MIDAZOLAM 2MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance: MIDAZOLAM

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2. 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 contained in Midazolam Injection
(see list under heading ‘What Midazolam Injection
contains’ in section 6)
• have severe breathing problems
• have severe liver problems.
If any of the above statements apply to you, you should
not be given Midazolam Injection.
Speak to your doctor before you are given
Midazolam Injection if you:
• are elderly
• are very run down and lack strength
• have problems with your liver, kidneys or lungs
• have a condition called myasthenia gravis which
causes very weak muscles
• have a personality disorder, depression,
aggressive tendencies or if you feel suicidal
• have had problems with addiction to drugs or alcohol
Special care should be taken if the patient is in a coma.

Product Summary
1.NAME OF THE MEDICINAL PRODUCT
Midazolam 2mg/ml Solution for Injection or Infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Midazolam 2mg/ml. Each 5ml ampoule contains 10mg
midazolam. Contains less than 1mmol sodium (23mg) per
5ml ampoule.
3. PHARMACEUTICAL FORM
Solution for injection or infusion
4. CLINICAL PARTICULARS
4.1 Therapeutic indication
Midazolam may be used as an intravenous sedative
before and during minor medical, dental and surgical
procedures.
As an intravenous sedative, (either by continuous infusion
or intermittent bolus injection) in critically ill patients in
intensive care.
As an alternative intravenous agent for the induction of
anaesthesia in high risk and elderly patients where
cardiovascular stability is of particular importance.
Induction is more reliable when heavy opiate medication
has been administered or when midazolam injection is
given with a narcotic analgesic such as fentanyl.
4.2 Posology and method of administration
Dosage depends on the individual response, age and
weight. Midazolam 2mg/ml may be given by intravenous
or slow intravenous injection.
Intravenous sedation
One or more intravenous injections to be administered
over a single operating session.
Dosage should be titrated according to an individual's
response, age and weight. The end-point of this titration is
dependent on the procedure. Full sedation will be evident
by drowsiness and slurred speech, although a response to
commands will be maintained.

therefore be assessed carefully before being allowed to go midazolam should be titrated carefully to the sedative
needs of the patient. Low doses of midazolam 0.01 to
home or resume normal activities.
0.1mg/kg/hour may be used to start.
Sedation in the critically ill patient:Midazolam injection can be given intravenously by two
The use of these two groups of drugs can increase the
methods for this purpose, either by continuous infusion or risk of respiratory depression. If the patient is being given
by intermittent bolus dose. Both have their own
ventilatory support using a mode that depends upon
advantages and disadvantages and the appropriate
some spontaneous effort by the patient, then the minute
method of giving midazolam injection will need to be
volume may decrease.
determined for each patient.
Whenever a continuous infusion of midazolam is used
The dose of midazolam injection needed to sedate
(with or without an opioid analgesic), its need should be
critically ill patients varies considerably between patients. assessed on a daily basis in order to reduce the risk of
The dose should be titrated to the desired state of
accumulation and prolonged recovery. Each day the
sedation. This will depend on clinical need, physical
infusion of midazolam should be stopped or its rate
status, age and concomitant medication.
reduced and the patient seen to recover from its effect. If
recovery is prolonged (>2 hours) a lower dose should be
Midazolam injection can also be given in combination with used when it is restarted. A sedation score should be
an opioid. The opioid may be used for its analgesic effects used routinely.
or as an antitussive agent to help the patient tolerate the
tracheal tube and ventilatory support.
When midazolam has been given for a number of days
and then gradually withdrawn, patients may be awake but
Patients receiving midazolam injection for sedation in the show signs of residual sedation for the next 12 to 24
intensive care situation should receive ventilatory support. hours. This can cause difficulties because patients may
not cough and expectorate well if they are then weaned
Safe use for midazolam for periods of over 14 days in
from ventilatory support. However, while recovering from
duration has not been established in clinical trials.
the effects of midazolam, patients may not be sufficiently
sedated to tolerate ventilatory support. In such
Potential drug interactions:circumstances sedation may be provided with a shorter
The critically ill patient is exposed to many drugs.
acting agent while there is recovery from the effects of
Because of this, there is a potential for drug interactions.
midazolam.
(Refer to Section 4.5 Interactions with other medicaments
and other forms of interaction).
The recommended concentration of a solution for infusion
in a critically ill adult patient is 1mg/ml.
After prolonged iv administration of midazolam injection,
abrupt discontinuation may be accompanied by
Induction of anaesthesia by slow intravenous injection
One or more bolus intravenous injections should be
withdrawal symptoms, therefore a gradual reduction of
administered over a single anaesthetic session.
the drug is recommended.
Sedation by intermittent bolus dose in intensive care

Adults
The dose should be titrated against the individual
response of the patient. Midazolam injection should be
given by slow intravenous injection until there is a loss of
eyelid reflex, response to commands and voluntary
movements.

