Zylam

Each mL of the solution contains: Midazolam (as hydrochloride) 1 mg.

Pharmacology: Pharmacodynamics: Midazolam is a derivative of the imidazobenzodiazepine group. The free base is a lipophilic substance with low solubility in water.
The basic nitrogen in position 2 of the imidazobenzodiazepine ring system enables midazolam to form water-soluble salt with acids. These produce a stable solution suitable for oral administration.
The pharmacological action of midazolam is characterized by short duration because of rapid metabolic transformation. Midazolam has a sedative and sleep-inducing effect of pronounced intensity. It also exerts an anxiolytic, an anticonvulsant and a muscle-relaxant effect.
After IM or IV administration, anterograde amnesia of short duration occurs (the patient does not remember events that occurred during the maximal activity of the compound).
Mechanism of Action: Midazolam is a derivative of the imidazobenzodiazepine group. The pharmacological effects of benzodiazepines are the consequence of reversible interactions with the gamma aminobutyric acid (GABA) receptor in the central nervous system (CNS). Benzodiazepines intensify the physiological mechanisms of GABA, the most common inhibitory neurotransmitter within the CNS.
Pharmacokinetics: Absorption after IM injection: Absorption of midazolam from the muscle tissue is rapid and complete. Maximum plasma concentrations are achieved within 30 minutes. The absolute bioavailability after IM injection is over 90%.
Absorption after rectal administration: After rectal administration midazolam is absorbed quickly. Maximum plasma concentrations are reached within 30 minutes. The absolute bioavailability is about 50%.
Distribution: When midazolam is injected IV, the plasma concentration-time curve shows one or two distinct phases of distribution. The volume of distribution at steady state is 0.7-1.2 L/kg. 96-98% midazolam is bound to plasma proteins. The major function of plasma protein binding is due to albumin. There is a slow and insignificant passage of midazolam into the cerebrospinal fluid. In humans, midazolam has been shown to cross the placenta slowly and to enter fetal circulation. Small amounts of midazolam are found in breast milk.
Metabolism: Midazolam is almost entirely eliminated by biotransformation. The fraction of the dose extracted by the liver has been estimated to be 30-60%. Midazolam is hydroxylated by the cytochrome P450 CYP3A4 isozymes and the major urinary and plasma metabolite is alpha-hydroxymidazolam. Plasma concentrations of alpha-hydroxymidazolam are 12% of those of the parent compound. Alpha-hydroxymidazolam is pharmacologically active, but contributes only minimally (about 10%) to the effects of intravenous midazolam.
Elimination: In healthy volunteers, the elimination half-life of midazolam is between 1.5-2.5 hours. Plasma clearance is in the range of 300-500 ml/min. Midazolam's metabolites are excreted mainly by renal route (60-80% of the injected dose) and recovered as glucuronide conjugated alpha-hydroxymidazolam. Less than 1 % of the dose is recovered in urine as unchanged drug. The elimination half-life of alpha-hydroxymidazolam is shorter than 1 hour. When midazolam is given by IV infusion, its elimination kinetics do not differ from those following bolus injection.
Special Populations: Elderly: In adults over 60 years of age, the elimination half-life may be prolonged up to four times.
Children: The rate of rectal absorption in children is similar to that in adults but the bioavailability is lower (5-8%). The elimination half-life after IV and rectal administration is shorter in children 3-10 years old (1-1.5 hours) as compared with that in adults. The difference is consistent with an increased metabolic clearance in children.
Neonates: In neonates the elimination half-life is on average 6-12 hours, probably due to liver immaturity and the clearance is reduced.
Obese: The mean half-life is greater in obese than in non-obese patients (5.9 vs 2.3 hours). This is due to an increase of approximately 50% in the volume of distribution corrected for total body weight. The clearance is not significantly different in obese and non-obese patients.
Patients with hepatic impairment: The elimination half-life in cirrhotic patients may be longer and the clearance smaller as compared to those in healthy volunteers.
Patients with renal impairment: The elimination half-life of patients with chronic renal impairment is similar to that in healthy volunteers.
Critically ill patients: The elimination half-life of midazolam is prolonged up to six times in the critically ill patients. Patients with cardiac insufficiency: The elimination half-life is longer in patients with congestive heart failure compared with that in healthy subjects.

