SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Paramol Soluble Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Paracetamol Ph Eur 250 mg

Paracetamol (direct compression containing gelatin) 260mg Dihydrocodeine tartrate BP 7.46 mg

3 PHARMACEUTICAL FORM

Effervescent tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone including headache, migraine, period pain, toothache and other dental pain, back pain, muscular and joint pains, neuralgia and as an antipyretic.

4.2 Posology and method of administration

For oral administration.

Paramol Soluble Tablets should be taken during or after meals. The tablets should be dissolved in water.

Adults and children over 12 years:

1 or 2 tablets every four to six hours. Do not exceed eight tablets in any 24 hour period. Do not take for more than 3 days continuously without medical review.

Children under 12 years:

Not recommended.

Elderly:

Caution should be observed in increasing the dose in the elderly.

4.3 Contraindications

Known hypersensitivity to paracetamol, dihydrocodeine, other opioids or other constituents of the tablets.

Respiratory depression, obstructive airways disease, convulsive disorders. Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembranous colitis.

4.4 Special warnings and precautions for use

Paramol Soluble Tablets should be used with caution in patients with:

■    Hepatic function impairment (avoid if severe) and those with non-cirrhotic alcoholic liver disease. The hazards of overdose are greater in those with alcoholic liver disease.

■    Prolonged use of Paramol Soluble Tablets may cause hepatic necrosis.

■    Renal function impairment.

■    Hypothyroidism (risk of depression and prolonged CNS depression is increased).

■    Inflammatory bowel disease - risk of toxic megacolon.

■    Opioids should not be administered during an asthma attack.

■    Convulsions - may be induced or exacerbated.

■    Drug abuse, dependence (including alcoholism), enhanced instability, suicidal ideation or attempts - predisposed to drug abuse.

■    Head injuries or conditions where intracranial pressure is raised.

■    Gall bladder disease or gall stones - opioids may cause biliary contraction.

■    Gastro-intestinal surgery - use with caution after recent GI surgery as opioids may alter GI motility.

■    Prostatic hypertrophy or recent urinary tract surgery.

■    Adrenocortical insufficiency, e.g. Addison’s Disease.

■    Hypotension and shock.

■    Myasthenia gravis.

■    Phaeochromocytoma - opioids    may    stimulate    catecholamine release by

inducing the release of endogenous    histamine.

The label will state:

Do not exceed the recommended dose.

Do not take with any other paracetamol-containing products. Immediate medical attention should be sought in the event of an overdose, even if you feel well.

May cause dizziness, if affected do not drive or operate machinery.

If symptoms persist, consult your doctor.

Keep out of the reach and sight of children.

Front of Pack

•    Can cause addiction

•    For three days use only

Back of Pack

•    List of indications as agreed in 4.1 of the SmPC

•    If you need to take this medicine continuously for more than three days you should see your doctor or pharmacist

•    This medicine contains codeine [or dihydrocodeine] which can cause addiction if you take it continuously for more than three days. If you take this medicine for headaches for more than three days it can make them worse

The leaflet will state:

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

Headlines section (to be prominently displayed)

•    This medicine can only be used for.......(indications)

•    You should only take this product for a maximum of three days at a time. If you need to take it for longer than three days you should see your doctor or pharmacist for advice

•    This medicine contains codeine [or dihydrocodeine] which can cause addiction if you take it continuously for more than three 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 three days it can make them worse

Section 1: What the medicine is for

•    Succinct description of the indications from 4.1 of the SmPC Section 2: Before taking

•    This medicine contains codeine [or dihydrocodeine] which can cause addiction if you take it continuously for more than three 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 three days it can make them worse

Section 3: Dosage

•    Do not take for more than 3 days. If you need to use this medicine for more than three days you must speak to your doctor or pharmacist

•    This medicine contains codeine [or dihydrocodeine] and can cause addiction if you take it continuously for more than three 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.

Section 4: Side effects

•    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.

Insert a new paragraph as follows:

How do I know if I am addicted?

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 your doctor:

•    You need to take the medicine for longer periods of time

•    You need to take more than the recommended dose

•    When you stop taking the medicine you feel very unwell but you feel better if you start taking the medicine again

4.5 Interaction with other medicinal products and other forms of interaction 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.

The depressant effects of opioid analgesics are enhanced by other CNS depressants such as alcohol, anaesthetics, anxiolytics, hypnotics, tricyclic antidepressants and antipsychotics.

Dihydrocodeine tartrate may interact with monoamine oxidase inhibitors (MAOI’s), such that opioids should not be used in patients taking MAOI’s or within 14 days of stopping such treatment. If opioid analgesics are required they should be given with extreme caution.

