Anadin Analgesic Tablets

In section 6.1, the spelling of sulphate has changed to sulfate.

In section 10, the date of revision has changed to December

In section 10, the date of revision has been updated to March 2015.

In section 3, The following text has been removed: debossed on both faces with ‘ANADIN’

the following text has been added:

The tablets have ‘325/15’ embossed on both sides.

Quinine Sulphate has been reclassified as an excipient (rather than active ingredient). This has impacted the following sections:
1; 2; 4.6; 5.1; 5.2; 6.1

In section 4.4, the following text has been added:

In patients suffering from severe glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, aspirin is known to rarely cause haemolytic anaemia.

The following text has been removed:

As NSAIDs  can interfere with platelet function , they should be used with caution in patients with intercranial haemorrhage and bleeding diathesis.

In 4.6, the title has been updated to match QRD template, and sub headings 'Pregnancy', 'Breast feeding' and 'Fertility' have been added. The following text has been added:

Fertility

 If acetylsalicylic acid is used by a woman attempting to conceive the dose should be kept as low as possible and the duration of use as short as possible. Animal studies have shown an increased risk of pre -implantation loss and various malformations including cardiovascular.

In 4.8, the undesirable effects 'anaemia, aplastic anaemia, pancytopenia' have been added. The HPRA reporting information has also been added.

The title of 6.6. has been updated to match QRD wording.

In section 8, MA number has been reformatted, with zeros added: PA0822/165/001

In section 10, the date of revision has been updated from December 2012 to August 2014.

MAH is Pfizer Healthcare Ireland, Citywest Business Campus, Dublin 24.
PA 822/165/1.

4.2 Posology and Method of Administration

Adults and Adolescents over 16 years: Take 2 tablets every 4 hours if necessary. Do not exceed 12 tablets in any 24 hour period.
Take 2 tablets every 4 hours if necessary. Do not exceed 12 tablets in any 24 hour period.

4.3 Contra-indications

Patients with a history of hypersensitivity reactions (e.g. bronchospasm, rhinitis, urticaria) in response to Anadin Analgesic Film-coated Tablets, aspirin or other non-steroidal anti-inflammatory drugs or any of the other constituents.
Children and adolescents under 16 years.
Breast-feeding.
Last-trimester of pregnancy.
Concurrent anti-coagulant therapy.
Patients with severe renal failure.
Intake of more than 15mg methotrexate per week.


4.4 Special Warnings and Precautions for Use

As NSAIDs can interfere with platelet function, they should be used with caution in patients with intracranial haemorrhage and bleeding diathesis.

4.5 Interactions with other medicinal products and other forms of interactions

Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the
effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These
interactions should be considered in patients taking Anadin Analgesic Film-coated Tablets concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.


4.6 Pregnancy and Lactation

Acetylsalicylic acid should not be used during the first and second trimester of pregnancy unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimesters, the dose should be kept as low as possible and the duration of use as short as possible. It has been suggested in epidemiological studies that prostaglandin synthesis inhibition in early pregnancy is associated with an increased risk of miscarriage, cardiac malformation and gastroschisis. Animal studies have shown an increased risk of pre and post-implantation loss and various malformations including cardiovascular.

In the third trimester, there is also the risk of cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension) and renal dysfunction.

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.

5.1 Pharmacodynamic Properties

ATC code: N02BE51
Pharmacotherapeutic group: Other analgesics and antipyretics

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 heat-regulating 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

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

7.         MARKETING AUTHORISATION HOLDER

 

                                    Pfizer Consumer Healthcare Ltd

                        Ramsgate Road, Sandwich

                        Kent CT13 9NJ

                        United Kingdom
 
(Formally Wyeth Consumer Healthcare) 

1. Renewal completed and the product name was changed in line with EU guidance.
2. Product information brought in line with EU warnings on disturbances in female fertility, cardiovascular and G.I. safety and serious skin reactions. Thrombotic risks.
3. Interactions of aspirin and ibuprofen.