United Kingdom - English - eMC (Electronic Medicines Compendium)
Zamadol SR 200mg prolonged-release hard capsules
Patient Information Leaflet
Read all of this leaflet carefully before you start taking this medicine,
because it contains important information for you.
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.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. See section 4.
Your medicine is called Zamadol SR 200mg prolonged-release hard
capsules and will be referred to as Zamadol SR prolonged-release hard
capsules throughout the rest of this leaflet. Please note that the leaflet also
contains information about other strengths of the medicine, Zamadol SR
50mg prolonged-release hard capsules, Zamadol SR 100mg
prolonged-release hard capsules and Zamadol SR 150mg prolonged-release
What is in this leaflet:
What Zamadol SR prolonged-release hard capsules is and what it is
What you need to know before you take Zamadol SR
prolonged-release hard capsules
How to take Zamadol SR prolonged-release hard capsules
Possible side effects
How to store Zamadol SR prolonged-release hard capsules
Contents of the pack and other information
What Zamadol SR prolonged-release hard
capsules is and what it is used for
Zamadol SR prolonged-release hard capsules belongs to a group of
medicines called analgesics, commonly known as pain killers or pain
relievers. The active substance, tramadol hydrochloride, interrupts the pain
messages being sent to your brain, and it also acts in your brain to stop pain
messages from being felt. This means that Zamadol SR prolonged-release
hard capsules does not stop the pain from happening, but you will not be
able to feel the pain as much.
Zamadol SR prolonged-release hard capsules is used to relieve moderate to
severe pain. (for example, pain after an operation, or after an injury).
What you need to know before you take Zamadol SR
prolonged-release hard capsules
Do not take Zamadol SR prolonged-release hard capsules:
if you are allergic to tramadol hydrochloride or to any of the other
ingredients of this medicine (listed in section 6) resulting in a skin rash,
swelling of face or dif culty in breathing
if you are taking, or you have taken in the last two weeks, monoamine
oxidase inhibitors (MAOIs) to treat your depression (see section 2,
“Other medicines and Zamadol SR prolonged-release hard capsules”)
if you have epilepsy which is not controlled by treatment
if you have drunk enough alcohol to make you feel woozy or drunk
if you have taken more than prescribed dose of your sleeping tablets,
antipsychotics, antidepressants (antipsychotics and antidepressants
are medicines that affect mood and emotions) or other pain killers, which
can slow down your breathing and reactions.
Warnings and precautions
Talk to your doctor or pharmacist before taking Zamadol SR
prolonged-release hard capsules, if:
you have had an allergic reaction to any morphine-like medicines.
you have been taking Zamadol SR prolonged-release hard capsules or
any other tramadol containing medicine for a long time.
you are addicted to morphine.
you have severe problems with your liver or kidneys.
you have recently had a head injury or have a very bad headache that
makes you sick.
you have ever had convulsions (fits) or do you suffer from epilepsy.
you have asthma or trouble breathing.
you are going to have surgery requiring a general anaesthetic.
There is rare possibility that Zamadol SR prolonged-release hard capsules
may cause convulsions (fits). The risk is increased if doses above
the daily maximum are taken and if you are also taking anti-depressants or
You have a tendency to drug addiction or abuse you should take Zamadol
SR prolonged-release hard capsules for short periods only. Please
tell your doctor about this as he/she may want to monitor your pain control
You should not take this product for the treatment of withdrawal symptoms, if
you are addicted to drugs.
Tramadol is transformed in the liver by an enzyme. Some people have a
variation of this enzyme and this can affect people in different
ways. In some people, they may not get enough pain relief but other people
are more likely to get serious side effects. If you notice any of
the following side effects, you must stop taking this medicine and seek
immediate medical advice: slow or shallow breathing, confusion,
sleepiness, small pupils, feeling or being sick, constipation, lack of appetite.
Children and adolescents:
Zamadol SR prolonged-release hard capsules prolonged-release capsules,
hard should not be used in children under 12 years of age.
Use in children with breathing problems
Tramadol is not recommended in children with breathing problems, since the
symptoms of tramadol toxicity may be worse in these children.
