TRAMADOL HYDROCHLORIDE 50MG TABLETS

Active substance: TRAMADOL HYDROCHLORIDE

View full screen / Print PDF » Download PDF ⇩

Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Tramadol Hydrochloride 50mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 50mg tramadol hydrochloride. For excipients, see 6.1.

3

PHARMACEUTICAL FORM
A white round oral tablet with T printed on one face and a breakline on the
reverse.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Management (treatment and prevention) of moderate to severe pain.

4.2

Posology and method of administration
For oral 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
selected.
ADULTS AND CHILDREN AGED 12 YEARS AND OVER
Acute pain
An initial dose of 100mg is usually necessary. This can be followed by doses of
50 or 100 mg not more frequently than 4 hourly, and duration of therapy should
be matched to clinical need.
Pain associated with chronic conditions

Use an initial dose of 50mg and then titrate dose according to pain severity. The
need for continued treatment should be assessed at regular intervals as
withdrawal symptoms and dependence have been reported (See Section 4.4,
Special Warnings and Precautions for Use).
A total daily oral dose of 400mg should not be exceeded except in special
clinical circumstances.
Geriatric patients
A dose adjustment is not usually necessary in patients up to 75 years without
clinically manifest hepatic or renal insufficiency. In elderly patients over 75
years 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 tramadol is
delayed. In these patients prolongation of the dosage intervals should be
carefully considered according to the patient's requirements.
Children under 12 years
Not recommended.

4.3

Contraindications
Tramadol should not be administered to patients who have previously demonstrated
hypersensitivity to it or in cases of acute intoxication with alcohol, hypnotics,
centrally acting analgesics, opioids or psychotropic drugs, or in patients suffering
from uncontrolled epilepsy. Tramadol must not be used for narcotic withdrawal
treatment. In common with other opioid analgesics it should not be administered to
patients who are receiving monoamine oxidase inhibitors or within two weeks of their
withdrawal.

4.4

Special warnings and precautions for use
Warnings
At therapeutic doses, tramadol has the potential to cause withdrawal
symptoms. Rarely, cases of dependence and abuse have been reported.
At therapeutic doses, withdrawal symptoms have been reported at a reporting
frequency of 1 in 8,000. Reports of dependence and abuse have been less
frequent. Because of this potential, the clinical need for continued analgesic
treatment should be reviewed regularly.
In patients with a tendency to drug abuse or dependence, treatment should be
for short periods and under strict medical supervision.

Tramadol is not suitable as a substitute in opioid-dependent patients.
Although it is an opioid agonist, tramadol cannot suppress morphine
withdrawal symptoms.
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 - Interactions with other
Medicaments and other Forms of Interactions).
Precautions
Tramadol should be used with caution in patients with head injury, increased
intracranial pressure, severe impairment of hepatic and renal function and in
patients prone to convulsive disorders or in shock.
Care should be taken when treating patients with respiratory depression, or if
concomitant CNS depressant drugs are being administered, as the possibility
of respiratory depression cannot be excluded in these situations. At
therapeutic doses, respiratory depression has infrequently been reported.
In one study, use of tramadol during general anaesthesia with enflurane and
nitrous oxide was reported to enhance intraoperative recall. Until further
information is available use of tramadol during light planes of general
anaesthesia should be avoided.
Caution should be exercised in patients with a previous history of
hypersensitivity to other opiates, and in patients with decreased level of
consciousness of uncertain origin.

4.5

Interaction with other medicinal products and other forms of
interaction
Concomitant administration of tramadol with other centrally acting drugs
including alcohol may potentiate CNS depressant effect.
Tramadol can induce convulsions and increase the potential for selective
serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake
inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other seizure
threshold-lowering medicinal products (such as bupropion, mirtazapine,
tetrahydrocannabinol) to cause convulsions.
Simultaneous administration of carbamazepine markedly decreases serum
concentrations of tramadol to an extent that a decrease in analgesic effectiveness
and a shorter duration of action may occur.
Simultaneous administration with cimetidine is associated with clinically
insignificant changes in serum concentrations of tramadol. Therefore no

alteration of the tramadol dosage regimen is recommended for patients receiving
chronic cimetidine therapy.
There is a theoretical possibility that tramadol could interact with lithium due to
their respective mechanisms of action.
The simultaneous administration of Tramadol and MAOIs is contraindicated.
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. In case of concomitant administration of digoxine rare cases of
toxicity signs due to digoxine have been observed such as nausea, vomiting and
cardiac arrhythmias. Simultaneous administration of ritonavir can augment the
concentration of Tramadol in serum which can lead to a toxicity of Tramadol
(extreme sedation and respiratory depression) the dose of Tramadol must be reduced.
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.
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 is observed:
• Spontaneous clonus
• Inducible or ocular clonus with agitation or diaphoresis
• Tremor and 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.

4.6

Pregnancy and lactation
Pregnancy
Animal studies (rat and rabbit, exposure to tramadol up to 7 times that
expected in man) have not revealed teratogenic effects and minimal
embryotoxicity (delayed ossification). Fertility, reproductive performance and
development of offspring were unaffected. There is inadequate evidence
available on the safety of tramadol in human pregnancy, therefore tramadol
should not be used in pregnant women.
Lactation
Tramadol and its metabolites are found in small amounts in human breast
milk. An infant could ingest about 0.1% of the dose given to the mother.
Tramadol should not be administered during breast feeding.

4.7

Effects on ability to drive and use machines
Tramadol may cause drowsiness and this effect may be potentiated by alcohol
and other CNS depressants. Ambulant patients should be warned not to drive
or operate machinery if affected.

