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MIDAZOLAM 2MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): MIDAZOLAM

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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.

Sedation in the critically ill patient:Midazolam injection can be given intravenously by two
methods for this purpose, either by continuous infusion or
by intermittent bolus dose. Both have their own
advantages and disadvantages and the appropriate method
of giving midazolam injection will need to be determined for
each patient.
The dose of midazolam injection needed to sedate critically
ill patients varies considerably between patients. The dose
should be titrated to the desired state of sedation. This will
depend on clinical need, physical status, age and
concomitant medication.
Midazolam injection can also be given in combination with
an opioid. The opioid may be used for its analgesic effects
or as an antitussive agent to help the patient tolerate the
tracheal tube and ventilatory support.
Patients receiving midazolam injection for sedation in the
intensive care situation should receive ventilatory support.
Safe use for midazolam for periods of over 14 days in
duration has not been established in clinical trials.
Potential drug interactions:The critically ill patient is exposed to many drugs. Because
of this, there is a potential for drug interactions. (Refer to
Section 4.5 Interactions with other medicaments and other
forms of interaction).
After prolonged iv administration of midazolam injection,
abrupt discontinuation may be accompanied by withdrawal
symptoms, therefore a gradual reduction of the drug is
recommended.
Sedation by intermittent bolus dose in intensive care

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.

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.

Adults: 2mg, (1ml of 2mg/ml midazolam injection solution)
over a period of 30 seconds initially
Elderly: 1 to 1.5mg (0.5-0.75ml of 2mg/ml midazolam
injection solution) over a period of 30 seconds initially.

Midazolam injection and an opioid
When midazolam and an opioid are used together, the
opioid should be administered first. Both drugs need to be
titrated to the individual patient's response and to the level
of sedation thought to be necessary.

If adequate sedation is not achieved after two minutes,
incremental doses of 0.5-1mg, (0.25-0.5ml of 2mg/ml
midazolam injection solution) should be given until the
desired level of sedation is achieved, usually at a total
dose of 2.5-7.5mg (about 70 micrograms/kg) in adults.

Small doses of midazolam 1-2mg (0.5-1.0ml of 2mg/ml
midazolam injection solution) can be given, and repeated,
until the required degree of sedation is reached. In the
elderly, smaller doses as little as 0.5-1.0mg (0.25-0.5ml of
2mg/ml midazolam injection solution) may be adequate.

Renal/hepatic impairment: Reduce dose

The use of these two groups of drugs can increase the risk
of respiratory depression. If the patient is being given
ventilatory support using a mode that depends upon some
spontaneous effort by the patient, then the minute volume
may decrease.

Children
Not recommended. Midazolam injection has not been
evaluated as an intravenous sedative in children.
Combination therapy:If analgesia is provided by a narcotic analgesic, the
analgesic should be administered first. The dose of
midazolam injection should then be carefully titrated.
Low total doses of 1-2mg may be adequate with lower
total doses of 0.5-1mg in the elderly.
Mode of administration:For the administration of midazolam injection the patient
should be placed in a supine position and remain there
throughout the procedure. Resuscitation facilities should
always be available and a second person, fully trained in
the use of such equipment, always be present. It is
recommended that patients should remain under medical
supervision until at least one hour has elapsed from the
time of injection. They should always be accompanied
home by a responsible adult.
Patients who have received only midazolam injection for
iv sedation prior to minor procedures, should be warned
not to drive or operate machinery for 12 hours. Where
midazolam injection is used concurrently with other central
nervous system depressants (e.g. potent analgesics)
recovery may be prolonged. Patients should therefore be
assessed carefully before being allowed to go home or
resume normal activities.

Sedation by continuous infusion in intensive care
Midazolam injection only
Adults, Elderly and children
For patients already sedated or anaesthetised after an
operation, a loading dose of midazolam is unnecessary.
In other situations a loading dose of 0.03-0.3mg/kg given
over a five minute period is recommended, depending on
the level of sedation required. The loading dose should be
reduced or omitted in hypovolaemic, vasoconstricted or
hypothermic patients, renal or hepatic impairment.
Maintenance dose
A dose between 0.03-0.2mg/kg/hour is recommended,
starting at the lower dose.
The dose should be reduced in hypovolaemic,
vasoconstricted or hypothermic patients, renal or hepatic
impairment.
Midazolam injection and an opioid
When opioid analgesics are used, the rate of infusion
of midazolam should be titrated carefully to the
sedative needs of the patient. Low doses of midazolam
0.01 to 0.1mg/kg/hour may be used to start.

