New Zealand Data Sheet

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Hypnovel 150108 






New Zealand Data Sheet 





Midazolam 5mg/5ml and 15mg/3ml ampoules 


Short-acting benzodiazepine for premedication, sedation, induction and maintenance of 





Active Ingredient 

Midazolam as hydrochloride. 


Ampoules 5mg/5ml and 15mg/3ml midazolam for i.v., i.m., intranasal, oral and rectal administration. 



Sodium chloride (9 mg/ml sodium chloride in the 5mg/5ml Hypnovel ampoule, 5mg/ml sodium chloride 

in the 15mg/3ml Hypnovel ampoule), hydrochloric acid, sodium hydroxide, water for injection. 



Clear to slightly yellow liquid, odourless and practically free from particles in colourless glass 



Pharmacological Properties and Effects 


Midazolam, the active ingredient of Hypnovel, 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 the active ingredient of Hypnovel to form water-soluble 

salts with acids.  These produce a stable and well tolerated injection solution. 


The pharmacological action of midazolam is characterized by rapid onset and, because of rapid 

metabolic transformation, short duration.  Because of its low toxicity, midazolam has a wide therapeutic 



Hypnovel has a very rapid sedative and sleep-inducing effect of pronounced intensity.  It also exerts an 

anxiolytic, an anticonvulsant and a muscle-relaxant effect. 


After i.m. or i.v. administration anterograde amnesia of short duration occurs (the patient does not 

recall events that occurred during the peak of activity of the compound).  





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Absorption after i.m. injection  

Absorption of midazolam from the muscle tissue is rapid and complete.  Maximum plasma 

concentrations are reached within 30 minutes.  The absolute bioavailability after i.m. injection is over 



Absorption after rectal administration  

After rectal administration midazolam is absorbed quickly. Maximum plasma concentration is reached 

in about 30 minutes. The absolute bioavailability is about 50%.  


Absorption after intranasal administration 

Midazolam is absorbed quickly.  Mean peak plasma concentrations are reached within 10.2 to 12.6 

minutes.  The bioavailability is between 55 and 57%. 


Absorption after oral administration 

Oral midazolam is absorbed rapidly from the gastrointestinal tract and undergoes extensive first-pass 

hepatic metabolism.  Peak plasma concentrations are reached within 1 hour.  Bioavailability is between 

40 and 50%. 



When midazolam is injected i.v., 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% of midazolam 

is bound to plasma proteins. The major fraction 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 foetal circulation. Small quantities of midazolam 

are found in human milk. 



Midazolam is almost entirely eliminated by biotransformation.  Midazolam is hydroxylated by the 

cytochrome P450  3A4 isozyme. 


-hydroxymidazolam is the major urinary and plasma metabolite.  

Plasma concentrations of 


-hydroxymidazolam are 12% of those of the parent compound. The fraction 

of the dose extracted by the liver has been estimated to be 30-60%. 


-hydroxymidazolam is 

pharmacologically active, but contributes only minimally (about 10%) to the effects of intravenous 

midazolam. There is no evidence of a genetic polymorphism in the oxidative metabolism of midazolam 

(see Interactions).  



In healthy volunteers, the elimination half-life is between 1.5 -  2.5 hours.  Plasma clearance is in the 

range of 300-500  ml/min. 60-80% of the dose is excreted in urine as glucuroconjugated 



hydroxymidazolam.  Less than 1% of the dose is recovered in urine as unchanged drug. The 

elimination half-life of the metabolite is shorter than 1 hour. When midazolam is given by i.v. infusion, 

its elimination kinetics do not differ from those following bolus injection. 




Hypnovel 150108 






Pharmacokinetics in Special Populations  


In adults over 60 years of age, the elimination half-life may be prolonged up to four times. 



The rate of rectal absorption in children is similar to that in adults. However, the elimination half-life 

(t½) after i.v. and rectal administration is shorter in children 3-10 years as compared with that in adults. 

The difference is consistent with an increased metabolic clearance in children.  



In neonates the elimination half-life is on average 6-12 hours, probably due to liver immaturity and the 

clearance is reduced (see Precautions). 


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 (see Precautions). 


Patients with renal impairment 

The elimination half-life in patients with chronic renal failure is similar to that in healthy volunteers. 


Critically ill patients 

The elimination half-life of midazolam is prolonged in the critically ill. 