Midazolam 5 mg/ml is a short-acting sleep-inducing drug.
The indications are as follows: In adults: CONSCIOUS SEDATION before and during diagnostic or therapeutic procedures with or without local anaesthesia; ANAESTHESIA: Premedication before induction of anaesthesia. Induction of anaesthesia: As a sedative component in combined anaesthesia; SEDATION IN INTENSIVE CARE UNITS.
In children: CONSCIOUS SEDATION: before and during diagnostic or therapeutic procedures with or without local anaesthesia; ANAESTHESIA: Premedication before induction of anaesthesia; SEDATION IN INTENSIVE CARE UNITS.

STANDARD DOSAGE: Midazolam is a potent sedative agent that requires titration and slow administration. Dose 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 as follows. (See table.)

Click on icon to see table/diagram/image

CONSCIOUS SEDATION DOSAGE: For conscious sedation prior to diagnostic or surgical intervention, midazolam is administered IV. The dose must be individualised and titrated, and should not be administered by rapid or single bolus injection. The onset of sedation may vary individually depending on the physical status of the patient and the detailed circumstances of dosing (e.g. rate 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.
Adults: The IV injection of midazolam should be given slowly at a rate of approximately 1 mg in 30 seconds.
In adults below the age of 60 the initial dose is 2 to 2.5mg given 5 to 10 minutes before the beginning of the procedure. Further doses of 1mg may be given as necessary. Mean total doses have been found to range from 3.5 to 7.5mg. A total dose greater than 5mg is usually not necessary.
In adults over 60 years of age, debilitated or chronically ill patients, the initial dose must be reduced to 0.5-1.0mg and given 5-10 minutes before the beginning of the procedure. Further doses of 0.5 to 1 mg may be given as necessary.
Paediatric population: IV 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 month 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.
Paediatric patients 6 months to 5 years of age: initial dose 0.05 to 0.1mg/kg. A total dose up to 0.6mg/kg may be necessary to reach the desired endpoint, but the total dose should not exceed 6mg.
Prolonged sedation and risk of hypoventilation may be associated with the higher doses.
Paediatric patients 6 to 12 years of age: initial dose 0.025 to 0.05mg/kg. A total dose of up to 0.4mg/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.
Rectal administration: the total dose of midazolam usually ranges from 0.3 to 0.5mg/kg. Rectal administration of the ampoule/vial 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 10ml. 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.
IM administration: the doses used range between 0.05 and 0.15mg/kg. A total dose greater than 10 mg is usually not necessary. This route should only be used in exceptional cases. Rectal administration should be preferred as IM injection is painful.
In children less than 15kg 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 and preoperative impairment of memory. Midazolam can also be administered in combination with anticholinergics. For this indication midazolam should be administered IV or IM, deep into a large muscle mass 20 to 60 minutes before induction of anaesthesia), or preferably via the rectal route in children. Close and continuous monitoring of the patients after administration of premedication is mandatory as interindividual sensitivity varies and symptoms of overdose may occur.
Adults: For preoperative sedation and to impair memory of preoperative events, the recommended dose for adults of ASA Physical Status I & II and below 60 years is 0.07 to 0.1mg/kg administered IM. The dose must be reduced and individualised when midazolam is administered to adults over 60 years of age, debilitated, or chronically ill patients. A dose of 0.025 to 0.05mg/kg administered IM is recommended. The usual dose is 2 to 3 mg.
Paediatric population: Neonates and children up to 6 months of age: The use in children less than 6 months of age is not recommended as available data are limited.
Children over 6 months of age: Rectal administration: The total dose of midazolam, usually ranging from 0.3 to 0.5 mg/kg should be administered 15 to 30 minutes before induction of anaesthesia. 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.
IM administration: As IM injection is painful, this route should only be used in exceptional cases. Rectal administration should be preferred. However, a dose range from 0.08 to 0.2 mg/kg of midazolam administered IM has been shown to be effective and safe. In children between ages 1 and 15 years, proportionally higher doses are required than in adults in relation to body weight. 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. 
