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DIAZEPAM 5MG/ML SOLUTION FOR INJECTION

Active substance(s): DIAZEPAM

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Clearly mark any amendments on one proof and return to MPS

artwork.leicester@multipkg.com
Diazepam 5mg/ml injection leaflet

Wockhardt UK Limited

Measure bar should be 150mm at 100% scale

Customer

W-LFT001

Description

460 x 150mm

104323/5

Profile

5pt (main body) / 5.2pt (variables)

Item Code

Size

UK

Process Black

Colours Used

Keyline (non-printing)

Text Free Area (non-printing)

4.1 Therapeutic indications
Diazepam injection may be used in severe or disabling anxiety and agitation;
for the control of status epilepticus, epileptic and febrile convulsions; to relieve
muscle spasm; as a sedative in minor surgical and dental procedures; or other
circumstances in which a rapid effect is required.
4.2 Posology and method of administration
Dosage depends on individual response, age and weight.
Adults:
In severe anxiety or acute muscle spasm, diazepam 10mg may be given
intravenously or intramuscularly and repeated after 4 hours.
In tetanus, 0.1 to 0.3mg per kg bodyweight may be given intravenously and
repeated every 1-4 hours; alternatively, a continuous infusion of 3 to 10mg per kg
every 24 hours may be used or similar doses may be given by nasoduodenal tube.
In status epilepticus or epileptic convulsions, 0.15-0.25mg per kg (usually
10-20mg) is given by intravenous injection. The dose can be repeated if necessary
after 30 to 60 minutes. Once the patient is controlled, recurrence of seizures may
be prevented by a slow infusion (maximum total dose 3mg per kg over 24 hours).
In minor surgical procedures and dentistry, 0.1-0.2mg per kg by injection
(usually 10-20mg) adjusted to the patient’s requirements.
Elderly:
Elderly or debilitated patients should be given not more than half of the usual dose.
Hepatic/renal impairment
Dosage reduction may also be required in patients with liver or kidney dysfunction.
Children
In status epilepticus, epileptic or febrile convulsions: 0.2-0.3mg per kg
(or 1mg per year of life) is given by intravenous injection. The dose can be
repeated if necessary after 30 to 60 minutes.
Sedation or muscle relaxation: up to 0.2mg per kg may be given parenterally.
Neonates:
Not recommended; dosage has not been established and Diazepam Injection
contains benzyl alcohol which should be avoided in injections to neonates.
IMPORTANT: In order to reduce the likelihood of adverse effects during
intravenous administration the injection should be given slowly
(1.0ml solution per minute). It is advisable to keep the patient supine for
at least an hour after administration. Except in emergencies, a second
person should always be present during intravenous use and facilities for
resuscitation should always be available.
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, with a warning not to drive or operate
machinery for 24 hours.
Intravenous injection may be associated with local reactions and thrombophlebitis
and venous thrombosis may occur. In order to minimise the likelihood of these
effects, intravenous injections of diazepam should be given into a large vein of the
antecubital fossa.
Where continuous intravenous infusion is necessary it is suggested that
2ml Diazepam Injection is mixed with at least 200ml of infusion fluid such as
Sodium Chloride Injection or Dextrose Injection and that such solutions should
be used immediately. There is evidence that diazepam is adsorbed onto plastic
infusion bags and giving sets. It is therefore recommended that glass bottles
should be used for the administration of diazepam by intravenous infusion.
4.3 Contraindications
Known sensitivity to benzodiazepines or any of the ingredients
Severe or acute respiratory insufficiency/depression
Sleep apnoea syndrome
Severe hepatic insufficiency
Avoid injection in neonates (contains benzyl alcohol)
Diazepam injection should not be used in phobic or obsessional states nor be used
alone in the treatment of depression or anxiety associated with depression due
to the risk of suicide being precipitated in this patient group. Diazepam Injection
should not be used for the primary treatment of psychotic illness. In common
with other benzodiazepines the use of diazepam may be associated with amnesia
and Diazepam Injection should not be used in cases of loss or bereavement as
psychological adjustment may be inhibited.
4.4 Special warnings and precautions for use
Diazepam injection should be used with caution in patients with renal or
hepatic dysfunction (see 4.2 Posology and Method of Administration), chronic
pulmonary insufficiency, porphyria, muscle weakness, myasthenia gravis, coma,
a known history of drug or alcohol abuse, or organic brain changes, particularly
arteriosclerosis.
Diazepam may enhance the effects of other CNS depressants; their concurrent
use should be avoided.
Elderly and debilitated patients are more prone to the CNS effects of
benzodiazepines and, therefore, lower doses are required (see section 4.2
Posology and Method of Administration). Benzodiazepines should be used with
caution in the elderly as long term use is associated with an increased risk of
developing dementia.
Dependence and withdrawal symptoms
The dependence potential of diazepam increases with dose and duration of
treatment and is greater in patients with a history of alcohol or drug abuse
(see 4.8 Undesirable Effects). It is low when limited to short term use. 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 Withdrawal symptoms). This should be
considered when treating patients for more than a few days; abrupt discontinuation
should be avoided and the dose reduced gradually.
Amnesia
Benzodiazepines may induce anterograde amnesia (see 4.8 Undesirable Effects).
The condition occurs most often several hours after administration. To reduce
the risk, where appropriate and possible, patients should be able to have an
uninterrupted sleep of 7-8 hours after administration.
Use in patients with concomitant mental illness
As with other benzodiazepines, extreme caution should be used if prescribing
diazepam for patients with personality disorders. The disinhibiting effects of

