Azpamin Tablets

u2022 To reduce the risk of myocardial infarction in patients with unstable angina or in patients who have had a previous myocardial infarction.

u2022 To reduce the risk of recurrent transient ischaemic attacks or stroke in men who have had transient ischaemia of the brain due to fibrin platelet emboli.

u2022 To reduce the risk of graft occlusion following aorta coronary by-pass surgery.

Posology: The usual dose is 100 mg daily. For reducing the risk of myocardial ischaemic events in people with increased cardiovascular risk: 100 mg to be taken every day preferably at the same time each day accordingly to the individual needs of the patient, as determined by the medical practitioner.

Special populations: Patients with hepatic impairment: AZPAMIN 100 should be used with caution in patients with abnormal hepatic function (see section 4.4). Patients with renal impairment: AZPAMIN 100 should be used with caution in patients with abnormal renal function (see section 4.4). Paediatric population: AZPAMIN 100 should not be given to children under the age 16 unless specifically indicated.

Method of administration: For oral use. The tablets should preferably be taken at least 30 minutes before meals, with plenty of water.

u2022 Hypersensitivity to acetylsalicylic acid or other salicylates, or to any other components of AZPAMIN 100 (see section 6.1).

u2022 Should not be administered to patients with haemorrhagic diathesis, haemophilia, or a history of haemorrhagic disorders, with gout, or a history of asthma induced by the administration of aspirin (salicylates) or substances with a similar action, including non-steroidal anti-inflammatory medicines.

u2022 Patients with severe impaired renal or hepatic function.

u2022 Last trimester of pregnancy (see section 4.6).

u2022 Acute gastrointestinal ulcers and active or history of recurrent ulcer/haemorrhage/perforation.

u2022 Patients receiving oral anti-coagulant therapy.

u2022 Heart failure.

u2022 Combination with methotrexate at doses of 15 mg/week or more.

u2022 History of gastrointestinal perforation, ulceration or bleeding related to previous NSAIDs use, including AZPAMIN.

u2022 Patients with aspirin-induced nasal polyps.

AZPAMIN 100 should be administered with caution in the following cases:

• Hypersensitivity to analgesics / anti-inflammatory medicines / anti-rheumatic and in the presence of other allergies.
• 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, AZPAMIN 100 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.
• AZPAMIN 100 should be withdrawn 1 week before surgery. Due to its inhibitory effect on platelet aggregation which persists for several days after administration, AZPAMIN 100 may lead to an increased bleeding tendency during and after surgical operations (including minor surgeries, e.g. dental extractions).
• Do not exceed the recommended daily dose. In the event of overdosage and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital, or Poison Control Centre must be contacted immediately.
• At low doses, AZPAMIN 100 reduces the excretion of uric acid. This can possibly trigger gout attacks in predisposed patients.
• In view of the medicineu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.
• AZPAMIN 100 should be administered with caution to patients with impaired renal function, dyspepsia, anaemia, and when the patient is dehydrated.
• Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with aspirin as in AZPAMIN 100 therapy.
• Caution is required in patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) and should only be treated with aspirin after careful consideration.
• In patients suffering from severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, AZPAMIN 100 may induce haemolysis or haemolytic anaemia. Factors that may increase the risk of haemolysis are high dosage, fever, or acute infections.
• Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation (PUBs) which may be fatal. The risk of gastrointestinal bleeding or perforation (PUBs) is higher with increasing doses of AZPAMIN 100 in patients with a history of ulcer and the elderly. When gastrointestinal bleeding or ulceration occurs in patients receiving AZPAMIN 100, treatment with AZPAMIN 100 should be stopped.
• AZPAMIN 100 should be given with caution to patients with a history of gastrointestinal diseases (e.g. ulcerative colitis, Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the conditions may be exacerbated.
• Dermatological effects: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis may occur with the use of NSAIDs. AZPAMIN 100 should be discontinued at the first appearance of skin rash, mucosal lesions or any other hypersensitivity.

