SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Paramol Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Paracetamol 500mg Dihydrocodeine Tartrate 7.46mg

3    PHARMACEUTICAL FORM

Tablets

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 and as an antipyretic in conditions such as: headache; migraine period pain; toothache and other dental pain; back pain; muscular and joint pains and neuralgia.

4.2 Posology and method of administration

Route of Administration:    Oral

Recommended Doses and Dosage Schedules:

Paramol Tablets should, if possible be taken during or after meals.

Adults & Children over 12 years:

One or two tablets every four to six hours.

Do not exceed 8 tablets in any 24 hour period.

Do not take for more than 3 days continuously without medical review.

Children under 12 years:

Not recommended

The Elderly:

Caution should be exercised when increasing the dose in the elderly.

4.3    Contraindications

Hypersensitivity to paracetamol, or any other constituents, respiratory depression, obstructive airways disease.

Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembranous colitis.

Acute alcoholism, convulsive disorders, head injuries, and conditions in which intracranial pressure is raised.

4.4    Special warnings and precautions for use

Paramol Tablets should be given with caution to patients with allergic disorders and should not be given during an attack of asthma.

Dosage should be reduced in the elderly, in hypothyroidism and in chronic hepatic disease. An overdose can cause hepatic necrosis.

Paracetamol

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with noncirrhotic alcoholic liver disease

Dihydrocodeine

Care is advised in the administration of dihydrocodeine to patients with hypotension, adrenocortical insufficiency, prostatic hypertrophy, shock, obstructive and inflamatory bowel disorders, acute abdominal conditions, recent gastrointestinal surgery, gallstones and diseases of the biliary tract, myasthenia gravis, a history of arrhythmias and in patients with a history of drug abuse or emotional instability. This product should be avoided in patients with risk of paralytic ileus.

Dihydrocodeine 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.

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 dihydrocodeine is considered essential then great care should be taken in patients taking MAOIs or within 14 days of stopping MAOIs (see section 4.5).

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, because of the risk of delayed, serious liver damage.

If symptoms persist, consult your doctor.

Keep out of the sight and 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 SmPC

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

•    This medicine contains 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:

Headlines section (to be prominently displayed)

• This medicine can only be used for the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen and aspirin alone such as headache, migraine, period pain, toothache and other dental pain, backache, muscular and joint aches and pains and neuralgia

•    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 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 your medicine

•    This medicine contains 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 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.mhra.gov.uk/yellowcard; 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?

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

Paracetamol

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.

Opioids/Dihydrocodeine

The depressant effects of opioids are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics, sedatives, tricyclic antidepressants and antipsychotics (e.g.hydroxyzine).

The respiratory depressant effect caused by neuromuscular blocking agents may be additive to the central respiratory depressant effects of opioid analgesics.

The hypotensive actions of diuretics and anti-hypertensive agents may be potentiated when used concurrently with opioid analgesics.

Concurrent use of codeine/dihydrocodeine with antidiarrhoeal and antiperistaltic agents such as loperamide and kaolin may increase the risk of severe constipations.

Concomitant use of antimuscarinics or medications with antimuscarinic action may result in an increased risk of severe constipation which may lead to paralytic ileus and/or urinary retention.

Quinidine alters the metabolism of dihydrocodeine, but does not alter its analgesic effects.

Opioids may delay the absorption of mexiletine and thus reduce the antiarrhythmic effect of the latter. Codeine may antagonise the gastrointestinal effects of metoclopramide, cisapride and domperidone.

Cimetidine inhibits the metabolism of opioid analgesics resulting in increased plasma concentrations.

Naxolone may antagonise the analgesic, CNS and respiratory depressant effects of opioid analgesics. Naltrexone also blocks the therapeutic effect of opioids.

MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with dihydrocodeine, it is possible that a similar interaction may occur and therefore the use of dihydrocodeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation

Interference with laboratory tests:

Opioid analgesics interfere with a number of laboratory tests including plasma amylase, lipase, bilirubin, alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. Opioids may also interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.