Min. Point Size

4. CLINICAL PARTICULARS

Market

Solution for Injection.
Clear, colourless to pale yellow liquid.

English

3. PHARMACEUTICAL FORM

Language

Diazepam 5mg/ml
Excipients - Contains Benzoic acid (E210) 1mg/ml, Ethanol 96% 100mg/ml,
sodium benzoate (E211) 49mg/ml, Benzyl alcohol 15mg/ml, Propylene glycol
400mg/ml and Sodium Content - 0.34mmol/ml.
For a full list of excipients, see section 6.1

benzodiazepines may be manifested as the precipitation of suicide in patients who
are depressed or show aggressive behaviour towards self and others.
Benzyl alcohol poisoning
This medicinal product contains 15mg/ml of benzyl alcohol. There is a risk of
benzyl alcohol poisoning with prolonged use of high-dose intravenous infusions of
diazepam injection containing benzyl alcohol.
Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants
and children up to three years old. Must not be given to premature babies or
neonates.
This medicinal product contains benzoic acid and sodium benzoate which may
increase the risk of jaundice in newborn babies.
This medicinal product contains 0.34mmol sodium per ml. To be taken into
consideration by patients on a controlled sodium diet.
This medicinal product contains 12.5 vol % ethanol (alcohol), i.e. 100mg per ml.
Harmful for those suffering from alcoholism.
To be taken into account in pregnant or breast-feeding women, children and
high-risk groups such as patients with liver disease or epilepsy.
4.5 Interaction with other medicinal products and other forms of interaction
Alcohol: Enhanced sedation or respiratory or CNS depression with concomitant
administration of diazepam. Concomitant use should be avoided.
General anaesthetics and narcotic analgesics: Enhanced sedation or respiratory
and cardiovascular depression. If such centrally acting depressant drugs are
given parenterally in conjunction with intravenous diazepam, severe respiratory
and cardiovascular depression may occur; careful monitoring is required. When
intravenous diazepam is to be administered concurrently with a narcotic analgesic
agent (e.g. fentanyl), it is recommended that diazepam be given after the analgesic
and that the dose be carefully titrated to meet the patient’s needs. Premedication
with diazepam may decrease the dose of fentanyl derivatives required for induction
of anaesthesia.
Antibacterials: Agents that interfere with metabolism by hepatic enzymes (isoniazid
and to a lesser extent erythromycin) may reduce the clearance of diazepam and
potentiate its action. Known inducers of hepatic enzymes, for example, rifampicin,
may increase the clearance of diazepam.
Antidepressants: Enhanced sedation or respiratory or CNS depression with
concomitant administration of mirtazapine or tricyclic antidepressants. Diazepam
plasma levels increased by concomitant fluvoxamine or fluoxetine.
Antiepileptics: Enhanced sedation or respiratory and cardiovascular depression.
Known inducers of hepatic enzymes, for example, carbamazepine, phenobarbital
and phenytoin, may increase the clearance of benzodiazepines, however,
despite enzyme stimulation, the net effect of adding these antiepileptics can be
augmentation of benzodiazepine-induced sedation. Serum phenytoin levels may
rise, fall or remain unaltered. In addition, phenytoin may cause diazepam serum
levels to fall. Concomitant sodium valproate may increase serum levels of
diazepam, with associated drowsiness.
Antihistamines: Enhanced sedation or respiratory and cardiovascular depression
with sedative antihistamines.
Antihypertensives: Enhanced hypotensive effect with concomitant administration
of ACE inhibitors or beta-blockers or calcium-channel blockers or vasodilator