The use of these two groups of drugs can increase the risk
of respiratory depression. If the patient is being given
ventilatory support using a mode that depends upon some
spontaneous effort by the patient, then the minute volume
may decrease.
Whenever a continuous infusion of midazolam is used
(with or without an opioid analgesic), its need should be
assessed on a daily basis in order to reduce the risk of
accumulation and prolonged recovery. Each day the
infusion of midazolam should be stopped or its rate
reduced and the patient seen to recover from its effect.
If recovery is prolonged (>2 hours) a lower dose should
be used when it is restarted. A sedation score should be
used routinely.

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
When midazolam has been given for a number of days and disorders. The disinhibiting effects of benzodiazepines may
then gradually withdrawn, patients may be awake but show be manifested as the precipitation of suicide in patients
signs of residual sedation for the next 12 to 24 hours. This who are depressed or show aggressive behaviour towards
can cause difficulties because patients may not cough and self and others.
expectorate well if they are then weaned from ventilatory
This medicinal product contains 0.15mmol sodium per
support. However, while recovering from the effects of
ampoule. To be taken into consideration by patients on a
midazolam, patients may not be sufficiently sedated to
controlled sodium diet.
tolerate ventilatory support. In such circumstances
sedation may be provided with a shorter acting agent while
4.5 Interactions with other medicinal products and
there is recovery from the effects of midazolam.
other forms of interaction
Alcohol: Alcohol should be avoided for at least eight hours
The recommended concentration of a solution for infusion
before and after the administration of midazolam due to
in a critically ill adult patient is 1mg/ml.
increased sedative effects.
Induction of anaesthesia by slow intravenous injection
One or more bolus intravenous injections should be
Anaesthetics and narcotic analgesics: Enhanced sedation or
administered over a single anaesthetic session.
respiratory and cardiovascular depression. If such centrally
acting depressant drugs are given parenterally in conjunction
Adults
with intravenous midazolam, severe respiratory and
The dose should be titrated against the individual response cardiovascular depression may occur; careful monitoring is
of the patient. Midazolam injection should be given by slow required. When intravenous midazolam is to be administered
intravenous injection until there is a loss of eyelid reflex,
concurrently with a narcotic analgesic agent (e.g. fentanyl), it
response to commands and voluntary movements.
is recommended that midazolam be given after the analgesic
and that the dose be carefully titrated to meet the patient's
In anticipating the required dose of midazolam, both the
needs. Fentanyl may reduce midazolam clearance.
premedication already given and the age of the patient are
important. Young, fit unpremedicated patients may need at Antibacterials: Agents that interfere with metabolism
least 0.3mg/kg bodyweight, whereas patients premedicated by hepatic enzymes (e.g. isoniazid, erythromycin,
with an opiate usually need only 0.2mg/kg bodyweight.
clarithromycin, quinupristin/dalfopristin) have been
shown to reduce the clearance of benzodiazepines and
Use in the elderly
may potentiate their actions, whilst known inducers of
The elderly are more sensitive to the effects of
hepatic enzymes, for example, rifampicin, may increase
benzodiazepines. Induction may be adequate with
the clearance of benzodiazepines.
0.1mg/kg body weight in premedicated patients and
0.2mg/kg body weight in unpremedicated patients.
Antidepressants: Enhanced sedation or respiratory and
cardiovascular depression. Midazolam plasma levels
Renal/hepatic impairment: Reduce dose.
increased by concomitant nefazodone.
Children over seven years
Midazolam injection has been shown to be an effective
Antiepileptics: Enhanced sedation or respiratory or
agent for induction of anaesthesia in children over seven
cardiovascular depression. Midazolam may interact with
years of age, at a dose of 0.15mg/kg body-weight.
other hepatically metabolised drugs, e.g. phenytoin,
causing potentiation.
Mode of administration:For the administration of midazolam injection the patient
Antifungals: Ketoconazole, itraconazole, and possibly
should be placed in a supine position and remain there
fluconazole, have been shown to reduce the clearance of
throughout the procedure. Resuscitation facilities should
benzodiazepines and may potentiate their actions
always be available and a second person, fully trained in
the use of such equipment, always be present. It is
Antihistamines: Enhanced sedation or respiratory and
recommended that patients should remain under medical
cardiovascular depression with sedative antihistamines.
supervision until at least one hour has elapsed from the
time of injection. They should always be accompanied
Antihypertensives: Enhanced hypotensive effect. Enhanced
home by a responsible adult.
sedative effect possible with moxonidine.
4.3 Contraindications
Known hypersensitivity to benzodiazepines or any of the
ingredients. Severe or acute respiratory
insufficiency/depression.
Severe hepatic insufficiency

