PRODUCT SUMMARY

1. NAME OF THE MEDICINAL PRODUCT Anadin Original

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredients:

Aspirin BP 325mg/tablet Caffeine PhEur 15mg/tablet

For excipients see section 6.1

3.    PHARMACEUTICAL FORM

Tablet for oral administration.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains and aches and pains.

For the symptomatic treatment 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

Adults, the elderly and young persons aged 16 and over:

2 tablets every 4 hours to a maximum of 12 tablets in 24 hours.

Do not exceed 12 tablets in 24 hours.

Do not give to children aged under 16, unless specifically indicted (e.g. Kawasaki’s disease).

Contra-indications

Hypersensitivity to the active ingredients or any of the other constituents. Peptic ulceration and those with a history of peptic ulceration; haemophilia, concurrent anti-coagulant therapy; children under 16 years and when breast feeding because of possible risk of Reyes Syndrome.

4.4    Special warnings and precautions for use

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

Do not take if you have a stomach ulcer.

Do not exceed the stated dose.

If symptoms persist for more than 3 days consult your doctor.

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. Kawasaki’s disease).

4.5    Interactions with other medicinal products and other forms of interaction

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

Diuretics: Antagonism of the diuretic effect.

Anticoagulants: Increased risk of bleeding due to antiplatelet effect. Metoclopramide: Metoclopramide increases the rate of absorption of aspirin. However, concurrent use need not be avoided.

Phenytoin: The effect of phenytoin may be enhanced by aspirin. However, no special precautions are needed.

Valproate: The effect of valproate may be enhanced by aspirin.

Methotrexate: Delayed excretion and increased toxicity of methotrexate.

4.6 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 should not be used in late pregnancy.

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

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 known

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 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.

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

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 dose less than 100mg/kg are unlikely to cause serious poisoning.

Aspirin

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 old. 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 more common in children than adults.

Caffeine

Common features include CNS stimulation; anxiety, nervousness, restlessness, insomnia, excitement, muscle twitching, confusion, convulsions.

Cardiac Symptoms include tachycardia, cardiac arrhythmia. Gastric symptoms include abdominal or stomach pains.

Other symptoms of overdosage, associated with the caffeine component, include diuresis and facial flushing.

Management

Aspirin

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 intraveneous 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 10 years or over 70 years have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

Caffeine

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Mechanisms of action/effect

Salicylates inhibit the activity of the enzyme cyclo-oxygenase to decrease the formation of precursors of prostaglandins 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 (Nonsteriodal)

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.

Antipyretic

May produce antipyresis by acting centrally on the hypothalamic heatregulating centre to produce peripheral vasodilation resulting in increased cutaneous blood flow, sweating and heat loss.

CAFFEINE

Mechanisms of action/effect

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

Analgesia adjunct

Caffeine constricts cerebral vasculature with an accompanying decrease in the cerebral blood flow and in the oxygen tension of the brain. It is believed that caffeine helps to relieve headache by providing more rapid onset of action and/or enhancing 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.

5.2 Pharmacokinetic properties

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.

CAFFEINE

Absorption and fate

Caffeine is completely and rapidly absorbed after oral administration with peak concentrations occurring between 5 and 90 minutes after dose in fasted subjects. There is no evidence of presystemic metabolism. Elimination is almost entirely by hepatic metabolism in adults.

In adults, marked individual variability in the rate of elimination occurs. The mean plasma elimination half life is 4.9 hours with a range of 1.9 - 12.2 hours. Caffeine distributes into all body fluids. The mean plasma protein binding of caffeine is 35%.

Caffeine is metabolised almost completely via oxidation, demethylation, and acetylation, and is excreted in the urine. The major metabolites are 1-methylxanthine, 7-methylxanthine, 1,7-dimethylxanthine (paraxanthine). Minor metabolites include 1-methyluric acid and 5-acetylamino-6 formylamino 3-methyluracil (AMFU).

5.3 Preclinical safety data

None stated.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Quinine Sulfate Ph Eur Maize Starch Ph Eur Microcrystalline Cellulose Ph Eur

Hydroxypropyl Methylcellulose (Methocel E5) Ph Eur Hydroxypropyl Methylcellulose (Methocel E15) Ph Eur Polyethylene Glycol (Carbowax 3350) USNF Calcium Stearate USNF

6.2 Incompatibilities

None known

6.3    Shelf life

36 Months:

Cartons containing PVC/ aluminium glassine paper blister strip 4, 6, 8, 12, 16, 24, 32 tablets.

24 Months:

Paper/Polyethylene strip 4, 8 Polypropylene drum with CRC cap 24, 32

Aluminium containers with approved polyethylene CRC Cap 16, 32 Paper/Polyethylene laminated strip packs 4, 8

6.4    Special precautions for storage

Do not store above 25 °C.

6.5 Nature and contents of container

Cartons containing PVC/ aluminium glassine paper blister strip 4, 6, 8, 12, 16, 24, 32 tablets.

Paper/Polyethylene strip 4, 8 Polypropylene drum with CRC cap 24, 32

Aluminium containers with approved polyethylene CRC Cap 16, 32 Paper/Polyethylene laminated strip packs 4, 8

6.6 Instructions for Use, Handling and Disposal

Not applicable

MARKETING AUTHORISATION HOLDER

Pfizer Consumer Healthcare Ltd

Ramsgate Road

Sandwich

Kent

CT13 9NJ United Kingdom

8. MARKETING AUTHORISATION NUMBER(S)

PL 0165/0060

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

31 August 1993

10 DATE OF REVISION OF THE TEXT

06/01/2016