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MIDAZOLAM 2MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): MIDAZOLAM

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Midazolam 2mg/ml Solution for Injection or Infusion
Midazolam 5mg/ml Solution for Injection or Infusion
Midazolam
• regularly take recreational drugs or you have had
problems with drug use in the past
• are pregnant or think you may be pregnant (see
‘Pregnancy and breast-feeding’).

Read all of this leaflet carefully before you start
using this medicine because it contains important
information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor
or nurse.
- If you get any side effects, talk to your doctor or nurse.
This includes any possible side effects not listed in this
leaflet. See section 4.
The name of your medicine is Midazolam Solution for
Injection or Infusion. In the rest of this leaflet it is called
Midazolam Injection.
What is in this leaflet:
1. What Midazolam Injection is and what it is used for
2. What you need to know before you are given
Midazolam Injection
3. How Midazolam Injection should be given
4. Possible side effects
5. How to store Midazolam Injection
6. Contents of the pack and other information
1. WHAT MIDAZOLAM INJECTION IS AND WHAT IT
IS USED FOR
Midazolam belongs to a group of medicines known as
benzodiazepines. It is a short- acting medicine that is
used to induce sedation (a very relaxed state of calm,
drowsiness or sleep) and relieves anxiety and muscle
tension.
This medicine is used for:
• conscious sedation (an awake but very relaxed state
of calm or drowsiness during a medical test or
procedure) in adults and children.
• sedation of adults and children, in intensive care units.
• anaesthesia in adults, used alone or with other
medicines.
• premedication (medicine used to cause relaxation,
calm and drowsiness before an anaesthetic) in adults
and children.
2. WHAT YOU NEED TO KNOW BEFORE YOU ARE
GIVEN MIDAZOLAM INJECTION
You should not be given Midazolam Injection if you:
• are allergic to midazolam or any of the other
ingredients of this medicine (listed in section 6)
• are allergic to other benzodiazepine medicines, such
as diazepam or nitrazepam
• have severe breathing problems and you are going
to have this medicine for conscious sedation
• have severe liver problems.
If any of the above statements apply to you, you should not
be given Midazolam Injection. If you are not sure, talk to
your doctor or nurse before you are given this medicine.
Warnings and precautions
Before you are given Midazolam Injection, let your
doctor or nurse know if you:
• are over 60 years of age
• have a long term illness (such as breathing problems
or kidney, liver or heart problems)
• are debilitated (have an illness that makes you feel
very weak, run down and short of energy)
• have myasthenia gravis (a neuromuscular disease
causing muscle weakness)
• have a personality disorder, depression, aggressive
tendencies, or if you feel suicidal.
• regularly drink large amounts of alcohol or you have
had problems with alcohol use in the past

