SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Alka-Seltzer Original

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Acetylsalicylic acid    324 mg

Citric acid    965 mg

Sodium hydrogen carbonate    1744 mg

The active ingredients in water become sodium citrate 1296mg, sodium acetylsalicylate 364mg and sodium hydrogen carbonate 328mg.

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Effervescent tablets for oral administration.

White, round tablet, embossed ‘Alka Seltzer’ on one side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For rapid relief of pain including migraine, headache, period pains, neuralgia, toothache, sore throat.

Symptomatic relief of rheumatic pain, sciatica, lumbago, fibrositis, muscular aches and pains.

Symptomatic relief of influenza, feverishness, feverish colds.

4.2    Posology and method of administration

Alka-Seltzer Original tablets may always be dissolved in a glass of water prior to oral administration. The tablets dissolve more quickly in warm water.

The dose in adults, elderly and children aged 16 years and over, is two tablets in water. The dose may be repeated every four hours, as required, with a maximum of four dosages in 24 hours. These dosages should not be continued for more than three days without consulting a physician. The stated dose must not be exceeded.

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

4.3 Contraindications

Alka-Seltzer Original should not be administered to patients:

•    with known hypersensitivity reactions (e.g. bronchospasm, rhinitis, urticaria) in response to acetylsalicylic acid, other salicylates or substances with similar actions eg non-steroidal anti-inflammatory drug.

•    with known hypersensitivity to any of the other ingredients, refer to section 6.1.

•    with active peptic ulceration or a history of peptic ulceration.

•    with haemorrhagic diseases such as haemophilia.

•    in the last trimester of pregnancy (see sections 4.4 and 4.6).

•    receiving doses of methotrexate at 15mg/week or greater (see section 4.5).

4.4 Special warnings and special precautions for use

Acetylsalicylic acid should be used with particular caution in the following cases:

■    hypersensitivity to analgesics / anti-inflammatory agents / anti-rheumatics and in the presence of other allergies,

■    with a history of gastrointestinal disorders,

■    with concomitant treatment with anticoagulants (see interactions with other medicinal products and other forms of interaction),

■    patients with impaired renal function or patients with impaired cardiovascular circulation (e.g. renal vascular disease, congestive heart failure, volume depletion, major surgery, sepsis or major haemorrhagic events), since acetylsalicylic acid may further increase the risk of renal impairment and acute renal failure,

■    impaired hepatic function.

Acetylsalicylic acid may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions. Risk factors are pre-existing asthma, hay fever, nasal polyps, or chronic respiratory disease. This also applies to patients exhibiting allergic reactions (e.g. cutaneous reactions, itching, urticaria) to other substances.

Due to its inhibitory effect on platelet aggregation which persists for several days after administration, acetylsalicylic acid may lead to an increased

bleeding tendency during and after surgical operations (including minor surgeries, e.g. dental extractions).

At low doses, acetylsalicylic acid reduces the excretion of uric acid. This can possibly trigger gout attacks in predisposed patients.

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 aged under 16 unless specifically indicated (e.g. Kawasaki’s disease).

In patients suffering from severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, acetylsalicylic acid may induce haemolysis or haemolytic anaemia. Factors that may increase the risk of haemolysis are high dosage, fever, or acute infections, for example.

This medicinal product contains 477mg sodium per tablet. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

Alka-Seltzer Original may:

•    Enhance the activity of anticoagulants, insulin and sulphonylurea hypoglycaemic agents.

•    Enhance the activity of methotrexate and increase its toxicity (see section 4.3).

•    Diminish the effects of uricosuric agents.

•    Diminish the effects of diuretics.

•    Potentiate the risk of gastro-intestinal bleeding during concomitant therapy with corticosteroids.

•    Potentiate the effects and side-effects of other non-steroidal antiinflammatory drugs.

•    Enhance the plasma concentrations of digoxin.

•    Enhance the effects of some anti-epileptics, such as sodium valproate and phenytoin.

•    Interact with antihypertensive medicines.

•    Increased risk of bleeding with thrombolytics and other anti-platelet agents e.g. ticlopidine.