Antipsychotics: Enhanced sedation or respiratory and
cardiovascular depression. Severe hypotension, collapse,
respiratory depression, potentially fatal respiratory arrest
and unconsciousness have been reported in a few patients
on benzodiazepines and clozapine. Caution is advised
when initiating clozapine therapy in patients taking
benzodiazepines.

4.4 Special warnings and precautions for use
Midazolam injection should be used with caution in patients
with renal or hepatic dysfunction (see 4.2 Posology and
Antivirals: Concomitant use of midazolam with HIV-protease
Method of Administration), chronic pulmonary insufficiency, inhibitors (e.g. amprenavir, ritonavir) should be avoided due
myasthenia gravis, coma, or a known history of drug or
to the risk of extreme sedation and respiratory depression.
alcohol abuse.
Anxiolytics and hypnotics: Enhanced sedation or
Midazolam may enhance the effects of other CNS
respiratory and cardiovascular depression with other
depressants and may result in severe respiratory or
anxiolytics and hypnotics.
cardiovascular depression. Their concurrent use should be
avoided. Elderly or debilitated patients are more prone to the Calcium-channel blockers: Diltiazem and verapamil have
CNS effects of benzodiazepines and, therefore, lower doses been shown to reduce the clearance of benzodiazepines
are required (see 4.2 Posology and Method of Administration). and may potentiate their actions.

