8 years old the mean half-life of diazepam has been reported to be 18 hours. Diazepam accumulates upon multiple dosing and there is some evidence that the terminal elimination half-life is slightly prolonged. The clearance of diazepam is 20 to 30 mL/min in young adults. Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates. The terminal elimination half-life of the active metabolite N-desmethyldiazepam is up to 100 hours. The initial distribution phase is followed by a prolonged terminal elimination phase (half-life up to 48 hours). Temazepam and oxazepam are largely eliminated by glucuronidation. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam. The initial distribution phase has a half-life of approximately 1 hour, although it may range up to > 3 hours.ĭiazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. The decline in the plasma concentration-time profile after oral administration is biphasic. In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg. Diazepam and its metabolites cross the blood-brain and placental barriers and are also found in breast milk in concentrations approximately one tenth of those in maternal plasma (days 3 to 9 post-partum). This results in an average decrease in C max of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food.ĭiazepam and its metabolites are highly bound to plasma proteins (diazepam 98%). There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting. In the presence of food, mean lag times are approximately 45 minutes as compared with 15 minutes when fasting. Absorption is delayed and decreased when administered with a moderate fat meal. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS).Īfter oral administration of diazepam, > 90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 to 1.5 hours with a range of 0.25 to 2.5 hours. ![]() Abrupt discontinuation or rapid dosage reduction of diazepam after continued use may precipitate acute withdrawal reactions, which can be life-threatening. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. The continued use of benzodiazepines, including diazepam, may lead to clinically significant physical dependence.Before prescribing diazepam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see WARNINGS). Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. The use of benzodiazepines, including diazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death.Follow patients for signs and symptoms of respiratory depression and sedation (see WARNINGS AND PRECAUTIONS).Limit dosages and durations to the minimum required. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. ![]() WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS ABUSE, MISUSE, AND ADDICTION and DEPENDENCE AND WITHDRAWAL REACTIONSĬoncomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
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