1. Name Of The Medicinal Product
Tylex Effervescent.
Medocodene 30/500 Effervescent
2. Qualitative And Quantitative Composition
Each effervescent tablet contains 500mg of paracetamol Ph. Eur and 30 mg of codeine phosphate Ph.Eur.
3. Pharmaceutical Form
Effervescent 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 and should be dissolved in at least half a tumblerful of water before taking. 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 eight tablets 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 EFFERVESCENT should not be administered to patients who have previously exhibited hypersensitivity to either paracetamol or codeine, or to any of its excipients.
TYLEX EFFERVESCENT 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.
These tablets should be used with caution in patients with head injuries, increased intracranial pressure, acute abdominal conditions, the elderly and debilitated, and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy or urethral stricture, myasthenia gravis, biliary tract disorders (including recent biliary tract surgery).
The hazard of overdose is greater in those with non-cirrhotic 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.
These tablets contain 326.6 mg sodium/tablet and this should be taken into account when prescribing for patients for whom sodium restriction is indicated. The product also contains 25 mg aspartame/tablet and therefore care should be taken in phenylketonuria.
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/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 taking' 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):
· Do not take for longer than directed by your prescriber as taking codeine regularly for a long time can lead to addiction
4.5 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 EFFERVESCENT may exhibit an additive depressant effect. When such therapy is contemplated, the dose of one or both agents should be reduced.
Concurrent use of MAO 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.
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 EFFERVESCENT 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
Regular prolonged use of codeine is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is stopped.
Prolonged use of a painkiller for headaches can make them worse.
Reported adverse reactions seem more prominent in ambulatory than non-ambulatory patients and some of these effects may be alleviated if the patient lies down.
The most frequently observed reactions include light headedness, dizziness, sedation, shortness of breath, nausea and vomiting. These effects seem more prominent in ambulatory than nonambulatory patients and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include allergic reactions, (including skin rash), euphoria, dysphoria, constipation, abdominal pain and pruritus.
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.
4.9 Overdose
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol. The following groups are at risk of liver damage from paracetamol doses of 5g or more:
• patients on long-term treatment with drugs which induce liver enzymes (e.g. barbiturates, St John's Wort);
• people who regularly drink excessive amounts of alcohol;
• patients with depleted glutathione levels (e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia).
Symptoms of paracetamol overdose include:
• pallor, nausea, vomiting, anorexia and abdominal pain within 24 hours of ingestion;
• 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, cerebral oedema and death;
• Acute renal failure with acute tubular necrosis (loin pain, haematuria and proteinuria), may develop regardless of severe liver damage;
• Cardiac arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential. 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 within 1 hour of overdose. Plasma paracetamol concentration should be measured at 4 hours or more post-ingestion (to ensure the measurement is reliable). Treatment with N-acetylcysteine is most effective up to 8 hours after ingestion but may be used up to 24 hours after overdose. Antidote effectiveness declines sharply after 8 hours. If required, administer N-acetylcysteine intravenously, 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 more than 24h after 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. Acid-based 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 mixedfunction 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
Citric Acid Anhydrous
Sodium Bicarbonate
Sodium Carbonate Anhydrous
Aspartame
Polyethylene Glycol 6000
Magnesium Stearate
Ethanol 96 % (not detected in the finished product)
6.2 Incompatibilities
None pertinent
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
Store at room temperature (at or below 25°C) in a dry place. Protect from light
6.5 Nature And Contents Of Container
Paper/aluminium laminate blister strips packed in cardboard cartons.
Pack sizes: 1, 6, 8, 24, 30, 36, 42, 48, 90, 100 and 102 tablets.
Not all pack sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
None
7. Marketing Authorisation Holder
UCB Pharma Limited
208 Bath Road
Slough
Berkshire
SL1 3WE
United Kingdom
8. Marketing Authorisation Number(S)
PL 00039/750
9. Date Of First Authorisation/Renewal Of The Authorisation
05/11/2009
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