If any of the above apply to you, or if you are not sure, talk Do not breast-feed for 24 hours after being given
to your doctor or nurse before you are given this medicine. Midazolam Injection. This is because midazolam may
pass into your breast milk.
Special care should be taken if the patient is in a coma.
Driving and using machines
You should not drive or operate machinery for at least
Children and babies
twelve hours after receiving Midazolam Injection. You
If your child is going to be given this medicine:
• It is particularly important to tell your doctor or nurse if should speak to your doctor about driving if you also
your child has cardiovascular disease (heart problems). take other medicines that can cause sedation.
Your child will be carefully monitored and the dose will
The medicine can affect your ability to drive as it may
be adjusted specially.
• Children must be carefully monitored. For infants and make you sleepy or dizzy.
babies under 6 months this will include monitoring of • Do not drive while taking this medicine until you know
how it affects you.
breathing and oxygen levels.
• It is an offence to drive if this medicine affects your
ability to drive.
Other medicines and Midazolam Injection
Tell your doctor or nurse if you are taking, have recently • However, you would not be committing an offence if:
o The medicine has been prescribed to treat a
taken or might take any other medicines.
medical or dental problem and
o You have taken it according to the instructions
This is extremely important, as using more than one
given by the prescriber or in the information
medicine at the same time can strengthen or weaken
provided with the medicine and
the effect of the medicines involved.
o It was not affecting your ability to drive safely
In particular, tell your doctor or nurse if you are taking
Talk to your doctor or pharmacist if you are not sure
any of the following medicines:
• tranquilisers (for anxiety or to help you sleep)
whether it is safe for you to drive while taking this
• hypnotics (medicines to make you sleep)
medicine.
• sedatives (to make you feel calm or sleepy)
• antidepressants (medicines for depression)
Midazolam Injection contains sodium
• narcotic analgesics (very strong pain killers,
This medicinal product contains 3.3mg sodium per 1 ml.
e.g. fentanyl)
• antihistamines (used to treat allergies)
3. HOW MIDAZOLAM INJECTION SHOULD BE GIVEN
• medicines to treat fungal infections (ketoconazole,
Midazolam Injection should be given only by
voriconazole, fluconazole, itraconazole, posaconazole) experienced healthcare professionals (doctor or nurse).
• antibiotics, (used to treat bacterial infections,
It should be given in a place (hospital, clinic or surgery)
e.g. erythromycin, clarithromycin, quinupristin
equipped to monitor and support the patient’s breathing,
with dalfopristin)
heart and circulation (cardiovascular function) and
• diltiazem (used to treat high blood pressure)
recognise the signs of and manage the expected side
• medicines for HIV called protease inhibitors
effects of anaesthesia.
(e.g. saquinavir)
• atorvastatin (used to treat high cholesterol)
Normal adult dose
• medicines used for tuberculosis (e.g. isoniazid
Your doctor will decide on a suitable dose for you.
or rifampicin)
The dose you are given will depend on why you are
• the herbal medicine St John’s Wort
being treated and the type of sedation needed. Your
• medicines used for epilepsy (e.g. phenytoin)
weight, age, your state of health, how you respond to
• some antihistamines (used to treat hayfever)
Midazolam Injection and whether other medicines are
• medicines used for mental illness (e.g. clozalpine)
needed at the same time will also influence the dose
• levodopa (used in the treatment of Parkinson’s disease) that you are given.
• disulfiram (used for alcohol dependence)
• medicines used to relax your muscles during an
If you need strong painkillers, you will be given these
operation (e.g. baclofen)
first and then be given Midazolam Injection. The dose
• nabilone (used to treat vomiting due to cancer therapy) will be adjusted specially for you.
• medicines used for pain relief and inflammation
(e.g. aspirin)
Midazolam Injection may be given to you in one of
• probenecid (used for gout)
four different ways:
• medicines used to treat stomach ulcers (e.g. cimetidine, • by slow injection into a vein (intravenous injection)
ranitidine or omeprazole)
• through a tube into one of your veins (intravenous
• medicines containing caffeine (e.g. some painkillers)
infusion)
If any of the above apply to you, or if you are not sure,
• by injection into a muscle (intramuscular injection)
talk to your doctor or nurse before you are given this
• into your back passage (rectum).
medicine.
You should always be taken home by a responsible adult
Operations
after your treatment.
If you are going to have an inhaled anaesthetic (one that
you breathe in) for an operation or for dental treatment, Children and babies
it is important to tell your doctor or dentist that you have • In infants and babies under 6 months of age
been given this medicine.
Midazolam Injection is only recommended for
sedation in intensive care units. The dose will be
Midazolam Injection with food, drink, alcohol
given gradually into a vein.
and smoking:
• Children 12 years and under will usually be given
Do not drink alcohol if you have been given Midazolam
Midazolam Injection into a vein. When Midazolam
injection. This is because alcohol can increase the
Injection is used for premedication (to cause relaxation,
sedative effect of midazolam and may cause problems
calm and drowsiness before an anaesthetic) it may be
with your breathing.
given into the back passage (rectum).
Talk to your doctor or nurse before drinking drinks
containing caffeine, as they may reverse the sedative
effect of midazolam.
Talk to your doctor or nurse before smoking as nicotine
may reduce the effects of midazolam.