Other medicines and Zamadol SR prolonged-release hard capsules
Tell your doctor or pharmacist or dentist if you are taking, have recently
taken or might take any other medicines, including those obtained
Do not take Zamadol SR prolonged-release hard capsules at the same time,
or within 14 days of taking medicines called monoamine oxidase inhibitors
(moclobemide or phenelzine for depression, selegiline for Parkinson’s
The pain relieving effect of Zamadol SR prolonged-release hard capsules
may be weakened and/or shortened if you also take medicines
- carbamazepine (used to treat epilepsy)
- buprenorphine, nalbuphine, or pentazocine (pain killers)
- ondansetron (prevents nausea)
Your doctor will tell you whether you should take Zamadol SR
prolonged-release hard capsules and what dose.
The risk of side effects increases if you are taking medicines which may
cause convulsions (fits), such as certain antidepressants or antipsychotics.
The risk of having a fit may increase if you take Zamadol SR
prolonged-release hard capsules at the same time. Your doctor will tell you
whether Zamadol SR prolonged-release hard capsules are suitable for you.
The risk of side effect increases, if you are taking certain antidepressants.
Zamadol SR prolonged-release hard capsules may interact with these
medicines and you may experience symptoms such as involuntary, rhythmic
contractions of muscles, including the muscles that control movement of the
eye, agitation, excessive sweating, tremor, exaggeration of reflexes,
increased muscle tension, body temperature above 38°C.
Medicines that act on the nervous system such as hypnotics, tranquillisers,
sleeping pills and pain killers may make you feel drowsier or faint
when taken with Zamadol SR prolonged-release hard capsules.
Anticoagulants to thin your blood such as warfarin. The effectiveness of the
medicines may be altered if you are also taking Zamadol SR
prolonged-release hard capsules.
You must tell your doctor if you are taking these medicines.
Concomitant use of Zamadol SR prolonged-release hard capsules and
sedative medicines such as benzodiazepines or related drugs
increases the risk of drowsiness, difficulties in breathing (respiratory
depression), coma and may be life-threatening. Because of this,
concomitant use should only be considered when other treatment options
are not possible.
However if your doctor does prescribe Zamadol SR prolonged-release hard
capsules together with sedative medicines the dose and duration of
concomitant treatment should be limited by your doctor.
Please tell your doctor about all sedative medicines you are taking, and
follow your doctor’s dose recommendation closely. It could be helpful to
inform friends or relatives to be aware of the signs and symptoms stated
above. Contact your doctor when experiencing such symptoms.
Zamadol SR prolonged-release hard capsules with food, drink and
Zamadol SR prolonged-release hard capsules should be taken with some
water, with or without the meal. Avoid drinking alcohol while taking this
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are
planning to have a baby, ask your doctor or pharmacist for advice
before taking this medicine. Please contact your doctor if you become
pregnant during your treatment.
Zamadol SR prolonged-release hard capsules should not be taken during
pregnancy or while breast-feeding. This is because it is not yet known how
safe it is to take this medicine when you are pregnant. Contact your doctor if
you become pregnant during your treatment.
Tramadol is excreted into breast milk. For this reason, you should not take
Zamadol SR prolonged-release hard capsules more than once during
breast-feeding, or alternatively, if you take Zamadol SR prolonged-release
hard capsules more than once, you should stop breast-feeding.
Driving and using machines
Zamadol SR prolonged-release hard capsules may cause drowsiness and
this effect may be potentiated by alcohol, anti-histamines and other CNS
depressants. If patients are affected they should be warned not to drive or
Zamadol SR prolonged-release hard capsules contains sucrose.
If you have been told by your doctor that you have intolerance to some
sugars, contact your doctor before taking this medicinal product.
Patient Information Leaflet (continued)
How to take Zamadol SR prolonged-release
Always take this medicine exactly as your doctor has told you. Check with
your doctor or pharmacist if you are not sure.
The dosage should be adjusted to the intensity of your pain and your
individual pain sensitivity. In general the lowest pain-relieving dose
should be taken.
Swallow the capsules whole with water without chewing.
If you have difficulty in swallowing, you may open the capsules. You must
open them very carefully by pulling and twisting each end over a
spoon so that all the pellets stay in the spoon. Do not chew. Swallow all the
pellets with water.