Midazolam may enhance the effects of other CNS
depressants and may result in severe respiratory or
cardiovascular depression. Their concurrent use should be
avoided. Elderly or debilitated patients are more prone to
the CNS effects of benzodiazepines and, therefore, lower
doses are required (see 4.2 Posology and Method of
Administration).
Dependence and withdrawal symptoms
The dependence potential of midazolam increases with
dose and duration of treatment and is greater in patients
with a history of alcohol or drug abuse. It is low when
limited to short term use. Due to the possibility of
withdrawal symptoms, midazolam should be gradually
reduced following a prolonged iv administration; abrupt
discontinuation should be avoided. Withdrawal symptoms
may occur with benzodiazepines following normal use of
therapeutic doses for only short periods and may be
associated with physiological and psychological sequelae
(see Section 4.8 Undesirable effects). This should be
considered when treating patients for more than a few
days.
As with other benzodiazepines, extreme caution should be
used if prescribing midazolam for patients with personality
disorders. The disinhibiting effects of benzodiazepines
may be manifested as the precipitation of suicide in
patients who are depressed or show aggressive
behaviour towards self and others.
This medicinal product contains 0.15mmol sodium per
ampoule. To be taken into consideration by patients on a
controlled sodium diet.
4.5 Interactions with other medicinal products and
other forms of interaction
Alcohol: Alcohol should be avoided for at least eight hours
before and after the administration of midazolam due to
increased sedative effects.