INDUCTION: Adults: If midazolam is used for induction of anaesthesia before other anaesthetic agents have been administered, the individual response is variable. The dose should be titrated to the desired effect according to the patient's age and clinical status. When midazolam is used before or in combination with other IV or inhalation agents for induction of anaesthesia, the initial dose of each agent should be significantly reduced, at times to as low as 25% of the usual initial dose of the individual agents. The desired level of anaesthesia is reached by stepwise titration. The IV induction dose of midazolam should be given slowly in increments. Each increment of not more than 5mg should be injected over 20 to 30 seconds allowing 2 minutes between successive increments.
In adults below the age of 60 years, an IV dose of 0.15 to 0.2 mg/kg will usually suffice. Non-premedicated adults below the age of 60 the dose usually require a higher dose (0.3 to 0.35 mg/kg IV).
If needed to complete induction, increments of approximately 25% of the patient's initial dose may be used. Induction may instead be completed with inhalational anaesthetics.
In resistant cases, a total dose of up to 0.6 mg/kg may be used for induction, but such larger doses may prolong recovery.
For Adults over 60 years of age, debilitated or chronically ill patients, the dose should be 0.1 to 0.2 mg/kg administered IV.
Non-premedicated adults over 60 years of age usually require more midazolam for induction; an initial dose of 0.15 to 0.3mg/kg is recommended. Non-premedicated patients with severe systemic disease or other debilitation usually require less midazolam for induction. An initial dose of 0.15 to 0.25mg/kg will usually suffice.
SEDATIVE COMPONENT IN COMBINED ANAESTHESIA: Adults: Midazolam can be given as a sedative component in combined anaesthesia by either further intermittent small IV doses (range between 0.03 and 0.1mg/kg) or continuous infusion of IV midazolam (range between 0.03 and 0.1 mg/kg/h) typically in combination with analgesics. The dose and the intervals between doses vary according to the patient's individual reaction.
In adults over 60 years of age, debilitated or chronically ill patients, lower maintenance doses will be required.
SEDATION IN INTENSIVE CARE UNITS (ICU): The desired level of sedation is reached by stepwise titration of midazolam followed by either continuous infusion or intermittent bolus, according to the clinical need, physical status, age and concomitant medication.
Adults: IV loading dose: 0.03 to 0.3 mg/kg should be given slowly in increments. Each increment of 1 to 2.5 mg should be injected over 20 to 30 seconds allowing 2 minutes between successive increments. In hypovolaemic, vasoconstricted, or hypothermic patients the loading dose should be reduced or omitted. When midazolam is given with potent analgesics, the latter should be administered first so that the sedative effects of midazolam can be safely titrated on top of any sedation caused by the analgesic.
IV maintenance dose: doses can range from 0.03 to 0.2 mg/kg/h. In hypovolaemic, vasoconstricted, or hypothermic patients the maintenance dose should be reduced. The level of sedation should be assessed regularly. With long-term sedation, tolerance may develop and the dose may have to be increased.
Children over 6 months of age: In intubated and ventilated paediatric patients, a loading dose of 0.05 to 0.2 mg/kg IV should be administered slowly over at least 2 to 3 minutes to establish the desired clinical effect. Midazolam should not be administered as a rapid intravenous dose. The loading dose is followed by a continuous IV infusion at 0.06 to 0.12 mg/kg/h (1 to 2 µg/kg/min). The rate of infusion can be increased or decreased (generally by 25% of the initial or subsequent infusion rate) as required or supplemental IV doses of midazolam can be administered to increase or maintain the desired effect.
When initiating an infusion with midazolam in haemodynamically compromised patients, the usual loading dose should be titrated in small increments and the patient monitored for haemodynamic instability, e.g., hypotension. These patients are also vulnerable to the respiratory depressant effects of midazolam and require careful monitoring of respiratory rate and oxygen saturation.
Neonates and children up to 6 months of age: Midazolam should be given as a continuous IV infusion, starting at 0.03 mg/kg/h (0.5 µg/kg/min) in neonates with a gestational age <32 weeks, or 0.06 mg/kg/h (1 µg/kg/min) in neonates with a gestational age >32 weeks and children up to 6 months.
Intravenous loading doses are not recommended in premature infants, neonates and children up to 6 months, rather the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels. The rate of infusion should be carefully and frequently reassessed, particularly after the first 24 hours so as to administer the lowest possible effective dose and reduce the potential for drug accumulation.
Careful monitoring of respiratory rate and oxygen saturation is required.
In premature infants, neonates and children less than 15kg of body weight, midazolam solutions with concentrations higher than 1mg/mL are not recommended. Higher concentrations should be diluted to 1 mg/mL.