Dosage for adults and adolescents from 12 years of age:
The usual initial dose is 50–100 mg twice daily, in the morning and in the
evening. Your doctor may increase this dose up to 150–200 mg twice daily
according to your needs. You should normally take your Zamadol SR
prolonged-release hard capsules every 12 hours, at the same time each
morning and evening.
The maximum dose is usually 400 mg daily.
Use in children:
Under 12 years of age – Zamadol SR prolonged-release hard capsules
should not be taken by children under 12 years of age.
Use in elderly patients:
In elderly patients (above 75 years of age) the excretion of tramadol may be
delayed. If this applies to you, your doctor may recommend
prolonging the dosage interval.
Use in patients with severe liver or kidney disease (insufficiency)/
Patients with severe liver and/or kidney insufficiency should not take
Zamadol SR prolonged-release hard capsules. If in your case the
problem is mild or moderate your doctor may recommend prolonging the
If you take more Zamadol SR prolonged-release hard capsules than
If you accidentally take more capsules than your prescribed dose, tell your
doctor or pharmacist immediately and if necessary contact your
nearest hospital casualty department. Remember to take the pack and any
remaining medicines with you.
If you forget to take Zamadol SR prolonged-release hard capsules
Do not take a double dose to make up for a forgotten dose.
If you stop taking Zamadol SR prolonged-release hard capsules
You should not suddenly stop taking this medicine unless your doctor tells
you to. If you want to stop taking your medicine, discuss this with your doctor
first, particularly if you have been taking it for a long time. Your doctor will
advise you when and how to stop, which may be by lowering the dose
gradually to reduce the chance of developing unnecessary side effects
People who have been taking Zamadol SR prolonged-release capsules,
hard for some time may feel unwell if they abruptly stop taking them.
They may feel agitated, anxious, nervous or shaky. They may be
hyperactive, have difficulty sleeping and have stomach or bowel disorders.
If you experience any of these complaints after stopping Zamadol SR
prolonged-release capsules, hard please consult your doctor.
If you have any further questions on the use of this medicine, ask your
doctor or pharmacist.
Possible side effects
Like all medicines, Zamadol SR prolonged-release hard capsules can cause
side effects, although not everybody gets them.
The most serious side effects which may occur include allergic reaction
(difficulty in breathing, wheezing and swelling of the face or throat),
anaphylactic reaction (an extreme allergic reaction resulting in difficulty
breathing, changes in heart rate, faintness, collapse or unconsciousness
due to a drop in blood pressure) or convulsions (fits). If you have any of
these symptoms you must stop taking Zamadol SR prolongedrelease
hard capsules immediately and seek medical advice.
Very common (may affect more than 1 in 10 people)
Vomiting and nausea (being and feeling sick)
Common (may affect up to 1 in 10 people)
Drowsiness, sleepiness (fatigue)
Constipation, dry mouth
Uncommon (may affect up to 1 in 100 people)
Rapid heartbeat, palpitation, sudden drops in blood pressure. These
adverse effects may occur especially on intravenous administration
and in patients who are physically stressed
Itching, skin rash
Retching, feeling bloated or full
Rare (may affect up to 1 in 1,000 people)
Psychic effects including: changes in mood, activity behaviour and
perception, hallucinations, confusion, restlessness sleep disturbances
Tingling sensation and trembling
Slow heart-beat, increase in blood pressure
Difficulty or inability in passing urine
Very rare (may affect up to 1 in 10,000 people)
Vertigo (feeling of dizziness or “spinning”)
Asthma and breathing difficulties
Elevated liver enzymes
Not known: frequency cannot be estimated from the available data
Decrease in blood sugar level
Withdrawal symptoms including: agitation, anxiety, nervousness, difficulty
sleeping, restlessness, trembling and gastro-intestinal problems
(see section 3. How to take Zamadol SR prolonged-release hard capsules).
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 at:
ww.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the
Google Play or Apple App Store.
By reporting side effects you can help provide more information on the
safety of this medicine.
How to store Zamadol SR prolonged-release hard
KEEP OUT OF THE SIGHT AND REACH OF CHILDREN
Store in the original package in order to protect from moisture.
Do not store above 25 °C.
Do not take this medicine after the expiry date which is printed on the
blister or carton label. If your doctor tells you to stop taking the medicine,
take any remaining medicine back to the pharmacist for safe disposal.
