SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Extra Power Pain Reliever Tablets Extra Power Pain Reliever Caplets Aspirin Extra Tablets

Paramed Extra Power Pain Reliever Tablets Superdrug Extra Power Pain Reliever Wilko Extra Power Pain Reliever Tablets Teva Extra Power Pain Reliever Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

INGREDIENT	QTY	UNIT	DOSE
Active
Aspirin	300	mg	Tablet
Paracetamol	200	mg	Tablet
Caffeine	45	mg	Tablet

3 PHARMACEUTICAL FORM

Tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains, symptomatic relief of sprains, strains, rheumatic pain, sciatica, lumbago, fibrositis, muscular aches and pains, joint swelling and stiffness, influenza, feverishness and feverish colds.

4.2 Posology and method of administration

For oral administration.

Adults and young persons over 16 years:-

1 or 2 tablets every 4 hours as required. Dose not to be taken more frequently than every 4 hours, with a maximum of 6 tablets in 24 hours.

Do not give to children under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease).

Adult dosage is suitable for the elderly.

4.3 Contraindications

Peptic ulceration and those with a history of peptic ulceration; haemophilia; concurrent anti-coagulant therapy; hypersensitivity to aspirin, paracetamol and/or other constituents; children under 16 years and when breast feeding because of possible risk of Reye's Syndrome.

4.4 Special Warnings and Precautions for Use

Hypersensitivity - asthma - aspirin may provoke or worsen asthma.

There is a possible association between aspirin and Reye’s syndrome when given to children. Reye’s 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 under 16 years unless specifically indicated (e.g. for Kawasaki’s disease).

Caution should be exercised in patients with asthma, allergic disease, impairment of hepatic or renal function (avoid if severe) and dehydration.

Do not take it you have a stomach ulcer.

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

Do not take anything else containing paracetamol while taking this medicine.

Talk to your doctor at once if you take too much of this medicine, even if you are feel well. This is because too much paracetamol can cause delayed, serious liver damage.

Patients should be advised that paracetamol may cause severe skin reactions. If a skin reaction such as skin reddening, blisters, or rash occurs, they should stop use and seek medical assistance right away.

The following warnings will appear on the pack:-

If symptoms persist consult your doctor.

Do not exceed 6 tablets in any 24 hours.

Do not give to children under 16 unless your doctor tells you to.

Keep this medicine out of the sight and reach of children.

CONTAINS ASPIRIN AND PARACETAMOL.

Do not exceed the stated dose.

“Do not take any other paracetamol-containing products whilst taking this product” and

“Immediate medical advice should be sought in the event of an overdose, even if you feel well.”

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

The leaflet shall say “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”.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

4.5 Interactions with other medicinal products and other forms of Interaction

The following are noted, but are unlikely to apply when the product is used for a short-term symptomatic relief, as directed:-

ASPIRIN

Increase excretion of aspirin in

Increased risk of bleeding - avoid 8-12 days after administration of

Antagonism of diuretic effect.

Increased risk of bleeding.

Increased risk of bleeding.

Increased risk of bleeding.

Enhance the effect of aspirin.

Enhance the effect of aspirin. However no special precautions are needed

Enhance the effect of.

Enhance the effect of valproate

Delayed excretion and increased toxicity of

methotrexate.

Inhibition of uricosurics.

Other NSAIDS and corticosteroids: Concurrent use of other NSAIDS or corticosteroids may increase the likelihood of GI side effects.

Diuretics, such as spironlactone: Antagonism of the diuretic effect.

Anticoagulants, such as heparin, phenindone, warfarin and other coumarins: Increased risk of bleeding due to antiplatelet effect.

PARACETAMOL

Metoclopramide and domperidone: The speed of absorption of paracetamol is increased by Metoclopramide and domperidone. However concurrent use need not be avoided.

Colestyramine may reduce the absorption of paracetamol. Colestyramine: therefore, the colestyramine should not be taken within one hour if maximal analgesia is required.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Chloramphenicol: Increased plasma concentration of chloramphenicol.

4.6 Fertility, Pregnancy and Lactation

There is clinical and epidemiological evidence of safety of aspirin in pregnancy, but it may prolong labour and contribute to maternal and neonatal bleeding, and so is best discontinued in late pregnancy.

Aspirin appears in breast milk, and regular high doses may affect neonatal clotting. Not recommended with breast feeding due to possible risk of Reye's syndrome as well as neonatal bleeding due to hypoprothrombinaemia.

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.

Caffeine appears in breast milk. Irritability and poor sleeping pattern in the infant have been reported.

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable Effects

Side effects are mild and infrequent, but there is a high incidence of gastrointestinal irritation with slight asymptomatic blood loss. Increased bleeding time. Aspirin may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions, such as skin reactions (including angioedema and face oedema) in susceptible individuals.

Aspirin may induce gastro-intestinal haemorrhage, occasionally major. It may precipitate gout in susceptible individuals. Possible risk of Reye's Syndrome in children under 16 years.