Patients with cardiac insufficiency  

The elimination half-life is longer in patients with congestive heart failure compared with that in healthy 

subjects (see Precautions). 




Premedication before induction of anaesthesia (i.m. or, especially in children, rectal, intranasal or oral 



Conscious sedation before diagnostic or surgical interventions carried out under local anaesthesia (i.v. 

administration), or in children intranasal or oral administration. 


Long-term sedation in intensive care units (i.v. administration as bolus injection or continuous infusion). 


Induction and maintenance of anaesthesia.  As an induction agent in inhalation anaesthesia or a sleep-

inducing component in combined anaesthesia, including total intravenous anaesthesia (i.v. injection, 

i.v. infusion). 


Ataralgesia in combination with ketamine in children (i.m. administration). 


Dosage and Administration 


In the case of elderly patients with organic cerebral changes or impaired cardiac  and respiratory 

function, the dosage should be determined with caution, the special factors relating to each patient 

being taken into consideration. 




Hypnovel 150108 






Initial and subsequent intravenous injections must be given slowly (approximately 2.5mg in 10 seconds 

for  induction of anaesthesia and 1mg in 30 seconds for conscious sedation).  The medicine takes 

effect about two minutes after the injection is started. 


Premedication before an Operation 

Intramuscular administration 

In patients suffering from pain before an intervention. 


Administration alone or in combination with anticholinergics and possibly analgesics. 

These doses should be administered about 30 minutes before induction of anaesthesia. 


Adults:    0.07-0.10 mg per kg bodyweight i.m. according to age and general condition of the patient.  

Usual dosage about 5mg. 


Children:  proportionately higher doses are required than in adults in relation to bodyweight (0.15-0.20 

mg per kg bodyweight i.m.). 


Elderly and debilitated patients:  0.025 - 0.05 mg/kg bodyweight i.m. 


Rectal administration 

Children:  for preoperative sedation. Rectal administration of the ampoule solution by means of a 

plastic applicator fixed on the end of a syringe, 0.35-0.45 mg/kg bodyweight 20-30 minutes before 

induction of general anaesthesia.  If the volume to be administered is too small, water may be added 

up to a total volume of 10 ml. 


Intranasal administration 

Children:  0.2mg/kg, 10-15 minutes prior to anaesthesia. 


Oral administration 

Children:  0.5mg / kg, 15-30 minutes prior to anaesthesia. 


Conscious Sedation  

Intravenous conscious sedation 

For conscious sedation in diagnostic or surgical interventions carried out under local anaesthesia. 


Adults:  the initial dose should not exceed 2.5mg i.v. 5-10 minutes before the beginning of the 

operation.  Further doses of 1mg may be given as necessary.  A total dose greater than 5mg is not 

usually necessary to reach the desired endpoint.  In cases of severe illness, particularly if the patient is 

in poor general condition or of advanced age, the initial dose must be reduced to 1-1.5mg.  Total doses 

greater than 3.5mg are not usually necessary. 


Intranasal conscious sedation 

Children:  0.2mg / kg, 10-15 minutes before the intervention. 


Oral conscious sedation 

Children:  0.2 - 0.5mg / kg, 15-30 minutes before the intervention. 





Hypnovel 150108 






Sedation in Intensive Care Units 

Intravenous sedation 

For sedation in ICU, the dosage should be individualised and Hypnovel titrated to the desired state of 

sedation according to the clinical need, physical status, age, concomitant medication. 



Loading dose:  0.03 - 0.3 mg/kg. 


Maintenance dose:  0.03  -  0.2 mg/kg/hr.  The dosage should be reduced or the loading dose should 

even be omitted in hypovolemic, vasoconstricted and hypothermic patients. 


Induction and Maintenance of Anaesthesia 

Intravenous injection 


Induction:  the dose is 10-15 mg i.v. in combination with analgesics.  A sufficiently deep level of sleep is 

generally achieved after 2-3 minutes. 


Maintenance:  for maintenance of the desired level of unconsciousness, further small doses should be 

injected i.v.  The dose and the intervals between doses vary according to the individual patient's 

reaction.  Alternatively, Hypnovel can be administered by continuous infusion. 


Intravenous continuous infusion 

Adults:  for intravenous anaesthesia combined with ketamine, 0.03 - 0.1 mg/kg/hr; narcotics, 0.03 - 0.3 

mg/kg/hr.  High-risk surgical patients, elderly and debilitated patients require lower dosages. 