Anaesthetics and narcotic analgesics: Enhanced sedation
or respiratory and cardiovascular depression. If such
centrally acting depressant drugs are given parenterally in
conjunction with intravenous midazolam, severe
respiratory and cardiovascular depression may occur;
Adults: 2mg, (1ml of 2mg/ml midazolam injection solution)
careful monitoring is required. When intravenous
In anticipating the required dose of midazolam, both the
over a period of 30 seconds initially
midazolam is to be administered concurrently with a
Midazolam injection and an opioid
premedication already given and the age of the patient are narcotic analgesic agent (e.g. fentanyl), it is recommended
When midazolam and an opioid are used together, the
important. Young, fit unpremedicated patients may need
Elderly: 1 to 1.5mg (0.5-0.75ml of 2mg/ml midazolam
that midazolam be given after the analgesic and that the
opioid should be administered first. Both drugs need to be at least 0.3mg/kg bodyweight, whereas patients
injection solution) over a period of 30 seconds initially.
dose be carefully titrated to meet the patient's needs.
titrated to the individual patient's response and to the level premedicated with an opiate usually need only 0.2mg/kg Fentanyl may reduce midazolam clearance.
of sedation thought to be necessary.
bodyweight.
If adequate sedation is not achieved after two minutes,
incremental doses of 0.5-1mg, (0.25-0.5ml of 2mg/ml
Antibacterials: Agents that interfere with metabolism by
Small doses of midazolam 1-2mg (0.5-1.0ml of 2mg/ml
Use in the elderly
midazolam injection solution) should be given until the
hepatic enzymes (e.g. isoniazid, erythromycin,
midazolam injection solution) can be given, and repeated, The elderly are more sensitive to the effects of
desired level of sedation is achieved, usually at a total
clarithromycin, quinupristin/dalfopristin) have been shown
until the required degree of sedation is reached. In the
benzodiazepines. Induction may be adequate with
dose of 2.5-7.5mg (about 70 micrograms/kg) in adults.
to reduce the clearance of benzodiazepines and may
elderly, smaller doses as little as 0.5-1.0mg (0.25-0.5ml of 0.1mg/kg body weight in premedicated patients and
potentiate their actions, whilst known inducers of hepatic
2mg/ml midazolam injection solution) may be adequate.
0.2mg/kg body weight in unpremedicated patients.
Renal/hepatic impairment: Reduce dose
enzymes, for example, rifampicin, may increase the
clearance of benzodiazepines.
The use of these two groups of drugs can increase the
Renal/hepatic impairment: Reduce dose.
Children
risk of respiratory depression. If the patient is being given Children over seven years
Not recommended. Midazolam injection has not been
Antidepressants: Enhanced sedation or respiratory and
ventilatory support using a mode that depends upon
Midazolam injection has been shown to be an effective
evaluated as an intravenous sedative in children.
cardiovascular depression. Midazolam plasma levels
some spontaneous effort by the patient, then the minute
agent for induction of anaesthesia in children over seven
increased by concomitant nefazodone.
volume may decrease.
years of age, at a dose of 0.15mg/kg body-weight.
Combination therapy:If analgesia is provided by a narcotic analgesic, the
Antiepileptics: Enhanced sedation or respiratory or
analgesic should be administered first. The dose of
Sedation by continuous infusion in intensive care
Mode of administration:cardiovascular depression. Midazolam may interact with
midazolam injection should then be carefully titrated. Low Midazolam injection only
For the administration of midazolam injection the patient
other hepatically metabolised drugs, e.g. phenytoin,
Adults, Elderly and children
total doses of 1-2mg may be adequate with lower total
should be placed in a supine position and remain there
causing potentiation.
For patients already sedated or anaesthetised after an
doses of 0.5-1mg in the elderly.
throughout the procedure. Resuscitation facilities should
operation, a loading dose of midazolam is unnecessary.
always be available and a second person, fully trained in
Antifungals: Ketoconazole, itraconazole, and possibly
Mode of administration:the use of such equipment, always be present. It is
fluconazole, have been shown to reduce the clearance of
For the administration of midazolam injection the patient
In other situations a loading dose of 0.03-0.3mg/kg given recommended that patients should remain under medical benzodiazepines and may potentiate their actions
should be placed in a supine position and remain there
over a five minute period is recommended, depending on supervision until at least one hour has elapsed from the
throughout the procedure. Resuscitation facilities should
the level of sedation required. The loading dose should be time of injection. They should always be accompanied
Antihistamines: Enhanced sedation or respiratory and
always be available and a second person, fully trained in
reduced or omitted in hypovolaemic, vasoconstricted or
home by a responsible adult.
cardiovascular depression with sedative antihistamines.
the use of such equipment, always be present. It is
hypothermic patients, renal or hepatic impairment.
recommended that patients should remain under medical
4.3 Contraindications
Antihypertensives: Enhanced hypotensive effect.
Maintenance dose
supervision until at least one hour has elapsed from the
Known hypersensitivity to benzodiazepines or any of the
Enhanced sedative effect possible with moxonidine.
A dose between 0.03-0.2mg/kg/hour is recommended,
time of injection. They should always be accompanied
ingredients. Severe or acute respiratory
Antipsychotics: Enhanced sedation or respiratory and
starting at the lower dose.
home by a responsible adult.
insufficiency/depression.
cardiovascular depression. Severe hypotension, collapse,
Severe hepatic insufficiency
respiratory depression, potentially fatal respiratory arrest
Patients who have received only midazolam injection for iv The dose should be reduced in hypovolaemic,
4.4 Special warnings and precautions for use
and unconsciousness have been reported in a few
sedation prior to minor procedures, should be warned not vasoconstricted or hypothermic patients, renal or hepatic
Midazolam injection should be used with caution in
patients on benzodiazepines and clozapine. Caution is
impairment.
to drive or operate machinery for 12 hours. Where
patients with renal or hepatic dysfunction (see 4.2
advised when initiating clozapine therapy in patients
midazolam injection is used concurrently with other
Posology and Method of Administration), chronic
taking benzodiazepines.
Midazolam injection and an opioid
central nervous system depressants (e.g. potent
pulmonary insufficiency, myasthenia gravis, coma, or a
When opioid analgesics are used, the rate of infusion of
analgesics) recovery may be prolonged. Patients should
known history of drug or alcohol abuse.
Midazolam injection only
The exact dose of midazolam needs to be titrated to the
individual patient response. Small doses of midazolam
1.0-2.0mg can be given, and repeated, until the required
degree of sedation is reached.

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IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Midazolam Injection is used:
• for sedation before and during minor medical, dental
or surgical procedures
• for sedation of patients in intensive care
• at the start of a general anaesthetic

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.

1. WHAT MIDAZOLAM INJECTION IS
AND WHAT IT IS USED FOR
The active ingredient in Midazolam Injection is
midazolam which belongs to a group of sedative
medicines called benzodiazepines.

100997-7

In this leaflet:
1. What Midazolam Injection is and what it is used for
2. Before you are given Midazolam Injection
3. How Midazolam Injection should be given
4. Possible side effects
5. How to store Midazolam Injection
6. Further information

Item Code

The name of your medicine is Midazolam 2mg/ml
Solution for Injection or Infusion. In the rest of this leaflet
it is called Midazolam Injection.

