MIDAZOLAM

STANDARD DOSAGE

Midazolam is a potent sedative agent that requires titration and slow administration. Titration is strongly recommended to safely obtain the desired level of sedation according to the clinical need, physical status, age and concomitant medication.

In adults over 60 years, debilitated or chronically ill patients and paediatric patients, dose should be determined with caution and risk factors related to each patient should be taken into account. Standard dosages are provided in the table below.

Additional details are provided in the text following the table. v. v. v. m. v. m. v. m. m. v. v. v. v. v. v. v. v. v. The dose must be individualised and titrated, and should not be administered by rapid or single bolus injection. g. speed of administration, amount of dose).

If necessary, subsequent doses may be administered according to the individual need. The onset of action is about 2 minutes after the injection. Maximum effect is obtained in about 5 to 10 minutes. v. injection of midazolam should be given slowly at a rate of approximately 1 mg in 30 seconds.

5 mg given 5 to10 minutes before the beginning of the procedure. Further doses of 1mg may be given as necessary. 5 mg. A total dose greater than 5 mg is usually not necessary. 0 mg and given 5-10 minutes before the beginning of the procedure.

5 to 1 mg may be given as necessary. Since in these patients the peak effect may be reached less rapidly, additional midazolam should be titrated very slowly and carefully. 5 mg is usually not necessary. V. administration: midazolam should be titrated slowly to the desired clinical effect.

The initial dose of midazolam should be administered over 2 to 3 minutes. One must wait an additional 2 to 5 minutes to fully evaluate the sedative effect before initiating a procedure or repeating a dose. If further sedation is necessary, continue to titrate with small increments until the appropriate level of sedation is achieved.

Infants and young children less than 5 years of age may require substantially higher doses (mg/kg) than older children and adolescents. • Paediatric patients less than 6 months of age: paediatric patients less than 6 months of age are particularly vulnerable to airway obstruction and hypoventilation.

For this reason, the use in conscious sedation in children less than 6 months of age is not recommended. 1 mg/kg. 6 mg/kg may be necessary to reach the desired endpoint, but the total dose should not exceed 6 mg. Prolonged sedation and risk of hypoventilation may be associated with the higher doses.

05 mg/kg. 4 mg/kg to a maximum of 10mg may be necessary. Prolonged sedation and risk of hypoventilation may be associated with the higher doses. • Paediatric patients 12 to 16 years of age: should be dosed as adults. 5 mg/kg. Rectal administration of the ampoule solution is performed by means of a plastic applicator fixed on the end of the syringe.

If the volume to be administered is too small, water may be added up to a total volume of 10 ml. Total dose should be administered at once and repeated rectal administration avoided. The use in children less than 6 months of age is not recommended, as available data in this population are limited.

M. 15 mg/kg. 0 mg is usually not necessary. This route should only be used in exceptional cases. m. injection is painful. In children less than 15 kg of body weight, midazolam solutions with concentrations higher than 1mg/ml are not recommended.

Higher concentrations should be diluted to 1 mg/ml. ANAESTHESIA DOSAGE PREMEDICATION Premedication with midazolam given shortly before a procedure produces sedation (induction of sleepiness or drowsiness and relief of apprehension) and preoperative impairment of […]

The following undesirable effects have been reported (frequency not known, cannot be estimated from the available data) to occur when midazolam is injected: Frequency categories are as follows: Very common: ≥1/10; Common ≥1/100 to <1/10; Uncommon ≥1/1,000 to <1/100 Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) Blood and lymphatic system disorders frequency not known Blood dyscrasias Immune System Disorders frequency not known Hypersensitivity, angioedema, anaphylactic shock Psychiatric Disorders frequency not known Confusional state, euphoric mood, hallucinations Agitation*, hostility*, rage*, aggressiveness*, excitement,* disinhibition, irritability, increased anxiety Physical drug dependence and withdrawal syndrome Abuse Postoperative delirium, numbed emotions In susceptible patients, an unnoticed depression may become evident.

Nervous System Disorders frequency not known Involuntary movements (including tonic/clonic movements and muscle tremor)*, hyperactivity* Sedation (prolonged and postoperative), alertness decreased, somnolence, headache, dizziness, ataxia, anterograde amnesia**, the duration of which is directly related to the administered dose Slurred speech, extrapyramidal effects Convulsions have been reported in premature infants and neonates Eye Disorders frequency not known Visual disturbances Cardiac Disorders frequency not known Cardiac arrest.

Bradycardia, chest pain and decreases in cardiac output and stroke volume. These effects are important in those patients with a reduced myocardial oxygen delivery capacity or suffering hypovolaemia. Vascular Disorders frequency not known Hypotension, vasodilation, thrombophlebitis, thrombosis.

