Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Owing to the risk of bleeding, Aggrenox, in common other antiplatelet agents, should be used with caution in patients at increased bleeding risk. Patients should be monitored carefully for any signs of bleeding, including occult bleeding.

Caution is required in patients receiving concomitant medication which may increase the risk of blee- ding, such as antiplatelet agents (e.g. clopidogrel, ticlopidine or ASA) or selective serotonin reuptake inhibitors (SSRIs).

Headache or migraine-like headache, which may occur especially at the beginning of Aggrenox ther- apy, must not be treated with analgesic doses of ASA.

Owing to the vasodilator properties of dipyridamole, Aggrenox should be used with caution in patients with severe coronary heart disease (including unstable angina or recent myocardial infarction), left ve- ntricular outflow obstruction or haemodynamic instability (e.g. decompensated heart failure).

Aggrenox should be discontinued 24 h prior to stress testing for coronary heart disease with intrave- nous dipyridamole. Clinical experience shows that failure to do so may impair the sensitivity of the test.

During treatment with Aggrenox, readjustment of therapy may be necessary in patients with myasthe- nia gravis (see section 4.5: Interaction with other medicinal products and other forms of interaction).

In a small number of patients, unconjugated dipyridamole was shown to be incorporated into gallsto- nes to a variable extent (up to 70% by dry weight of stone). These patients were all elderly, had sus- pected ascending cholangitis and had been treated with dipyridamole for a number of years. There is no evidence that dipyridamole was the initiating factor in causing gallstones to form in these patients.
Bacterial deglucuronidation of conjugated dipyridamole in bile may be the mechanism responsible for the presence of dipyridamole in gallstones.

Because of its ASA component, Aggrenox should be used with caution in patients with asthma, aller- gic rhinitis, nasal polyps, chronic or recurring gastric or duodenal complaints, renal or hepatic impair- ment, glucose-6-phosphate dehydrogenase deficiency, other allergies (such as those involving skin re- actions, urticaria and pruritus) or chronic respiratory diseases.

In addition, caution is required in patients who are hypersensitive to non-steroidal anti-inflammatory drugs (NSAIDs).

Patients receiving concomitant therapy with anticoagulants such as coumarin derivatives and heparin (although not low-dose heparin) require particularly careful medical supervision.

The dose of ASA in Aggrenox has not been investigated in clinical trials on the secondary prevention of myocardial infarction.

It should be borne in mind that Aggrenox may prolong bleeding time if taken prior to surgical proced- ures (including minor procedures such as dental extraction).

There is a possible association between ASA and Reye's syndrome in children. Because of the risk of Reye's syndrome, Aggrenox is contraindicated in children or adolescents with febrile diseases or viral infections (with or without fever). Reye's syndrome is a very rare disease which affects the brain and liver and can be fatal.

Aggrenox contains 53 mg lactose and 11.3 mg sucrose per capsule (equivalent to 106 mg lactose and 22.6 mg sucrose per maximum recommended daily dose). Patients with rare hereditary galactose or fructose intolerance, lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insuf- ficiency should not take Aggrenox.

Effects on Driving

4.7 Effects on ability to drive and use machines
In studies carried out in groups of 24 subjects, Aggrenox had no effect on safety-related performance compared with placebo. In particular, no sedative effects or interactions with alcohol were observed.
There is therefore no evidence that, when used in accordance with the prescribing instructions, Aggr- enox will affect the ability to drive, use machines or carry out other potentially hazardous tasks.
However, patients should be advised that symptoms such as dizziness and confusional state have been reported in clinical trials. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience such symptoms they should avoid potentially hazardous tasks such as driving or operating machinery.