Decreased blood salicylate levels may occur when aspirin is taken

concomitantly with glucocorticoids. There is a risk of salicylate overdose

when glucocorticoids treatment is stopped.

At doses of 3g/day or more, aspirin may:

•    Increase risk of ulcers and gastro-intestinal bleeding when taken with

other NSAIDs.

•    Decrease glomerular filtration when taken with diuretics.

Decrease glomerular filtration and antihypertensive effect when taken with ACE inhibitors.

4.6 Pregnancy and lactation

(See section 4.3 and 4.4)

Although clinical and epidemiological evidence suggests the safety of acetylsalicylic acid for use in pregnancy, caution should be exercised when administered to pregnant patients.

Acetylsalicylic acid has the ability to alter platelet function and, therefore, there may be a risk of haemorrhage in infants whose mothers have consumed acetylsalicylic acid during pregnancy. The onset of labour may be delayed and the duration increased , with an increase in maternal blood loss. Therefore, analgesic doses should be avoided during the last trimester.

High doses of acetylsalicylic acid may result in closure of foetal ductus arteriosus in utero and possible persistent pulmonary hypertension in the new born. Kernicterus may be a consequence of jaundice in neonates.

Administration of aspirin at doses greater than 300mg/day, shortly before birth can lead to intra-cranial haemorrhages, particularly in premature babies.

The intake of acetylsalicylic acid by breast-feeding patients should be avoided as there is a risk of Reye's syndrome. Regular use of high doses could impair platelet function and produce hypoprothrombinaemia in the infant if neonatal vitamin K stores are low.

When aspirin has been taken regularly or high doses have been taken then breast-feeding should be discontinued early.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Gastrointestinal disorders have been reported for acetylsalicylic acid containing products e.g. nausea, diarrhoea, vomiting and gastro-intestinal

bleeding which can lead to anaemia in some cases. Gastrointestinal ulcers may develop, which may lead to haemorrhaging and perforation.

Rare cases of bronchospasm, asthmatic or hypersensitivity reactions have been reported for acetylsalicylic acid containing products.

Isolated cases of liver function disturbances and severe skin reactions have also been reported.

Due to the effect of platelet aggregation aspirin may be associated with an increased risk of bleeding.

Dizziness and tinnitus have also been reported but these side effects are more commonly indicative of an overdose.

4.9 Overdose

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.

Symptoms

Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of four years. In children aged four years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Nervous system, other analgesics and antipyretics -acetylsalicylic acid, ATC code: N02BA01

The therapeutic uses of Alka-Seltzer Original are based on the following pharmacological properties of the active ingredients. Acetylsalicylate has analgesic, anti-pyretic and anti-inflammatory properties. The buffer converts acetylsalicylic acid to sodium acetylsalicylate and promotes gastric emptying.

5.2 Pharmacokinetic properties

Acetylsalicylate is rapidly absorbed from the small intestine after oral ingestion of Alka-Seltzer Original and rapidly distributed to all body tissues. Peak plasma levels occur at approximately 20 minutes.

Excretion is mainly renal.

5.3 Preclinical safety data

None relevant.

6.1 List of excipients

Alka-Seltzer Original tablets contain no additional excipients.

6.2 Incompatibilities

None known.

6.3 Shelf life

Shelf-life of the product as packaged for sale: 36 months.

6.4 Special precautions for storage

Do not store above 25°C. Store in the original package.

6.5 Nature and contents of container

Primary packaging consists of laminated paper/polyethylene/aluminium foil with surlyn heat foil or a direct printed lamination of aluminium and surlyn heat seal.

Aluminium foil pouches, each containing two tablets. Available in pack sizes of 2, 8, 10, 12, 20 or 30 tablets.

6.6 Special precautions for disposal

The tablets should not be removed from the foil pouches until immediately before use. If only one tablet from the foil pouch is used, the remaining one should be disposed of.

If a foil pouch is damaged and/or the tablets are powdery or discoloured, they should not be used. However, in the event that tablets are used, they are not harmful.