Special populations

Paediatric population: AZPAMIN 100 should not be used in children and adolescents for viral infections with or without fever without consulting a doctor. In certain viral illnesses, especially influenza A, influenza B and varicella, there is a risk of Reyeu2019s syndrome, a possibly life-threatening illness requiring immediate medical action. The risk may be increased when AZPAMIN 100 is given concomitantly. Should persistent vomiting occur with such diseases, this may be a sign of Reyeu2019s syndrome.

Excipient warning: AZPAMIN 100 contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially u2018sodium-freeu2019.

Contraindicated interactions:

Methotrexate used at doses of 15 mg/week or more: Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory medicines in general and displacement of methotrexate from its plasma protein binding by salicylates), (see section 4.3).

Combinations requiring precautions for use:

• Methotrexate used at doses of less than 15 mg/week: Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory medicines in general and displacement of methotrexate from its plasma protein binding by salicylates).
• Anticoagulants, thrombolytics/other inhibitors of platelet aggregation/haemostasis: Increased risk of bleeding. AZPAMIN 100 may enhance the effects of coumarin anti-coagulants such as warfarin.
• Other non-steroidal anti-inflammatory drugs with salicylates: Increased risk of ulcers and gastrointestinal bleeding due to synergistic effect.
• Selective Serotonin Re-uptake Inhibitors (SSRIs): Increased risk of upper gastrointestinal bleeding due to a possible synergistic effect.
• Digoxin: Plasma concentrations of digoxin are increased due to a decrease in renal excretion.
• Antidiabetic Medicines, e.g. insulin, sulphonylureas: Increased hypoglycaemic effect by high doses of AZPAMIN via hypoglycaemic action of AZPAMIN and displacement of sulphonylurea from its plasma protein binding sites.
• Diuretics in combination with AZPAMIN 100: Decreased glomerular filtration via decreased renal prostaglandin synthesis.
• Systemic glucocorticoids, except hydrocortisone used as replacement therapy in Addison's disease: Decreased blood salicylate levels during corticosteroid treatment and risk of salicylate overdose, after this treatment is stopped, via increased elimination of salicylates by corticosteroids.
• Angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers in combination with acetylsalicylic acid: Decreased glomerular filtration via inhibition of vasodilatory prostaglandins. Furthermore, decreased antihypertensive effect.
• Valproic acid: Increased toxicity of valproic acid due to displacement from protein binding sites.
• Alcohol: Increased damage to gastro-intestinal mucosa and prolonged bleeding time due to additive effects of AZPAMIN and alcohol.
• Uricosurics such as benzbromarone, probenecid: Decreased uricosuric effect (competition of renal tubular uric acid elimination). Aspirin diminishes the effects of uricosuric medicines such as probenecid and sulphinpyrazone.
• NSAIDs: The use of two or more NSAIDs concomitantly could result in an increase in side effects.
• Ibuprofen: Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly.
• Metoclopramide: May enhance the effect of AZPAMIN 100.
• Phenytoin: Salicylate diminishes the binding of phenytoin to plasma albumin. This may lead to decreased total phenytoin levels in plasma, but increased free phenytoin fraction. The unbound concentration, and thereby the therapeutic effect, does not appear to be significantly altered.
• Alkaliser of urine such as antacids, citrates: Increased excretion of aspirin.

Pregnancy: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from studies raise concern about an increased risk of mis-carriage and of malformations after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. During the first and second trimester of pregnancy, AZPAMIN 100 should not be given. If AZPAMIN 100 is used by a woman attempting to conceive, or during the first and second trimesters of pregnancy, the dose should be kept as low, and the duration of treatment kept as short, as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension),
• renal dysfunction, which may progress to renal failure with oligo-hydroamniosis.

Prostaglandin synthesis inhibitors may expose both the mother and the child at the end of pregnancy to:

• possible prolongation of bleeding time/increased INR, an anti-aggregating effect which may occur even after very low doses,
• inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, AZPAMIN 100 is contraindicated during the third trimester of pregnancy (see section 4.3).

