Midazolam may lead to a potentiation of the anaesthetic or sedative effect of other centrally acting agents, such as neuroleptics, tranquillisers, antidepressants, anticonvulsants, hypnotics, analgesics, anaesthetics and sedative antihistamines; this includes respiratory depression.
The risk of respiratory depression is particularly high with co-administration of narcotic analgesics.
Displacement of midazolam from its plasma protein binding sites by sodium valproate may increase the response to midazolam and, therefore, care should be taken to adjust the midazolam dosage in patients with epilepsy.
The mutual potentiation of midazolam and alcohol may lead to unforeseeable reactions in some cases; patients must therefore not take any alcoholic drinks before and at least 12 hours after injection.
A clinically relevant interaction may occur between midazolam and substances that inhibit specific liver enzymes (principally cytochrome P 450 3A). These substances are known to be capable of influencing midazolam pharmacokinetics and of leading to deeper and longer lasting anaesthesia. The following substances are currently known to produce such reactions: cimetidine, erythromycin, clarithromycin, roxithromycin, diltiazem, verapamil, ketoconazole, itraconazole, fluoxetin, nefazodon. If possible, therefore, administration of midazolam should be avoided in patients concomitantly receiving one of the above substances or other agents inhibiting cytochrome P 450 3A. If this is not possible, the dosage must be reduced to 50-75%. These patients must be closely monitored.
The hypotensive effect of antihypertensive and vasodilatory drugs may be potentiated by midazolam.
Incompatibilities: This medicinal product must not be diluted with other solutions for parenteral use other than those mentioned in Dosage & Administration. Compatibility study must be checked before administration, if intended to be mixed with other drugs.
Midazolam precipitates in solutions containing bicarbonate. Theoretically, the midazolam injection solution is likely to be unstable in solutions of neutral or alkaline pH. If midazolam is mixed with albumin, amoxicillin sodium, ampicillin sodium, bumetamide, dexamethasone sodium phosphate, dimenhydrinate, floxacillin sodium, furosemide, hydrocortison sodium succinate, pentobarbital sodium, perphenazine, prochlorperazine edisylate, ranitidine or thiopental sodium or trimethoprim-sulfa-methoxazole, a white precipitate forms immediately.
A haze is formed immediately followed by a white precipitate with nafcillin sodium. With ceftazidime a haze is formed.
With methotrexate sodium a yellow precipitate forms. With clonidine hydrochloride an orange discoloration forms. With omeprazole sodium a brown discoloration forms, followed by a brown precipitate. With forscarnet sodium a gas is produced.
Further midazolam should not be mixed with aciclovir, albumin, alteplase, acetazolam disodium, diazepam, enoximone, flecainide acetate, fluorouracil, imipenem, mezlocillin sodium, phenobarbital sodium, phenytoin sodium, potassium canrenoate, sulbactam sodium, theophylline, trometamol, urokinase.