Skip to Content

UK Edition. Click here for US version.

ZYMEROL 50MG/ML SOLUTION FOR INJECTION

Active substance(s): PETHIDINE HYDROCHLORIDE / PETHIDINE HYDROCHLORIDE / PETHIDINE HYDROCHLORIDE

View full screen / Print PDF » Download PDF ⇩
Transcript
Booklet front

ARTWORK
INFORMATION:
PRODUCT: Pethidine 50 mg/ml,
Solution for Injection
LICENCE:

PL 17507/0014

ITEM / SIZE: Generic PIL; 280 mm
(h) x 296 mm (w) [flat]
ID CODE:

A1000052/1

VERSION:

2; 19/08/2015

INK:

Black

FORMAT:

4 page booklet

PATIENT INFORMATION LEAFLET

APPROVED FOR
SUBMISSION:

Pethidine 50mg/ml Solution for Injection

Pethidine hydrochloride
(50mg in 1ml ampoules and 100mg in 2ml ampoules)
This leaflet contains important information about Pethidine Injection.
Read all of this leaflet carefully before you start your treatment with this medicine.
1. Keep this leaflet. You may need to read it again.
2. If you have further questions, please ask your doctor.
3. 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.

Space for
pharmacode

In this leaflet
1. What is Pethidine Injection and what is it for
2. Before you are given Pethidine Injection
3. How Pethidine Injection is used
4. Possible side effects
5. How Pethidine Injection is stored
6. Further information
1. What is Pethidine Injection and what is it
used for
Pethidine belongs to a group of medicines called
opiates. It is used as a pain killer (an analgesic) to
relieve moderate to severe pain or pain during
pregnancy and labour.
It can be used in addition to other pain killers when
other pain killers are not effective enough.
It is also used as a pre-medication before an
operation.

2. Before you are given Pethidine Injection
Pethidine Injection should not be used if you ...
• Think you are allergic (hypersensitive) to pethidine
or any of the other ingredients of Pethidine
injection (see section 6: Further Information).
Signs of an allergic reaction include: a rash,
swallowing or breathing problems, swelling of your
lips, face, throat or tongue.
• suffer from any illness which causes severe
breathing difficulties for example severe asthma.
• are taking, or have taken in the last two weeks,
any of the antidepressant medicines called
monoamine oxidase inhibitors (MAOIs), including
moclobemide.
• are taking, or have taken in the last two weeks,
any of the Parkinson’s disease medicines called
selegiline or rasagiline.
• have severe liver or kidney disease.
• have alcohol addiction problems or suffering from
alcohol withdrawal symptoms such as trembling,
hallucinations, anxiety, sweating and sudden feelings
of terror.
• have a condition called status epilepticus
(a form of epilepsy).
• are taking an anti-viral product called ritonavir.
• have a condition known as supraventricular
tachycardia (a faster than normal heart beat).
• have phaeochromocytoma (a tumour which
causes increased blood pressure, palpitations,
increased heart rate and headaches).
• have a head injury.
• have raised intracranial pressure (raised pressure of
the fluid around the brain).
• have a risk of paralysis of the intestine.
• have a condition called diabetic ketoacidosis.
• are in a coma.
Always tell your doctor or nurse about any of these
before having your injection.

Take special care with Pethidine:
Before you take this medicine, tell your doctor if:
• you have epilepsy
• you suffer from breathing difficulties for example
asthma

A1000052_2 V1 Pethidine 50mg_ml PIL.indd 1

APPROVED BY
HEALTH AUTHORITY:

• you have liver or kidney disease
• you have low thyroid function (hypothyroid)
• you have a problem wtih your bile ducts
• you have problems with your adrenal glands.
These are linked to your kidneys
• you have an enlarged prostate gland
• you have low blood pressure
• you are in shock
• you have a muscle weakness disease called
myasthenia gravis
• you suffer from inflammatory bowel disease such
as ulcerative colitis and Crohn’s disease
• you are extremely ill or an older person. You may
be more sensitive to the medicine.
• if a baby, who is being given pethidine, is new-born
or premature.
Only use the dose prescribed for you by your doctor
because higher doses could be fatal.