Intramuscular administration 

Children:  a combination of the sleep-inducing and amnesia-inducing Hypnovel with ketamine 

(ataralgesia) is recommended.  Hypnovel i.m. (0.15-0.20 mg per kg bodyweight) in combination with 

50-100 mg ketamine i.m. (4-8 mg per kg bodyweight).  A sufficiently deep level of sleep is generally 

achieved after 2-3 minutes. 


Rectal administration 

Children:  see Premedication before an Operation. 


Special Dosage Instructions 

When Hypnovel is given with potent analgesics, the latter should be administered first so that the 

sedative effects of Hypnovel can be safely titrated on top of any sedation caused by the analgesic. 


Compatibility with infusion solutions. The Hypnovel ampoule solution can be diluted with sodium 

chloride 0.9%, dextrose 5% and 10%, levulose 5%, Ringer's solution and Hartmann's solution in a 

mixing ratio of 15 mg midazolam per 100-1,000 ml infusion solution.  These solutions remain physically 

and chemically stable for 24 hours at room temperature (or three days at 5




When administered orally, the bitter taste of Hypnovel injection may be masked by small quantities of 

apple juice, sweetened fruit syrup or powdered soft drink. 






Hypnovel 150108 








Use of this medicine in patients with known hypersensitivity to benzodiazepines or to any component of 

the product. 




Hypnovel ampoules should be used only when age-  and size-appropriate resuscitation facilities are 

available, as i.v. administration of Hypnovel may depress myocardial contractility and cause apnoea. 

Severe cardiorespiratory adverse events have occurred on rare occasions. These have included 

respiratory depression, apnoea, respiratory arrest and/or cardiac arrest. Such life-threatening incidents 

are more likely to occur in adults over 60 years of age, those with pre-existing respiratory insufficiency 

or impaired cardiac function and paediatric patients with cardiovascular instability, particularly when the 

injection is given too rapidly or when a high dosage is administered. 



When Hypnovel is used for premedication, adequate observation of the patient after administration is 

mandatory as interindividual sensitivity varies and symptoms of overdose may occur.  


High-Risk Patients 

Special caution should be exercised when administering Hypnovel parenterally to patients representing 

a higher risk group:  



adults over 60 years of age 



debilitated or chronically ill patients 



patients with impaired respiratory function 



patients with impaired kidney function, impaired hepatic function or with impaired cardiac 




paediatric patients with cardiovascular instability 


These higher-risk patients require lower dosages (see Dosage and Administration) and should be 

continuously monitored for early signs of alterations of vital functions. 



Some loss of efficacy has been reported when Hypnovel has been used as long-term sedation in 

intensive care units (ICU). 



When Hypnovel is used in long-term sedation in ICU, it should be borne in mind that physical 

dependence on Hypnovel 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 Hypnovel ampoules 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 that the 

dose is decreased gradually. 




Hypnovel 150108 






Concomitant use of Alcohol/CNS Depressants 

The concomitant use of Hypnovel with alcohol and/or CNS depressants should be avoided. Such 

concomitant use has the potential to increase the clinical effects of Hypnovel possibly including severe 

sedation, clinically relevant respiratory and/or cardiovascular depression. 


Medical History of Alcohol or Drug Abuse 

Hypnovel should be avoided in patients with a medical history of alcohol or drug abuse. 



Hypnovel 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.  


Discharging Criteria 

After receiving Hypnovel parenterally, patients should be discharged from hospital or consulting room 

only  when recommended by the treating physician and if accompanied by an attendant.  It is 

recommended that the patient is accompanied when returning home after discharge. 


"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 Hypnovel. 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  the elderly. Should such symptoms 

suggestive of a paradoxical reaction occur, the response to Hypnovel should be evaluated before 



Altered Elimination of midazolam 

Elimination of midazolam may be altered in patients receiving compounds that inhibit or induce certain 

hepatic enzymes (particularly cytochrome P450  3A4)  and the dose of midazolam may need to be 

adjusted accordingly (see Interactions). 


When midazolam is given intravenously for a prolonged period and in combination with saquinavir, an 

initial dose reduction of midazolam of 50% is recommended (see Interactions). 