Only keep this medicine if your doctor tells you to.
If your medicine becomes discoloured or shows any other signs of
deterioration, ask your pharmacist who will advise you what to do.
Medicines should not be disposed of 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.
Contents of the pack and other information
What Zamadol SR prolonged-release hard capsules contains:
The active substance is tramadol hydrochloride.
Each capsules contains 200mg of tramadol hydrochloride.
The other ingredients of the capsule contents are: sugar spheres (sucrose
and maize starch), colloidal anhydrous silica, ethylcellulose, shellac and talc.
The capsule contains: gelatin, titanium dioxide (E171) and iron oxide yellow
The printing ink contains: shellac, iron oxide black (E172), propylene glycol
and ammonium hydroxide.
What Zamadol SR prolonged-release hard capsules looks like and
contents of the pack
Zamadol SR 200mg prolonged-release hard capsules are yellow marked
with T200SR in black ink.
Each pack contains 60 prolonged-release hard capsules.
Manufacturer and Licence Holder
This medicine is manufactured by Temmler Pharma GmbH, Marburg, Germany
and is procured from within the EU and repackaged by the Product Licence
Holder: Lexon (UK) Limited, Unit 18, Oxleasow Road, East Moons Moat,
Redditch, Worcestershire, B98 0RE.
If you have any questions or are not sure about anything, ask your doctor or
pharmacist. They will have additional information about this medicine and
will be able to advise you.
Zamadol SR 200mg prolonged-release
Zamadol is a registered trademark of MEDA Pharma GmbH & Co. KG.
Revision date: 16/07/19
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Zamadol SR 200mg prolonged-release hard capsules
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Zamadol SR 200 mg prolonged-release hard capsules
QUALITATIVE AND QUANTITATIVE COMPOSITION
One capsule contains 200mg of tramadol hydrochloride
Excipients with known effect
This product contains sucrose (37.5 mg/capsule).
For the full list of excipients, see section 6.1.
Prolonged release hard capsule
The 200 mg capsules are yellow of about 19 – 19.5 mm, marked T200SR
Treatment of moderate to severe pain.
Posology and method of administration
The dose should be adjusted to the intensity of the pain and the sensitivity of the
individual patient. The lowest effective dose for analgesia should generally be
Dosage for adults and adolescents from 12 years of age:
The usual initial dose is 50-100 mg twice daily, in the morning and in the evening.
This dose may be titrated up to 150-200 mg twice daily according to pain severity.
If long-term pain treatment with tramadol hydrochloride is necessary in view of the
nature and severity of the illness, then careful and regular monitoring should be
carried out (if necessary with breaks in treatment) to establish whether and to what
extent further treatment is necessary.
A total oral daily dose of 400 mg should not be exceeded except in special clinical
Zamadol SR prolonged-release hard capsules should not be used in children under 12
years of age since safety and efficacy have not been established.
A dose adjustment is usually not necessary in patients up to 75 years of age without
clinically manifest hepatic or renal insufficiency. In elderly patients over 75 years of
age elimination may be prolonged. Therefore, if necessary the dosage interval is to be
extended according to the patient’s requirements.
Renal insufficiency/dialysis and hepatic impairment:
In patients with renal and/or hepatic insufficiency the elimination of Zamadol SR
prolonged-release capsules is delayed. In these patients prolongation of the dosage
intervals should be carefully considered according to the patient’s requirements.
Zamadol SR capsules are not recommended for patients with severe hepatic and/or
Method of administration
The capsules are intended for twice daily oral administration and can be taken
independently of meal times, swallowed whole with water.
Patients who have swallowing problems:
Zamadol SR prolonged-release hard capsules can be opened, carefully, so that the
pellets are deposited on a spoon. The spoon and pellets should be taken into the
mouth, followed by a drink of water to rinse the mouth of all pellets. The pellets must
not be chewed or crushed.
With hypersensitivity to the active substance tramadol hydrochloride or to
any of the excipients listed in section 6.1.
With acute intoxication with hypnotics, centrally acting analgesics, opioids,
psychotropic drugs or alcohol.
If monoamine oxidase inhibitors (specific drugs acting against depression)
are taken concomitantly or have been taken within the last 14 days before
treatment with Zamadol SR prolonged-release hard capsules
Who are suffering from uncontrolled epilepsy.