hypertensives e.g. hydralazine. Enhanced sedative effect with alpha blockers and
possibly moxonidine.
Antipsychotics: Enhanced sedation or respiratory and cardiovascular depression.
Increased plasma concentrations of zotepine. 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.
Increased risk of hypotension, bradycardia and respiratory depression with
concomitant administration of parenteral benzodiazepines with intramuscular
olanzapine.
Antivirals: Amprenavir, ritonavir and saquinavir have been shown to reduce the
clearance of diazepam and may potentiate its actions, with risk of extreme sedation
and respiratory depression – avoid concomitant use.
Anxiolytics: Enhanced sedation or respiratory and cardiovascular depression with
other anxiolytics.
Digoxin: Reduced clearance of digoxin.
Disulfiram: has been shown to reduce clearance and may potentiate actions of
benzodiazepines.
Diuretics: Enhanced hypotensive effect when benzodiazepines and diuretics are
used concomitantly.
Dopaminergic agents: diazepam may cause inhibition of levodopa.
Hypnotics: Enhanced sedation or respiratory and cardiovascular depression.
Lofexidine: Enhanced sedation or respiratory and cardiovascular depression.
Muscle relaxants: Increased CNS depressant effects with baclofen and tizanidine.
Nabilone: Enhanced sedation or respiratory and cardiovascular depression.
Nicotine: Diazepam metabolism is accelerated by smoking.
Nitrates: Enhanced hypotensive effect when benzodiazepines and nitrates are
used concomitantly.
Oral contraceptives: May reduce the clearance of diazepam and may potentiate
its actions.
Sedatives: Enhanced sedation or respiratory and cardiovascular depression.
Sodium oxybate: Enhanced CNS depressant effects of sodium oxybate with
concomitant benzodiazepines.
Ulcer-healing drugs: Cimetidine, omeprazole and esomeprazole have been shown
to reduce the clearance of diazepam and may potentiate its actions.
Xanthines: Diazepam metabolism is accelerated by theophylline. Sedative effects
of diazepam reduced by caffeine. Sedative effects of diazepam reversed with
concomitant administration of aminophylline
4.6 Pregnancy and lactation
There is no evidence regarding the safety of diazepam in pregnancy, however,
diazepam and its metabolite desmethyldiazepam freely cross the placenta and
accumulate in the fetal circulation. 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 the discontinuance of the product if she
intends to become or suspects that she is pregnant.
There may be a small increase in the risk of congenital malformation, particularly
oral cleft, with the use of benzodiazepines in the first trimester.
In labour, high single doses or repeated low doses have been reported to produce
effects on the neonate, such as hyperbilirubinaemia, hypothermia, hypotonia,
respiratory depression and poor suckling (floppy infant syndrome) in the neonate
and irregularities in the foetal heart.
Infants born to mothers who take benzodiazepines chronically during the latter
stages of pregnancy may develop physical dependence and may be at some risk
for developing withdrawal symptoms in the postnatal period. A small number of
children exposed in utero to benzodiazepines have shown slow development in the
early years but by four years of age had developed normally.
Since benzodiazepines are found in the breast milk, benzodiazepines should not
be given to breast feeding mothers.

gill.kennedy

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Proof By

Diazepam 5mg/ml Solution for Injection

2

SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF MEDICINAL PRODUCT

Proof No.