Other medicines that cause sedation:
• sleeping tablets
• medicines used to treat anxiety e.g. other
benzodiazepines
• medicines used to treat depression, such
as nefazodone
• medicines for epilepsy, such as phenytoin
• some antihistamines, used to treat hayfever
• medicines used for mental illness, such as clozapine Talk to your doctor or pharmacist if you are not sure
• nabilone, used to treat vomiting due to cancer therapy whether it is safe for you to drive while taking this
medicine.
Medicines used during operations:
Alcohol and Midazolam Injection
• anaesthetics
• certain pain killers (e.g. fentanyl) – If you take or are You should not drink alcohol for at least eight hours
given these drugs you should have them before you before or after having an injection of midazolam.
receive your Midazolam Injection and will need to be
carefully monitored for problems with your breathing Important information about the sodium content of
Midazolam Injection
and your heart
This medicinal product contains less than 1 mmol
• medicines used to relax your muscles during an
sodium (23mg) per ampoule, i.e. it is essentially
operation (e.g. baclofen)
‘sodium-free’.
Medicines that fight infections:
• antibiotics, used to treat bacterial infections, such as 3. HOW MIDAZOLAM INJECTION
SHOULD BE GIVEN
erythromycin, clarithromycin, quinupristin with
You will only be given Midazolam Injection in places
dalfopristin
with adequate resuscitation equipment and when there
• drugs used to treat fungal infections, such as
is a second member of staff present to help your doctor.
ketoconazole, itraconazole or fluconazole
Midazolam Injection will be given into a vein in your arm
• drugs used to treat virus infections, such as
(intravenous injection) whilst you are lying down.
amprenavir or ritonavir used for HIV
• drugs used for tuberculosis, such as isoniazid or
Your doctor will decide which dose is suitable for you.
rifampicin
The dose used will depend on what the injection is
being given for and on your general physical condition,
Other medicines:
• medicines to lower your blood pressure, such as to age, weight, what other medicines you are taking and
your response to the drug.
diltiazem, verapamil or moxonidine
• medicines used for pain relief and inflammation such
For sedation before and during minor surgery or
as aspirin
dental procedures
• medicines used to treat stomach ulcers, such as
cimetidine, ranitidine or omeprazole
Adults
• levodopa, a drug used in the treatment of
The usual adult dose for sedation of adults before and
Parkinson's disease
during minor surgery or dental procedures is 2mg
• theophylline, a drug used for asthma and lung
given into a vein over a period of 30 seconds. Further
disease
injections of 0.5 - 1mg may be given every two
• probenecid, used for gout.
minutes until you are properly sedated. The total dose
required is usually 2.5 to 7.5mg.
If you have any doubts about whether you should be
given this medicine then discuss matters with your
Elderly
doctor.
The usual dose for the elderly is 1 to 1.5mg, given into
a vein over a period of 30 seconds. Further 0.5 - 1mg
Pregnancy and breast-feeding
You should not usually be given Midazolam Injection if injections may be given every two minutes until you
are properly sedated.
you are pregnant. If Midazolam Injection is given to
women in the first three months of pregnancy, there is Children
a small risk of congenital malformation in the baby
Midazolam Injection is not used in this way in
particularly a split in the mouth (cleft palate). Infants
children.
born to mothers who are given Midazolam Injection
during the late stages of pregnancy may experience
If you have kidney or liver disease
withdrawal symptoms or slow development.
If you have kidney or liver disease you will be given a
lower dose.
If your doctor has decided that you should be given this
medicine during labour, your baby might have a low
If you are in intensive care
body temperature, floppiness, an abnormal heart rate Adults, Elderly and Children
and breathing or feeding difficulties.
Small doses of 1 to 2mg may be given directly into a
vein and repeated until sedation is achieved. For the
If you wish to become pregnant, you should speak to
elderly even smaller doses of 0.5 to 1mg may be
your doctor about the use of Midazolam Injection.
adequate.

LFT MIDAZOLAM 2MG-ML AMP

Read all of this leaflet carefully before you start
using this medicine.
- Keep this leaflet. You may need to read it again.
- If you have further questions, please ask your doctor
or nurse.
- This medicine has been prescribed for you personally
and you should not pass it on to others. It may harm
them, even if their symptoms are the same as yours.

The medicine can affect your ability to drive as it may
make you sleepy or dizzy.
• Do not drive while taking this medicine until you
know how it affects you.
• It is an offence to drive if this medicine affects your
ability to drive.
• However, you would not be committing an offence if:
o The medicine has been prescribed to treat a
medical or dental problem and
o You have taken it according to the instructions given
by the prescriber or in the information provided
with the medicine and
o It was not affecting your ability to drive safely

Description

Alcohol and smoking:
• alcohol
• disulfiram, a drug used for alcohol dependence
• nicotine, from smoking

Driving and operating machines
You should not drive or operate machinery for at least
twelve hours after receiving Midazolam Injection.
You should speak to your doctor about driving if you
also take other medicines that can cause sedation.

