Midazolam dosage

This interaction is of clinical importance be alert for the need to reduce the midazolam dosage in the presence of saquinavir. The authors of the study suggest that continuous intravenous midazolam doses should be reduced by 50%, but do not consider dose adjustments to single intravenous doses necessary. The same precautions would seem appropriate with triazolam. However, the manufacturer of saquinavir contraindicates the concurrent use of oral midazolam and triazolam. They note that no studies have been conducted with ritonavir-boosted saquinavir but that a 3 to 4-fold increase in intravenous midazolam levels would be expected. Use of intravenous midazolam with saquinavir is not contraindicated but they... 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

Like fluoxetine, erythromycin and other macrolides inhibit the CYP-3A isoenzyme and increase the levels and effects of the triazolobenzodiazepines (Shader and Greenblatt, 1995 Chouinard et ah, 1999). Midazolam should be avoided or the dosage dropped by 50% in patients receiving erythromycin (Olkkola et ah, 1993). Ketoconazole and itraconazole may also interact with triazolam and midazolam, and combinations of these drugs should be avoided (Varhe et ah, 1994 Chouinard et ah, 1999). 

Induce and maintain anesthesia using a mixture of fentanyl/ fluanisone with midazolam (Hypnorm/Hypnovel see Note 4). The dosage for these agents is 0.25 mL of each active ingredient plus 0.5 mL of water given IP at a rate of 0.1 mL per mouse. 

Macrolides cause increases in the serum concentrations, AUCs, and half-lives and reductions in the clearance of triazolam and midazolam (138-140). These changes can result in clinical effects, such as prolonged psychomotor impairment, amnesia, or loss of consciousness (141). Erythromycin can increase concentrations of midazolam and triazolam by inhibition of CYP3A4, and dosage reductions of 50% have been proposed if concomitant therapy is unavoidable (142). 

In 113 patients undergoing general anesthesia, intravenous midazolam 15 mg slowed recovery of the twitch height after vecuronium and atracurium compared with diazepam. The recovery index was not altered (162). However, in another study in 20 patients, midazolam 0.3 mg/kg did not affect the duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation produced by suxamethonium 1 mg/kg, nor the duration of blockade and adequacy of relaxation for tracheal intubation produced by pancuronium 0.025 mg/kg in incremental doses until 99% depression of muscle-twitch tension was obtained (161). Furthermore, in 60 patients undergoing maintenance anesthesia randomly assigned to one of six regimens (etomidate, fentanyl, midazolam, propofol, thiopental plus nitrous oxide, or isoflurane plus nitrous oxide), midazolam did not alter rocuronium dosage requirements (165). 

The incidence of hypotension with the use of midazolam for pre-hospital rapid-sequence intubation of the trachea has been assessed in a retrospective chart review of two aeromedical crews (19). The rapid-sequence protocols were identical, except for the dose of midazolam. Both crews used 0.1 mg/kg, but one crew had a maximum dose of 5 mg imposed. This meant that patients over 50 kg received lower doses of midazolam they also had a higher incidence of hypotension. This relation was also present in patients with traumatic brain injury, implying that cerebral perfusion could be compromised at a critical time in those without dosage restriction. 

The protease inhibitor saquinavir, propofol, and fluconazole (53,58,59) increased the systemic availability and peak plasma concentrations and prolonged the half-life of midazolam, thus increasing its sedative effects. The dosage of midazolam should be reduced in patients taking these drugs. 

Erythromycin can increase concentrations of midazolam and triazolam by inhibition of CYP3A4, and dosage reductions of 50% have been proposed if concomitant therapy is unavoidable (59). 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

A. Additive effect with other CNS depressants that may result in lower propofol dosage requirements if given concomitantly. Through its inhibition of cytochrome P-450, propofol may increase levels of midazolam, diazepam, and other opiates such as sufentanyl and alfentanyl, causing respiratory depression, bradycardia, and hypotension. 

It is very difficult to assess and compare the results of the very many studies of this interaction because of the differences between the tests, their duration, the dosages of the benzodiazepines and alcohol, whether given chronically or acutely, and a number of other variables. However, the overall picture seems to be that benzodiazepines and related drugs including diazepam, " alprazolam,bromazepam, brotizolam, chlo-rdiazepoxide, " clobazam, dipotassium clorazepate, flunitrazepam, flurazepam, loprazolam, " lorazepam, lormetazepam, medazepam, midazolam, nitrazepam, " " oxazepam, temazepam, " triazolam, and zopiclone enhance the effects of alcohol i.e. cause increased drowsiness, impaired performance and driving skills. 

Information is limited but what is known shows that the effects of midazolam are increased by aspirin. Be alert for the need to reduce the dosage. However, note also that regular aspirin use may increase the risk of bleeding during surgery, and in some situations this may justify avoidance of aspirin in the week before surgery. ... 

The effects of alprazolam and brotizolam are increased and prolonged by ketoconazole and itraconazole, but the extent of this is less than that seen with midazolam or triazolam. However, some dosage reductions may still be necessary. 

The interactions of midazolam with erythromycin and triazolam with clarithromycin, erythromycin or troleandomycin appear to be established, and of clinical importance. The dosages of the midazolam and triazolam should be reduced 50 to 75% when these antibacterials are used if excessive effects (marked drowsiness, memory loss) are to be avoided. Remember too that the hypnotic effects are also prolonged so that patients should be warned about hangover effects the following morning if they intend to drive. Much less is known about the use of midazolam with clarithromycin but similar precautions may be necessary. The manufacturers of zaleplon say that patients should be advised that increased sedation is possible with erythromycin, although a dose adjustment is usually not required. ... 

The interactions of nefazodone with alprazolam, midazolam, triazolam and zopiclone are established and clinically important. The practical consequences are that the effects of alprazolam, midazolam and triazolam are expected to be increased but the extent is uncertain. Be alert for any evidence of any psychomotor impairment, drowsiness etc. and reduce the benzodiazepine dosage if necessary. More study is needed. Lorazepam does not interact with nefazodone. There seems to be no direct information about other benzodiazepines and related drugs. 

On the basis of an experimental study in 9 patients it was concluded that the dosage of midazolam needs no adjustment in those taking ciclosporin. Midazolam also appears to have no effect on ciclosporin pharmacokinetics. ... 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

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