Your doctor will decide the right dose for you. The dosage
depends on the condition being treated, weight and age.
If you do not understand what you are being given then ask your
doctor or nurse. The usual doses are as follows:
Adults
In severe anxiety or acute muscle spasm:
• 10mg given into a vein or into a muscle
• This may be repeated after 4 hours, if necessary
In tetanus (lockjaw):
• 0.1-0.3mg per kg bodyweight given into a vein every one to
four hours or
• 3-10mg per kg bodyweight given continuously over 24 hours
through a nasoduodenal tube ( a tube passed through the
nose into the gut)
In epileptic fits:
• 0.15-0.25mg per kg bodyweight given slowly into a vein
• this may be repeated if needed after 30-60 minutes.

282

3. How to take Diazepam Injection

Pharma
Code

You should NOT be given Diazepam Injection if you:
• a
 re allergic (hypersensitive) to diazepam, any other
benzodiazepines or to any of the other ingredients in
Diazepam Injection (see section 6, Further information)
• are suffering from phobias (irrational fears) or obsessions
• have breathing problems
• s uffer from obstructive sleep apnoea (a condition where you
stop breathing during sleep)
• have severe liver disease
• h
 ave suffered recent loss or bereavement as diazepam can
cause memory loss
• s uffer from depression, anxiety or other long standing mental
illness, for which you are not being treated.
Diazepam Injection should not be used in premature or
newborn babies.
Talk to your doctor before being given Diazepam Injection
if you:
• have a kidney or liver disease
• suffer from lung disease
• s uffer from porphyria (a disease of blood proteins affecting the
skin, gut and nervous system)
• s uffer from myasthenia gravis (a disease of the nervous
system causing muscle weakness)
• have a history of alcohol and/or drug abuse
• s uffer from brain disease (particularly diseases affecting the
blood circulation of the brain)
• if you take any medicines which affect the central nervous
system.
Caution should be taken when giving Diazepam Injection to
the elderly and comatose patients.
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have
recently taken any other medicines, including medicines
obtained without prescription. The following medicines can affect
or be affected by treatment with Diazepam Injection:
• m
 edicines used to treat bacterial infections (e.g. erythromycin,
isoniazid and rifampicin)
• m
 edicines used to treat depression (e.g. mirtazapine,
fluvoxamine and fluoxetine)
• m
 edicines used to treat fits (e.g. carbamazepine,
phenobarbital, phenytoin and sodium valproate)
• m
 edicines used in surgery (general anaesthetics) and strong
pain killers (narcotic analgesics e.g. fentanyl)
• m
 edicines used to treat allergies, including hay fever and
insect bites (antihistamines)
• medicines used to treat high blood pressure
• m
 edicines used to treat psychosis, schizophrenia and other
mental illnesses (e.g. onlanzapine, clozapine and zotepine)
• m
 edicines used to treat HIV infection (e.g. amprenavir,
saquinavir and ritonavir)

11/01/2016

2. Before you take Diazepam Injection

625416

The name of your medicine is Diazepam Injection; the active
ingredient is diazepam. This medicine belongs to a group of
medicines called benzodiazepines. Diazepam Injection is used:
• to treat anxiety and agitation
• as a sedative on minor surgical and dental procedures
• as an anticonvulsant (medicine to control fits)
• as a muscle relaxant