Taking other medicines
Tell your doctor if you are taking or have recently
taken any medicines including medicines obtained
without a prescription. Pethidine can interfere with the
action of some other drugs and some drugs can have
an effect on Pethidine. The following drugs can cause
some problems when taken together with Pethidine
Injection:
• strong pain killers, antidepressants, anxiolytics
(for anxiety), barbiturates or sedatives
• medicines to treat depression (monoamine oxidase
inhibitors including moclobemide, tricyclic
antidepressants e.g. trazodone and SSRI
antidepressants e.g. fluoxetine).
• an anti-viral product called ritonavir
• a medicine used to treat epilepsy called phenytoin
• a medicine for reducing stomach acid called
cimetidine
• medicines used to help treat Parkinson’s disease
called selegiline and rasagiline
• medicines to treat psychosis called phenothiazines
• medicines to treat feelings of being sick or
vomiting called domperidone
• an antibiotic product called ciprofloxacin
• a medicine used to treat abnormal heart rate
called mexiletine
• alcohol.

Pregnancy and Breast-feeding
• Always tell your doctor if you are pregnant, think
you might be pregnant or are trying to become
pregnant.
• You should stop breast-feeding while having
pethidine treatment as it can get into breast milk
and harm your baby.

26/08/2015 11:54

Booklet inside spread, page 1
Driving and using machines

4. Possible side effects

• Pethidine may make you feel sleepy. Do not drive
or operate any tools or machines as you may not
be safe.

Like all medicines, Pethidine can cause side effects
although not everyone gets them.

This 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:
- The medicine has been prescribed to treat a
medical or dental problem and
- You have taken it according to the instructions
given by the prescriber or in the information
provided with the medicine and
- It was not affecting your ability to drive safely.
Talk to your doctor or pharmacist if you are not sure
whether it is safe for you to drive while taking this
medicine.

3. How Pethidine Injection is used
Pethidine will be given to you by injection under the
skin, into a muscle or into a vein. If you have any
doubts or questions about your treatment speak to
your doctor or nurse.
For the treatment of pain:
The usual dose is 25-100mg into muscle or under the
skin or 25-50mg slowly into a vein every 4 hours.
If it is a child, the amount of pethidine given into a
muscle will depend on the child’s weight (0.5 - 2mg
per kg body weight).
For the treatment of pain during pregnancy or
labour:
The usual dose is SD-100mg into muscle or under the
skin every 1-3 hours, if necessary, (up to 400mg in 24
hours).
Before an operation:
The usual dose is 50-100mg into muscle one hour
before the operation.
If it is a child, the amount of pethidine given into a
muscle will depend on the child’s weight (1-2mg per
kg body weight)
To improve pain relief:
10-25mg may be given slowly into a vein as required.
You may be prescribed a lower dose if you are elderly
or ill.

If more Pethidine is used than should be:
You may feel sleepy or excited, have problems
breathing, feel floppy or have balance problems,
tremors or have cold, clammy skin and very small
pupils. It can also affect your heart and blood pressure
or give you a fit.
Tell your doctor or healthcare professional if you have
any of these side effects so that he/she can give
appropriate treatment.
If you have already left the medical premises, contact
your nearest hospital, doctor or pharmacist.

If you miss a dose of Pethidine:
It is unlikely that you will miss a dose as your doctor
or nurse will be giving it to you. However, it is
important not to have a double dose if you have
missed one. Ask your doctor or nurse when you
should have the next dose.
If you have any further questions on the use of this
product, ask your doctor or nurse.

If any of the following symptoms occur contact your
doctor or nearest accident and emergency department
immediately as these are symptoms of a serious
allergic reaction:
• Difficulty in breathing, skin rash or itching or
swollen face
Other side effects that may occur include the
following:
• Dependence to pethidine if taken regularly
• Confusion, changes of mood, a feeling of
well-being, hallucinations and a feeling of being
unwell
• Drowsiness, dizziness, muscle twitches, fits,
headache and fainting
• Dry eyes, reduction of pupil size and reduction of
automatic eyelid closure
• Fast, slow or abnormal beating of the heart
• High blood pressure, low blood pressure and
facial redness
• Shallow breathing
• Nausea, vomiting, dry mouth and constipation
• Spasm of the tube from the gallbladder or urinary
bladder
• Sweating, rash and itchy skin
• Difficulty urinating and pain in passing urine
• A decrease in sexual function may be experienced
• A feeling of being cold, weakness and irritation or
hardening may be experienced at the site of the
injection.
Reporting of side effects:
If you get any side effects, talk to your doctor or
pharmacist. This includes any possible side effects
not listed in this leaflet. You can also report side
effects directly via the Yellow Card Scheme (Website:
www.mhra.gov.uk/yellowcard). By reporting side
effects you can help provide more information on the
safety of this medicine.

