Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Eurocept International BV, Trapgans 5, 1244 RL Ankeveen, The Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Severe renal disease. Patients with severe renal impairment should not receive para-aminosalicylic acid. Patients with severe renal disease will accumulate the inactive acetyl metabolite of paraaminosalicylic acid.
Given that the metabolites of para-aminosalicylic acid are largely excreted via glomerular filtration, caution is warranted in patients with mild to moderate renal impairment (see also section 4.3).
Para-aminosalicylic acid should be used with caution in patients with peptic ulcer.
Para-aminosalicylic acid should be used with caution in patients with hepatic impairment.
Para-aminosalicylic acid may cause hepatitis. The first symptoms usually appear within three months of the start of therapy with a rash as the most common adverse reaction followed by fever and much less frequently by gastrointestinal disturbances of anorexia, nausea or diarrhoea. Treatment should be stopped immediately in this case.
The patient must be monitored carefully during the first three months of therapy and treatment must be discontinued immediately at the first sign of a rash, fever or other premonitory signs of intolerance. See section 4.2 for posology adjustments for desensitization.
Para-aminosalicylic acid may be associated with an increased risk of hypothyroidism in HIV coinfected patients. Thyroid function should be monitored in HIV co-infected patients before commencing treatment and regularly during treatment, in particular when para-aminosalicylic acid is co-administered with ethionamide/prothionamide.
Patients should be advised that the skeletons of the granules may be seen in the stools.
No interaction studies have been performed.
Results from literature suggest the following:
Vitamin B12 absorption may be reduced by para-aminosalicylic acid with clinically significant erythrocyte abnormalities developing after depletion; patients on therapy of more than one month should be considered for maintenance of vitamin B12.
Para-aminosalicylic acid may decrease the gastrointestinal absorption of digoxin, by inhibiting the absorption function of intestinal cells. Serum digoxin levels should be monitored in patients on concomitant therapy.
Co-administration of para- aminosalicylic acid and ethionamide may intensify adverse reactions of para-aminosalicylic acid, mainly the gastrointestinal effects, including jaundice, hepatitis, nausea, vomiting, diarrhoea, abdominal pain or anorexia. Ethionamide should be withdrawn if these effects are significant.
This medicinal product decreases the gastrointestinal absorption of para-aminosalicylic acid, and should not be administered concomitantly.
No drug interaction studies have been conducted in patients with HIV infection taking antiretroviral agents and para-aminosalicylic acid. Given the metabolic pathway of para-aminosalicylic acid no significant drug interaction is anticipated.
There are no or limited amount of data from the use of para-aminosalicylic acid in pregnant women. Studies in animals have shown some reproductive toxicity (see section 5.3).
GRANUPAS is not recommended during pregnancy and in women of childbearing potential not using contraception.
Literature reports on para- aminosalicylic acid in pregnant women always report co-administration of other medicinal products. As there are no adequate and well controlled studies of para- aminosalicylic acid in humans, para-aminosalicylic acid should be given to a pregnant woman only if clearly needed.
Para-aminosalicylic acid is excreted in human milk. There is insufficient information on the effects of para-aminosalicylic acid in newborns/infants.
GRANUPAS should not be used during breast-feeding.
There is no evidence available on the effect of para-aminosalicylic acid on fertility.
Para-aminosalicylic acid has negligible influence on the ability to drive and use machines.
Most frequent adverse reactions were related to the gastrointestinal system. Cutaneous hypersensitivity reactions were also frequent as well as adverse reactions related to the nervous system.
In the table below all adverse reactions are listed by system organ class and by frequency. Frequency is defined as 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 availabledata). Within each frequency grouping, adverse reactions are presented in order of decreasingseriousness
Very rare: Thrombocytopenia, purpura, leukopenia, anemia, methemoglobinemia, agranulocytosis.
Rare: Hypothyroidism*.
Very rare: Hypoglycemia.
Very rare: Tendon pain, headache, visual abnormalities, peripheral neuropathy, dizziness.
Common: Giddiness, vestibular syndrome.
Common: abdominal pain, vomiting, nausea, bloating, diarrhea, soft stools.
Uncommon: Anorexia.
Rare: Malabsorption syndrome*, peptic ulcer, gastrointestinal bleeding, jaundice, metallic taste.
Common: Cutaneous hypersensitivity, skin rash.
Rare: Urticaria.
Very rare: Decreased prothrombine level, hepatocytolysis. Increased blood alkaline phosphatase, transaminases, weight loss.
* see Description of selected adverse reactions below
Hypothyroidism in HIV co-infected patients is a very common event and occurs in ≥1/10 subjects, particularly when para-aminosalicylic acid is administered with ethionamide/prothionamide.
A malabsorption syndrome can develop in patients on para-aminosalicylic acid, but is usually not complete. The complete syndrome includes steatorrhoea, an abnormal small bowel pattern on x-ray, villus atrophy, depressed cholesterol, reduced D-xylose and iron absorption. Triglyceride absorption is always normal.
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
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 national reporting system listed in Appendix V.
Not applicable.
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