Date

1. What Diazepam Injection is and what it is used for

• medicines used to treat anxiety and sleep disturbance
• digoxin (used to treat abnormal heart rhythms and heart
failure)
• disulfiram (used to treat alcoholism)
• levodopa (used to treat Parkinson’s Disease)
• lofexidine (used to reduce symptoms of heroin withdrawal)
• baclofen and tizanidine (muscle relaxants)
• nabilone (used to treat nausea and nerve pain)
• oral contraceptives (“The Pill”)
• theophylline and aminophylline (used in asthma and lung
diseases)
• cimetidine, esomeprazole and omeprazole (used to treat
excess stomach acid and ulcers)
• diuretics (water tablets)
• nitrates, used in the treatment of angina
• sodium oxybate, used to prevent episodes of sudden onset of
sleep (narcolepsy) with muscle weakness.
Taking Diazepam Injection with food and drink
You should avoid smoking and drinking alcohol whilst taking this
medicine. Some of the ingredients of coffee (caffeine) will affect
the way Diazepam Injections work.
Pregnancy and breast-feeding
You should not use this medicine if you are pregnant or breast
feeding (unless your doctor decides it is essential). Tell your
doctor straight away if you think you may be pregnant or intend
to start a pregnancy.
Driving and using machinery
This medicine can affect your ability to drive.
Do not drive whilst taking this medicine until you know how this
medicine affects you.
It may be an offence to drive if your ability to drive safely is
affected.
There is further information for patients who are intending to
drive in Great Britain – go to http://www.gov.uk/drug-driving-law
Important information about some of the ingredients in
Diazepam Injection
This medicine contains
• 12.5 vol % ethanol (alcohol) i.e. 100mg per ml, equivalent to
10ml beer, 4ml wine per dose. It is therefore harmful to those
suffering from alcoholism. This should also be taken into
account in pregnant or breast-feeding women, children and
high risk groups such as patients with liver disease or epilepsy.
• 15mg/ml of benzyl alcohol and so must not be given
to premature or newborn babies. It may cause toxic and/or
allergic reactions in infants and children up to three years.
• sodium benzoate (E211) and benzoic acid (E210) which may
increase the risk of jaundice in newborn babies.
• 0.34mmol/ml of sodium. This should be considered in patients
on a controlled sodium diet.

Artwork No.

In this leaflet:
1. W
 hat Diazepam Injection is and what it is used for
2. Before you take Diazepam Injection
3. How to take Diazepam Injection
4. Possible side effects
5. How to store Diazepam Injection
6. Further information

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.

(Refer to as Diazepam Injection in this leaflet)
Read all of this leaflet carefully before you start to take this medicine.
- Keep this leaflet. You may need to read it again while you are receiving your treatment.
- If you have any further questions, please ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their
symptoms are the same as yours.
- If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell
your doctor or pharmacist.

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

PACKAGE LEAFLET: INFORMATION FOR THE USER
Diazepam 5mg/ml Solution for Injection
Diazepam 5mg/ml

460 x 150mm

W-LFT001

8

MARKETING AUTHORISATION NUMBER(S)

PL 29831/0065
PA 1339/6/1
PA 1339/6/2
MA 154/01103

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
UK: 08/02/2008
Ireland: 22/05/2009
Malta: 29/05/2009

10 DATE OF REVISION OF THE TEXT
08/2015
104323/5

Process Black

MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd
Ash Road North
Wrexham
LL13 9UF
UK

Colours Used

7

Keyline (non-printing)

PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Benzoic acid (E210)
Ethanol
Propylene glycol
Sodium benzoate (E211)
Benzyl alcohol
Water for Injections
6.2 Incompatibilities
Diazepam Injection should not be mixed with other drugs in the same infusion
solution or the same syringe.
6.3 Shelf life
Three years
For single use only. Discard any remaining contents.
6.4 Special precautions for storage
Keep container in the outer carton to protect from light.
Do not store above 25°C
6.5 Nature and contents of container
Amber Type I PhEur glass ampoules (2ml or 4ml) packed in 10s in an outer printed
carton.
6.6 Special precautions for disposal
None

Text Free Area (non-printing)

6

Measure bar should be 150mm at 100% scale

Profile

5pt (main body) / 5.2pt (variables)