INFORMATION FOR HEALTHCARE PROFESSIONALS
Midazolam 2mg/mlSolution for Injection or Infusion
Midazolam 5mg/mlSolution for Injection or Infusion
Please refer to the Summary of Product Characteristics for full prescribing information.
Presentation
Midazolam 2mg/ml Solution for Injection or Infusion is available in cartons containing 10 x 5ml glass
ampoules. Each ampoule contains 10mg of the active ingredient in 5ml of solution.
Midazolam 5mg/ml Solution for Injection or Infusion is available in cartons containing 10x2ml glass
ampoules. Each ampoule contains 10mg of the active ingredient in 2ml of solution.
Midazolam Injection contains sodium
Each 1 ml of Midazolam 2mg/ml Solution for Injection or Infusion contains 0.15mmol (3.3mg) of sodium.
Each 1 ml of Midazolam 5mg/ml Solution for Injection or Infusion contains 0.14mmol (3.1mg) of sodium.
Posology and method of administration
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.
Indication

Adults <60 y

Adults 60 y / debilitated or
chronically ill

Children

i.v.
Initial dose: 2-2.5 mg
Titration doses: 1 mg
Total dose: 3.5-7.5 mg

i.v.
Initial dose: 0.5-1 mg
Titration doses:
0.5-1 mg
Total dose: <3.5 mg

i.v. 6 months- 5 years
Initial dose:
0.05-0.1 mg/kg Total dose:
<6 mg
i.v. 6-12 years
Initial dose:
0.025-0.05 mg/kg
Total dose: <10 mg
rectal >6 months
0.3-0.5 mg/kg
i.m. 1-15 years
0.05-0.15mg/kg

Conscious
sedation

Anaesthesia
premedication

Anaesthesia
induction

i.v.
1-2 mg repeated
i.m.0.07-0.1 mg/kg

i.v.
Initial dose: 0.5mg Slow
uptitration as needed
i.m.0.025-0.05 mg/kg

i.v.
0.15-0.2 mg/kg
(0.3-0.35 without
premedication)

i.v.
0.05-0.15 mg/kg (0.15-0.3
without premedication)

i.v.
intermittent doses of
Sedative component 0.03-0.1 mg/kg
in combined
or continuous
anaesthesia
infusion of
0.03-0.1 mg/kg/h

Sedation in ICU

rectal >6 months
0.3-0.5 mg/kg
i.m. 1-15 years
0.08-0.2 mg/kg

If you are given more Midazolam Injection than you
should
Your medicine will be given to you by a doctor or nurse.
If you are accidentally given too much Midazolam
Injection you may:
• experience confusion
• experience reduction in consciousness
• experience muscle weakness

CONSCIOUS SEDATION DOSAGE
For conscious sedation prior to diagnostic or surgical intervention, midazolam is administered i.v. 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. 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.
Adults: the i.v. injection of midazolam should be given slowly at a rate of approximately 1 mg in 30 seconds.
Adults below the age of 60: the initial dose is 2 to 2.5 mg given 5 to 10 minutes before the beginning of
the procedure. Further doses of 1 mg may be given as necessary. Mean total doses have been found to
range from 3.5 to 7.5 mg. A total dose greater than 5 mg is usually not necessary.
Adults over 60 years of age, debilitated or chronically ill patients: the initial dose must be reduced to
0.5-1.0 mg and given 5-10 minutes before the beginning of the procedure. Further doses of 0.5 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. A total dose greater than 3.5 mg is usually not
necessary.
Children i.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.
Children 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.
Children 6 months to 5 years of age: initial dose 0.05 to 0.1 mg/kg. A total dose up to 0.6 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.
Children 6 to 12 years of age: initial dose 0.025 to 0.05 mg/kg. A total dose of up to 0.4 mg/kg to a
maximum of 10 mg may be necessary. Prolonged sedation and risk of hypoventilation may be associated
with the higher doses.
Children 12 to 16 years of age: should be dosed as adults.
Children rectal administration: the total dose of midazolam usually ranges from 0.3 to 0.5 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.

i.v.
lower doses than
recommended for adults
<60 years

i.v.
Loading dose: 0.03-0.3 mg/kg in increments of
1-2.5 mg
Maintenance dose: 0.03-0.2 mg/kg/h

Pregnancy and breast-feeding
Talk to your doctor if you are pregnant, or think you are
pregnant. Your doctor will decide if this medicine is
suitable for you.