It is advisable to lower doses of intravenous midazolam when co-administered with erythromycin (see 



Displacement of midazolam from its plasma protein binding sites by sodium valproate may increase 

the response to midazolam. Care should be taken to adjust the midazolam dose in patients with 

epilepsy on treatment with sodium valproate (see Interactions). 


Elimination of midazolam may also be delayed, in patients with liver dysfunction, low cardiac output 

and in neonates (see Pharmacokinetics in special populations).  


Pre-term Infants and Neonates 

Due to an increased risk of apnoea, extreme caution is advised when sedating pre-term and former 

pre-term patients whose trachea is not intubated. 


Rapid injection should be avoided in the neonatal population. 




Hypnovel 150108 






The neonate also has reduced and/or immature organ function and is also vulnerable to profound 

and/or prolonged respiratory effects of Hypnovel. Therefore, careful monitoring of respiratory rate and 

oxygen saturation is required. 


Paediatric Patients  

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 Pre-term Infants and Neonates above). 


Adverse haemodynamic events have been reported in paediatric patients with cardiovascular 

instability; rapid intravenous administration should be avoided in this population. 


Effects on Ability to Drive or Use Machines 

Sedation, amnesia, impaired concentration and impaired muscular function adversely affect the ability 

to drive or use machines. Prior to receiving Hypnovel, the patient should be warned not to drive a 

vehicle or operate a machine until completely recovered. 



As with any substance with CNS depressant and/or muscle-relaxant properties, particular care should 

be taken when administering Hypnovel to a patient with myasthenia gravis, owing to pre-existing 

muscle weakness. 


Pregnancy and Nursing Mothers  


Insufficient data are available on midazolam to assess its safety during pregnancy. Benzodiazepines 

should be avoided during pregnancy unless there is no safer alternative. The administration of 

midazolam in the last trimester of pregnancy or at high doses during labour has been reported to 

produce irregularities in the foetal heart rate, hypotonia, poor sucking and hypothermia and moderate 

respiratory depression in the neonate. Moreover, infants born to mothers who received 

benzodiazepines  chronically during the latter stage of pregnancy may have developed physical 

dependence and may be at some risk of developing withdrawal symptoms in the postnatal period. 


Since midazolam passes into breast milk, Hypnovel should not be administered to breast-feeding 



Adverse Effects  


The following adverse effects have been reported to occur post-marketing when Hypnovel is injected: 


Central and peripheral nervous system and psychiatric disorders 

Drowsiness and prolonged sedation, reduced alertness, confusion, euphoria, hallucinations, fatigue, 

headache, dizziness, ataxia, postoperative sedation,  anterograde amnesia, the duration of which is 

directly related to the administered dose. Anterograde amnesia may still be present at the end of the 

procedure and in isolated cases prolonged amnesia has been reported. 





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Paradoxical reactions such as agitation, involuntary movements (including tonic/clonic movements and 

muscle tremor), hyperactivity, hostility, rage reaction, aggressiveness, paroxysmal excitement and 

assault, have been reported, particularly among children and the elderly.  


Convulsions have been reported in premature infants and neonates. 



Use of Hypnovel - even in therapeutic doses - may lead to the development of physical dependence. 

After prolonged i.v. administration, discontinuation, especially abrupt discontinuation of the product, 

may be accompanied by withdrawal symptoms including withdrawal convulsions. 


Gastrointestinal system disorders 

Nausea, vomiting, constipation, dry mouth. 


Cardiorespiratory disorders 

Severe cardiorespiratory adverse events have occurred on rare occasions. These have included 

respiratory depression, apnoea, respiratory arrest and/or cardiac arrest. Such life-threatening incidents 

are more likely to occur in adults over 60 years of age and those with pre-existing respiratory 

insufficiency or impaired cardiac function, particularly when the injection is given too rapidly or when a 

high dosage is administered (see Precautions).  


The following other cardiorespiratory adverse events have been reported: hypotension, slight increase 

in heart rate,  bradycardia, vasodilating effects, dyspnoea  and  hiccough. In isolated cases 

laryngospasm has occurred following injection of Hypnovel. 


Skin and appendages disorders 

Skin rash, urticarial reaction, pruritus. 


Immune System Disorders 

Generalised hypersensitivity  reactions (skin reactions, cardiovascular reactions, bronchospasm), 

angioedema, anaphylactic shock. 


Local reactions 

Erythema and pain on injection site, thrombophlebitis, thrombosis. 