Lactation: Safety in breastfeeding has not been established. Salicylates and their metabolites pass into breast milk in small quantities. Mothers on treatment with AZPAMIN 100 should not breastfeed their babies.

Fertility: Limited data available. Studies in humans showed no consistent effect of aspirin as in AZPAMIN 100 on impairment of fertility and there is no conclusive evidence from animal studies.

AZPAMIN 100 has none to negligible influence on the ability to drive and use of machines. However, due to side effect such as dizziness, patients should check how they react to AZPAMIN 100 before driving a vehicle or operating machinery.

The most frequent adverse effects occurring with therapeutic doses of aspirin are gastrointestinal disturbances such as nausea, hepatotoxicity particularly in patients with juvenile arthritis and other connective tissue disorders.

System Organ Class Frequency Side effects

Blood and the lymphatic system disorders Frequency unknown Hypoprothrombinaemia, thrombocytopenia, aplastic anaemia, agranulocytosis, pancytopenia

Immune system disorders Frequency unknown Various skin eruptions, pyrexia, angioedema, and oedema

Metabolism and Nutrition Disorders Frequency unknown Sodium retention and fluid retention

Nervous system disorders Frequency unknown Meningitis, headache and dizziness

Cardiac Disorders Frequency unknown Hypertension, cardiac failure

Vascular Disorders Frequency unknown Hypertension

Respiratory, Thoracic and Mediastinal Disorders Frequency unknown Respiratory tract reactivity, bronchospasm, asthma, dyspnoea, and rhinitis

Gastrointestinal disorders Frequency unknown Gastrointestinal disturbances including nausea, vomiting and dyspepsia. Gastrointestinal haemorrhage melaena, haematemesis, gastritis, diarrhoea, constipation, flatulence, peptic ulcer, and mouth ulceration (ulcerative stomatitis)

Hepato-biliary disorders Less frequent Frequency unknown Transaminases increased Hepatotoxicity

Skin and subcutaneous tissue disorders Frequency unknown Stevens-Johnson syndrome and toxic epidermal necrolysis, rash, urticaria and pruritis, drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (see section 4.4)

Renal and urinary disorders Frequency unknown Increased blood uric acid

Investigations Frequency unknown Bleeding time prolonged, platelet adhesiveness decreased

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Salicylate toxicity may result from chronic, therapeutically acquired intoxication, and from potentially life-threatening, acute intoxications (overdose), ranging from accidental ingestions in children to incidental intoxications.

Chronic salicylic intoxication: Chronic salicylate poisoning can be insidious as signs and symptoms are non-specific. Mild chronic salicylate intoxication, or salicylism, usually occurs only after repeated use of large doses. Symptoms include dizziness, vertigo, tinnitus, deafness, sweating, nausea and vomiting, headache, and confusion, and may be controlled by reducing the dosage.

Acute salicylate intoxication: The principal feature of acute intoxication is severe disturbance of the acid-base balance, which may vary with age and severity of intoxication. Symptoms of acute or severe intoxication following overdose include hyperventilation, fever, ketosis, respiratory alkalosis and metabolic acidosis. Depression of the central nervous system may lead to coma, cardiovascular collapse, or respiratory failure. The most frequent presentation for a child is drowsiness and metabolic acidosis, hypoglycaemia may be severe. The severity of poisoning cannot be estimated from plasma concentration alone. Absorption of acetylsalicylic acid can be delayed due to reduced gastric emptying, formation of concretions in the stomach, or as a result of ingestion of enteric-coated preparations.

Management of AZPAMIN 100 intoxication is determined by its extent, stage and clinical symptoms and according to standard poisoning management techniques. Fluid and electrolyte management is the mainstay of treatment with the immediate aim being correction of acidosis, hyperpyrexia, hypokalaemia and dehydration. Salicylate remaining in the stomach may be absorbed by activated charcoal. Alkaline diuresis, haemodialysis or haemoperfusion are effective methods of removing salicylate from the plasma.