Wockhardt UK Limited

Please check with your doctor if you are taking or have
been given any of the following (or any other medication):

Midazolam can enter breast milk. You should not be
given Midazolam Injection if you are breast-feeding or
wish to breast-feed.

Customer

Midazolam 2mg/ml Solution for Injection
or Infusion
Midazolam

Taking other medicines
Taking another medicine while you are being given
Midazolam Injection can affect how it or the other
medicine works. Please inform your doctor or nurse if
you are taking or have recently taken any other
medicines, drugs or herbal products, including those
you may have bought yourself without a prescription.

Measure bar should be 150mm at 100% scale

PACKAGE LEAFLET
INFORMATION FOR THE USER

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 or
nurse.

Gut problems:
• dry mouth
• stomach problems
Other side effects include:
• fatigue
• hangover effect
• pain on injection
• hiccups
• problems with your vision
• jaundice (a yellowing of the skin and whites of
the eyes)
• difficulty in passing water
• incontinence (the inability to control when you go
the toilet)
• changes in sexual desire
• blood problems
• some patients, particularly if they are children or
elderly, may become irritable, aggressive, hostile,
overexcited, uninhibited, overanxious or have
hallucinations.

Anxiolytics and hypnotics: Enhanced sedation or
respiratory and cardiovascular depression with other
anxiolytics and hypnotics.
Calcium-channel blockers: Diltiazem and verapamil have
been shown to reduce the clearance of benzodiazepines
and may potentiate their actions.
Dopaminergic agents: Midazolam may cause inhibition of
levodopa.
Disulfiram: Has been shown to reduce clearance of
benzodiazepines and may potentiate their actions.
Muscle relaxants: e.g. baclofen Midazolam may cause
potentiation, with increased CNS depressant effects.
Nabilone: Enhanced sedation or respiratory and
cardiovascular depression.
Nicotine: Benzodiazepine metabolism is accelerated by
smoking.
Non-steroidal anti-inflammatory drugs: The induction of
anaesthesia with midazolam is more rapid in patients
pre-treated with aspirin.
Probenecid: May reduce midazolam clearance.
Sedatives: Enhanced sedation or respiratory and
cardiovascular depression.

This medicine can impair cognitive function and can affect
a patient’s ability to drive safely. This class of medicine is in
the list of drugs included in regulations under 5a of the
Road Traffic Act 1988. When prescribing this medicine,
patients should be told:
• The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects
you
• It is an offence to drive while under the influence of this
medicine
• However, you would not be committing an offence
(called ‘statutory defence’) if:
o The medicine has been prescribed to treat a
medical or dental problem and
o You have taken it according to the instructions given
by the prescriber and in the information provided
with the medicine and
o It was not affecting your ability to drive safely
4.8 Undesirable effects
Side-effects are usually mild.
Cardiovascular: Midazolam may cause bradycardia, chest
pain and decreases in cardiac output, stroke volume and
systemic vascular resistance. These effects are important
in those patients with a reduced myocardial oxygen
delivery capacity or suffering hypovolaemia. Also,
hypotension, particularly with high dosage, and cardiac
arrest. Local thrombophlebitis may occur.
CNS: Elderly or debilitated patients are particularly
susceptible to the CNS side effects of benzodiazepines. It
is recommended that dosage be limited to the smallest
effective dose and increased gradually, if necessary, to
decrease the possibility of development of ataxia,
dizziness and oversedation, which may lead to falls and
other accidents (see 4.2 Posology and method of
administration).