Injury, poisoning and procedural complications 

There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those 

taking concomitant sedatives (including alcoholic beverages) and in the elderly. 




The metabolism of midazolam is predominantly mediated by cytochrome P450  3A4 (CYP3A4) 

isozyme. Approximately 25 % of the total cytochrome P450 system in the adult liver is from the 

CYP3A4 subfamily. Inhibitors (see Precautions) and inducers  of this isozyme may lead to interaction 

with midazolam. 





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Interactions Studies conducted with Hypnovel Ampoules 

CYP3A4 inhibitors 

Azole antifungals 

Ketoconazole  increased the plasma concentration of intravenous midazolam by 5-fold while the 

terminal half-life increased by about 3-fold. If parenteral midazolam is co-administered with the strong 

CYP3A inhibitor ketoconazole, it should be done in an intensive care unit (ICU) or similar setting which 

ensures close clinical monitoring and appropriate medical management in case of respiratory 

depression  and/or prolonged sedation. Staggered dosing and dosage  adjustment should be 

considered, especially if more than a single iv dose of midazolam is administered. 


Fluconazole and itraconazole both increased the plasma concentrations of intravenous midazolam by  

2 – 3-folds associated with an increase in terminal half-life by 2.4-fold for itraconazole and 1.5-fold for 

fluconazole, respectively. 


Posaconazole increased the plasma concentrations of intravenous midazolam by about 2-fold 



Co-administration of Hypnovel and erythromycin prolonged the elimination half-life of midazolam from 

3.5 to 6.2 hours. Although only relatively minor pharmacodynamic changes were observed, it is 

advised to adjust doses of intravenous midazolam, especially if high doses are being administered 

(see Precautions). 


Cimetidine and ranitidine 

Cimetidine increased the steady-state plasma concentration of midazolam by 26%, whereas ranitidine 

had no effect. 


Co-administration of midazolam and cimetidine or ranitidine had no clinically significant effect on the 

pharmacokinetics and pharmacodynamics of midazolam. These data indicate that intravenous 

midazolam can be used in usual doses with cimetidine and ranitidine and dosage adjustment is  not 




There is no pharmacokinetic and pharmacodynamic interaction between cyclosporin and midazolam. 

Therefore, the dosage of midazolam needs no adjustment when given concomitantly with cyclosporin. 



Nitrendipine did not affect the pharmacokinetics and pharmacodynamics of midazolam. Both 

medicines can be given concomitantly and no dosage adjustment of midazolam is required. 


HIV Protease Inhibitors 

Saquinavir and other HIV protease inhibitors:  Upon co-administration with ritonavir boosted lopinavir, 

the plasma concentrations of intravenous midazolam increased by 5.4-fold, associated with a similar 

increase in terminal half-life.  If parenteral midazolam is co-administered with HIV protease inhibitors, 

treatment setting should follow the description in the section above for ketoconazole within azole 



(see Precautions).



Oral contraceptives 

The pharmacokinetics of intramuscular midazolam was not affected by the use of oral contraceptives.  

Both medicines can be given concomitantly and no dosage adjustment of midazolam is required. 





Hypnovel 150108 







Other interactions 

Sodium valproate  

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 (see Precautions).  



Midazolam had no effect on the plasma protein binding of lidocaine in patients undergoing anti-

arrhythmic therapy or regional anaesthesia with lidocaine. 


Alcohol may enhance the sedative effect of midazolam. 


The i.v. administration of Hypnovel decreases the minimum alveolar concentration (MAC) of halothane 

required for general anaesthesia. 





The symptoms of overdose are mainly an intensification of the pharmacological effects; drowsiness, 

mental confusion, lethargy and muscle relaxation or paradoxical excitation. As with other 

benzodiazepines, overdosage should not present a threat to life unless combined with other CNS 

depressants including alcohol. More serious symptoms would be areflexia, hypotension, 

cardiorespiratory depression, apnoea and, rarely, coma.  Coma, if it occurs, usually lasts a few hours 

but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory 

depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the 

effects of other central nervous system depressants, including alcohol. 



In most cases only observation of vital functions is required  and initiate  supportive measures as 

indicated by the patient’s clinical state. In the management of overdose special attention should be 

paid to the respiratory and cardiovascular functions in intensive care.  


If taken orally further absorption should be prevented using an appropriate method (e.g. treatment 

within 1-2 hours with activated charcoal). If activated charcoal is used airway protection is imperative 

for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a 

routine measure. 