Symptoms: Overdose symptoms essentially represent an increase of the pharmacological effects: somnolence, mental confusion, drowsiness and muscle relaxation or paradoxical excitement. The most serious symptoms would be areflexia, apnoea, hypotension, cardiorespiratory depression and coma.
Treatment: In most of the cases, simply monitor the patient's vital signs. For overdose treatment, special attention should be paid to cardiorespiratory function at the intensive care unit. Flumazenil, a benzodiazepine antagonist is indicated for serious overdose accompanied by coma or respiratory depression. Flumazenil is to be used with extreme caution in the presence of mixed overdose and in patients with epilepsy already treated with benzodiazepines. Flumazenil should not be used in patients receiving tricyclic antidepressants, or epileptogenic drugs, or in patients with ECG alterations (QRS or QT prolongation).

Hypersensitivity to benzodiazepines or to any of the excipients of the product.

Midazolam should be administered only in a setting with monitoring and cardiopulmonary resuscitation equipment available, suitable for the corresponding age and size, as IV administration of midazolam may depress the myocardial contractility and cause apnea. Severe cardiorespiratory adverse events have been reported. These have included respiratory depression, apnoea, 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.
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.
Special caution should be exercised when administering midazolam to high- risk patients: adults over 60 years of age, chronically ill or debilitated patients, patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or impaired cardiac function, paediatric patients especially those with cardiovascular instability.
These high-risk patients require lower dosages and should be continuously monitored for early signs of alterations of vital functions.
Benzodiazepines should be used with caution patients with a history of alcohol or drug abuse.
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.
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. 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 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: headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, rebound insomnia, mood changes, hallucinations and seizures. Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, it is recommended to decrease doses gradually.
Amnesia: Anterograde amnesia may occur at therapeutic doses (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. In the event of these reactions, 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. Midazolam elimination may also be delayed in patients with liver dysfunction, low cardiac output and in neonates.
Premature infants and neonates: Due to an increased risk of apnoea, extreme caution is advised when sedating neonates and premature infants. Careful monitoring of respiratory rate and oxygen saturation is required. Rapid injection should be avoided in the neonatal population.
Adverse haemodynamic events have been reported in paediatric patients with cardiovascular instability; rapid intravenous administration should be avoided in this population.

Pregnancy: Insufficient data are available on midazolam to assess its safety during pregnancy. Animal studies do not indicate a teratogenic effect, but fetotoxicity was observed as with other benzodiazepines.
No data on exposed pregnancies are available for the first two trimesters of pregnancy.
The administration of high doses of midazolam in the last trimester of pregnancy, during labour or when used as an induction agent of anaesthesia for caesarean section has been reported to produce maternal or foetal adverse effects (inhalation risk in mother, irregularities in the foetal heart rate, hypotonia, poor sucking, hypothermia and respiratory depression in the neonate).
Moreover, infants born from mothers who received benzodiazepines in the latter stage of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
Consequently, midazolam should not be used during pregnancy unless clearly necessary. It is preferable to avoid using it for caesarean.
The risk for neonate should be taken into account in case of administration of midazolam for any surgery near the term.
Breastfeeding: Midazolam passes in low quantities into breast milk. Nursing mothers should be advised to discontinue breast-feeding for 24 hours following administration of midazolam.

Skin and subcutaneous tissue disorders: skin rash, urticarial, pruritus.
Central and peripheral nervous system and psychiatric disorders: somnolence and prolonged sedation, alertness decreased, confusional state, euphoric mood, hallucinations, fatigue, headache, dizziness, ataxia, postoperative sedation and anterograde amnesia, the duration of which is directly related to the administered dose. Anterograde amnesia may persist at the end of the procedure and in isolated cases prolonged amnesia has been reported.
Paradoxical reactions such as agitation, involuntary movements (including tonic/clonic seizures and muscle tremor), hyperactivity, hostility, rage reaction, aggressiveness, paroxysmal excitement and assault, particularly in children and elderly, have been reported.
Seizures have been more frequently reported in neonates and premature infants.
The use of midazolam-even therapeutic doses-may enhance the development of a physical dependence after a prolonged IV administration; the abrupt drug discontinuation may be accompanied by withdrawal symptoms, such as seizures.
Gastrointestinal disorders: nausea, vomiting, constipation, hiccup and dry mouth.
Cardiorespiratory disorders: severe cardiorespiratory adverse events; respiratory depression, apnea, respiratory arrest or cardiac arrest, hypotension, heart rate disorder, vasodilator effects, dyspnea and glottis spasm Life-threatening incidents are more likely to occur in case of adults older than 60 years old and of those patients with prior respiratory failure or impairment of cardiac function, particularly when the injection is administered too rapidly or when a high dose is applied.
General disorders: general hypersensitivity reactions: skin reactions, cardiovascular reactions, bronchospasm, anaphylactic shock.
Administration site disorders: erythema and pain on injection site, thrombophlebitis and thrombosis.