5. How Pethidine Injection is stored
• Keep out of the reach and sight of children
• Do not use Pethidine Injection after the expiry
date which is stated on the ampoule and carton
after Exp:. The expiry date refers to the last day
of that month.
• Medicines should not be disposed via waste
water or household waste. Ask your pharmacist
how to dispose of medicines no longer required.
These measures will help to protect the
environment.

6. Further information
Pethidine Injection is a sterile solution for injection
containing Pethidine hydrochloride. It also contains water
and may include sodium hydroxide and/or hydrochloric
acid.
The product is available in 1 ml ampoules (50mg pethidine
hydrochloride) and 2ml ampoules (100mg pethidine
hydrochloride) in packs of 10 ampoules.
The Marketing Authorisation for Pethidine Injection
is held by Auden Mckenzie (Pharma Division) Ltd.,
Mckenzie House, Bury Street, Ruislip, Middlesex,
HA4 7TL, UK.
Pethidine Injection is manufactured by
SNS Pharmaceuticals Ltd., Mckenzie House,
Bury Street, Ruislip, Middlesex, HA4 7TL, UK.
This leaflet was updated in August 2015.

A1000052/1

A1000052_2 V1 Pethidine 50mg_ml PIL.indd 2

26/08/2015 11:54

Booklet inside spread, page 2

Information for the Healthcare Professional
(Please detach prior to giving the leaflet to the patient)

Pethidine 50mg/ml Solution for Injection

Pethidine hydrochloride
(50mg in 1ml ampoules and 100mg in 2ml ampoules)
1 NAME OF THE MEDICINAL PRODUCT
Pethidine 50mg/ml, Solution for Injection
or, ZyMerol 50mg/ml, solution for Injection

Repeated use may result in dependence of the morphine type.
Pethidine should be used with caution in patients with acute or
chronic airflow obstruction including asthma.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Pethidine hydrochloride 50mg/ml
(50mg in 1ml and 100mg in 2ml total volume)

Pethidine should be used with caution or in reduced doses in
patients with myasthenia gravis.

4 CLINICAL PARTICULARS

Special care should be taken with patients with hepatic impairment
as clearance of pethidine may be prolonged. Renal impairment
may result in accumulation of the potentially toxic metabolite
norpethidine, particularly with repeat dosing. The drug should be
used with caution and in reduced doses in neonates with
premature infants, elderly or debilitated patients, in patients with
hypothyroidism, biliary tract disorders, adrenocortical insufficiency,
prostatic hypertrophy, hypotension and shock.

4.1 Therapeutic indications
Treatment of moderate to severe pain.
As a pre-medication.
Obstetric analgesia.
Enhancement of analgesia.

Although less spasmogenic than morphine, pethidine may
precipitate spasm of the ureter or Sphincter of Oddi. Subsequently
it should be used with caution in patients with prostatic hypertrophy
and biliary tract disorders including those with pain secondary to
gallbladder pathology.

4.2 Posology and method of administration
Method of administration: Intramuscular, intravenous or
subcutaneous injection.

Avoid use in severe inflammatory bowel disease due to its effects
on the gastrointestinal tract where it may precipitate toxic
megacolon.

Adults:
For moderate to severe pain
Usual single dose (usually not to be repeated more often than 4
hourly)

4.5 Interaction with other medicinal products and other forms
of interaction
Monoamine Oxidase Inhibitors
The concurrent use of MAOls (including moclobemide) is
contra-indicated (see section 4.3) as they may result in CNS
excitation or depression.

For excipients, see Section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection
(Colourless solution)

By intramuscular or subcutaneous injection 25-100mg
By slow intravenous injection

25-50mg

Obstetric analgesia
By intramuscular or subcutaneous injection 50-100mg
repeated every 1-3 hours, if necessary,
(maximum 400mg in 24 hours).
As a pre-medication
By intramuscular injection
one hour prior to the operation
For the enhancement of analgesia
By slow intravenous injection

50-100mg

10-25mg as required.

Elderly and debilitated patients:
Initial doses should not exceed 25mg as this group of patients may
be especially sensitive to the central depressant effect of the drug.
Children:
For moderate to severe pain
By intramuscular injection 0.5 - 2mg per kg
bodyweight.
As a pre-medication
By intramuscular injection
one hour prior to the operation

1 - 2mg per kg
bodyweight.