Tramadol must not be used for narcotic withdrawal treatment.
Special warnings and precautions for use
Risk from concomitant use of sedative medicines such as benzodiazepines or related
Concomitant use of Zamadol SR prolonged-release hard capsules and sedative
medicines such as benzodiazepines or related drugs may result in sedation, respiratory
depression, coma and death. Because of these risks, concomitant prescribing with
these sedative medicines should be reserved for patients for whom alternative
treatment options are not possible. If a decision is made to prescribe Zamadol SR
prolonged-release hard capsules concomitantly with sedative medicines, the lowest
effective dose should be used, and the duration of treatment should be as short as
The patients should be followed closely for signs and symptoms of respiratory
depression and sedation. In this respect, it is strongly recommended to inform patients
and their caregivers to be aware of these symptoms (see section 4.5).
Risk of tolerance, dependence and withdrawal symptoms:
Tolerance, psychic and physical dependence may develop, especially after long-term
use. When a patient no longer requires therapy with tramadol, it may be advisable to
taper the dose gradually to prevent symptoms of withdrawal. In patients with a
tendency to drug abuse or dependence, treatment should be for short periods under
strict medical supervision. In rare cases at therapeutic doses, tramadol has the
potential to cause withdrawal symptoms.
Zamadol SR prolonged-release hard capsules are not a suitable substitute in opioid
dependent patients. The product does not suppress morphine withdrawal symptoms
although it is an opioid agonist.
Tramadol is metabolised by the liver enzyme CYP2D6. If a patient has a deficiency
or is completely lacking this enzyme an adequate analgesic effect may not be
obtained. Estimates indicate that up to 7% of the Caucasian population may have this
deficiency. However, if the patient is an ultra-rapid metaboliser there is a risk of
developing side effects of opioid toxicity even at commonly prescribed doses.
General symptoms of opioid toxicity include confusion, somnolence, shallow
breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe
cases this may include symptoms of circulatory and respiratory depression, which
may be life threatening and very rarely fatal. Estimates of prevalence of ultra-rapid
metabolisers in different populations are summarised below:
3.4% to 6.5%
1.2% to 2%
3.6% to 6.5%
1% to 2%
Convulsions have been reported at therapeutic doses and the risk may be increased at
doses exceeding the usual upper daily dose limit. Patients with a history of epilepsy or
those susceptible to seizures should only be treated with tramadol if there are
compelling reasons. The risk of convulsions may increase in patients taking tramadol
and concomitant medication that can lower the seizure threshold (see section 4.5)
Zamadol SR prolonged-release hard capsules should be used with prudence in
patients who have shown previous hypersensitivity to opiates, and in patients with
severe renal or hepatic impairment, head injury, decreased level of consciousness,
increased intracranial pressure, or patients in shock or at risk of convulsions.
At recommended therapeutic doses Zamadol SR prolonged-release hard capsules are
unlikely to produce clinically relevant respiratory depression. Care should however be
taken when administering Zamadol SR prolonged-release hard capsules to patients
with existing respiratory depression or excessive bronchial secretion and in those
patients taking concomitant CNS depressant drugs.
Post-operative use in children:
There have been reports in the published literature that tramadol given post-
operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep
apnea, led to rare, but life threatening adverse events. Extreme caution should be
exercised when tramadol is administered to children for post-operative pain relief and
should be accompanied by close monitoring for symptoms of opioid toxicity
including respiratory depression.
Children with compromised respiratory function:
Tramadol is not recommended for use in children in whom respiratory function might
be compromised including neuromuscular disorders, severe cardiac or respiratory
conditions, upper respiratory or lung infections, multiple trauma or extensive surgical
This medicinal product contains sucrose and therefore should not be used by patients
with rare hereditary problems of fructose intolerance, glucose-galactose
malabsorption or sucrase-isomaltase insufficiency.
Interaction with other medicinal products and other forms of interaction
Patients treated with monoamine oxidase inhibitors within 14 days prior to the
administration of the opioid pethidine have experienced life-threatening interactions
affecting the central nervous system as well as the respiratory and circulatory centres.
The possibility of similar interactions occurring between monoamine oxidase
inhibitors and tramadol cannot be ruled out.
