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TYLEX TABLETS

Active substance: PARACETAMOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Tylex Tablets.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 500mg of paracetamol Ph. Eur and 30 mg of codeine phosphate
Ph. Eur.

3

PHARMACEUTICAL FORM
Film-coated tablets.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the relief of severe pain.

4.2

Posology and method of administration
ADULTS
The tablets are given orally. The usual dose is one or two tablets every four hours as
required. The total daily dose should not exceed 240 mg of codeine phosphate (i.e.,
not more than four doses per 24 hours should be taken).
ELDERLY
A reduced dose may be required.
CHILDREN

Use in children under 12 years of age is not recommended.
Dosage should be adjusted according to the severity of the pain and the response of
the patient. However, it should be kept in mind that tolerance to codeine can develop
with continued use and that the incidence of untoward effects is dose related. Doses
of codeine higher than 60 mg fail to give commensurate relief of pain but merely
prolong analgesia and are associated with an appreciably increased incidence of
undesirable side effects.

4.3

Contraindications
TYLEX TABLETS should not be administered to patients who have previously
exhibited hypersensitivity to either paracetamol or codeine, or to any of its excipients.
TYLEX TABLETS is not recommended for children under the age of 12 years.

4.4

Special warnings and precautions for use
The risk-benefit of continued use should be assessed regularly by the prescriber.
Because safety and effectiveness in the administration of paracetamol with codeine in
children under 12 years of age have not been established, such use is not
recommended.
TYLEX TABLETS should be used with caution in patients with head injuries,
conditions in which intracranial pressure is raised, in patients sensitive to the effects
of opioids e.g. the elderly and debilitated patients, with CNS depression,
hypothyroidism, Addison's disease, prostatic hypertrophy or urethral stricture,
myasthenia gravis, inflammatory or obstructive bowel disorders, pre-existing
respiratory depression or those with the potential to develop respiratory depression..
Care is advised in the administration of paracetamol to patients with severe renal or
severe hepatic impairment. The hazards of overdose are greater in those with noncirrhotic alcoholic liver disease.
Chronic heavy alcohol abusers may be at increased risk of liver toxicity from
excessive paracetamol use, although reports of this event are rare. Reports almost
invariably involve cases of severe chronic alcoholics and the dosages of paracetamol
most often exceed recommended doses and often involve substantial overdose.
Professionals should alert their patients who regularly consume large amounts of
alcohol not to exceed recommended doses of paracetamol.

Administration of pethidine and possibly other opioid analgesics to patients taking a
monoamine oxidase inhibitor (MAOI) has been associated with very severe and
sometimes fatal reactions. If the use of codeine is considered essential then great care
should be taken in patients taking MAOIs or within 14 days of stopping MAOIs (see
section 4.5).
At high doses codeine has most of the disadvantages of morphine, including
respiratory depression. Codeine can produce drug dependence of the morphine type,
and therefore has the potential for being abused. Codeine may impair the mental
and/or physical abilities required for the performance of potentially hazardous tasks.
Patients should be advised that immediate medical advice should be sought in the
event of an overdose, because of the risk of delayed, serious liver damage. They
should be advised not to exceed the recommended dose, not to take other
paracetamol-containing products concurrently, to consult their doctor if symptoms
persist and to keep the product out of the reach of children.

The leaflet will state in a prominent position in the ‘Before you take’ section:


Do not take for longer than directed by your prescriber



Taking codeine regularly for a long time can lead to addiction, which might
cause you to feel restless and irritable when you stop the tablets.



Taking a painkiller for headaches too often or for too long can make them
worse.

The label will state (To be displayed prominently on outer pack -not boxed):


4.5

Do not take for longer than directed by your prescriber as taking codeine
regularly for a long time can lead to addiction

Interaction with other medicinal products and other forms of interaction
Patients receiving other central nervous system depressants (including other opioid
analgesics, tranquillisers, sedative hypnotics and alcohol) concomitantly with TYLEX
TABLETS may exhibit an additive depressant effect. When such therapy is
contemplated, the dose of one or both agents should be reduced.
Concurrent use with centrally acting muscle relaxants may increase the risk of
respiratory depression.
Concurrent use of MAOI inhibitors or tricyclic antidepressants with codeine may
increase the effect of either the antidepressant or codeine. Concurrent use of
anticholinergics and codeine may produce paralytic ileus.
MAOIs taken with pethidine have been associated with severe CNS excitation or
depression (including hypertension or hypotension). Although this has not been
documented with codeine, it is possible that a similar interaction may occur and
therefore the use of codeine should be avoided while the patient is taking MAOIs and
for 2 weeks after MAOI discontinuation.