Midazolam is metabolized almost exclusively by other 3A4 of the cytochrome P450 (CYP450). The inhibitors and the inducers of CYP3A4, but also other active ingredients, may interact with midazolam.
As midazolam has a significant first-step effect, parenterally administered midazolam would theoretically be subject to less metabolic interactions and the relevant clinical responses would be limited.
ITRACONAZOLE, FLUCONAZOLE AND KETOCONAZOLE: When midazolam was administered as a single dose by bolus injection for short-term sedation, the effect of midazolam was neither increased nor extended by itraconazole at a clinically significant level, so there is no need to reduce the dosage. However, the administration of high doses on long-term infusions of midazolam to patients treated itraconazole, fluconazole or ketoconazole, for example, during their stay at ICU, may cause long-term hypnotic effects, delay recover and produce respiratory depression, which requires to adapt the doses.
VERAPAMIL AND DILTIAZEM: No in vivo interaction studies have been made with intravenous midazolam and verapamil or diltiazem. Although one cannot expect clinically significant interactions when using midazolam for short-term sedation, one must be cautious when administering midazolam concomitantly with verapamil or diltiazem by the intravenous route.
MACROLIDE ANTIBIOTICS: ERYTHROMYCIN AND CLARITHROMYCIN: When midazolam was administered as a single dose by bolus injection for short-term sedation, the effect of midazolam was neither increased nor extended by erythromycin at a clinically significant level, although there was a significant reduction of the plasma clearance. Caution is recommended when midazolam is given concomitantly with erythromycin or clarithromycin by the intravenous route. No clinically significant interactions have been shown of midazolam with other macrolide antibiotics.
CIMETIDINE AND RANITIDINE: The co-administration of cimetidine (in doses equal to or higher than 800 mg/day) and intravenous midazolam slightly increased the plasma concentration of midazolam –in a state of balance- which could delay recovery, whereas co-administration of ranitidine had no effect. Cimetidine and ranitidine did not affect the pharmacokinetics of oral midazolam. These data suggest that midazolam may be administered intravenously with the standard dosage of cimetidine (that is, 400 mg/day) and ranitidine without titrating their dosage.
SAQINAVIR: Co-administration of a single intravenous dose of 0.05 mg/kg of midazolam after 3 or 5 days of saquinavir administration (1,200 mg three times per day) to 12 healthy volunteers reduced midazolam elimination by 56% and increased the elimination half-life from 4.1 to 9.5 hours. Saquinavir intensified only the subjective effects of midazolam (visual analog scale with the item “global effect” of the medicine).
Thus, a single intravenous midazolam bolus dose can be given in combination with saquinavir. Nevertheless, during a prolonged infusion of midazolam, it is recommended to reduce the total dose so as not to delay the recovery.
OTHER PROTEASE INHIBITORS: RITONAVIR, INDINAVIR, NELFINAVIR AND AMPRENAVIR: No in vivo interaction studies have been made with intravenous midazolam and other protease inhibitors. Considering that saquinavir is characterized by the poorest inhibitory potency of CYP3A4 among all protease inhibitors, the midazolam dose must be systematically reduced during prolonged infusion when administered concomitantly with protease inhibitors other than saquinavir.
CNS DEPRESSANTS: Other sedative drugs may increase midazolam effects. The pharmacological groups of CNS depressants are the opiates (when used as analgesics, antitussives or replacement therapy), antipsychotics, other benzodiazepines used as anxiolytics or hypnotics, phenobarbital, sedative antidepressants, antihistamines and centrally antihypertensive drugs.
Additional sedation must be considered when midazolam is combined with other sedatives. Moreover, an additional increase of the respiratory depression should be monitored in case of concomitant treatment with opiates, phenobarbital or benzodiazepines.
Alcohol may considerably enhance the sedative effect of midazolam. Alcohol consumption must be avoided when midazolam is administered.
OTHER INTERACTIONS: IV administration of midazolam decreases the minimum alveolar concentration (MAC) of inhalational anesthetics required for general anesthetics.

Store at temperatures not exceeding 30°C. Do not freeze. Precipitate may be formed which will dissolve upon agitation at room temperature.

Hypnotics & Sedatives

N05CD08 - midazolam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.

DD, Rx