Tramadol may potentiate the CNS depressant effects of other centrally acting drugs
(including alcohol) when administered concomitantly with such drugs.
The concomitant use of opioids with sedative medicines such as benzodiazepines or
related drugs increases the risk of sedation, respiratory depression, coma and death
because of additive CNS depressant effect. The dose and duration of concomitant use
should be limited (see section 4.4).
Tramadol can induce convulsions and increase the potential for selective serotonin
reuptake inhibitors (SSRIs),serotonin-norepinephrine reuptake inhibitors (SNRIs),
tricyclic antidepressants (TCAs), antipsychotics and other seizure threshold-lowering
drugs (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions
(see section 4.4)
Concomitant therapeutic use of tramadol and serotonergic drugs such as selective
serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors
(SNRIs), MAO inhibitors (see section 4.3), tricyclic antidepressants and mirtazapine
may cause serotonin toxicity. Serotonin syndrome is likely when one of the following
Inducible or ocular clonus with agitation or diaphoresis
Tremor or hyperreflexia
Hypertonia and body temperature > 38
C and inducible or ocular clonus.
Withdrawal of the serotonergic drugs usually brings about a rapid improvement.
Treatment depends on the type and severity of the symptoms.
Administration of Zamadol SR prolonged-release hard capsules together with
carbamazepine results in markedly decreased serum concentrations of tramadol which
may reduce analgesic effectiveness and shorten the duration of action.
Caution should be exercised during concomitant treatment with tramadol and
coumarin derivatives (e.g. warfarin) due to reports of increased INR and ecchymoses
in some patients.
The combination of mixed agonists/antagonists (e.g. buprenorphine, nalbuphine,
pentazocine) and tramadol is not recommended because it is theoretically possible
that the analgesic effect of a pure agonist is attenuated under these circumstances.
The analgesic effect of tramadol is in part mediated by inhibition of the re-uptake of
norepinephrine and enhancement of the release of serotonin (5-HT). In studies the
pre- or postoperative application of the antiemetic 5-HT3 antagonist ondansetron
increased the requirements of tramadol in patients with postoperative pain.
There is no interaction with food.
Fertility, pregnancy and lactation
Zamadol SR prolonged-release hard capsules should not be used during pregnancy as
there is inadequate evidence available to assess the safety of tramadol in pregnant
women. Tramadol - administered before or during birth - does not affect uterine
contractility. In neonates it may induce changes in the respiratory rate which are
usually not clinically relevant.
Approximately 0.1% of the maternal dose of tramadol is excreted in breast milk. In
the immediate post-partum period, for maternal oral daily dosage up to 400 mg, this
corresponds to a mean amount of tramadol ingested by breast-fed infants of 3% of the
maternal weight-adjusted dosage. For this reason tramadol should not be used during
lactation or alternatively, breast-feeding should be discontinued during treatment with
tramadol. Discontinuation of breast-feeding is generally not necessary following a
single dose of tramadol.
Animal studies did not show an effect of tramadol on fertility, reproductive
performance and development of offspring.
Effects on ability to drive and use machines
Zamadol SR prolonged-release hard capsules may cause drowsiness and this effect
may be potentiated by alcohol, anti-histamines and other CNS depressants. If patients
are affected they should be warned not to drive or operate 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 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’)
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 and in
the information provided with the medicine and
It was not affecting your ability to drive safely
The most commonly reported adverse drug reactions are nausea and dizziness, both
occurring in more than 10% of patients.
Immune system disorders:
1/10,000 to < 1/1,000): Allergic reactions (e.g. dyspnoea, bronchospasm,
wheezing, angioneurotic oedema) and anaphylaxis.
Metabolism and nutrition disorders:
1/10,000 to < 1/1,000): Changes in appetite.
Frequency not known (cannot be estimated from the available data): Hypoglycaemia
1/10,000 to < 1/1,000): psychic side-effects may occur following
administration of tramadol which vary individually in intensity and nature (depending
on personality and duration of medication). These include changes in mood (usually
elation, occasionally dysphoria), changes in activity (usually suppression,
occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision
behaviour, perception disorders), hallucinations, confusion, sleep disturbances and
Prolonged administration of Zamadol SR prolonged-release hard capsules may lead to
dependence (see section 4.4) Symptoms of withdrawal reactions, similar to those
occurring during opiate withdrawal, may occur as follows: agitation, anxiety,
nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms.