Children i.m. administration: the doses used range between 0.05 and 0.15 mg/kg. A total dose greater
than 10.0 mg is usually not necessary. This route should only be used in exceptional cases. Rectal
administration should be preferred as i.m. injection is painful.

i.v. in neonates <32 weeks
gestational age
0.03 mg/kg/h
i.v in neonates >32 weeks
and children up to 6 months
0.06 mg/kg/h
i.v. >6 months
Loading dose:
0.05-0.2 mg/kg
Maintenance dose:
0.06-0.12 mg/kg/h

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 1mg/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 memory. Midazolam
can also be administered in combination with anticholinergics. For this indication midazolam should be
administered i.v. or i.m., deep into a large muscle mass 20 to 60 minutes before induction of anaesthesia,
or preferably via the rectal route in children (see below). Close and continuous monitoring of the patients
after administration of premedication is mandatory as inter-individual sensitivity varies and symptoms of
overdose may occur.

• feel drowsy
• lose your co-ordination (ataxia) and reflexes
• have problems with your speech (dysarthria)
• have involuntary eye movements (nystagmus)
• develop low blood pressure (hypotension)
• stop breathing (apnoea) and suffer cardiorespiratory
depression (slowed or stopped breathing and heart
beat) and coma.
As the level of medicine falls in your blood you may get
severe agitation; inability to sleep and possibly major fits.
If you think you have missed a dose of Midazolam
Injection
A doctor or nurse will give you this medicine. If you think
you have missed a dose, inform your doctor of nurse.
Stopping Midazolam Injection
If you receive long term treatment with Midazolam
Injection (are given the medicine for a long time) you may:
• become tolerant to Midazolam Injection. The medicine
becomes less effective and does not work as well
for you
• become dependent upon this medicine and get
withdrawal symptoms (see below). Your doctor will
reduce your dose gradually to avoid these effects
happening to you.
Withdrawal symptoms
Benzodiazepine medicines, like Midazolam Injection,
may make you dependent if used for a long time (for
instance in intensive care). This means that if you stop
treatment suddenly, or lower the dose too quickly, you
may get withdrawal symptoms.
Withdrawal symptoms include feeling very worried
(anxious), tense, restless, confused or bad-tempered
(irritable), mood changes, muscle pain, depression,
impaired concentration, problems with sleeping
(insomnia), hallucinations (seeing and possibly hearing
things that are not there), headache, dizziness, ringing in
your ears, loss of appetite, tremor, sweating, increased
sensation, abnormal taste, feeling sick, being sick,
stomach pains, rapid heart beat, high blood pressure or
low blood pressure on standing. Rare and more serious
withdrawal symptoms include muscle twitching,
confusion, paranoia, fits, hallucinations, and delirium.
Broken sleep with vivid dreams may persist for some
weeks after withdrawal.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can side effects,
although not everybody gets them.
The following undesirable effects have been reported
(frequency not known).
Stop having Midazolam Injection and see a doctor
straight away if you notice any of the following side
effects. They can be life-threatening and you may
need urgent medical treatment:
• anaphylactic shock (a life-threatening allergic
reaction). Signs may include a sudden rash, itching or
lumpy rash (hives) and swelling of the face, lips,
tongue or other parts of the body. You may also have
shortness of breath, wheezing or trouble breathing
• heart attack (cardiac arrest). Signs may include chest
pain which may spread to your neck and shoulders
and down your left arm
• breathing problems or complications (sometimes
causing the breathing to stop)
• choking and sudden blockage of the airway
(laryngospasm).
Life-threatening side effects are more likely to occur in
adults over 60 years of age and those who already have
breathing difficulties or heart problems, particularly if
the injection is given too fast or at a high dose.
Other possible side effects
Blood problems:
• disorder of the blood
Immune system problems:
• general allergic reactions (skin reactions, heart and
blood system reactions, wheezing)
Effects on behaviour:
• agitation, irritability, increased anxiety
• restlessness
• hostility, rage or aggression
• excitement, disinhibition.
Muscle problems:
• muscle spasms and muscle tremors (shaking of your