28/10/2015
Date

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LFT MIDAZOLAM 2MG-ML AMP

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
Read all of this leaflet carefully before you start
• medicines used for mental illness, such as clozapine Talk to your doctor or pharmacist if you are not sure
using this medicine.
• nabilone, used to treat vomiting due to cancer therapy whether it is safe for you to drive while taking this
- Keep this leaflet. You may need to read it again.
medicine.
- If you have further questions, please ask your doctor
Medicines used during operations:
or nurse.
Alcohol and Midazolam Injection
- This medicine has been prescribed for you personally • anaesthetics
• certain pain killers (e.g. fentanyl) – If you take or are You should not drink alcohol for at least eight hours
and you should not pass it on to others. It may harm
before or after having an injection of midazolam.
given these drugs you should have them before you
them, even if their symptoms are the same as yours.
receive your Midazolam Injection and will need to be
carefully monitored for problems with your breathing Important information about the sodium content of
The name of your medicine is Midazolam 2mg/ml
Midazolam Injection
Solution for Injection or Infusion. In the rest of this leaflet and your heart
This medicinal product contains less than 1 mmol
• medicines used to relax your muscles during an
it is called Midazolam Injection.
sodium (23mg) per ampoule, i.e. it is essentially
operation (e.g. baclofen)
‘sodium-free’.
In this leaflet:
Medicines that fight infections:
1. What Midazolam Injection is and what it is used for
• antibiotics, used to treat bacterial infections, such as 3. HOW MIDAZOLAM INJECTION
2. Before you are given Midazolam Injection
SHOULD BE GIVEN
erythromycin, clarithromycin, quinupristin with
3. How Midazolam Injection should be given
You will only be given Midazolam Injection in places
dalfopristin
4. Possible side effects
with adequate resuscitation equipment and when there
• drugs used to treat fungal infections, such as
5. How to store Midazolam Injection
is a second member of staff present to help your doctor.
ketoconazole, itraconazole or fluconazole
6. Further information
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.
1. WHAT MIDAZOLAM INJECTION IS
amprenavir or ritonavir used for HIV
AND WHAT IT IS USED FOR
• drugs used for tuberculosis, such as isoniazid or
Your doctor will decide which dose is suitable for you.
rifampicin
The active ingredient in Midazolam Injection is
The dose used will depend on what the injection is
midazolam which belongs to a group of sedative
being given for and on your general physical condition,
Other medicines:
medicines called benzodiazepines.
age, weight, what other medicines you are taking and
• medicines to lower your blood pressure, such as to
your response to the drug.
diltiazem, verapamil or moxonidine
Midazolam Injection is used:
• for sedation before and during minor medical, dental • medicines used for pain relief and inflammation such For sedation before and during minor surgery or
as aspirin
or surgical procedures
dental procedures
• medicines used to treat stomach ulcers, such as
• for sedation of patients in intensive care
cimetidine,
ranitidine
or
omeprazole
• at the start of a general anaesthetic
Adults
• levodopa, a drug used in the treatment of
The usual adult dose for sedation of adults before and
Parkinson's disease
2. BEFORE YOU ARE GIVEN MIDAZOLAM
during minor surgery or dental procedures is 2mg
• theophylline, a drug used for asthma and lung
INJECTION
given into a vein over a period of 30 seconds. Further
disease
injections of 0.5 - 1mg may be given every two minutes
You should not be given Midazolam Injection if you: • probenecid, used for gout.
until you are properly sedated. The total dose required
• are allergic to midazolam or any of the other
is usually 2.5 to 7.5mg.
ingredients contained in Midazolam Injection
If you have any doubts about whether you should be
(see list under heading ‘What Midazolam Injection
given this medicine then discuss matters with your
Elderly
contains’ in section 6)
doctor.
The usual dose for the elderly is 1 to 1.5mg, given into
• have severe breathing problems
a vein over a period of 30 seconds. Further 0.5 - 1mg
• have severe liver problems.
Pregnancy and breast-feeding
injections may be given every two minutes until you
You should not usually be given Midazolam Injection if
are properly sedated.
If any of the above statements apply to you, you should you are pregnant. If Midazolam Injection is given to
not be given Midazolam Injection.
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
Speak to your doctor before you are given
particularly a split in the mouth (cleft palate). Infants
children.
Midazolam Injection if you:
born to mothers who are given Midazolam Injection
• are elderly
during the late stages of pregnancy may experience
If you have kidney or liver disease
• are very run down and lack strength
withdrawal symptoms or slow development.
If you have kidney or liver disease you will be given a
• have problems with your liver, kidneys or lungs
lower dose.
• have a condition called myasthenia gravis which
If your doctor has decided that you should be given this
causes very weak muscles
medicine during labour, your baby might have a low
If you are in intensive care
• have a personality disorder, depression,
body temperature, floppiness, an abnormal heart rate
Adults, Elderly and Children
aggressive tendencies or if you feel suicidal
and breathing or feeding difficulties.
Small doses of 1 to 2mg may be given directly into a vein
• have had problems with addiction to drugs or alcohol
and repeated until sedation is achieved. For the elderly
If you wish to become pregnant, you should speak to
even smaller doses of 0.5 to 1mg may be adequate.
Special care should be taken if the patient is in a coma. your doctor about the use of Midazolam Injection.

Description

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

Wockhardt UK Limited

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.

Customer

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.

Measure bar should be 150mm at 100% scale

Taking other medicines
Taking another medicine while you are being given
Midazolam Injection can affect how it or the other
Midazolam 2mg/ml Solution for Injection or medicine works. Please inform your doctor or nurse if
you are taking or have recently taken any other
Infusion
medicines, drugs or herbal products, including those
Midazolam
you may have bought yourself without a prescription.
PACKAGE LEAFLET
INFORMATION FOR THE USER

Withdrawal symptoms
Withdrawal symptoms include anxiety, depression,
impaired concentration, inability to sleep, headache,

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.
Ulcer-healing drugs: Cimetidine, ranitidine and omeprazole
have been shown to reduce the clearance of
benzodiazepines and may potentiate their actions.

By reporting side effects you can help provide more
information on the safety of this medicine.

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).
Disorders of the eye: Visual disturbances.
Gastrointestinal: dry mouth, gastrointestinal disturbances.