If CNS depression is severe,  consider the use of  the benzodiazepine antagonist Anexate® (active 

ingredient: flumazenil). This should only be administered under closely monitored conditions. It has a 

short half-life (about an hour); therefore patients administered flumazenil will require monitoring after its 

effects have worn off. Flumazenil is to be used with extreme caution  in the presence of drugs that 

reduce seizure threshold (e.g. tricyclic antidepressants). 


Special Remarks 



Do not dilute Hypnovel ampoule solutions with macrodex 6% in dextrose  (see Special Dosage 





Hypnovel 150108 







Do not mix Hypnovel ampoule solutions in alkaline injections. Midazolam precipitates in sodium 




Store below 30


C (approved to 35




Keep the ampoules in the outer carton in order to protect from light. 


Ampoules are for use in one patient only. 


Hypnovel ampoules should not be frozen because they can burst. Furthermore, precipitation can occur 

which dissolves on shaking at room temperature. 



This medicine should not be used after the expiry date shown on the pack. 


Medicine Classification 


Controlled Drug (C5) 


Package Quantities 


Ampoules, 5mg/5ml 


Ampoules, 15mg/3ml 



Name and Address 


Roche Products (New Zealand) Ltd 

PO Box 109113 

Newmarket, Auckland 1149 


Medical enquiries: 

0800 656 464 


Date of Preparation 


8 January 2015 



Document Outline

  • New Zealand Data Sheet
  • Hypnovel®
    • Midazolam 5mg/5ml and 15mg/3ml ampoules
  • Composition
    • Active Ingredient
    • Excipients
    • Appearance
  • Pharmacological Properties and Effects
  • Pharmacokinetics
    • Absorption
      • Absorption after i.m. injection
      • Absorption after rectal administration
      • Absorption after intranasal administration
      • Absorption after oral administration
    • Distribution
    • Metabolism
    • Elimination
    • Pharmacokinetics in Special Populations
      • Elderly
      • Children
      • Neonates
      • Patients with hepatic impairment
      • Patients with renal impairment
      • Critically ill patients
      • Patients with cardiac insufficiency
  • Indications
  • Dosage and Administration
    • Premedication before an Operation
      • Intramuscular administration
      • Rectal administration
      • Intranasal administration
      • Oral administration
    • Conscious Sedation
      • Intravenous conscious sedation
      • Intranasal conscious sedation
      • Oral conscious sedation
    • Sedation in Intensive Care Units
      • Intravenous sedation
    • Induction and Maintenance of Anaesthesia
      • Intravenous injection
      • Intravenous continuous infusion
      • Intramuscular administration
      • Rectal administration
    • Special Dosage Instructions
  • Contraindications
  • Precautions
    • Premedication
    • Tolerance
    • Dependence
    • Withdrawal Symptoms
    • Amnesia
    • "Paradoxical" Reactions
    • Pre-term Infants and Neonates
    • Paediatric Patients
    • Effects on Ability to Drive or Use Machines
  • Pregnancy and Nursing Mothers
  • Adverse Effects
    • Central and peripheral nervous system and psychiatric disorders
    • Gastrointestinal system disorders
    • Cardiorespiratory disorders
    • Skin and appendages disorders
    • Immune System Disorders
    • Local reactions
  • Interactions
    • Interactions Studies conducted with Hypnovel Ampoules
      • CYP3A4 inhibitors
        • Azole antifungals
        • Ketoconazole increased the plasma concentration of intravenous midazolam by 5-fold while the terminal half-life increased by about 3-fold. If parenteral midazolam is co-administered with the strong CYP3A inhibitor ketoconazole, it should be done in an...
        • Erythromycin
        • Cimetidine and ranitidine
        • Nitrendipine
        • HIV Protease Inhibitors
        • Saquinavir and other HIV protease inhibitors: Upon co-administration with ritonavir boosted lopinavir, the plasma concentrations of intravenous midazolam increased by 5.4-fold, associated with a similar increase in terminal half-life. If parenteral mi...
        • Oral contraceptives
      • Other interactions
        • Sodium valproate
        • Lidocaine
  • Overdosage
    • Symptoms
    • Treatment
  • Special Remarks
    • Incompatibilities
    • Storage
    • Stability
  • Medicine Classification
  • Package Quantities
  • Name and Address
  • Date of Preparation

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