Nervous system disorders:
Very common (
1/100 to < 1/10): headache, drowsiness.
1/10,000 to < 1/1,000): epileptiform convulsions occurred mainly after
administration of high doses of tramadol or after concomitant treatment with drugs
which can lower the seizure threshold or themselves induce cerebral convulsions (e.g.
antidepressants or anti-psychotics, see section 4.5 "Interaction with other medicinal
products and other forms of interaction".
Paraesthesia and tremor.
Very rare (< 1/10,000): vertigo
1/10,000 to < 1/1,000): blurred vision.
1/1,000 to < 1/100): effects on cardiovascular regulation (palpitation,
tachycardia, postural hypotension or cardiovascular collapse). These adverse effects
may occur especially on intravenous administration and in patients who are physically
1/10,000 to < 1/1,000): bradycardia, increase in blood pressure.
Very rare (< 1/10,000): flushing.
Very common (
1/10): vomiting, nausea.
1/100 to < 1/10): constipation, dry mouth.
1/1,000 to < 1/100): retching, gastrointestinal irritation (a feeling of
pressure in the stomach, bloating).
In a few isolated cases an increase in liver enzyme values has been reported in a
temporal connection with the therapeutic use of tramadol.
Skin and subcutaneous tissue disorders:
1/100 to < 1/10): sweating.
1/1,000 to < 1/100): dermal reactions (e.g. pruritus, rash, urticaria).
Musculoskeletal, connective tissue and bone disorders:
1/10,000 to < 1/1,000): motorial weakness.
Renal and urinary system disorders:
1/10,000 to < 1/1,000): micturition disorders (difficulty in passing urine and
General disorders and administration site conditions:
1/100 to < 1/10): fatigue.
Worsening of asthma has also been reported, though a causal relationship has not
Respiratory depression has been reported. If the recommended doses are considerably
exceeded and other centrally depressant substances are administered concomitantly
(see section 4.5 "Interaction with other medicinal products and other forms of
interaction") respiratory depression may occur.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA
Yellow Card in the Google Play or Apple App Store.
Symptoms of tramadol overdose include vomiting, miosis, sedation, seizures,
respiratory depression and hypotension, with circulatory failure and coma.
Respiratory failure may also occur. Such symptoms are typical of opioid
Treatment of overdose requires the maintenance of the airway and
cardiovascular functions. Respiratory depression may be reversed using
naloxone and fits controlled with diazepam. Naloxone administration may
increase the risk of seizures.
The treatment of acute overdose of tramadol using haemodialysis or
haemofiltration alone is not sufficient or suitable due to the slow elimination
of tramadol from the serum by these routes.
Pharmacotherapeutic group: Other opioids, ATC code: N02AX02
Tramadol is a centrally acting analgesic which possesses opioid agonist
properties. Tramadol consists of two enantiomers, the (+)-isomer is
predominantly active as an opioid with preferential activity for the
The (-)-isomer potentiates the analgesic effect of the (+)-isomer and is active
as an inhibitor of noradrenaline and serotonin-uptake thereby modifying the
transmission of pain impulses.
Tramadol also has an antitussive action. At the recommended dosages, the effects of
tramadol given orally on the respiratory and cardiovascular systems appear to be
clinically insignificant. The potency of tramadol is reported to be 1/10 to 1/6 of
Effects of enteral and parenteral administration of tramadol have been investigated in
clinical trials involving more than 2000 paediatric patients ranging in age from
neonate to 17 years of age. The indications for pain treatment studied in those trials
included pain after surgery (mainly abdominal), after surgical tooth extractions, due
to fractures, burns and traumas as well as other painful conditions likely to require
analgesic treatment for at least 7 days.
At single doses of up to 2mg/kg or multiple doses of up to 8mg/kg per day (to a
maximum of 400mg per day) efficacy of tramadol was found to be superior to
placebo, and superior or equal to paracetamol, nalbuphine, pethidine or low dose
morphine. The conducted trials confirmed the efficacy of tramadol. The safety
profile of tramadol was similar in adult and paediatric patients older that 1 year (see
About 90% of tramadol released from Zamadol SR prolonged-release hard capsules is
absorbed after oral administration. The mean absolute bioavailability is approximately
70%, irrespective of concomitant intake of food.