The effects of dihydrocodeine tartrate in reducing gastrointestinal motility may interfere with the absorption of antiarrhythmics such as mexiletine, and may counteract the stimulatory effect of metoclopramide and domperidone.

Cimetidine inhibits the metabolism of some opioids

4.6 Pregnancy and lactation

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.

The depressant effects of opioid analgesics are enhanced by other CNS depressants such as alcohol, anaesthetics, anxiolytics, hypnotics, tricyclic antidepressants and antipsychotics.

Dihydrocodeine tartrate may interact with monoamine oxidase inhibitors (MAOI’s), such that opioids should not be used in patients taking MAOI’s or within 14 days of stopping such treatment. If opioid analgesics are required they should be given with extreme caution.

The effects of dihydrocodeine tartrate in reducing gastrointestinal motility may interfere with the absorption of antiarrhythmics such as mexiletine, and may counteract the stimulatory effect of metoclopramide and domperidone.

4.7 Effects on ability to drive and use machines

Opioid analgesics can impair mental function and can cause blurred vision and dizziness. Patients should make sure they are not affected before driving or operating machinery.

4.8 Undesirable effects

Adverse effects of paracetamol are rare but hypersensitivity, including skin rash, may occur. There have been rare reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Constipation if it occurs, is readily treated with a mild laxative. Nausea, headache, vertigo, dizziness and urinary retention may occur in a few patients.

Regular prolonged use of dihydrocodeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped. Prolonged use of a painkiller for headaches can make them worse.

4.9 Overdose

Paracetamol:

Symptoms: Pallor, nausea, vomiting, anorexia and abdominal pain in the first 24 hours. 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. coma and

death.

Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias have been reported.

Liver damage is likely in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Treatment: 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 and any patient who had ingested around 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine, which may have a beneficial effect up to at least 48 hours after the overdose, may be required.

General supportive measures must be available.

Opioids:

Symptoms: cold clammy skin, confusion, convulsions, severe drowsiness, tiredness, low blood pressure, pinpoint pupils of eyes, slow heart beat and respiratory rate coma.

Treatment: Treat respiratory depression or other life-threatening adverse effects first.

Empty the stomach via gastric lavage or induction of emesis.

The opioid antagonist naloxone (0.4-2mg subcutaneous) can be given and repeated at 2-3 minute intervals to a maximum of 10mg. Naloxone may also be given by intramuscular injection or intravenous infusion. The patient should be monitored as the duration of opioid analgesic may exceed that of the antagonist.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Paracetamol is an effective analgesic possessing a remarkably low level of side effects. Its broad clinical utility has been extensively reported, and it now largely replaces aspirin for routine use. Paracetamol is well tolerated; having a bland effect on gastric mucosa, unlike aspirin, it neither exacerbates symptoms of peptic ulcer nor precipitates bleeding. Dihydrocodeine tartrate has been widely used for a number of years as a powerful analgesic; 30 mg of dihydrocodeine has been reported to have analgesic potency equal to 60 or 120 mg codeine.

In addition the compound exhibits well-defined anti-tussive activity.

Fortifying paracetamol with 7.46 mg dihydrocodeine tartrate provides an effective combination of drugs for the treatment of severe pain.

5.2 Pharmacokinetic properties

Dihydrocodeine is well absorbed from the gastrointestinal tract. Like other phenanthrene derivatives, dihydrocodeine is mainly metabolised in the liver with the resultant metabolites being excreted mainly in the urine. Metabolism of dihydrocodeine includes

o-demethylation, n-demethylation and 6-keto reduction.

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 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.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Citric Acid (anhydrous, added as citric acid monohydrate) Sodium hydrogen carbonate Sodium carbonate (anhydrous)

Sodium benzoate Saccharin sodium Povidone

Incompatibilities

None known.

6.3 Shelf life

24 Months.

6.4 Special precautions for storage

Store at or below 25 °C.

6.5 Nature and contents of container

1. Blister packs: 43pm soft tempered aluminium foil coated with 25 pm nylon on the outside and 25 pm polyethylene on the inside.

2.    Aluminium foil strip packs: 25 pm aluminium foil coated with 40g/m² paper and 12g/m2 polyethylene on the outside and 18g/m2 surlyn on the inside.

Packs sizes : 2, 12, 24 tablets.

6.6 Special precautions for disposal

None stated.

7 MARKETING AUTHORISATION HOLDER

SSL International plc.

Venus

No 1 Old Park Lane Trafford Quays Manchester M41 7HA

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