SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Paracetamol 1000 mg Film Coated Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film- coated tablet contains Paracetamol 1000 mg For the full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Tablet.

White colored, caplet shaped, film coated tablets, with ‘K’, bisect break line ‘02’ on one side and break line on the other side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the management of mild to moderate pain and fever

4.2    Posology and method of administration

Paracetamol 1000 mg film coated tablets are for oral administration.

Adults (including the elderly):

One tablet up to 4 times daily as required.

Not to be given to children under 16 years.

The minimum dosing interval is 4 hours and the maximum daily dose is 4000 mg (4 tablets).

4.3    Contraindications

• Hypersensitivity to paracetamol or any of the other excipients.

4.4 Special warnings and precautions for use

Patients should be advised not to take other paracetamol-containing products concurrently.

Caution is advised in the administration of paracetamol to patients with moderate and severe renal insufficiency, mild to moderate hepatic insufficiency (including Gilbert’s syndrome), severe hepatic insufficiency (Child-Pugh>9), acute hepatitis, concomitant treatment with medicinal products affecting hepatic functions, glucose-6- phosphate dehydrogenase deficiency, haemolytic anaemia, alcohol abuse, dehydration and chronic malnutrition.

The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Caution should be exercised in case of chronic alcoholism. The daily dose should not exceed 2000 mg in such case. Alcohol should not be used during the treatment with Paracetamol.

Do not exceed the stated dose.

This product should only be used when clearly necessary.

If symptoms persist consult your doctor.

Keep out of the sight and reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

The speed of absorption of paracetamol depends on the gastric depletion rate. The gastric depletion rate can be altered by the concomitant use of other medications such as anticholinergic or opioid drugs (e.g. metoclopramide, domperidone or codeine) which increase paracetamol absorption.

The absorption of paracetamol is reduced by concomitant administration of colestyramine.

The anticoagulant effect of warfarin and other coumarins may be enhanced (may lead to slight variations in INR values) with prolonged regular daily use of paracetamol (4g per day for at least 4 days).This may increase the risk of bleeding; therefore should be closely monitored.

Extreme caution and medical supervision is advised in prolonged use with drugs / substances which induce hepatic monooxygenases (e.g., cimetidine, zidovudine, rifampicin, isoniazid and antiepileptic agents glutethimide, phenobarbital and carbamazepine).

Concomitant administration of paracetamol and chloramphenicol can prolong the half-life of chloramphenicol and increase its toxic effects.

Probenecid causes an almost two-fold reduction in clearance of paracetamol by inhibiting its conjugation with glucuronic acid. A reduction in the paracetamol dose should be considered if it is to be used concomitantly with probenecid.

Salicylamide may prolong the elimination half-life of paracetamol.

4.6 Fertility, pregnancy and lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. Paracetamol is excreted in breast milk, but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

4.7 Effects on ability to drive and use machines

Paracetamol 1000 mg film coated tablets have no known influence on the

ability to drive and use machinery.

4.8 Undesirable effects

Adverse effects of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but postmarketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Accordingly, events reported from extensive post-marketing experience, the following undesirable effects can be listed:

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome/toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders	Bronchospasm*
Hepatobiliary disorders	Hepatic dysfunction

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard.

4.9 Overdose

Paracetamol

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

If the patient

•    Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

•    Regularly consumes ethanol in excess of recommended amounts.

Or

•    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 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.

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.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: analgesics and antipyretics, anilides ATC-code: N02BE01

Paracetamol is an antipyretic analgesic. The mechanism of action is probably similar to that of aspirin and dependent on the inhibition of prostaglandin synthesis. This inhibition appears, however to be on a selective basis.

5.2 Pharmacokinetic properties

Absorption: Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration in plasma reaches a peak in 30 to 60 minutes. Plasma half-life is 1 - 4 hours

Distribution: Paracetamol is relatively uniformly distributed throughout most body fluids. Binding of the drug to plasma proteins is variable; 20 to 30% may be bound at the concentrations encountered during acute intoxication. Metabolism: paracetamol is metabolized mainly in the liver following two major metabolic pathways: glucuronic acid and sulfuric acid conjugates. The latter route is rapidly saturated at doses higher than the therapeutic dose. A minor route, catalyzed by the cytochrome P450 (mostly CYP2E1), results in the formation of an intermediate reagent, N-acetyl-p-benzoquinoneimine, which under normal conditions of use is rapidly detoxified by glutathione and eliminated in the urine, after conjugation with cystein and mercaptopuric acid. Conversely, when massive intoxication occurs, the quantity of this toxic metabolite is increased.

Elimination: elimination is essentially through the urine. 90% of the ingested dose is eliminated via the kidneys within 24 hours, principally as glucuronide (60 to 80%)

Renal Insufficiency: in cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of paracetamol metabolites is delayed.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize starch Pregelatinised starch Talc

Povidone

Magnesium stearate Film coating: Hypromellose (E464) Titanium dioxide (E171) Macrogol (E1521)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

36 Months.

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

PVC/ Alu Blister - 12, 16, 100

HDPE Bottle with Polypropylene screw closure- 32, 100, 300 & 500 tablets. Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal products and waste materials should be disposed of in accordance local requirements.

7    MARKETING AUTHORISATION HOLDER

DAWA Limited 5 Sandridge Close,

Harrow, Middlesex,

HA1 1XD,

UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 30684/0233

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22/10/2015

10    DATE OF REVISION OF THE TEXT

22/10/2015