Xanthines: Benzodiazepine metabolism is accelerated by
xanthines.
4.6 Pregnancy and lactation
There is no evidence regarding the safety of midazolam in
pregnancy. It should not be used, especially in the first and
third trimesters, unless the benefit is considered to
outweigh the risk.
If the product is prescribed to a woman of childbearing
potential she should be warned to contact her physician
regarding discontinuance of the product if she intends to
become or suspects that she is pregnant.

General: Fatigue and a hangover effect. Local pain on
injection. Hiccups.
Haematological: Blood dyscrasias.
Hepatic: Jaundice.
Immunological: Skin reactions and other hypersensitivity
reactions, including anaphylaxis, are rare.

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Marketing Authorisation Holder: Wockhardt UK Ltd,
Ash Road North, Wrexham, LL13 9UF, UK.
Manufacturer: CP Pharmaceuticals Ltd, Ash Road
North, Wrexham, LL13 9UF, UK.
Other formats:
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large print or audio please call, free of charge:
0800 198 5000 (UK Only)
Please be ready to give the following information:
Product Name

Reference Number

Midazolam 2mg/ml
Solution for Injection
or Infusion

29831/0140

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This leaflet was last revised in 11/2015.

100997/8

suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.
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.

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.
6.4 Special precautions for storage
Do not store above 25°C. Keep container in outer carton.