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Diazepam is a psychotropic substance from the class of 1,4-benzodiazepines
with marked properties of suppression of tension, agitation and anxiety as well
as sedative and hypnotic effects. In addition, diazepam demonstrates muscle
relaxant and anticonvulsive properties. It is used in the short-term treatment of
anxiety and tension states, as a sedative and premedicant, in the control of muscle
spasm and in the management of alcohol withdrawal symptoms.
Diazepam binds to specific receptors in the central nervous system and particular
peripheral organs. 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, diazepam augments the inhibitory effect of
GABA-ergic transmission.
5.2 Pharmacokinetic properties
Diazepam 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 an
adequate intravenous dose of diazepam, effective plasma concentrations are
usually reached within 5 minutes (ca. 150-400 ng/ml).
Absorption is erratic following intramuscular administration and lower peak plasma
concentrations may be obtained than those following oral administration.
Diazepam is extensively protein bound (95-99%). The volume of distribution is
between 0.95 and 2 l/kg depending on age. Diazepam and its main metabolite,
N-desmethyldiazepam, cross the placenta and are secreted in breast milk.
Diazepam is metabolised predominantly in the liver. Its metabolites,
N-desmethyldiazepam (nordiazepam), temazepam and oxazepam, which appear
in the urine as glucuronides, are also pharmacologically active substances.
Only 20% of the metabolites are detected in the urine in the first 72 hours.
Diazepam has a biphasic half life with an initial rapid distribution phase followed
by a prolonged terminal elimination phase of 1-2 days. For the active
metabolites N-desmethyldiazepam, temazepam and oxazepam, the half lives
are 30-100 hours, 10-20 hours and 5-15 hours, respectively.
Excretion is mainly renal and also partly biliary. It is dependent on age as well as
hepatic and renal function.
Metabolism and elimination in the neonate are markedly slower than in children
and adults. In the elderly, elimination is prolonged by a factor of 2 to 4.
In patients with impaired renal function, elimination is also prolonged.
In patients with hepatic disorders (liver cirrhosis, hepatitis), elimination is prolonged
by a factor of 2.
5.3 Preclinical safety data
Chronic toxicity studies have demonstrated no evidence of drug induced changes.
There are no long term animal studies to investigate the carcinogenic potential of
diazepam. Several investigations pointed to a weakly mutagenic potential at doses
far above the human therapeutic dose.
Local tolerability has been studied following single and repeat dose applications
into the conjunctival sac of rabbits and the rectum of dogs. Only minimal irritation
was observed. There were no systemic changes.
In humans it would appear that 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.

Wockhardt UK Limited

Size

UK

5

Diazepam 5mg/ml injection leaflet

Min. Point Size

Benzodiazepines potentiate the effects of other central nervous system
depressants, including alcohol.
b) Treatment
Treatment is symptomatic. Respiration, heart rate, blood pressure and body
temperature should be monitored and supportive measures taken to maintain
cardiovascular and respiratory function.
Flumazenil is indicated to counteract the central depressive effect of
benzodiazepines but expert advice is essential since adverse effects
may occur (e.g. convulsions in patients dependent on benzodiazepines).
Flumazenil should not be used in mixed overdoses or as a diagnostic test.
Flumazenil is contraindicated in the presence of drugs that reduce seizure
threshold (e.g. tricyclic antidepressants).

Customer

Market

English

104323/5

Description

Language

gill.kennedy

This leaflet was last revised in 08/2015

104323/5

Proof By

2

Product name
Reference number
Diazepam 5mg/ml solution for
PL 29831/0065
injection
This is a service provided by the Royal National Institute of
Blind People.
Marketing Authorisation Holder: Wockhardt UK Ltd, Ash Road
North, Wrexham, LL13 9UF, UK
Manufacturer: CP Pharmaceuticals Ltd, Ash Road North,
Wrexham, LL13 9UF, UK.

Item Code

Proof No.

11/01/2016

What Diazepam Injection contains
The active ingredient is: diazepam 5mg/ml
The other ingredients are: benzoic acid (E210), ethanol,
propylene glycol, sodium benzoate (E211), benzyl alcohol and
water for injections.
What Diazepam Injection looks like and the content of
the pack
Diazepam Injection is a clear colourless to yellow solution.
The medicine is supplied in 2ml or 4ml amber glass ampoules in
a cardboard outer carton.
Other formats:
To listen to or request a copy of this leaflet in Braille, large print
or audio please call, free of charge:
0800 198 5000 (UK Only).
Please be ready to give the following information:

artwork.leicester@multipkg.com

Date

6. Further information

282

Keep out of reach and sight of children.
• Diazepam Injection should not be stored above 25°C. Store
in the original container to protect from light; do not transfer to
another container.
• Diazepam Injection should not be taken after expiry date on
the label; the expiry date refers to the last day of the month,
your doctor will check this.
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.

