Pharmaniaga Midazolam Warnings

IV Midazolam has been associated with severe respiratory depression and respiratory arrest, especially when used for conscious sedation. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy resulted. IV Midazolam should be used only in hospital or ambulatory care settings that provide for continuous monitoring of respiratory and cardiac functions. Assure immediate availability of resuscitative drugs, equipments, appropriate antidote and personnel trained in their use.
Dosage of IV Midazolam must be individualized for each patient. Lower doses are usually required for elderly, debilitated or higher risk surgical patients.
When Midazolam is administered intravenously for conscious sedation, it should be injected slowly (over at least 2 minutes); it should not be administered by rapid or single bolus IV injection because of respiratory depression and/or arrest, especially in elderly or debilitated patients. The initial dose may be as little as 1mg, but should not exceed 2.5mg in a normal healthy adult; administer over at least 2 minutes and allow additional 2 or more minutes to fully evaluate sedative effect. If further titration is necessary, use small increments to the appropriate level of sedation, allowing an additional 2 or more minutes after each increment to fully evaluate sedative effect. See Dosage & Administration for complete dosing information.
Anaphylaxis (severe allergic reaction) and angioedema (severe facial swelling) which can occur as early as first time the product is taken.
Complex sleep - related behaviors which many include sleep driving, making phone calls, preparing and eating food while asleep.
Special caution is required if midazolam is administered in high-risk patients: These include elderly patients, patients in a poor general condition, obese patients, patients with obstructive airways diseases, chronic renal or liver failure, sleep apnoea syndrome, cardiac decompensation and paediatric patients with cardiovascular instability.
In these patients, the dose and rate of infusion must be reduced and individually adjusted; the patients must be monitored continuously; particular attention must be paid to early signs of changes in vital functions. In elderly patients and patients with chronic renal insufficiency and cardiac decompensation, the midazolam excretion rate may be reduced.
In neonates and infants up to 4-6 months of age (especially in premature infants) the clearance of midazolam is markedly reduced. In this group of patients the administration of midazolam is, therefore, suitable after careful risk/benefit evaluation only.
Benzodiazepines are contraindicated in patients with severe liver insufficiency because they may encourage the onset of encephalopathy.
As the exacerbation of an acute psychosis cannot completely be ruled out special care is required in patients suffering from schizophrenia or endogene depression.
A current lack of volume should be balanced by infusion before anaesthesia.
As documentation of efficacy and safety of intravenous midazolam in children and adolescents younger than 18 years is limited the expected benefit should carefully be balanced against possible risks.
The risk of severe undesirable effects is particularly great after high doses or rapid administration. There have been reports of reactions such as restlessness, reflex movements (e.g. tonic and clonic movements and muscle tremor), hyperactivity and striking movements. These reactions may be caused by inadequate, excessive or incorrect administration of midazolam; however, the possibility of cerebral hypoxia or paradoxical reactions must also be considered. If such reactions occur, the response to each dose of midazolam, and to all other drugs, including local anaesthetics, must be evaluated.
An intraarterial injection must be avoided in any case as it can cause vasal tissue damage and even necrosis in certain cases. As in comparable cases of parenteral administered hypnotics a venous access should be ascertained at least during the period of operation under basic sedation.
The risk of dependence increases with dose and duration of treatment and some loss of efficacy has been reported during long-term sedation in intensive care units.
After prolonged intravenous administration, abrupt discontinuation may lead to withdrawal symptoms. Therefore, a gradual reduction is recommended in such cases.