6.5 Nature and contents of container
Neurological: Headaches, confusion, slurred speech, tremor,
Midazolam binds to specific receptors in the central
Neutral glass ampoules Type I Ph Eur 5ml packed in
drowsiness, reduced alertness, anterograde amnesia,
nervous system (CNS). The benzodiazepine receptors in the
5 or 10s in an outer printed carton
extrapyramidal effects.
CNS have a close functional connection with receptors of
There may be a small increase in the risk of congenital
the GABA-ergic transmitter system. After binding to the
6.6 Special precautions for disposal
malformation, particularly oral cleft, with the use of
Psychiatric: Increased risk of postoperative delirium.
benzodiazepine receptor, midazolam augments the
The injection is for single patient use and should be used
benzodiazepines in the first trimester. In labour, high single Numbed emotions. In susceptible patients, an unnoticed
inhibitory effect of GABA-ergic transmission.
immediately after opening. The injection should not be
doses or repeated low doses have been reported to
depression may become evident. Paradoxical reactions
used if particles are present. Any unused portion should
produce effects on the neonate, such as hypothermia,
(including aggressive behaviour, hostility, hallucinations,
5.2 Pharmacokinetic properties
be discarded.
hypotonia, moderate respiratory depression, irregularities in disinhibition, excitation, irritability and increased anxiety)
Midazolam is highly lipid soluble and crosses the blood
the foetal heart rate, and poor suckling in the neonate
are known to occur with benzodiazepines and are more
brain barrier. These properties qualify it for intravenous use
Midazolam for infusion may be prepared by dilution with
(floppy infant syndrome).
likely in children and the elderly.
in short term anaesthetic procedures since it acts promptly
infusion fluids containing 5% glucose, 4% glucose with
on the brain, and its initial effects decrease rapidly as it is
0.18% sodium chloride or 0.9% sodium chloride.
Infants born to mothers who take benzodiazepines
Reproductive: Changes in libido
distributed into fat deposits and tissues. Following the
chronically during the latter stages of pregnancy may
administration of 150 micrograms/kg intravenously,
Chemical and physical in-use stability has been
develop physical dependence and may be at some risk for Respiratory: Midazolam can produce, respiratory
plasma concentrations in the range 291-425 ng/ml are
demonstrated for 24 hours at 25°C.
developing withdrawal symptoms in the postnatal period.
depression, apnoea and may cause respiratory arrest
reached within five minutes.
following iv administration, especially in the elderly with
From a microbiological point of view, the product should be
A small number of children exposed in utero to
pre-existing respiratory insufficiency or when the dose is
Midazolam is almost completely absorbed following
benzodiazepines have shown slow development in the early excessive or administered too rapidly.
intramuscular injection, peak plasma levels being attained used immediately. If not used immediately, in-use storage
times and conditions prior to use are the responsibility of
years but by four years of age have developed normally.
within 45 minutes.
the user and would normally not be longer than 24 hours at
Urinary: urinary retention, incontinence.
2-8°C, unless dilution has taken place in controlled and
Since benzodiazepines are found in the breast milk,
Midazolam is extensively protein bound (94-98%). The
validated aseptic conditions.
benzodiazepines should not be given to breast-feeding
Withdrawal symptoms:
volume of distribution is between 0.8 and 1.7 litres/kg.
mothers.
Development of dependence is common after regular use,
Midazolam crosses the placenta. It is not known whether
7. MARKETING AUTHORISATION HOLDER
even in therapeutic doses for short periods, particularly in
midazolam enters breast milk, but this is likely as it is
Wockhardt UK Ltd, Ash Road North
4.7 Effects on ability to drive and use machines
patients with a history of drug or alcohol abuse or marked
known to occur with other benzodiazepines.
Wrexham, LL13 9UF
The concurrent use of midazolam with other central
personality disorders. Discontinuation may be associated
nervous system depressants, may result in a prolonged
with withdrawal symptoms or rebound phenomena
Midazolam is extensively metabolised in the liver,
8. MARKETING AUTHORISATION NUMBER(S)
recovery. A careful assessment should be undertaken
(see 4.4 Special Warnings and Precautions for Use).
involving the P450 IIIA enzymes. The principal metabolite,
prior to allowing the patient to go home or resume
Symptoms of benzodiazepine withdrawal include anxiety,
1-hydroxy midazolam, appears in the urine as a glucuronide. PL 29831/0140
normal activities.
depression, impaired concentration, insomnia, headache,
The metabolite is less pharmacologically active than
9. DATE OF FIRST AUTHORISATION/RENEWAL OF
dizziness, tinnitus, loss of appetite, tremor, perspiration,
midazolam and has a shorter half-life of about one hour.
THE AUTHORISATION
Patients treated with midazolam injection should not drive
irritability, perceptual disturbances such as hypersensitivity Midazolam has a mean elimination half-life of two to three
27 March 2007
or use machinery for twelve hours after receiving this
to physical, visual, and auditory stimuli and abnormal taste, hours. The half-life is short compared with other
medicine.
nausea, vomiting, abdominal cramps, palpitations, mild
benzodiazepines. Less than 1% midazolam is excreted
10. DATE OF REVISION OF THE TEXT
systolic hypertension, tachycardia, and orthostatic
unchanged via the kidneys and the drug is cleared virtually
November 2015
This medicine can impair cognitive function and can affect hypotension, Rare and more serious withdrawal symptoms entirely by the liver. The half-life of midazolam is prolonged
a patient’s ability to drive safely. This class of medicine is in include muscle twitching, confusional or paranoid
in neonates, in the elderly and patients with liver disorders.
psychosis, convulsions, hallucinations, and a state
the list of drugs included in regulations under 5a of the
resembling delirium tremens. Broken sleep with vivid
Road Traffic Act 1988. When prescribing this medicine,
5.3 Preclinical safety data
dreams and increased REM sleep may persist for some
patients should be told:
In vitro and in vivo microbial and mammalian test systems
weeks after withdrawal of benzodiazepines.
• The medicine is likely to affect your ability to drive
have revealed no evidence of mutagenicity. No evidence of
• Do not drive until you know how the medicine affects
carcinogenic potential was seen in rats or mice given oral
Reporting of suspected adverse reactions
you
midazolam maleate in doses up to 25 times the human
• It is an offence to drive while under the influence of this Reporting suspected adverse reactions after authorisation
recommended daily dose for two years.
of the medicinal product is important. It allows continued
medicine
monitoring of the benefit/risk balance of the medicinal
• However, you would not be committing an offence
In humans, the risk of congenital abnormalities from the
product. Healthcare professionals are asked to report any
(called ‘statutory defence’) if:
ingestion of therapeutic doses of benzodiazepines is slight, 100997/8

Artwork No.

606116

28/10/2015
Date

English
Language

1

UK
Market

Proof No.

6pt (main body) / 8.5pt (variables)
Min. Point Size

matt.pirie-scott

185 x 475mm
Size

Proof By

As per uploaded pdf

100997/8
Item Code

Profile

Pharma
Code

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

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

What Midazolam Injection looks like and contents of
the pack
Midazolam Injection is a clear, colourless solution.