The difference between absorbed and non-metabolised available tramadol is probably
due to low first-pass effect. The first pass-effect after oral administration is a
maximum of 30%.
Tramadol has a high tissue affinity with an apparent volume of distribution of 203 ±
40 litres after oral dosing in healthy volunteers. Protein binding is limited to 20%.
After single dose administration of Zamadol SR 50 mg prolonged-release hard
capsules the peak plasma concentration C
70 ± 16 ng/ml is reached after 5.3 h.
After administration of Zamadol SR 100 mg prolonged-release hard capsules C
137 ± 27 ng/ml is reached after 5.9 h. Following administration of Zamadol SR 200
mg prolonged-release hard capsules C
294 ± 82 ng/ml is reached after 6.5 h. The
reference product (Tramadol Immediate Release Capsules, given as a total dose of
200 mg tramadol hydrochloride) reached a peak concentration of C
640 ± 143
ng/ml after 2.0 hours.
The relative bioavailability for the slow release formulation after single dose
administration is 89% and increases to 100% after multiple dose administration in
comparison to the reference product.
Tramadol passes the blood-brain and placenta barriers. Very small amounts of the
substance and its O-demethyl derivative are found in the breast-milk (0.1% and
0.02% respectively of the applied dose).
In humans tramadol is mainly metabolised by means of N- and O-demethylation and
conjugation of the O-demethylation products with glucuronic acid. Only O-
desmethyltramadol is pharmacologically active. There are considerable
interindividual quantitative differences between the other metabolites. So far, eleven
metabolites have been found in the urine. Animal experiments have shown that O-
desmethyltramadol is more potent than the parent substance by the factor 2-4. Its half
(6 healthy volunteers) is 7.9 h (range 5.4-9.6 h) and is approximately that of
The inhibition of one or both types of the isoenzymes CYP3A4 and CYP2D6
involved in the biotransformation of tramadol may affect the plasma concentration of
tramadol or its active metabolite.
Elimination of half-life t
is approximately 6 h, irrespective of the mode of
administration. In patients above 75 years of age it may be prolonged by a factor of
Tramadol and its metabolites are almost completely excreted via the kidneys.
Cumulative urinary excretion is 90% of the total radioactivity of the administered
dose. In cases of impaired hepatic and renal function the half-life may be slightly
prolonged. In patients with cirrhosis of the liver, elimination half-lives of 13.3 ± 4.9 h
(tramadol) and 18.5 ± 9.4 h (O-desmethyltramadol), in an extreme case 22.3 h and 36
h respectively have been determined. In patients with renal insufficiency (creatinine
clearance < 5 ml/min) the values were 11 ± 3.2 h and 16.9 ± 3 h, in an extreme case
19.5 h and 43.2 h, respectively.
Tramadol has a linear pharmacokinetic profile within the therapeutic dosage range.
The relationship between serum concentrations and the analgesic effect is dose-
dependent, but varies considerably in isolated cases. A serum concentration of 100 -
300 ng/ml is usually effective.
The pharmacokinetics of tramadol and O-desmethyltramadol after single-dose and
multiple-dose oral administration to subjects aged 1 year to 16 years were found to be
generally similar to those in adults when adjusting for dose by body weight, but with
a higher between-subject variability in children aged 8 years and below.
In children below 1 year of age, the pharmacokinetics of tramadol and O-
desmethyltramadol have been investigated, but have not been fully characterized.
Information from studies including this age group indicates that the formation rate of
O-desmethyltramadol via CYP2D6 increases continuously in neonates, and adult
levels of CYP2D6 activity are assumed to be reached at about 1 year of age. In
addition, immature glucuronidation systems and immature renal function may result
in slow elimination and accumulation of O-desmethyltramadol in children under 1
year of age.
Preclinical safety data
Pre-clinical data reveal no special hazard for humans based on conventional studies of
safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.
Studies of tramadol in rats and rabbits have revealed no teratogenic effects. However,
embryo toxicity was shown in the form of delayed ossification. Fertility, reproductive
performance and development of offspring were unaffected.