4.8

Undesirable effects
The most commonly reported adverse drug reactions are nausea and dizziness,
both occurring in more than 10% of patients.
Cardiovascular system disorders:
Uncommon (<1%): cardiovascular regulation (palpitation, tachycardia,
postural hypotension or cardiovascular collapse). These adverse effects may
occur especially on intravenous administration and in patients who are
physically stressed.
Rare (<0.1%): bradycardia, increase in blood pressure, syncope, blood
dyscrasias.
Central and peripheral nervous system disorders:
Common (1-10%): headache, muzziness
Rare (<0.1%): changes in appetite, paraesthesia, tremor, vertigo, respiratory
depression, epileptiform convulsions.
Psychiatric disorders:
Rare (<0.1%): hallucinations, confusion, somnolence, sleep disturbance and
nightmares. 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
ability (e.g. decision behaviour, perception disorders). Dependence may
occur.
Vision disorders:
Rare (<0.1%): blurred vision.
Respiratory system disorders:
Worsening of asthma has been reported, though a casual relationship has not
been established.
Gastrointestinal disorders:
Very common (>10%): nausea

Common (1-10%): vomiting, constipation, diarrhoea, dry mouth.
Uncommon (<1%): retching; gastrointestinal irritation (a feeling of pressure in
the stomach, bloating.
Skin and appendages disorders:
Common (1-10%): sweating
Uncommon (<1%): dermal reactions (e.g. pruritus, rash, urticaria)
Rare (<0.1%): flushing
Musculo-Skeletal System Disorders:
Rare (<0.1%): muscle weakness
Liver and biliary system disorders:
In rare cases, increases in liver enzyme values have been reported in a
temporal connection with the therapeutic use of tramadol.
Urinary System Disorders:
Rare (0.1%): micturition disorders (difficulty in passing urine and urinary
retention).
Body as a Whole:
Rare (<0.1%): Allergic reactions (e.g. dyspnoea, bronchospasm, wheezing,
angioneurotic oedema) and anaphylaxis; symptoms of withdrawal reactions,
similar to those occurring during opiate withdrawal, may occur as follows:
agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and
gastrointestinal symptoms.

4.9

Overdose
Symptoms of overdosage are typical of other opioid analgesics, and include
miosis, vomiting, cardiovascular collapse, sedation and coma, seizures and
respiratory depression.
Supportive measures such as maintaining the patency of the airway and
maintaining cardiovascular function should be instituted; naloxone should be
used to reverse respiratory depression; fits can be controlled with diazepam.
Tramadol is minimally eliminated from the serum by haemodialysis or
haemofiltration. Therefore treatment of acute intoxication with tramadol with
haemodialysis or haemofiltration alone is not suitable for detoxification.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: N02AX02
Tramadol is a centrally acting analgesic with two mechanisms of action. It is a
non-selective pure agonist at opioid receptors with a higher affinity for μ
receptors. It is also an inhibitor of neuronal reuptake of noradrenaline and
serotonin.

5.2

Pharmacokinetic properties
Tramadol has a half-life of approximately six hours. It is eliminated
metabolically and by the kidneys. The terminal half-life may therefore be
increased in renal and hepatic impairment.
The half-life of the terminal elimination phase (t1/ß) was 6.0 ± 1.5 h in young
volunteers. Tramadol pharmacokinetics show little age dependence in
volunteers up to the age of 75 years. In volunteers aged over 75 years, t1/2ß
was 7.0 ± 1.6 h on oral administration.
Since tramadol is eliminated both metabolically and renally, the terminal halflife t½ß may be prolonged in impaired hepatic or renal function. However, the
increase in the t½ß values is relatively low if at least one of these organs is
functioning normally. In patients with liver cirrhosis t½ß tramadol was a mean
of 13.3 ±4.9 h. in patients with renal insufficiency (creatinine clearance ≤5
ml/min) it was 11.0 ±3.2 h.
The poor metabolisers of Tramadol may have approximately up to 10 times
lower 0-desmethyltramadol levels compared with the extensive metabolisers
in terms of AUC.
The inhibition of one or both P450 isoenzymes, CYP3A4 and CYP2D6
involved in the metabolism of tramadol, may affect the plasma concentration
of tramadol or its active metabolite. Up to now, clinically relevant
interactions have not been reported.

5.3

Preclinical safety data
Single and repeat-dose animal studies demonstrate that 10 times the expected
human dose is needed before hepatotoxicity is observed. Carcinogenicity and
mutagenicity tests in animals were negative.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Microcrystalline cellulose
Carmellose sodium
Magnesium stearate

6.2

Ph. Eur.
Ph. Eur.
Ph. Eur.
Ph. Eur.

Incompatibilities
Not applicable.

6.3

Shelf life
Tramadol hydrochloride tablets have a shelf life of five years.

6.4

Special precautions for storage
Store in the original package, below 25oC

6.5

Nature and contents of container
Blister strips formed from 25μm thick soft aluminium cover foil and
250μm thick opaque PVC foil
Blister packs of 10, 30, 60 and 100 tablets.

6.6

Special precautions for disposal
Not applicable

7

MARKETING AUTHORISATION HOLDER
Eurogenerics N.V.

Heizel Esplanade b 22,
1020 Brussel,
Belgie

8

MARKETING AUTHORISATION NUMBER(S)
PL 20907/0002

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
24/01/2003 / 12/10/2003

10

DATE OF REVISION OF THE TEXT
06/12/2012

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.

When it’s more than a bad back. Learn about ankylosing spondylitis. Click Here

Close
Hide
(web2)