ASPIRIN AND CODEINE TABLETS BP

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Aspirin and Codeine Tablets BP

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION Active ingredient Codeine Phosphate EP Aspirin mg 8.00 400.0

3.

PHARMACEUTICAL FORM Tablet.

4
4.1

CLINICAL PARTICULARS
Therapeutic indications For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as: headache, migraine, neuralgia, toothache, period pain and rheumatic pains.

4.2

Posology and method of administration
For oral administration. Adults and children over 16 years: 1 to 2 tablets. This dose may be taken, up to 4 times a day at intervals of not less than 4 hours. Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki's disease). Elderly: The normal adult dose is still appropriate in the elderly. Do not take for more than 3 days continuously without medical review.

4.3.

Contraindications Hypersensitivity to any of the ingredients. Active peptic ulceration or a history of ulceration, haemophilia or other clotting disorders. Gout, asthma, urticaria, rhinitis or other evidence of hypersensitivity to aspirin. Aspirin should be avoided in patients with severe renal or hepatic impairment. Obstructive airways disease, respiratory depression, acute alcoholism, where there is risk of paralytic ileus, head injuries and conditions in which intracranial pressure is raised. Breast feeding.

4.4

Special warnings and precautions for use If symptoms persist consult your doctor. There is a possible association between aspirin and Reye's syndrome when given to children. Reyes syndrome is a very rare disease, which affects the brain and liver, and can be fatal. For this reason aspirin should not be given to children aged under 16 years unless specifically indicated (e.g. for Kawasakis disease). Codeine should be taken with caution or in reduced doses by patients with hypotension, decreased respiratory reserve, convulsive disorders, hypothyroidism, adrenocortical insufficiency, impaired kidney or liver function, prostatic hypertrophy, shock, inflammatory or obstructive bowel disorders and myasthenia gravis. Codeine is partially metabolised by CYP2D6. If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. 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 an increased risk of developing side effects of opioid toxicity even at low doses. General symptoms of opioid toxicity include nausea, vomiting, constipation, lack of appetite and somnolence. In severe cases this may include symptoms of circulatory and respiratory depression. Estimates indicate that up to 1 to 2% of the caucasian population may be ultra-rapid metabolisers. Aspirin and other NSAIDs may cause salt and water retention and renal failure especially in patients with pre-existing renal impairment. Aspirin should be used with caution by patients with asthma, allergic disease, dehydration, glucose-6-phosphate dehydrogenase deficiency and the elderly. Keep all medicines out of the reach of children.

The Label will state: Front of pack Can cause addiction For three days use only Back of pack List of indications as agreed in 4.1 of the SPC If you need to take this medicine continuously for more than 3 days you should see your doctor or pharmacist This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. If you take this medicine for headaches for more than 3 days it can make them worse. The leaflet (or combined label/leaflet) will state: Headlines section (to be prominently displayed) This medicine can only be used for.....(indications) You should only take this product for a maximum of 3 days at a time. If you need to take it for longer than 3 days you should see your doctor or pharmacist for advice. This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it. If you take this medicine for headaches for more than 3 days it can make them worse. What this medicine is for section Succinct description of the indications from 4.1 of the SPC Before you take this medicine section This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it. If you take a painkiller for headaches for more than 3 days it can make them worse. How to take this medicine section Do not take for more than 3 days. If you need to use this medicine for more than 3 days you must speak to your doctor or pharmacist. This medicine contains codeine and can cause addiction if you take it continuously for more than 3 days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms. Possible side effects section Some people may have side effects when taking this medicine. If you have any unwanted side effects you should seek advice from your doctor, pharmacist or other healthcare professional. Also you can help to make sure that medicines remain as safe as possible by reporting any unwanted

side-effects via the internet at www.yellowcard.gov.uk; alternatively you can call Freephone 0808 100 3352 (available between 10am-2pm Monday-Friday) or fill in a paper form available from your local pharmacy. How do I know if I am addicted? section If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to you doctor: You need to take the medicine for longer periods of time You need to take more than the recommended amount When you stop taking the medicine you feel very unwell but you feel better if you start taking the medicine again 4.5. Interactions with other medicinal products and other forms of interaction Alcohol and corticosteroids may enhance the effects of aspirin on the gastrointestinal tract. Aspirin may enhance the effects of coumarin anticoagulants and oral hypoglycaemics of sulphonylurea type. The toxicity of methotrexate may be enhanced by concomitant use of aspirin. Aspirin diminishes the uricosuric action of probenecid and sulphinpyrazone. Codeine may delay the absorption of mexiletine and thus reduce the antiarrhythmic effect of the latter. The depressant effects of codeine are enhanced by depressants of central nervous system such as hypnotics, sedatives, tricyclic antidepressants and phenothiazines. Codeine may antagonise the gastrointestinal effects of metoclopramide and domperidone.