Clearly mark any amendments on one proof and return to MPS

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.

5. How to store Diazepam Injection

Pharma
Code

4.7 Effects on ability to drive and use machines
Patients treated with Diazepam Injection should not drive or use machinery.
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 of 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
The side effects of diazepam are usually mild and infrequent.
Blood and lymphatic system disorders: Blood dyscrasias including
thrombocytopenia and agranulocytosis have been reported with diazepam.
Immune system disorders: Hypersensitivity reactions, including anaphylaxis,
are rare.
Psychiatric disorders: Numbed emotions. In susceptible patients, an unnoticed
depression may become evident. Paradoxical reactions (including aggression,
rage, hostility, hallucinations, nightmares, disinhibition, euphoria, excitation,
irritability, restlessness, increased anxiety, agitation, inappropriate behaviour and
insomnia) are known to occur with benzodiazepines and may be quite severe with
diazepam. They are more likely to occur in children and the elderly.
Nervous system disorders: Elderly or debilitated patients are particularly
susceptible to the CNS 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). Long term use of benzodiazepines in the elderly may
be associated with an increased risk of dementia. Headaches, confusion, slurred
speech, tremor, reduced alertness and drowsiness. Anterograde amnesia may
occur using therapeutic doses, the risk increasing at higher doses (see 4.4 Special
Warnings and Special Precautions for Use). Amnestic effects may be associated
with inappropriate behaviour. Extrapyramidal effects and convulsions have
occurred rarely with diazepam.
Eye disorders: Visual disturbances.
Ear and labyrinth disorders: Rarely, vertigo
Cardiac disorders: Hypotension, particularly with high dosage, bradycardia,
chest pain. Cardiac arrest may occur with diazepam injection.
Vascular disorders: Diazepam injection may be associated with thrombophlebitis
and venous thrombosis.
Respiratory, thoracic and mediastinal disorders: Rarely, respiratory depression and
apnoea, particularly with high dosage.
Gastrointestinal disorders: Rarely, salivation changes, including dry mouth
or excessive salivation and gastrointestinal disturbances including nausea.
Hepatobiliary disorders: Raised liver enzymes, jaundice and cholestasis.
Skin and subcutaneous tissue disorders: Skin reactions such as Steven-Johnson
syndrome, urticaria, rash.
Musculoskeletal and connective tissue disorders: Muscle weakness.
Renal and urinary disorders: Urinary retention, incontinence.
Reproductive system and breast disorders: Inhibition of female orgasm, changes
in libido, gynaecomastia and rarely, increased prolactin levels and galactorrhoea.
Plasma testosterone concentrations may be increased in men taking diazepam.
General disorders and administration site conditions: Fatigue and a hangover
effect. Diazepam injection may be associated with pain. Inadvertent intra-arterial
administration of diazepam has resulted in ischaemia and tissue necrosis.
Withdrawal symptoms: Development of dependence is common after regular use,
even in therapeutic doses for short periods, particularly in patients with a history
of drug or alcohol abuse or marked personality disorders. Discontinuation may
be associated with withdrawal symptoms or rebound phenomena (see 4.4 Special
Warnings and Precautions for Use). Symptoms of benzodiazepine withdrawal
include anxiety, depression, impaired concentration, insomnia, headache,
dizziness, tinnitus, loss of appetite, tremor, perspiration, irritability, perceptual
disturbances such as hypersensitivity to physical, visual, and auditory stimuli and
abnormal taste, nausea, vomiting, abdominal cramps, muscle aches/cramps,
palpitations, mild systolic hypertension, tachycardia, and orthostatic hypotension.
Rare and more serious withdrawal symptoms include muscle twitching, confusional
or 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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product
is important. It allows continued monitoring of the benefit/risk balance of the
medicinal product. Healthcare professionals are asked to report any suspected
adverse reactions via the national reporting system:
United Kingdom
Yellow Card Scheme
www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
Malta
ADR Reporting
www.medicinesauthority.gov.mt/adrportal
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, nystagmus, 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.
Coma usually lasts for only a few hours but in elderly people it may be more
protracted and cyclical. Benzodiazepine respiratory depressant effects are
more serious in patients with severe chronic respiratory disease.
As drug levels fall, severe agitation, insomnia and, possibly, major
convulsions may develop.