Enzyme-inducing medicines, such as some antiepileptic drugs (phenytoin,
phenobarbital, carbamazepine) have been shown in pharmacokinetic studies to reduce
the plasma AUC of paracetamol to approximately 60 %. Other substances with
enzyme-inducing properties, e.g.rifampicin and St. John's wort (hypericum) are also
suspected of causing lowered concentrations of paracetamol. In addition, the risk of
liver damage during treatment with maximum recommended doses of paracetamol
will be higher in patients being treated with enzyme-inducing agents.
The speed of absorption of paracetamol may be increased by metoclopramide or
domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by
prolonged regular daily use of paracetamol with increased risk of bleeding;
occasional doses have no significant effect.

4.6

Pregnancy and lactation
The use of TYLEX TABLETS is not recommended during pregnancy or lactation
since safety in pregnant women or nursing mothers has not been established.

4.7

Effects on ability to drive and use machines
Patients should be advised not to drive or operate machinery if affected by dizziness
or sedation.

4.8

Undesirable effects
Reported adverse reactions seem more prominent in ambulatory than nonambulatory patients and some of these effects may be alleviated if the patient
lies down.
A tabulated list of adverse reactions is outlined below:
System Organ Class

Adverse Effects (Frequency not know)

Blood and lymphatic system
disorders

Thrombocytopenia, agranulocytosis

Immune system disorders

Anaphylactic reaction, hypersensitivity

Psychiatric disorders

Dysphoria, euphoria

Nervous system disorders

Dizziness, sedation, headache

Ear and labyrinth disorders

Deafness1

Respiratory thoracic and
mediastinal disorders

Bronchospasm, dyspnoea

Gastro-intestinal disorders

Nausea, vomiting, constipation,
abdominal pain, pancreatitis2

Skin and subcutaneous tissue
disorders

Pruritus, rash, urticaria

1

Deafness has been reported in patients after long term use of high doses of
codeine – paracetamol.

2

Drug-induced pancreatitis associated with paracetamol has been reported in
literature to be a rare reaction only occurring in patients taking in excess of the
recommended doses. Literature reports have also associated cases of
pancreatitis with codeine.

There have been cases of bronchospasm with paracetamol, but these are more
likely in asthmatics sensitive to aspirin or other NSAIDs.
In clinical use of paracetamol containing products, there have been a few
reports of blood dyscrasias including thrombocytopenia and agranulocytosis
but these were not necessarily causally related to paracetamol.
Anaphylaxis, angiodema and toxic epidermal necrolysis have also been
associated with the use of paracetamol.
Prolonged use of a painkiller for headaches can make them worse.
Regular prolonged use of codeine is known to lead to addiction and tolerance.
Symptoms of restlessness and irritability may result when treatment is
stopped.
4.9

Overdose
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol.
Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has
risk factors (see below).
Risk factors
If the patient
a, Is on long term treatment with carbamazepine, phenobarbital, phenytoin,
primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.
Or
b, Regularly consumes ethanol in excess of recommended amounts.
Or
c, Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV
infection, starvation, cachexia.

Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea,
vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48
hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis
may occur. In severe poisoning, hepatic failure may progress to encephalopathy,
haemorrhage, hypoglycaemia, hypokalaemia, cerebral oedema, and death. Acute
renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria
and proteinuria, may develop even in the absence of severe liver damage. Cardiac
arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential in the management of paracetamol overdose. Despite
a lack of significant early symptoms, patients should be referred to hospital urgently
for immediate medical attention. Symptoms may be limited to nausea or vomiting and
may not reflect the severity of overdose or the risk of organ damage. Management
should be in accordance with established treatment guidelines, see BNF overdose
section.
Treatment with activated charcoal should be considered if the overdose has been
taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours
or later after ingestion (earlier concentrations are unreliable). Treatment with Nacetylcysteine may be used up to 24 hours after ingestion of paracetamol, however,
the maximum protective effect is obtained up to 8 hours post-ingestion. The
effectiveness of the antidote declines sharply after this time. If required the patient
should be given intravenous N-acetylcysteine, in line with the established dosage
schedule. If vomiting is not a problem, oral methionine may be a suitable alternative
for remote areas, outside hospital. Management of patients who present with serious
hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or
a liver unit.
Codeine
Simultaneous ingestion of alcohol and psychotropic drugs will potentiate the effects
of overdosage.
Symptoms of codeine overdose may include:
Central nervous system depression (including respiratory depression) but this is
unlikely to be severe unless the overdose is large, or there is co-ingestion with
other sedative agents or alcohol;
pinpoint sized pupils;
nausea and vomiting;
hypotension and tachycardia are possible but unlikely.
Management
General symptomatic and supportive measures including a clear airway and
monitoring of vital signs until stable. Consider activated charcoal if an adult presents
within 1 hour after ingesting more than 350 mg or a child more than 5 mg/kg. Give
naloxone if coma or respiratory depression is present. Naloxone is a competitive

antagonist with a short half-life, so large and repeated doses may be required in a
seriously poisoned patient. Observe patients for at least 4 hours after ingestion.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Paracetamol has analgesic and antipyretic actions similar to those of aspirin with
weak anti-inflammatory effects. Paracetamol is only a weak inhibitor of
prostaglandin biosynthesis, although there is some evidence to suggest that it may be
more effective against enzymes in the CNS than those in the periphery. This fact may
partly account for its well documented ability to reduce fever and to induce analgesia,
effects that involve actions on neural tissues. Single or repeated therapeutic doses of
paracetamol have no effect on the cardiovascular and respiratory systems. Acidbased changes do not occur and gastric irritation, erosion or bleeding is not produced
as may occur after salicylates. There is only a weak effect upon platelets and no
effect on bleeding time or the excretion of uric acid.
Codeine is an analgesic with uses similar to those of morphine but has only mild
sedative effects. The major effect is on the CNS and the bowel. The effects are
remarkably diverse and include analgesia, drowsiness, changes in mood, respiratory
depression, decreased gastrointestinal motility, nausea, vomiting and alterations of the
endocrine and autonomic nervous systems. The relief of pain is relatively selective,
in that other sensory modalities, (touch, vibration, vision, hearing etc.) are not
obtunded.

5.2

Pharmacokinetic properties
Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma
concentration occurring about 30 minutes to 2 hours after ingestion. It is metabolised
in the liver and excreted in the urine mainly as the glucuronide and sulphate
conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination
half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual
therapeutic concentrations but increases with increasing concentrations.
A minor hydroylated metabolite which is usually produced in very small amounts by
mixed-function oxidases in the liver and which is usually detoxified by conjugation
with liver glutathione may accumulate following paracetamol overdosage and cause
liver damage.
Codeine and its salts are absorbed from the gastro intestinal tract. Ingestion of
codeine phosphate produces peak plasma codeine concentrations in about one hour.
Codeine is metabolised by O- & N-demethylation in the liver to morphine and

norcodeine. Codeine and its metabolites are excreted almost entirely by the kidney,
mainly as conjugates with glucuronic acid.
The plasma half-life has been reported to be between 3 and 4 hours after
administration by mouth or intravascular injection.

5.3

Preclinical safety data
None stated

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Powdered cellulose (grade 40 FCC)
Sodium Starch Glycolate
Maize Starch
Pregelatinized Starch
Magnesium Stearate
Colloidal Silica Anhydrous
Carnauba Wax
Opadry® II White
TekPrint ® SB 1010 N Red
Purified Water

6.2

Incompatibilities
None pertinent

6.3

Shelf life
24 months

6.4

Special precautions for storage
Store at or below 25°C. Protect from light

6.5

Nature and contents of container
Tamper-evident high density polyethylene bottles fitted with low density
polyethylene caps, containing 8, 24, 32, 40, 48, 56, 64, 100 or 500 tablets.

6.6

Special precautions for disposal
None

7

MARKETING AUTHORISATION HOLDER
UCB Pharma Limited
208 Bath Road
Slough
Berkshire
SL1 3WE
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00039/0748

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28 March 1996

10

DATE OF REVISION OF THE TEXT
21/03/2011

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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