4.6

Pregnancy and lactation The safety of aspirin and codeine tablets during pregnancy has not been established and use in this period should be avoided. The use of aspirin during pregnancy, particularly during the third trimester, should be avoided since the drug may affect maternal and new born haemostatic mechanisms, leading to an increased risk of haemorrhage. Aspirin may also delay the onset and increase the duration of labour. With high doses, there may be premature closure of the ductus arteriosus, leading possibly to persistent pulmonary hypertension. In addition, codeine during pregnancy has been associated with respiratory and heart malformations. As aspirin is secreted into breast milk in low concentrations, use of aspirin and codeine tablets should be avoided during lactation because of the risk of Reye's syndrome and the fact that high doses of aspirin could potentially impair platelet function.

At normal therapeutic doses codeine and its active metabolites may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolites may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant. If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

4.7.

Effects on ability to drive and use machines May cause drowsiness and therefore may influence the ability to drive and operate machinery.

4.8

Undesirable effects
Dyspepsia, nausea, vomiting, constipation, increased bleeding time, drowsiness, confusion, dry mouth, sweating, facial flushing, vertigo, bradycardia, tachycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, changes of mood, miosis, respiratory depression, difficulty in micturition and possibly ureteric or biliary spasm, headache, hallucinations, dysphoria, decreased libido or potency, pruritis. Less commonly irritation of the gastrointestinal mucosa may lead to erosion, ulceration, gastrointestinal bleeding. Hepatotoxicity which occurs rarely. Aspirin may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions including urticaria, rhinitis and angioneurotic oedema in susceptible individuals. Aspirin may also cause salt and water retention as well as deterioration in renal function (see also section 4.4). Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is then stopped. Prolonged use of a painkiller for headaches can make them worse.

4.9.

Overdose Salicylate poisoning is usually associated with plasma concentrations >350mg/L (2.5mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1mmol/L). Single doses less than 100mg/kg are unlikely to cause serious poisoning. Common features of salicylate poisoning include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases. A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of 4 years. In children aged 4 years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier. Uncommon features of salicylate poisoning include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema. Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children. Give activated charcoal if an adult presents within one hour of ingestion of more than 250mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema. Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700mg/L (5.1mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under 10 years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage. The effects of codeine in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs. Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been coingested, including alcohol, or the overdose is very large. The pupils may be

pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely. Management should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350mg or a child more than 5mg/kg. Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least 4 hours after ingestion, or eight hours if a sustained release preparation has been taken.

5. 5.1.

PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties Aspirin has analgesic, antipyretic and anti inflammatory actions which are considered to be due to inhibition of synthesis of prostaglandins. Codeine phosphate is an opioid analgesic which acts via the central nervous system.

5.2.

Pharmacokinetic properties Absorption of non-ionised aspirin occurs in the stomach and intestine. Some aspirin is hydrolysed to salicylate in the gut wall. After absorption aspirin is rapidly converted to salicylate but during the first 20 minutes following oral administration, aspirin is the predominant form of the drug in the plasma. Aspirin is bound to plasma proteins and is widely distributed. Plasma aspirin concentrations decline rapidly (half life 15-20 minutes) as plasma salicylate concentrations increase. Salicylate is mainly eliminated by hepatic metabolism the metabolites including salicylic acid, salicyl phenolic glucuronide, salicylic acyl glucuronide, gentisic acid and gentisuric acid. As a result of zero order kinetics, plasma steady state salicylate concentrations increase disproportionately with dose. Salicylate is also excreted unchanged in the urine to an extent which depends on the dosage and urinary pH. Renal excretion involves glomerular filtration, active renal tubular secretion and passive tubular reabsorption. Codeine phosphate is absorbed from the gastrointestinal tract and peak plasma concentrations occur after about one hour. Codeine is metabolised by O- and

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.

5.3.

Preclinical safety data Not applicable.

6. 6.1.

PHARMACEUTICAL PARTICULARS List of excipients Specially Dried Maize Starch EP. Sodium Metabisulphite BP.

6.2.

Incompatibilities None known.

6.3.

Shelf life 36 months: For glass bottle 24 months: For HDPE bottle

6.4

Special precautions for storage
HDPE bottle: Do not store above 25C. Store in the original package

Glass bottle: None

6.5

Nature and contents of container
Amber glass bottle with a child-resistant polythene/polypropylene cap, fitted

with a lectraseal tamper-evident liner which is: surlyn/aluminium foil/polythene/bleached kraft paper/dot adhered to melinex coated carton board or a child-resistant polyethylene/polypropylene cap fitted with a waxed aluminium faced pulpboard liner. Pack sizes: 24, 25, 30, 32. or A white HDPE bottle with a polypropylene cap fitted with an induction heat seal membrane. Pack sizes: 24, 25, 30, 32.

7.

MARKETING AUTHORISATION HOLDER The Boots Company PLC 1 Thane Road West Nottingham NG2 3AA.

8.

MARKETING AUTHORISATION NUMBER PL: 00014/0155R.

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date first authorisation: 13 April 1981 Date most recent renewal granted: 13 April 1991.

10

DATE OF REVISION OF THE TEXT

08/03/2012