4.3 Contraindications
Do not use:1) In patients with known hypersensitivity to pethidine or to any of
the excipients.
2) In patients with severe respiratory depression or severe
obstructive airways disease.
3) In patients with severe renal impairment.
4) In patients with severe asthma.
5) Concurrently with monoamine oxidase inhibitors (including
modobemide and the monoamine oxidase B inhibitors
selegiline and rasagiline) or within 2 weeks of discontinuation
of treatment with them.
6) In patients with severe hepatic impairment.
7) In patients with acute alcoholism.
8) In patients suffering from delirium tremens.
9) In patients with raised intracranial pressure.
10) In patients with head injuries.
11) In patients suffering from convulsive slates such as status
epilepticus.
12) Concurrently with ritonavir.
13) In patients with supraventricular tachycardia.
14) In patients with phaeochromocytoma as it may result in
hypertensive crisis.
15) In patients with diabetic acidosis where there is danger of coma.
16) In comatose patients.
17) In patients with a risk of paralytic ileus.
4.4 Special warnings and precautions for use
Pethidine is controlled under the Misuse of Drugs Act 1971
(Schedule 2).
Pethidine should be used with caution in patients with a history of
convulsive disorders.

A1000052_2 V1 Pethidine 50mg_ml PIL.indd 3

CNS depressants
CNS depressants such as alcohol. hypnotics, anxiolytics and
sedatives, barbiturates and tricyclic antidepressants may increase
the general depressant effects of pethidine and should therefore
be used with caution.
Opioid agonists
Additive effects on CNS depression, respiratory depression and
hypotension can occur with concomitant use of opioid agonist
analgesics.
MAO-B inhibitors
Concomitant use of MAO-B inhibitors such as selegiline or
rasagiline is contraindicated (see section 4.3) as this may lead to
hyperpyrexia and CNS toxicity.
Anticonvulsants
Administration of phenytoin may cause an increase in hepatic
metabolism of pethidine and subsequently increased levels of
norpethidine (a toxic metabolite).
Antipsychotics
Concomitant use of phenothiazines and pethidine can induce
severe hypotension.
Anti-virals
Plasma concentrations of pethidine may be decreased by
concomitant administration of ritonavir, however levels of
norpethidine (a toxic metabolite) may rise. Concomitant
administration of ritanovir and pethidine should be avoided (see
section 4.3).
Histamine H2 antagonists
Cimetidine can reduce the metabolism of pethidine resulting in
increased plasma concentration.
Effects of pethidine on other drugs
Pethidine may have an effect on the activities of other drugs, for
example domperidone, as a consequence of reduced gastrointeslinal motility.
The plasma levels of ciprofloxacin may be reduced in the presence
of opiate premedicants.
Plasma levels of mexiletine may also be reduced in the presence
of opioid analgesics.
Possible increased serotonergic effects when pethidine is given
with SSRl’s.
4.6 Pregnancy and lactation
There is no available evidence of any teratogenic effects in
humans. Pethidine crosses the placental barrier and therefore a
careful risk/benefit assessment should be made before
administration to pregnant women and during labour because of
possible adverse effects such as respiratory depression in the
neonate.
Lactation: Pethidine is excreted into breast milk. Patients should be
advised to discontinue breast-feeding during treatment with
pethidine.

26/08/2015 11:54

Booklet reverse
4.7 Effects on ability to drive and use machines
Patients should not drive or use machines while taking pethidine
as it may cause drowsiness and reduce alertness.
The ability to drive or use machines may be severely affected
during and for some time after administration of pethidine.
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:
i. The medicine has been prescribed to treat a medical or
dental problem and
ii. You have taken it according to the instructions given by the
prescriber and in the information provided with the medicine
and
iii. It was not affecting your ability to drive safely.
4.8 Undesirable effects
There are no modern clinical studies available that can be used to
determine the frequency of undesirable effects. Therefore all the
undesirable effects listed are classified as “frequency unknown”.
The undesirable effects listed below include class effects for opioid
analgesics and effects related to the pharmacologically active
metabolite, norpethidine.
Immune system disorders:
General hypersensitivity reactions occur rarely.
Psychiatric disorders:
Dependence, confusion, mood altered, mild euphoria,
hallucinations, dysphoria
Nervous system disorders:
Drowsiness, dizziness, tremor, convulsions, headache, fainting