Systemic vascular resistance is important in those patients with a reduced myocardial oxygen delivery capacity or suffering hypovolaemia. 4). ***There have been reports of falls and fractures in benzodiazepine users. The risk of falls and fractures is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.

**** These events occur predominantly at the start of therapy and usually disappear with repeated administration.

Dependence:

Use of midazolam - even in therapeutic doses - may lead to the development of physical dependence. v. 4). Symptoms of benzodiazepine withdrawal include anxiety, depression, impaired concentration, insomnia, headache, dizziness, tinnitus, loss of appetite, tremor, perspiration, irritability, perceptual disturbances such as hypersensitivity to physical, visual, and auditory stimuli and abnormal taste, nausea, vomiting, abdominal cramps, palpitations, mild systolic hypertension, tachycardia, and orthostatic hypotension, Rare and more serious withdrawal symptoms include muscle twitching, confusional or paranoid psychosis, convulsions, hallucinations, and a state resembling delirium tremens.

Broken sleep with vivid dreams and increased REM sleep may persist for some weeks after withdrawal of benzodiazepines. Cases of abuse have been reported. Severe cardiorespiratory adverse events have occurred. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Midazolam should be administered only by experienced physicians in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function and by persons specifically trained in the recognition and management of expected adverse events including respiratory and cardiac resuscitation.

Severe cardiorespiratory adverse events have been reported. These have included respiratory depression, apnoea, respiratory arrest and/or cardiac arrest. 8). Special caution is required for the indication of conscious sedation in patients with impaired respiratory function.

Paediatric 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.

When midazolam is used for premedication, adequate observation of the patient after administration is mandatory as interindividual sensitivity varies and symptoms of overdose may occur. g. - patients with chronic respiratory insufficiency - patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - paediatric patients specially those with cardiovascular instability.

2) and should be continuously monitored for early signs of alterations of vital functions. 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.

Midazolam injection should be used with caution in patients with coma. As with other benzodiazepines, extreme caution should be used if prescribing midazolam for patients with personality disorders. The disinhibiting effects of benzodiazepines may be manifested as the precipitation of suicide in patients who are depressed or show aggressive behaviour towards self and others.

Tolerance Some loss of efficacy has been reported when midazolam was used as long-term sedation in intensive care units (ICU). Dependence When midazolam is used in long-term sedation in ICU, it should be borne in mind that physical dependence on midazolam may develop.

8). Withdrawal symptoms During prolonged treatment with midazolam in ICU, physical dependence may develop. Therefore, abrupt termination of the treatment will be accompanied by withdrawal symptoms. The following symptoms may occur: headaches, muscle pain, anxiety, tension, restlessness, confusion, irritability, rebound insomnia, mood changes, hallucinations and convulsions.

Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, it is recommended to decrease doses gradually. Amnesia Midazolam causes anterograde amnesia (frequently this effect is very desirable in situations such as before and during surgical and diagnostic procedures), the duration of which is directly related to the administered dose.

Prolonged amnesia can present problems in outpatients, who are scheduled for discharge following intervention. After receiving midazolam parenterally, patients should be discharged from hospital or consulting room only if accompanied by an attendant.

Paradoxical reactions Paradoxical reactions such as agitation, involuntary movements (including tonic/clonic convulsions and muscle tremor), hyperactivity, hostility, rage reaction, aggressiveness, paroxysmal excitement and assault, have been reported to occur with midazolam.

These reactions may occur with high doses and/or when the injection is given rapidly. The highest incidence to such reactions has been reported among children and the elderly. 5). 2). Preterm infants and neonates Due to an increased risk of apnoea, extreme caution is advised when sedating preterm and former preterm non intubated patients.

Careful monitoring of respiratory rate and oxygen saturation is required. Rapid injection should be avoided in the neonatal population. Neonates have reduced and/or immature organ function and are also vulnerable to profound and/or prolonged respiratory effects of midazolam.

Adverse haemodynamic events have been reported in paediatric patients with cardiovascular instability; rapid intravenous administration should be avoided in this population. Paediatric patients less than 6 months In this population, midazolam is indicated for sedation in ICU only.

Paediatric 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 section 'Preterm infants' above).

Concomitant use of alcohol / CNS depressants The concomitant use of midazolam with alcohol or/and CNS depressants should be avoided. 5). Medical history of alcohol or drug abuse Midazolam as other benzodiazepines should be avoided in patients with a medical history of alcohol or drug abuse.

[…]

Use of this drug in patients with known hypersensitivity to benzodiazepines or to any excipient of the product. Use of this drug for conscious sedation in patients with severe respiratory failure or acute respiratory depression. Severe hepatic insufficiency