Midazolam Disease Interactions

There are 9 disease interactions with midazolam:

Acute Alcohol Intoxication Closed-Angle Glaucoma Respiratory Depression Seizures Prolonged Hypotension

Congestive Heart Failure Renal/Liver Disease Obesity Paradoxical Reactions

The use of benzodiazepines is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of benzodiazepines may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with benzodiazepines should be administered cautiously in patients who might be prone to acute alcohol intake.

The manufacturers consider the use of benzodiazepines to be contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma. These agents do not possess anticholinergic activity but have very rarely been associated with increased intraocular pressure.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

Abrupt cessation of benzodiazepine therapy may precipitate seizures and other withdrawal symptoms, particularly after prolonged use and/or excessive dosages. Status epilepticus may occur in patients with a history of seizures withdrawn rapidly from benzodiazepine therapy. Following chronic administration, cessation of benzodiazepine therapy should occur gradually with incrementally reduced dosages. Patients should be advised not to discontinue medication without first consulting with the physician.

Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

In patients with congestive heart failure, there appears to be a two-fold increase in the elimination half-life, a 25% decrease in the plasma clearance, and a 40% increase in the volume of distribution of midazolam. Therapy with midazolam should be administered cautiously at reduced initial dosages in patients with congestive heart failure, particularly if they are elderly. The possibility of profound and/or prolonged effect should be considered.

Midazolam is metabolized by the liver, and the metabolites are excreted in the urine. Reduced drug clearance and prolonged elimination half-life of parent drug and metabolites have been reported in patients with renal and/or hepatic impairment. Therapy with midazolam should be administered cautiously at reduced initial dosages in such patients. The possibility of profound and/or prolonged effect should be considered.

The plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam. Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.

Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

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