625416

Like all medicines, Diazepam Injection can cause side effects,
especially the elderly, although not everybody gets them.
As can happen with any medicine, a few people may develop an
allergic reaction. If you experience any of the following, tell your
doctor immediately:
• rash, itching, swelling of the face and eyes, difficulty breathing,
serious illness with blistering of the skin, mouth, eyes and genitals.
The side effects of diazepam are usually mild and infrequent.
Side effects that have been reported are:
Possible side-effects are listed below under the parts of the
body that might be affected.
Blood
• changes to blood cells
Psychiatric disorders
• hallucinations (seeing or
• feeling excited or over anxious
hearing things that are not
• aggression
there)
• restlessness and agitation
• sleep problems and
• depression
nightmares
• numbed emotions
Nervous System
• headaches
• clumsiness
• confusion
• memory loss
• tremor
• dizziness
• drowsiness
• unusual movements of
• reduced alertness
muscles of face
• slurred speech
• fits
• fatigue and a hangover effect
Eyes
• visual disturbances
Ears
• vertigo
Heart
• low blood pressure
• stoppage of heart
• slow heartbeat
• chest pain
Circulatory system
• inflammation of veins
• blood clots in veins (venous thrombosis)
Respiratory system
• breathing problems
Digestive system
• stomach and gut problems
• dry mouth or increased
• nausea
production in saliva
Liver
• raised liver enzymes
• jaundice (yellowing of the skin)
Skin
• itchiness and rashes
Muscles
• muscle weakness
• muscle aches or cramps
Kidneys
• inability to pass water
• urinary incontinence
Reproductive system
• increase in breast tissue in men
• change in sex drive (libido)
• inhibition of female orgasm
• production of milk from breast
• increased testosterone in men

Artwork No.

4. Possible side effects

Other parts of your body
• pain at injection site
• poor blood supply and tissue damage (if drug injected into
artery)
There may be a slight increase in
abnormalities, particularly hare lip,
in babies born to mothers given
benzodiazepines during the first
three months of pregnancy. Babies
exposed to benzodiazepines
during pregnancy may be slow
developers.
If a mother has received diazepam
towards the end of pregnancy
or during labour, the baby may
be affected, with feeling cold,
floppiness, difficulty breathing and
suckling,
or withdrawal symptoms.
Reporting of side effects
If you get any side effects, talk to your doctor, 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
www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail:medsafety@hpra.ie
Malta
ADR Reporting
www.medicinesauthority.gov.mt/adrportal
By reporting side effects you can help provide more information
on the safety of this medicine.

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

Sedation prior to minor surgical or dental procedures:
• 0.1-0.2mg per kg bodyweight by injection in the vein or
muscle, and adjusted according to response.
Doses in the elderly and in those with kidney or liver
problems should be reduced accordingly.
Children
Control of epileptic fits or febrile convulsions:
• 0.2-0.3mg per kg bodyweight (or 1mg for each year of age)
given into a vein
• doses can be repeated, if needed after 30-60 minutes.
Sedation or as a muscle relaxant:
• up to 0.2mg per kg bodyweight as an injection.
If you take more Diazepam Injection than you should
This medicine is administered by your doctor and so you are
unlikely to be given too much.
If you stop taking Diazepam Injection
Dependence on diazepam and other benzodiazepines can
occur when used over a long time and is more common in
patients with a history of drug or alcohol abuse. The risk of
dependence is low in small doses given over short periods.
If you have needed treatment with diazepam over a long period,
your doctor will not stop treatment immediately but will gradually
reduce your dose over time to stop withdrawal symptoms such
as anxiety, depression, stomach cramps, nausea and sweating.

Expand view ⇕

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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