Acetylsalicylic acid

Concomitant administration of alcohol and acetylsalicylic acid increases the risk of gastrointestinal bleeding.

Absorbable antacids

At therapeutic doses, they may result in an increase in the clearance rate of salicylates and a decrease in their effectiveness.

Non-absorbable antacids

They may result in inhibition of the absorption of acetylsalicylic acid and a decrease in its relationship to salicylic acid in plasma.

Antidiabetics, e.g. sulphonylureas and insulin

Salicylates may increase the hypoglycaemic effect of antidiabetics. Thus, some downward re-adjustment of the dosage of the antidiabetic may be appropriate if large doses of salicylates are used. Increased blood glucose controls are recommended.

Anticoagulants and thrombolytics e.g. coumarin, heparin, warfarin, alteplase

Increased risk of bleeding due to inhibited thrombocyte function, injury of the duodenal mucosa and displacement of oral anticoagulants from their plasma protein binding sites. The bleeding time should be monitored. Particularly, treatment with acetylsalicylic acid should not be initiated within the first 24 hours after treatment with alteplase in acute stroke patients. Concomitant use is therefore not recommended.

Anti-platelet agents (e.g clopidogrel, ticlopidine, cilostazol and dipyridamole)

Increased risk of gastrointestinal bleeding.

NSAIDs may decrease the antihypertensive effects of diuretics and other antihypertensive agents. Blood pressure should be well monitored.

Loop diuretics: Risk of acute renal failure due to the decreased glomerual filtration via decreased renal prostaglandin synthesis.

Hydrating the patient and monitoring renal function at the start of the treatment is recommended.

Concomitant administration with calcium-channel blocker increases the risk of acute renal insufficiency in combination with high-dose ASA.

Hydrating the patient and monitoring renal function at the start of the treatment is recommended. In case of association with verapamil the bleeding time should be monitored.

Concomitant administration with ACE-inhibitors and angiotensin II receptor antagonists increases the risk of acute renal insufficiency in combination with high-dose ASA.

The risk of gastrointestinal ulceration and bleeding may be increased when acetylsalicylic acid and corticosteroids are co-administered.

The use of salicylates should be avoided for 6 weeks after vaccination for varicella, as Reye's syndrome has been reported after the use of salicylates during infection with natural varicella virus.

Increased risk of gastrointestinal bleeding.

May result in severe acidosis and increased central nervous system toxicity.

Increased risk of ulcerations and gastrointestinal bleeding due to synergistic effects.

Uricosuric agents, e.g. probenecid, sulfinpyrazone:

Salicylates reverse the effect of probenecid and sulfinpyrazone. The combination should be avoided.

Concomitant administration of acetylsalicylic acid and crystalline penicillin G causes a decrease in half-life of crystalline penicillin G.

Concomitant use of NSAIDs and ciclospoin or tacrolimus may increase the nephrotoxic effect of ciclosporin and tacrolimus. The renal function should be monitored in case of concomitant use of these agents and acetylsalicylic acid.

Acetylsalicylic acid impairs the renal excretion of digoxin and lithium, resulting in increased plasma concentrations. Monitoring of plasma concentrations of digoxin and lithium is recommended when initiating and terminating treatment with acetylsalicylic acid. Dose adjustment may be necessary.

It can cause salicylate poisoning (even with proportionally smaller doses of the latter), while at the same time the natriuretic effect of furosemide can be reduced.

Griseofulvin may reduce the efficacy of acetylsalicylic acid. Griseofulvin should be avoided if possible when therapy with anti-inflammatory doses of salicylate are required.

Experimental data suggest that ibuprofen may inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose acetylsalicylic acid for cardioprotection.

The combined drugs, methotrexate and acetylsalicylic acid, may increase haematological toxicity of methotrexate due to decreased renal clearance of methotrexate by acetylsalicylic acid. Weekly blood count checks should be done during the first weeks of the combination. Enhanced monitoring should take place in the presence of even mildly impaired renal function, as well, as in elderly.

Increased absorption rate of salicylates.

Clinical pharmacodynamic data suggest that concomitant use of naproxen for more than one consecutive day may inhibit the effect of low-dose acetylsalicylic acid on platelet function, and this inhibition may persist for several days after discontinuation of naproxen therapy. The clinical significance of this interaction is unknown.

Acetylsalicylic acid has been reported to decrease the binding of valproate to serum albumin, thereby increasing its free plasma concentrations at steady state.

It may result in a reduction in the diuretic effect of spironolactone.

Urine acidifiers (e.g. vitamin C): Reduced renal excretion of salicylates.

Acetylsalicylic acid should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency.

Aspirin should be used with particular caution in the case of history of gastro-intestinal ulcers including chronic or recurrent ulcer disease or history of gastro-intestinal bleedings.

There is an increased risk of haemorrhage and prolongation of bleeding time particularly during or after surgery (even in cases of minor procedures, e.g. tooth extraction). Use with caution before surgery, including tooth extraction. Temporary discontinuation of treatment may be necessary.

Acetylsalicylic acid in low doses reduces uric acid excretion. Due to this fact, patients who tend to have reduced uric acid excretion may experience gout attacks.

Acetylsalicylic acid increases the activity of divalproex sodium.

Preparations containing acetylsalicylic acid should not be administered to children and adolescents with viral infections, with or without fever, without the advice of a doctor.

Low doses (up to 100 mg/day):

Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.

Doses of 100-500 mg/day:

There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendations below for doses of 500 mg/day and above apply also for this dose range.

Doses of 500 mg/day and above:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment 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;

the mother and the neonate, at the end of pregnancy, to:

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

Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.

Low quantities of salicylates and of their metabolites are excreted into the breast milk. Since adverse effects for the infant have not been reported up to now, short-term use of the recommended dose does not require suspending lactation. In cases of long-term use and/or administration of higher doses, breastfeeding should be discontinued.

No studies on the effects on the ability to drive and use machines have been performed with cetylsalicylic acid. Based on the pharmacodynamic properties and the side effects of acetylsalicylic acid, no influence on the reactivity and the ability to drive or use machines is expected.

Vascular indications

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)

Analgesic/ antipyretic indication

The listed adverse drug reactions are based on spontaneous reports, thus an organisation according to CIOMS III categories of frequency is not possible.

Blood and lymphatic system disorders: Haemorrhagic anaemia, iron deficiency anaemia with the respective laboratory and clinical signs and symptoms. Haemolysis, haemolytic anaemia

Cardiac disorders: Cardio-respiratory distress

Ear and labyrinth disorders: Tinnitus

Gastrointestinal disorders: Dyspepsia, gastrointestinal pain, abdominal pain, gingival bleeding, gastrointestinal inflammation, gastrointestinal ulcer, gastrointestinal haemorrhage, gastrointestinal ulcer haemorrhage and perforation with the respective laboratory and clinical signs and symptoms, intestinal diaphragm disease

Hepatobiliary disorders: Liver disorder, transaminases increased

Immune system disorders: Hypersensitivity, drug hypersensitivity, allergic edema and angioedema, anaphylactic reaction, anaphylactic shock with respective laboratory and clinical manifestations

Nervous system disorders: Cerebral and intracranial haemorrhage, dizziness

Renal and urinary disorders: Urogenital haemorrhage, renal impairment, renal failure acute

Respiratory, thoracic and mediastinal disorders: Epistaxis, analgaesic asthma syndrome, rhinitis, nasal congestion

Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus

Vascular disorders: Haemorrhage, operative haemorrhage, haematoma, muscle haemorrhage