4.6 Fertility, Pregnancy and lactation

Pregnancy

Epidemiological studies in human pregnancy have shown no effects due to paracetamol or dihydrocodeine in recommended dosage, but patients should follow the advice of their doctor regarding its use.

Dihydrocodeine:

Maternal use of this product during labour is not recommended because of the potential for respiratory depression in the neonate.

Lactation and breastfeeding Paracetamol:

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

Fertility:

Unknown

4.7 Effects on ability to drive and use machines

Opioid analgesics can impair mental function and can cause blurred vision, dizziness, drowsiness, double vision, confusion, hallucinations and convulsions.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When taking this medicine, patients should be told:

-    The medicine is likely to affect your ability to drive

-    Do not drive until you know how the medicine affects you

-    It is an offence to drive while under the influence of this medicine

-    However, you would not be committing an offence (called ‘statutory defence’) if:

-    The medicine has been taken to treat a medical or dental problem and

-    You have taken it according to the information provided with the medicine and

-    It was not affecting your ability to drive safely

4.8 Undesirable effects

Paracetamol

Adverse effects of paracetamol are rare but hypersensitivity, including skin rash, may occur. Very rare cases of serious skin reactions have been reported. There have been rare reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Dihydrocodeine

The most frequent undesirable effects of dihydrocodeine are constipation and drowsiness. Less frequent effects are nausea, vomiting, sweating, facial flushing, dry mouth, blurred or double vision, dizziness, orthostatic hypotension, malaise, tiredness, headache, vertigo, bradycardia, palpitations, respiratory depression, dyspnoea, allergic reactions (itch, skin rash, facial oedema) and difficulties in micturition (dysuria, increased frequency, decrease in amount). Side effects, which occur rarely, include convulsions, confusion, hallucinations, nightmares, muscle rigidity, mental depression, stomach cramps, reduced libido or potency, hypothermia, restlessness, change of mood, biliary spasm, uretic spasm, tachycardia and miosis.

Opioids may induce faecal impactation, producing incontinence, spurious diarrhoea, abdominal pain and rarely colonic obstruction.

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

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, phenobarbitone, 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, 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 a 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 N-acetylcysteine 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

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms

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

This 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 350 mg or a child more than 5 mg/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 four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol is an effective analgesic possessing a remarkably low level of side effects. It's broad clinical utility has been extensively reported and now largely replaces aspirin for routine use. Paracetamol is well tolerated, having a bland effect on the 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. 30mg of dihydrocodeine has the analgesic potency of 60 to 120mg of codeine. In addition the product exhibits well defined anti-tussive activity. Fortifying paracetamol with dihydrocodeine tartrate provides an effective combination of drugs for the treatment of mild to moderate pain and acts as an anti-pyretic.

5.2 Pharmacokinetic properties

Dihydrocodeine is well absorbed from the gastrointestinal tract. Like other Phenanthrene derivatives, dihydrocodeine is largely metabolised in the liver with the resultant metabolites being excreted mainly in the urine. Metabolism of dihydrocodeine includes O-demethylation, N-Demethylation and 6-Ketoreduction. Paracetamol is readily absorbed from the gastro-intestinal 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 glucuronide and sulphate conjugates.

5.3 Preclinical safety data

There are no preclinical tests performed on the product.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Magnesium Stearate Maize Starch Povidone Opadry Y-1-7000

6.2 Incompatibilities

None stated

6.3 Shelf life

36 Months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

250p PVC base material with an aluminium foil 20p coated with a 15p PVC layer containing 12, 24, or 32 tablets.

6.6 Special precautions for disposal

None stated.

7    MARKETING AUTHORISATION HOLDER

RECKITT BENCKISER HEALTHCARE (UK) LIMITED

103-105 BATH ROAD

SLOUGH

BERKSHIRE

SL1 3UH

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 00063/0693

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/09/1999 / 02/03/2009

10 DATE OF REVISION OF THE TEXT

10/09/2014