Dormicum Special Precautions

General: Film-coated tablet: Information should be given to the patients about following warnings and precautions.
Tolerance: Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.
Duration of treatment: The duration of treatment with benzodiazepine hypnotics should be as short as possible (see Dosage & Administration), and should not exceed 2 weeks. The tapering-off process should be tailored to the individual. Extension beyond this period should not take place without re-evaluation of the situation.
Rebound insomnia: When discontinuing Midazolam (Dormicum) therapy, insomnia may reoccur, possibly with a higher severity than before starting treatment ("rebound insomnia"). Rebound insomnia, a transient syndrome, may be accompanied by other reactions including mood changes, anxiety, and restlessness. The risk of rebound phenomena is greater after abrupt discontinuation of treatment. Therefore, it is recommended that the dosage of Midazolam (Dormicum) is decreased gradually (see Drug Abuse and Dependence as follows).
Amnesia: Midazolam (Dormicum) may cause anterograde amnesia, which occurs most frequently within the first few hours after ingesting the product. In order to reduce the risk, patients should ensure that they are able to have an uninterrupted sleep of 7-8 hours (see Adverse Reactions).
Residual effects: Provided the oral dose of Midazolam (Dormicum) is not larger than 15 mg/day and the patient is assured of at least 7 to 8 hours undisturbed sleep, no residual effect is observed following oral administration of Midazolam (Dormicum) tablet in standard patients as confirmed by clinical observations using sensitive pharmacological methods.
Psychiatric and 'paradoxical' reactions: Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, anxiety, and more rarely, delusion, anger, nightmares, hallucinations, psychoses, inappropriate behavior and other adverse behavioral effects are known to occur when using benzodiazepines.
Should this be so, use of the drug should be discontinued. These effects are more likely to occur in the elderly.
Specific patient groups: In elderly and/or debilitated patients, as well as in patients with respiratory or cardiovascular impairment, the recommended dose is 7.5 mg. These patients may be more sensitive to the clinical side effects of midazolam like cardio-respiratory depression. Thus, Midazolam (Dormicum) should be used very carefully in these patient populations and if needed a lower dose should be considered (see Special Dosage Instructions under Dosage & Administration).
Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with depression as suicide may occur in such patients.
Concomitant use of alcohol/CNS depressants: The concomitant use of Midazolam (Dormicum) with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Midazolam (Dormicum) possibly including severe sedation that could result in coma or death, clinically relevant respiratory and/or cardio-vascular depression (see Interactions).
Medical history of alcohol or drug abuse: Midazolam (Dormicum) should be avoided in patients with a medical history of alcohol or drug abuse.
Co-medication with drugs that alter CYP3A activity: Midazolam pharmacokinetics is altered in patients receiving concomitantly compounds that inhibit or induce CYP3A. Consequently, the clinical and adverse effects may be increased or decreased respectively (see Interactions).
Lactose intolerance: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Drug Abuse and Dependence: Dependence: Use of Midazolam (Dormicum) may lead to the development of physical and psychological dependence. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcohol and/or drug abuse.
Withdrawal: Withdrawal symptoms may consist of headaches, diarrhea, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or convulsions.
Since the risk of withdrawal phenomena/rebound insomnia is higher after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually (see Dosage & Administration and General as previously mentioned).
Laboratory Tests: No text.
Ability to Drive and Use Machines: Sedation, amnesia, impaired concentration and impaired muscular function adversely affect the ability to drive or to use machines. Prior to receiving Midazolam (Dormicum), the patient should be warned not to drive a vehicle or operate a machine until completely recovered. The physician should decide when these activities may be resumed.
If sleep duration is insufficient or alcohol is consumed, the likelihood of impaired alertness may be increased (see Interactions).
Use in Special Populations: Renal Impairment: There is a greater likelihood of adverse drug reactions in patients with severe kidney disease (see Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration and Contraindications.
Solution for injection: Midazolam should be used only when age- and size-appropriate resuscitation facilities are available, as I.V. administration of midazolam may depress myocardial contractility and cause apnea. Severe cardiorespiratory adverse events have occurred on rare occasions. These have included respiratory depression, apnea, respiratory arrest and/or cardiac arrest. Such life‑threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered (see Adverse Reactions).
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
In case of conscious sedation provided by non-anesthesiologist review of the latest practice guideline is strongly advised.
Premedication: When midazolam is used for premedication, adequate observation of the patient after administration is mandatory as inter-individual sensitivity varies and symptoms of overdose may occur.
High-risk patients: Special caution should be exercised when administering midazolam to high-risk patients: Adults over 60 years of age; Critically ill; Patients with impaired organ function: impaired respiratory function, impaired kidney function, impaired hepatic function (benzodiazepines may precipitate or exacerbate encephalopathy in patients with severe hepatic impairment), impaired cardiac function.
These high-risk patients require lower dosages (see Dosage & Administration) and should be continuously monitored for early signs of alterations of vital functions.