Ulcer-healing drugs: Cimetidine, ranitidine and omeprazole
have been shown to reduce the clearance of
Disorders of the eye: Visual disturbances.
benzodiazepines and may potentiate their actions.
Gastrointestinal: dry mouth, gastrointestinal disturbances.
General: Fatigue and a hangover effect. Local pain on
Xanthines: Benzodiazepine metabolism is accelerated by injection. Hiccups.
xanthines.
Haematological: Blood dyscrasias.
4.6 Pregnancy and lactation
Hepatic: Jaundice.
There is no evidence regarding the safety of midazolam in
pregnancy. It should not be used, especially in the first
Immunological: Skin reactions and other hypersensitivity
and third trimesters, unless the benefit is considered to
reactions, including anaphylaxis, are rare.
outweigh the risk.
Neurological: Headaches, confusion, slurred speech,
If the product is prescribed to a woman of childbearing
tremor, drowsiness, reduced alertness, anterograde
potential she should be warned to contact her physician
amnesia, extrapyramidal effects.
regarding discontinuance of the product if she intends to
become or suspects that she is pregnant.
Psychiatric: Increased risk of postoperative delirium.
Numbed emotions. In susceptible patients, an unnoticed
There may be a small increase in the risk of congenital
depression may become evident. Paradoxical reactions
malformation, particularly oral cleft, with the use of
(including aggressive behaviour, hostility, hallucinations,
benzodiazepines in the first trimester. In labour, high single disinhibition, excitation, irritability and increased anxiety)
doses or repeated low doses have been reported to
are known to occur with benzodiazepines and are more
produce effects on the neonate, such as hypothermia,
likely in children and the elderly.
hypotonia, moderate respiratory depression, irregularities
in the foetal heart rate, and poor suckling in the neonate
Reproductive: Changes in libido
(floppy infant syndrome).
Respiratory: Midazolam can produce, respiratory
Infants born to mothers who take benzodiazepines
depression, apnoea and may cause respiratory arrest
chronically during the latter stages of pregnancy may
following iv administration, especially in the elderly with
develop physical dependence and may be at some risk for pre-existing respiratory insufficiency or when the dose is
developing withdrawal symptoms in the postnatal period. excessive or administered too rapidly.
A small number of children exposed in utero to
benzodiazepines have shown slow development in the
early years but by four years of age have developed
normally.
Since benzodiazepines are found in the breast milk,
benzodiazepines should not be given to breast-feeding
mothers.
4.7 Effects on ability to drive and use machines
The concurrent use of midazolam with other central
nervous system depressants, may result in a prolonged
recovery. A careful assessment should be undertaken
prior to allowing the patient to go home or resume normal
activities.
Patients treated with midazolam injection should not drive
or use machinery for twelve hours after receiving this
medicine.

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Midazolam 2mg/ml
Solution for Injection
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Stopping Midazolam Injection
Date of leaflet preparation: March 2014
If you are given Midazolam Injection for a long time,
there is a risk of becoming dependent on it in which
If any of the side effects get serious, or if you notice 100997/7
case you may have withdrawal symptoms when you
any side effects not listed in this leaflet, please
stop taking it. The dose should be reduced gradually to contact your doctor or nurse immediately.
reduce the risk of withdrawal symptoms and you
should never stop your Midazolam Injection abruptly.
Your doctor will decide when to stop your treatment
with Midazolam Injection.

Antivirals: Concomitant use of midazolam with
HIV-protease inhibitors (e.g. amprenavir, ritonavir) should
be avoided due to the risk of extreme sedation and
respiratory depression.

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paranoid psychosis, convulsions, hallucinations, and a
state resembling delirium tremens. Broken sleep with
vivid dreams and increased REM sleep may persist for
some weeks after withdrawal of benzodiazepines.
4.9 Overdose
a) Symptoms
The symptoms of mild overdose may include confusion,
impairment of consciousness with somnolence or a
sleep-like state, little or no respiratory depression, ataxia,
dysarthria, hypotension and muscular weakness. Cardiac
rate and rhythm remain normal in the absence of anoxia
or severe hypotension.
In severe overdose, deep coma, or other manifestations of
severe depression of brainstem vital functions, particularly
the respiratory centre, may occur
As drug levels fall, severe agitation, insomnia and,
possibly, major convulsions may develop.
b) Treatment
Treatment is symptomatic. Respiration, heart rate, blood
pressure and body temperature should be monitored and
supportive measures taken to maintain cardiovascular
function. Ventilation should be used to support respiratory
function if appropriate.
Flumazenil is a specific antidote for use in midazolam
overdosage but expert advice is essential since adverse
effects may occur (e.g. convulsions in patients dependent
on benzodiazepines).
5. PHARMACOLOGICAL PROPERTIES
5.1Pharmacodynamic properties
Midazolam is a soluble benzodiazepine with marked
properties of suppression of tension, agitation and anxiety
as well as sedative and hypnotic effects. In addition,
midazolam demonstrates muscle relaxant and
anticonvulsive properties. In clinical use, the main action
is sleep induction.
Midazolam binds to specific receptors in the central
nervous system (CNS). The benzodiazepine receptors in
the CNS have a close functional connection with receptors
of the GABA-ergic transmitter system. After binding to the
benzodiazepine receptor, midazolam augments the
inhibitory effect of GABA-ergic transmission.
5.2 Pharmacokinetic properties
Midazolam is highly lipid soluble and crosses the blood
brain barrier. These properties qualify it for intravenous
use in short term anaesthetic procedures since it acts
promptly on the brain, and its initial effects decrease
rapidly as it is distributed into fat deposits and tissues.
Following the administration of 150 micrograms/kg
intravenously, plasma concentrations in the range
291-425 ng/ml are reached within five minutes.
Midazolam is almost completely absorbed following
intramuscular injection, peak plasma levels being attained
within 45 minutes.
Midazolam is extensively protein bound (94-98%). The
volume of distribution is between 0.8 and 1.7 litres/kg.
Midazolam crosses the placenta. It is not known whether
midazolam enters breast milk, but this is likely as it is
known to occur with other benzodiazepines.