Anti-convulsive therapy, oxygen, intravenous fluids, vasopressors
and other supportive measures should be employed as indicated.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics – Phenylpiperidine
derivatives. ATC code: N02A B.
Pethidine is a synthetic opioid analgesic similar to morphine
although less potent and shorter acting. Its analgesic effect usually
lasts for 2 to 4 hours. The analgesic effect occurs after about 10
minutes following parenteral administration.
It acts on the CNS system and smooth muscles via the peripheral
nervous system. However, it has a weaker action on smooth
muscle than morphine and therefore has less effect on cough,
bowel motility, biliary tone and secretion of pituitary hormones.
Pethidine also causes the release of histamine from mast cells
resulting in a number of allergic-type reactions.
5.2 Pharmacokinetic properties
Pethidine is rapidly absorbed following intramuscular or
subcutaneous injection. However, there are wide inter-individual
variations.
It is widely distributed in the tissues with a volume of distribution of
200-300L. It is extensively protein bound (60-80%).
Pethidine is metabolised in the liver and excreted via the urine
(70% in 24 hours). One of the metabolites. norpethidine, is
pharmacologically active and its accumulation can result in toxicity.
Urinary excretion is pH-dependent, the lower the pH the greater
the clearance. At normal urinary pH only a small amount of
pethidine is excreted unchanged.
Pethidine has a plasma elimination half-life of about 3 to 6 hours.
The metabolite norpethidine is eliminated more slowly with a
half-life of up to 20 hours and may accumulate with chronic use,
especially in the presence of renal impairment.
Pethidine crosses the placenta and is excreted in breast milk.

Eye disorders:
Dry eye, miosis, corneal reflex decreased

Both pethidine and norpethidine cross the blood/brain barrier and
are found in the cerebrospinal fluid.

Ear and labyrinth disorders:
Vertigo

5.3 Preclinical safety data
There is no additional information relevant to the prescriber.

Cardiac disorders:
Tachycardia, bradycardia, palpitations

6 PHARMACEUTICAL PARTICULARS

Vascular disorders:
Orthostatic hypotension, flushing, hypotension, hypertension
Respiratory, thoracic and mediastinal disorders:
Respiratory depression

6.1 List of excipients
Sodium hydroxide
Hydrochloric acid
Water for injections

Gastrointestinal disorders:
Nausea, vomiting, dry mouth, constipation

6.2 Incompatibilities
In the absence of incompatibility studies. Pethidine must not be
mixed with other medicinal products.

Hepatobiliary disorders:
Biliary spasm

6.3 Shelf life
36 months

Skin & subcutaneous tissue disorders:
Sweating, rash, urticaria, pruritus
Musculoskeletal and connective tissue disorders:
Muscle twitching
Renal & urinary disorders:
Difficulty in micturition, renal colic
Reproductive system and breast disorders:
Sexual dysfunction
General disorders & administration site conditions:
Hypothermia, weakness, injection site reactions including
induration and irritation
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Signs:
Respiratory depression, CNS depression with extreme
somnolence progressing to incoordination, stupor or coma,
convulsions. CNS stimulation, cyanosis, miosis, skeletal muscle
flaccidity or tremors, cold, clammy skin, hypothermia, bradycardia
and hypotension.
In severe overdosage, apnoea, circulatory collapse, pulmonary
oedema, mydriasis, cardiac arrest and death may occur.
Treatment:
Treatment is supportive. A patent airway must be established with
assisted or controlled ventilation. If signs of CNS toxicity are
exhibited the use of pethidine should be discontinued. Narcotic
antagonists may be required if there is evidence of significant
respiratory or cardiovascular depression. Naloxone should be
given intravenously as soon as possible and repeated every 2-3
minutes if necessary (refer to naloxone product literature for
details).

A1000052_2 V1 Pethidine 50mg_ml PIL.indd 4

6.4 Special precautions for storage
None
6.5 Nature and contents of container
1 ml and 2ml clear glass (Ph. Eur. Type I) ampoules containing
1 ml or 2ml solution for injection.
Pack size: 10 ampoules per carton.
6.6 Special precautions for disposal
Pethidine is controlled under the Misuse of Drugs Act 1971
(Schedule 2).
7 MARKETING AUTHORISATION HOLDER
Auden Mckenzie (Pharma Division) Ltd
Mckenzie House
Bury Street
Ruislip
Middlesex
HA4 7TL
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 17507/0014
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17/12/2008
10 DATE OF REVISION OF THE TEXT
Date of grant

Auden Mckenzie (Pharma Division) Ltd

A1000052/1

26/08/2015 11:54

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.

Hide