Discharging criteria: After receiving Midazolam (Dormicum), patients should be discharged from hospital or consulting room only when recommended by treating physician and if accompanied by an attendant. It is recommended that the patient is accompanied when returning home after discharge.
Tolerance: Some loss of efficacy has been reported when Midazolam (Dormicum) was used as long-term sedation in intensive care units (ICU).
Withdrawal symptoms: Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, especially after long-term sedation i.e. ≥2-3 days, it is recommended that the dose is decreased gradually. The following withdrawal symptoms may occur: headaches, diarrhea, muscle pain, extreme anxiety, tension, sleep disturbances, restlessness, confusion, irritability, mood changes, hallucinations and convulsions. In severe cases, the following symptoms may occur: depersonalization, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact.
Amnesia: Anterograde amnesia may occur with therapeutic doses, with the risk increasing at higher dosages. Prolonged amnesia can present problems in outpatients, who are scheduled for discharge following intervention.
Paradoxical reactions: Paradoxical reactions such as restlessness, agitation, irritability, involuntary movements (including tonic/clonic convulsions and muscle tremor), hyperactivity, hostility, delusion, anger aggressiveness, anxiety, nightmares, hallucinations, psychoses, inappropriate behavior and other adverse behavioral effects, paroxysmal excitement and assault, have been reported to occur with midazolam. These reactions may occur with higher doses and/or when the injection is given rapidly. The rare incidence of susceptibility to such reactions has been reported among children and at higher I.V. doses in elderly. Should this be so, discontinuation of the drug should be considered.
Altered elimination of midazolam: Midazolam elimination may be altered in patients receiving compounds that inhibit or induce CYP3A4, and the dose of midazolam may need to be adjusted accordingly. See Interactions.
Midazolam elimination may also be delayed, in patients with liver dysfunction, low cardiac output and in newborns (see Use in Special Populations as follows).
Sleep Apnea: Midazolam ampoules should be used with extreme caution in patients with sleep apnea syndrome and patients should be regularly monitored.
Preterm infants: Due to an increased risk of apnea, extreme caution is advised when sedating preterm infants less than 36 weeks of gestational age whose trachea is not intubated. Rapid injection should be avoided in the preterm infants less than 36 weeks of gestational age. Careful monitoring of respiratory rate and oxygen saturation is required.
Pediatric patients less than 6 months: Pediatric patients less than 6 months of age are particularly vulnerable to airway obstruction and hypoventilation, therefore titration with small increments to clinical effect and careful respiratory rate and oxygen saturation monitoring are essential (see also 'Preterm infants' as previously mentioned).
Concomitant use of alcohol/CNS depressants: The concomitant use of Midazolam (Dormicum) with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Midazolam (Dormicum) possibly including severe sedation that could result in coma or death, clinically relevant respiratory and/or cardiovascular depression (see Interactions).
Medical history of alcohol or drug abuse: Midazolam (Dormicum) should be avoided in patients with a medical history of alcohol or drug abuse.
Others: As with any substance with CNS depressant and/or muscle-relaxant properties, particular care should be taken when administering midazolam to a patient with myasthenia gravis.
Drug Abuse and Dependence: Dependence: When midazolam is used in long-term sedation, physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcohol and/or drug abuse.
Laboratory Tests: No text.
Ability to Drive and Use Machines: Sedation, amnesia, impaired concentration and impaired muscular function adversely affect the ability to drive or use machines. Prior to receiving Midazolam (Dormicum), the patient should be warned not to drive a vehicle or operate a machine until completely recovered. The physician should decide when these activities may be resumed.
If sleep duration is insufficient or alcohol is consumed, the likelihood of impaired alertness may be increased (see Interactions).
Use in Special Populations: Renal Impairment: There is a greater likelihood of adverse drug reactions in patients with severe renal impairment (see Special Dosing Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions). (See Table 2.)

Click on icon to see table/diagram/image

Hepatic Impairment: Hepatic impairment reduces the clearance of I.V. midazolam with a subsequent increase in terminal half-life. Therefore, the clinical effects may be stronger and prolonged. The required dose of midazolam may have to be reduced and proper monitoring of vital signs should be established (see Dosage & Administration and Precautions).
Use in Children: Film-coated tablet: See Contraindications.
Solution for injection: See Dosage & Administration and Precautions.
In preterm newborn infants, term newborn infants, and pediatrics less than 15 kg of body weight, midazolam solutions with concentrations higher than 1 mg/mL are not recommended. Higher concentrations should be diluted to 1 mg/mL.
IV and rectal administration in pediatric patients less than 6 months of age is not recommended with exception in ICU as they are vulnerable to airway obstruction and hypoventilation.
Midazolam (Dormicum) is not indicated in children in induction of anesthesia and as a sedative component in combined anesthesia as limited data is available.
Use in the Elderly: Film-coated tablet: See Special Dosage Instructions under Dosage & Administration and General as previously mentioned.
Solution for injection: Geriatric patients ≥60 years, require lower dosages and should be continuously monitored for early signs of alterations of vital functions (see Dosage & Administration and Precautions).