Malta:
muscles that you cannot control)
ADR Reporting
• muscle weakness.
Website: www.medicinesauthority.gov.mt/adrportal
Mental and nervous system problems:
By reporting side effects you can help provide more
• confusion
information on the safety of this medicine.
• euphoria (an excessive feeling of happiness or
excitement)
• numbed emotions
• depression
• delirium after surgery
• hallucinations (seeing and possibly hearing things that
are not really there)
• drowsiness and prolonged sedation
• reduced alertness
• headache
• dizziness
• difficulty co-ordinating muscles
• slurred speech
• fits (convulsions) in premature infants and new-born
babies
• temporary memory loss. How long this lasts depends on
how much Midazolam Injection you were given. You may
5. HOW TO STORE MIDAZOLAM INJECTION
experience this after your treatment. In isolated cases
this has been prolonged (lasted for a long time)
Keep out the sight and reach of children.
• drug dependence, abuse.
This medicine should not be used if the expiry date on
Eye problems:
the ampoule has passed. The expiry date refers to the
• problems with your vision.
last day of the month.
Heart and circulation problems:
• low blood pressure
• slow heart rate
• redness of the face and neck (flushing), fainting or
headache.
• chest pain
• low blood pressure
• inflammation of your veins.
Breathing problems:
• shortness of breath
• hiccup.
Stomach, gut and mouth problems:
• feeling sick or being sick
• constipation
• dry mouth.

This medicine should not be stored above 25°C. Store the
ampoule in the outer carton in order to protect from light.
Medicines should not be thrown away via wastewater or
household waste. Ask your pharmacist how to throw
away medicines no longer used. These measures will
help protect the environment.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Midazolam Injection contains
The active substance is midazolam.
The other ingredients are sodium chloride, hydrochloric
acid solution, sodium hydroxide solution and water for
injections.

What Midazolam Injection looks like and contents of
the pack
Midazolam Injection is a clear, colourless solution.
Liver problems:
• jaundice (a yellowing of the skin and whites of the eyes) Midazolam 2mg/ml Solution for Injection or Infusion is
available in cartons containing 10x5ml glass ampoules.
Skin problems:
Each ampoule contains 10mg of the active ingredient in
• rash
5ml of solution.
• hives (lumpy rash)
Midazolam 5mg/ml Solution for Injection or Infusion is
• itchiness.
available in cartons containing 10x2ml glass ampoules.
Each ampoule contains 10mg of the active ingredient in
Kidney and urinary problems:
2ml of solution.
• difficulty in passing water
• incontinence (the inability to control when you go to
Marketing Authorisation Holder:
the toilet).
Wockhardt UK Ltd, Ash Road North, Wrexham,
LL13 9UF, UK.
Injection site problems:
• redness
Manufacturer:
• swelling of the skin
CP Pharmaceuticals Ltd, Ash Road North, Wrexham,
• blood clots or pain at the injection site.
LL13 9UF, UK.
Injury:
Other sources of information:
Patients taking benzodiazepine medicines are at risk of
To listen to or request a copy of this leaflet in Braille,
falling and breaking bones. This risk is increased in the
elderly and those taking other sedatives (including alcohol). large print or audio please call, free of charge:
0800 198 5000 (UK only)
General:
Please be ready to give the following information:
• tiredness (fatigue)
• hangover effect
Product name
Reference number
• changes in sexual desire.
Midazolam 2mg/ml
PL 29831/0140
Elderly patients:
Solution for Injection
• Life-threatening side effects are more likely to occur in
or Infusion
adults over 60 years of age and those who already
Midazolam 5mg/ml
PL 29831/0141
have breathing difficulties or heart problems,
Solution for Injection
particularly when the injection is given too quickly or
or Infusion
at a high dose.
If any of the side effects become serious or troublesome, This is a service provided by the Royal National Institute
or if you notice any side effects not listed in this leaflet, of Blind People.
please tell your doctor or nurse.
For Malta, please call +44 1978 661261.
Reporting of side effects
This leaflet was last revised in 06/2016.
If you get any side effects, talk to your doctor, or
pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report
side effects directly via the national reporting systems
listed below:
United Kingdom:
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