Adverse effects of paracetamol are rare. Very rare cases of serious skin reactions have been reported. There have been reports of blood dyscrasias including thrombocytopenia purpura, methaemoglobinaemia and agranulocytosis, but these were not necessarily causality related to paracetamol.

High doses of caffeine can cause tremor and palpitations.

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

This product contains both paracetamol and aspirin, and as such, any overdose events should be assessed using information available on both active substances.

Symptoms

Common features exist for both active substances when taken in overdose, but

these can be tabulatec	as follows:
Paracetamol	Aspirin	Caffeine
Within the first 24 hours:	Common:	Other symptoms of overdosage, associated with the caffeine component include:
Pallor	Vomiting, Dehydration. Tinnitus	CSN Stimulation
Nausea	Vertigo, Deafness, Sweating	Anxiety, nervousness, restlessness, insomnia, excitement, muscle twitching,
Vomiting	Warm extremities with bounding pulses; Increased respiratory rate	Confusion
Anorexia,	Hyperventilation	Convulsions
Abdominal pain	Acid base disturbance	Cardiac: tachycardia, cardiac arrhythmia

After 12-48 hours	Mixed respiratory alkalosis	Gastric: Abdominal or
	and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) in adults and children aged over 4 years.	stomach pains
Liver damage	In children aged 4 years or	Other: diuresis, facial
	less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis can increase salicylate transfer across the blood brain barrier.	flushing
Abnormalities of glucose metabolism and metabolic acidosis	Uncommon
Severe poisoning	Haematemesis
Hepatic failure may progress to	Hyperpyrexia
Encephalopathy	Hypoglycaemia
Haemorrhage	Hypokalaemia
Hypoglycaemia	Thrombocytopenia
Cerebral oedema	Increased InR/PTR
Death	Intravascular coagulation
With or without severe liver damage:	Renal failure
Acute renal failure wit	Non-cardiac pulmonary oedema
Acute tubular necrosis	Confusion, disorientation,
strongly suggested by loin	coma and convulsions are
pan Haematuria and proteinuria Cardiac arrhythmias Pancreatitis	more common in children than adults

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 either anti-infectives, anti-epileptics, or 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.

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 or are under 10 years or over 70 years, beyond 24h from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit.

SALICYLATES/ASPIRIN

Salicylate poisoning is usually associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.

Management

Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/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 >700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

CAFFEINE

Management

Treatment of caffeine overdose is primarily symptomatic and supportive. Diuresis should be treated by maintain fluid and electrolyte balance and CNS symptoms can be controlled by intravenous administration of diazepam.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties ASPIRIN

White powder or crystals soluble in alcohol and slightly soluble in water. Mechanism of action/effect:

Salicylate inhibit the activity of the enzyme cyclo-oxygenase to decrease the formation of precursors of prostaglandin’s and thromboxanes from arachidonic acid. Although many of the therapeutic effects may result from inhibition of prostaglandin synthesis (and consequent reduction of prostaglandin activity) in various tissues, other actions may also contribute significantly to the therapeutic effects.

Analgesic:

Produces analgesia through a peripheral action by blocking pain impulse generation and via a central action, possibly in the hypothalamus.

Anti-inflammatory (non-steroidal):

Exact mechanisms have not been determined. Salicylates may act peripherally in inflamed tissue probably by inhibiting the synthesis of prostaglandins and possibly by inhibiting the synthesis and/or actions of other mediators of the inflammatory response.

PARACETAMOL

Analgesic:

The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting a prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.

Antipyretic:

Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat-regulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.

CAFFEINE

Central nervous system stimulant - Caffeine stimulates all levels of the CNS, although its cortical effects are milder and of shorter duration than those of amfetamines.

Analgesia Adjunct:

Caffeine constricts cerebral vasculature with an accompanying decrease in cerebral blood flow and in the oxygen tension of the brain. It is believed that caffeine helps to relieve headache by providing a more rapid onset of action and/or enhanced pain relief with lower doses of analgesic. Recent studies with ergotamine indicate that the enhancement of effect by the addition of caffeine may also be due to improved gastrointestinal absorption of ergotamine when administered with caffeine.

ATC code: R05X

5.2 Pharmacokinetic properties

Aspirin

Absorption and Fate

Absorption is generally rapid and complete following oral administration.

It is largely hydrolysed in the gastrointestinal tract, liver and blood to salicylate which is further metabolised primarily in the liver.

Paracetamol

Absorption and Fate

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 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. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours.

Plasma-protein is negligible at usual therapeutic concentrations but increases with increasing concentrations.

A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause liver damage.

5.3 Preclinical safety data

None stated.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Methyl cellulose Maize Starch

Microcrystalline Cellulose Sorbitol

Sodium Lauryl Sulphate Hydrogenated Cotton Seed Oil

6.2 Incompatibilities

None other than those listed under 4.5 interactions.

Shelf life

3 years.

22/12/2015