Document: spc-doc_PL 00071-0660 change

• spc-doc_PL 00071-0660
• spc-doc_PL 00071-0661
• spc-doc_PL 44673-0078
• spc-doc_PL 44673-0079

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Panadol Extra Advance 500 mg/65 mg Tablets Panadol Period Pain 500 mg/65 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Paracetamol 500 mg and Caffeine 65 mg.

For full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.

White to off-white, oval shaped, film-coated tablets debossed with ’xPx’, with the P enclosed within a circle on one side and plain on the other side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

A mild analgesic and antipyretic formulated to give extra pain relief. The tablets are recommended for the treatment of most painful and febrile conditions, for example, headache, including migraine, backache, toothache, rheumatic pain and dysmenorrhoea, and the relief of the symptoms of colds, influenza and sore throat.

4.2 Posology and method of administration

Oral use.

Adults:

Two tablets up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 8 tablets in 24 hours.

Elderly:

As for adults.

Not recommended for children under 12 years.

4.3 Contraindications

Hypersensitivity to paracetamol, caffeine or any of the other constituents.

4.4 Special warnings and precautions for use

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

Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.

Do not exceed the stated dose.

Sodium methyl-, sodium ethyl- and sodium propyl- parahydroxybenzoates (E 219, E 215 and E 217) may cause allergic reactions (possibly delayed).

Patients should be advised to consult their doctor if their headaches become persistent.

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

If symptoms persist consult your doctor.

Keep out of the reach and sight of children.

Pack Label:

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

Patient Information Leaflet:

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.

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 colestyramine. 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

Paracetamol-caffeine is not recommended for use during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.

Caffeine in breast milk may potentially have a stimulating effect on breast fed infants.

Due to the caffeine content of this product it should not be used if you are pregnant or breast feeding.

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class. 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.

Post marketing data

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome/toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders	Bromchospasm1
Hepatobiliary disorders	Hepatic dysfunction

4.9 Overdose

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 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.

Caffeine

Symptoms

Overdose of caffeine may result in epigastric pain, vomitting, diuresis, tachycardia or cardia arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).

It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol-related toxicity.

Management

Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose, but can be considered for up to four hours after the overdose. The CNS effects of overdose may be treated with intravenous sedatives.

Summary

Treatment of overdose requires assessment of plasma paracetamol levels for antidote treatment, with signs and symptoms of caffeine toxicity being managed symptomatically.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC code: N02B E51

The combination of paracetamol and caffeine is a well established analgesic combination.

5.2 Pharmacokinetic Properties

Paracetamol is rapidly and almost completely absorbed from the gastro-intestinal tract. It is relatively uniformly distributed throughout most body fluids and exhibits variable protein binding. Excretion is almost exclusively renal, in the form of conjugated metabolites. Caffeine is absorbed readily after oral administration. Maximal plasma concentrations are achieved within one hour and the plasma half-life is about 3.5 hours. 65 - 80% of administered caffeine is excreted in the urine as 1-methyluric acid and 1-methylxanthine.

Panadol Extra Advance 500 mg/65 mg Tablets contain a disintegrant system which accelerates tablet dissolution compared to standard parcetamol and caffeine tablets.

Human pharmacokinetic data demonstrate that the time taken to reach plasma paracetamol threshold (4-7 mcg/ml) is at least 44% faster with Panadol Extra Advance 500 mg/65 mg Tablets compared with standard paracetamol and caffeine tablets.

Total extent of absorption of paracetamol and caffeine from Panadol Extra Advance 500 mg/65 mg Tablets is equivalent to that from standard paracetamol and caffeine tablets.

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

Tablet core:

Starch pregelatinised,

Povidone k-25,

Calcium carbonate,

Crospovidone,

Alginic acid,

Magnesium stearate,

Sodium methyl (E 219), Sodium ethyl (E 215) and Sodium propyl (E 217) parahydroxyb enzoates.

Film coat and polish:

Titanium dioxide (E 171),

Hypromellose,

Macrogol,

Polysorbate 80,

Carnauba wax

6.2    Incompatibilities

None.

6.3 Shelf-life

24 months.

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

PVC 250 pm or 300 pm aluminium foil 30 pm blister packs in an outer cardboard carton, containing 4, 6, 8, 12, 14 or 16 tablets, or PVC/aluminium foil blister packs in a carboard/PVC wallet containing 14 or 16 tablets.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

SmithKline Beecham (SWG) Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

Trading as GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS, U.K.

8 MARKETING AUTHORISATION NUMBER(S)

PL 00071/0660

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

26/02/2010

10 DATE OF REVISION OF THE TEXT

30/03/2012

1

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