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 1-2 mg i.v. repeated as needed, or
0.07 to 0.1 mg/kg administered i.m. The dose must be reduced and individualised when midazolam is
administered to adults over 60 years of age, debilitated or chronically ill patients. The recommended
initial i.v. dose is 0.5 mg and should be slowly up titrated as needed. A dose of 0.025 to 0.05 mg/kg
administered i.m. is recommended. In case of concomitant administration of narcotics the midazolam
dose should be reduced. The usual dose is 2 to 3 mg.
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.
Children over 6 months of age, i.m. administration: As i.m. 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 i.m. 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 1 mg/ml
are not recommended. Higher concentrations should be diluted to 1 mg/ml.
ANAESTHESIA DOSAGE-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 i.v. 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 i.v. induction dose of midazolam should be given slowly in increments.
Each increment of not more than 5 mg should be injected over 20 to 30 seconds allowing 2 minutes
between successive increments.
Premedicated adults below the age of 60 years: an i.v. dose of 0.15 to 0.2 mg/kg will usually suffice.
Non-premedicated adults below the age of 60: the dose may be higher (0.3 to 0.35 mg/kg i.v.).
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.
Premedicated adults over 60 years of age, debilitated or chronically ill patients: the dose should
significantly be reduced, e.g., down to 0.05- 0.15 mg/kg administered i.v. over 20-30 seconds and
allowing 2 minutes for effect.
Non-premedicated adults over 60 years of age: usually require more midazolam for induction; an initial
dose of 0.15 to 0.3 mg/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 0.25 mg/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 i.v. doses (range between 0.03 and 0.1 mg/kg) or continuous infusion of i.v. 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.
Adults over 60 years of age, debilitated or chronically ill patients: lower maintenance doses will be
required.
SEDATION IN INTENSIVE CARE UNITS
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: i.v. 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.

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I.V. 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.
Neonates and children up to 6 months of age: Midazolam should be given as a continuous i.v. 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 is 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.
Children over 6 months of age: In intubated and ventilated paediatric patients, a loading dose of 0.05 to
0.2 mg/kg i.v. 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 i.v. 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 i.v. 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.
In premature infants, neonates and 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
1mg/ml.
USE IN SPECIAL POPULATIONS
Renal Impairment: In patients with renal impairment (creatinine clearance < 10 ml/min) the
pharmacokinetics of unbound midazolam following a single i.v. dose is similar to that reported in healthy
volunteers. However, after prolonged infusion in intensive care unit (ICU) patients, the mean duration of
the sedative effect in the renal failure population was considerably increased most likely due to
accumulation of α-hydroxymidazolam glucuronide.
There is no specific data in patients with severe renal impairment (creatinine clearance below 30 ml/min)
receiving midazolam for induction of anaesthesia.
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 be reduced and proper monitoring of vital signs should be established.
Incompatibilities
Midazolam is incompatible with alkaline solutions (due to reduced solubility) and some medicines.
Published data show that midazolam injection is incompatible with alkaline injections such as some
antibiotic and steroid injections, bumetanide, frusemide, omeprazole sodium, sodium bicarbonate and
thiopental sodium. It is also incompatible with dimenhydrinate, foscarnet sodium, imipenem with cilastin,
pentobarbital sodium, albumin, clonidine, perphenazine, prochlorperazine, ranitidine and certain parenteral
solutions, including parenteral nutrition solutions.
Mixture or dilution with Hartmann's solution is not recommended, as the potency of midazolam decreases.
Compatibility must be checked before administration, if intended to be mixed with other drugs.
Shelf life
Three years.
Special precautions for storage
Do not store above 25°C. Keep container in outer carton in order to protect from light.
This leaflet was last revised in 06/2016

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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