LFT MIDAZOLAM 2MG-ML AMP

The other ingredients are sodium chloride, hydrochloric
acid solution, sodium hydroxide solution and water for
injections.

Description

6. FURTHER INFORMATION
What Midazolam Injection contains
The active ingredient in Midazolam Injection is
midazolam. The injection is available in 5ml ampoules.
Each ampoule contains 10mg of the active ingredient in
5ml of solution.

Wockhardt UK Limited

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.

Customer

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

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.

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
If you think you have missed a dose of
the toilet)
Midazolam Injection
A doctor or nurse will give you this medicine. If you think • changes in sexual desire
• blood problems
you have missed a dose, inform your doctor or nurse.
• some patients, particularly if they are children or
elderly, may become irritable, aggressive, hostile,
Stopping Midazolam Injection
overexcited, uninhibited, overanxious or have
If you are given Midazolam Injection for a long time,
hallucinations.
there is a risk of becoming dependent on it in which
case you may have withdrawal symptoms when you
Reporting of side effects
stop taking it. The dose should be reduced gradually
If you get any side effects, talk to your doctor, or
to reduce the risk of withdrawal symptoms and you
pharmacist or nurse. This includes any possible side
should never stop your Midazolam Injection abruptly.
effects not listed in this leaflet. You can also report side
Your doctor will decide when to stop your treatment
effects directly via the Yellow Card Scheme at
with Midazolam Injection.
www.mhra.gov.uk/yellowcard

This medicine should not be stored above 25°C.

Clearly mark any amendments on one proof and return to MPS

Gut problems:
• dry mouth
• stomach problems

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.

artwork.leicester@multipkg.com

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.

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

Measure bar should be 150mm at 100% scale

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
Patients who have kidney or liver disease, who have include muscle twitching, confusion, paranoia, fits,
a low body temperature, or who are severely
hallucinations, and delirium. Broken sleep with vivid
dehydrated
dreams may persist for some weeks after withdrawal.
A smaller dose should be given.
4. POSSIBLE SIDE EFFECTS
Patients who are receiving certain pain killers
Like many medicines Midazolam Injection may cause
(e.g. fentanyl)
side effects in some patients, although not everybody
If you take or are given these drugs you should have
gets them. The side effects are generally mild. If you
them before you are given your Midazolam Injection.
are elderly or very run-down you are more likely to
Low doses of Midazolam Injection (0.01 to 0.1mg/kg
have side effects.
body weight per hour) may be used to start.
If you experience any of the following, you should
Monitoring of Response
contact your doctor or nurse immediately:
Patients who receive Midazolam Injection for sedation
rashes or other allergic reactions (with swelling
in intensive care should be on a ventilator. If you receive • skin
the face and eyes and difficulty breathing in severe
a continuous intravenous infusion of Midazolam Injection, of
the infusion should be stopped / reduced everyday to see • cases)
problems breathing or if you stop breathing. This is
how you recover from its effect. If recovery takes more
more likely to occur if you are elderly or if your dose is
than two hours, a lower dose should be used.
too high or it is given too quickly
• your heart stopping.
At the start of a general anaesthetic
One or more intravenous injections may be given until
Less serious side effects include:
you are sedated.
Heart and circulation problems
• slow pulse
Adults
If you have not received any pre-medication the usual • chest pain
adult dose is about 0.3mg/kg body weight. If you have • low blood pressure
• inflammation of your veins
received pre-mediation however, you may only need
about 0.2mg/kg body weight.
Nervous system problems:
• dizziness, lack of coordination and over sedation with
Elderly
a risk of falls and other accidents
The elderly are more sensitive to Midazolam Injection
so the doses required tend to be lower than for adults. • headaches
If you have not received any pre-medication the usual • confusion
• slurred speech
dose is about 0.2mg/kg body weight. However, if you
have received pre-medication you may only need about • drowsiness
• tremor
0.1mg/kg body weight.
• uncontrolled jerky movements
• reduced alertness
Children over seven years
• forgetfulness
The usual dose for children over seven years is about
0.15mg/kg body weight.
Mental problems:
• numbed emotions
If you have kidney or liver disease
• depression
If you have kidney or liver disease you will be given a
• delirium after surgery
lower dose.
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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