Midazolam is extensively metabolised in the liver, involving
the P450 IIIA enzymes. The principal metabolite,
1-hydroxy midazolam, appears in the urine as a
glucuronide. The metabolite is less pharmacologically
Withdrawal symptoms:
Development of dependence is common after regular use, active than midazolam and has a shorter half-life of about
even in therapeutic doses for short periods, particularly in one hour. Midazolam has a mean elimination half-life of
patients with a history of drug or alcohol abuse or marked two to three hours. The half-life is short compared with
personality disorders. Discontinuation may be associated other benzodiazepines. Less than 1% midazolam is
excreted unchanged via the kidneys and the drug is
with withdrawal symptoms or rebound phenomena (see
cleared virtually entirely by the liver. The half-life of
4.4 Special Warnings and Precautions for Use).
Symptoms of benzodiazepine withdrawal include anxiety, midazolam is prolonged in neonates, in the elderly and
depression, impaired concentration, insomnia, headache, patients with liver disorders.
dizziness, tinnitus, loss of appetite, tremor, perspiration,
irritability, perceptual disturbances such as hypersensitivity 5.3 Preclinical safety data
In vitro and in vivo microbial and mammalian test systems
to physical, visual, and auditory stimuli and abnormal
have revealed no evidence of mutagenicity. No evidence
taste, nausea, vomiting, abdominal cramps, palpitations,
of carcinogenic potential was seen in rats or mice given
mild systolic hypertension, tachycardia, and orthostatic
oral midazolam maleate in doses up to 25 times the
hypotension, Rare and more serious withdrawal
human recommended daily dose for two years.
symptoms include muscle twitching, confusional or
Urinary: urinary retention, incontinence.

In humans, the risk of congenital abnormalities from the
ingestion of therapeutic doses of benzodiazepines is slight,
although a few epidemiological studies have pointed to an
increased risk of cleft palate. There are case reports of
congenital abnormalities and mental retardation in
prenatally exposed children following overdosage and
intoxication with benzodiazepines.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Chloride
Hydrochloric Acid Solution 3M
Sodium Hydroxide Solution 3M
Water for Injections
6.2 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.
6.3 Shelf life
Three years.
6.4Special precautions for storage
Do not store above 25°C. Keep container in outer carton.
6.5 Nature and contents of container
Neutral glass ampoules Type I Ph Eur 5ml packed in 5 or
10s in an outer printed carton
6.6 Special precautions for disposal
The injection is for single patient use and should be used
immediately after opening. The injection should not be
used if particles are present. Any unused portion should
be discarded.
Midazolam for infusion may be prepared by dilution with
infusion fluids containing 5% glucose, 4% glucose with
0.18% sodium chloride or 0.9% sodium chloride.
Chemical and physical in-use stability has been
demonstrated for 24 hours at 25°C.
From a microbiological point of view, the product should
be used immediately. If not used immediately, in-use
storage times and conditions prior to use are the
responsibility of the user and would normally not be longer
than 24 hours at 2-8°C, unless dilution has taken place in
controlled and validated aseptic conditions.
7. MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd, Ash Road North
Wrexham, LL13 9UF
8. MARKETING AUTHORISATION NUMBER(S)
PL 29831/0140
9. DATE OF FIRST AUTHORISATION/RENEWAL OF
THE AUTHORISATION
27 March 2007
10. DATE OF REVISION OF THE TEXT
March 2014

100997/7

480844-483278

23/04/2014

Artwork No.

3

Date

English
Language

Proof No.

UK
Market

elkie.bramall

6pt

Proof By

185 x 475mm

Min. Point Size

Pharma
Code

Marketing Authorisation Holder: Wockhardt UK Ltd,
Ash Road North, Wrexham, LL13 9UF, UK.
Manufacturer: CP Pharmaceuticals Ltd, Ash Road
North, Wrexham, LL13 9UF, UK.

IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

If you are given more Midazolam Injection than
you should
A doctor or nurse will give you this medicine. If you
think that you have been given too much, inform your
doctor or nurse. Signs that you have been given too
much Midazolam Injection include: confusion; reduction
in consciousness; feeling drowsy; breathing difficulties;
lack of co-ordination; speech impairment; low blood
pressure and muscle weakness. In the case of a severe
overdose, coma can occur and you could stop
breathing. As the level of medicine falls in your blood
you may get severe agitation; inability to sleep and
possibly major fits.

Midazolam Injection is available in cartons containing
10x5ml glass ampoules.

Mental problems:
• numbed emotions
• depression
• delirium after surgery

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.

If you have kidney or liver disease
If you have kidney or liver disease you will be given a
lower dose.

Size

6. FURTHER INFORMATION
What Midazolam Injection contains
The active ingredient in Midazolam Injection is
Nervous system problems:
midazolam. The injection is available in 5ml ampoules.
Elderly
• dizziness, lack of coordination and over sedation with Each ampoule contains 10mg of the active ingredient in
The elderly are more sensitive to Midazolam Injection
a risk of falls and other accidents
5ml of solution.
so the doses required tend to be lower than for adults.
If you have not received any pre-medication the usual • headaches
The other ingredients are sodium chloride, hydrochloric
• confusion
dose is about 0.2mg/kg body weight. However, if you
acid solution, sodium hydroxide solution and water for
have received pre-medication you may only need about • slurred speech
injections.
• drowsiness
0.1mg/kg body weight.
• tremor
What Midazolam Injection looks like and contents
• uncontrolled jerky movements
Children over seven years
of the pack
• reduced alertness
The usual dose for children over seven years is about
Midazolam Injection is a clear, colourless solution.
• forgetfulness
0.15mg/kg body weight.

Use the pdf supplied

Medicines should not be disposed of via wastewater or
household waste. Ask your pharmacist how to dispose
of medicines no longer required. These measures will
help to protect the environment.

Profile

Store the ampoule in the outer carton in order to protect
from light.

100997-7

Less serious side effects include:
Heart and circulation problems
• slow pulse
• chest pain
• low blood pressure
• inflammation of your veins

This medicine should not be stored above 25°C.

Item Code

Adults
If you have not received any pre-medication the usual
adult dose is about 0.3mg/kg body weight. If you have
received pre-mediation however, you may only need
about 0.2mg/kg body weight.

If you experience any of the following, you should
contact your doctor or nurse immediately:
• skin rashes or other allergic reactions (with swelling
of the face and eyes and difficulty breathing in severe
cases)
• problems breathing or if you stop breathing. This is
more likely to occur if you are elderly or if your dose is
too high or it is given too quickly
• your heart stopping.

LFT MIDAZOLAM 2MG-ML AMP

At the start of a general anaesthetic
One or more intravenous injections may be given until
you are sedated.

4. POSSIBLE SIDE EFFECTS
Like many medicines Midazolam Injection may cause
side effects in some patients, although not everybody
gets them. The side effects are generally mild. If you
are elderly or very run-down you are more likely to
have side effects.

Description

Monitoring of Response
Patients who receive Midazolam Injection for sedation
in intensive care should be on a ventilator. If you receive
a continuous intravenous infusion of Midazolam
Injection, the infusion should be stopped / reduced
everyday to see how you recover from its effect. If
recovery takes more than two hours, a lower dose
should be used.

This medicine should not be used if the expiry date on
the ampoule has passed. The expiry date refers to the
last day of that month.

Wockhardt UK Limited

Patients who are receiving certain pain killers (e.g.
fentanyl)
If you take or are given these drugs you should have
them before you are given your Midazolam Injection.
Low doses of Midazolam Injection (0.01 to 0.1mg/kg
body weight per hour) may be used to start.

5. HOW TO STORE MIDAZOLAM INJECTION
Keep out of the reach and sight of children.

Customer

Patients who have kidney or liver disease, who
have a low body temperature, or who are severely
dehydrated
A smaller dose should be given.

Withdrawal symptoms
Withdrawal symptoms include anxiety, depression,
impaired concentration, inability to sleep, headache,
dizziness, ringing in your ears, loss of appetite, tremor,
sweating, irritability, 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.

Measure bar should be 150mm at 100% scale

Alternatively you may be given 0.03 to 0.3mg/kg body
weight over five minutes, followed by 0.03 to 0.2mg/kg
body weight every hour given by continuous
intravenous infusion (a continuous injection into a vein
in your arm).

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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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