Granupas

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



1. NAME OF THE MEDICINAL PRODUCT 
 
GRANUPAS 4 g gastro-resistant granules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sachet contains 4 g of para-aminosalicylic acid.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Gastro-resistant granules 
 
The granules are small off white/ light brown coloured approximately 1.5 mm diameter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
GRANUPAS is indicated for use as part of an appropriate combination regimen for multi-drug 
resistant tuberculosis in adults and paediatric patients from 28 days of age and older when an effective 
treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. 
 
Consideration should be given to official guidance on the appropriate use of antibacterial agents. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
4 g (one sachet) three times per day. 
The recommended schedule is 4 g every 8 hours. GRANUPAS can be taken with food. 
Maximum daily dose is 12 g. Usual duration of treatment is 24 months. 
 
Desensitization 
Desensitization can be accomplished by starting with 10  mg para-aminosalicylic acid (PAS) given as 
a single dose. The dosage is doubled every 2 days until reaching a total of 1 gram after which the 
dosage is divided to follow the regular schedule of administration. If a mild temperature rise or 
skin reaction develops, the increment is to be dropped back one level or the progression held for one 
cycle. Reactions are rare after a total dosage of 1.5 g. 
 
Paediatric population 
The optimal dose regimen in children is uncertain. Limited pharmacokinetic data suggest no 
substantial difference between adults and children. 
For infants, children and adolescents the dosage will be adapted to the patient’s weight at 150 mg/kg 
per day, divided in two intakes. A dosing spoon is provided to measure small doses below 4 g 
for young children. 
 
The safety and efficacy of para-aminosalicylic acid in neonates have not been established. No data are 
available. 
 
Method of administration  
 



Oral use. 
 
The contents of the sachet should be added to a glass of orange or tomato juice. They will not 
dissolve, but swirling the juice in the glass will help re-suspend the granules if they sink. It should be 
drunk at once ensuring that the granules are not left in the glass. Any granules left-over at the bottom 
of the glass should be swallowed immediately by adding a small quantity of liquid. Smaller doses in 
children should be measured using the dosing spoon and given by sprinkling on apple sauce or yogurt. 
 
The medicinal product should be swallowed immediately after mixing with orange juice, tomato juice, 
apple sauce and yogurt whilst the granules are intact. 
 
The granules should not be crushed or chewed, as this impairs the gastro-resistant coating. 
 
4.3 Contraindications 
 
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 para-
aminosalicylic acid. 
 
4.4 Special warnings and precautions for use 
 
Mild to moderate renal impairment 
 
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). 
 
Gastric ulcer 
 
Para-aminosalicylic acid should be used with caution in patients with peptic ulcer. 
 
Hepatic impairment 
 
Para-aminosalicylic acid should be used with caution in patients with hepatic impairment. 
 
Hepatic toxicity 
 
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. 
 
Hypersensitivity 
 
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. 

 
Hypothyroidism in HIV co-infected patients 
 
Para-aminosalicylic acid may be associated with an increased risk of hypothyroidism in HIV co-
infected 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. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed.  
 
Results from literature suggest the following: 
 
Vitamin B12 
 
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. 
 
Digoxin 
 
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. 
 
Ethionamide 
 
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. 
 
Diphenylhydramine 
 
This medicinal product decreases the gastrointestinal absorption of para-aminosalicylic acid, and 
should not be administered concomitantly. 
 
Antiretrovirals 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
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. 
 
Breast-feeding 
 
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. 
 
Fertility 
 
There is no evidence available on the effect of para-aminosalicylic acid on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Para-aminosalicylic acid has negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
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. 
 
Tabulated list of adverse reactions 
 
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 available data). Within each frequency grouping, adverse reactions are presented in order 
of decreasing seriousness. 
 

System Organ Class Frequency Adverse reaction 
Blood and lymphatic system 

disorders Very rare 
Thrombocytopenia, purpura, leukopenia, 
anemia, methemoglobinemia, agranulocytosis. 

Metabolism and nutrition 
disorders 

Rare Hypothyroidism*. 
Very rare Hypoglycemia. 

 
Nervous system disorders Very rare 

Tendon pain, headache, visual abnormalities, 
peripheral neuropathy, dizziness. 

Common Giddiness, vestibular syndrome. 
 
 

Gastrointestinal disorders 

Common abdominal pain, vomiting, nausea, bloating, diarrhea, soft stools. 
Uncommon Anorexia. 

 
Rare 

Malabsorption syndrome*, peptic ulcer, 
gastrointestinal bleeding, jaundice, metallic 
taste. 

Hepatobiliary disorders Unknown Hepatitis 
Skin and subcutaneous tissue 

disorders 
Common Cutaneous hypersensitivity, skin rash. 

Rare Urticaria. 
Renal and urinary disorders Very rare Crystalluria. 

 
Investigations 

 
Very rare 

Decreased prothrombine level, hepatocytolysis. 
Increased blood alkaline phosphatase, 
transaminases, weight loss. 

 
*see Description of selected adverse reactions below 
 
Description of selected adverse reactions 
 
Hypothyroidism 
 
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. 



 
Malabsorption syndrome 
 
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. 

 
Paediatric population 
 
Frequency, type and severity of adverse reactions in children are expected to be the same as in 
adults. 
 
Reporting of suspected adverse reactions 
 
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. 
 
4.9 Overdose 
 
There is no experience with overdose in humans.  In the event of overdose, it is recommended that 
the patient is monitored for any signs or symptoms of adverse reactions and that appropriate 
symptomatic treatment is instituted immediately.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antimycobacterials, drugs for treatment of tuberculosis, ATC code: 
J04AA01 
 
Mechanism of action 
 
Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of 
bacterial resistance to streptomycin and isoniazid. 
The mechanism of action of para-aminosalicylic acid resembles the sulfonamides, competing with 
paraminobenzoic acid (PABA) for dihydropteroate synthetase (DHP), a key enzyme in the 
biosynthesis of folates. However, para-aminosalicylic acid appears to be a weak inhibitor of DHP in 
vitro, raising the possibility that it may have a different target.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
GRANUPAS is a gastro-resistant preparation and, therefore, the acid-resistant coating of the granules 
protects against degradation in the stomach therefore preventing the formation of meta-aminophenol (a 
known hepatotoxin). The small granules are designed to escape the restriction on gastric emptying of 
large particles. Under neutral conditions as are found in the small intestine or in neutral foods, the 
acid-resistant coating is dissolved within one minute. 
 
Care must be taken in the administration of these granules to protect the acid-resistant coating by 
maintaining the granules in an acidic food during dosage administration. 
 



Because the granules are protected by an enteric coating, absorption does not commence until they 
leave the stomach. The soft skeletons of the granules remain and may be seen in the stools. 
 
In a single dose (4 grams) pharmacokinetic study in healthy adult volunteers (N=11) the initial time to 
a 2 µg/mL serum level of aminosalicylic acid was 2 hours with a range of 45 minutes to 24 hours; the 
median time to peak was 6 hours with a range of 1.5 to 24 hours; the mean peak level was 20 µg/mL 
with a range of 9 to 35µg/mL: a level of 2 µg/mL was maintained for an average of 8 hours with a 
range of 5 to 9.5 a level of 1 µg/mL was maintained for an average of 8.8 hours with a range of 
6 to 11.5 hours. 
 
Distribution 
 
Para-aminosalicylic acid is distributed in various tissues and fluids including the lungs, kidneys, liver 
and peritoneal fluid. Pleural or synovial fluid concentrations are approximately equal to plasma. The 
drug does not cross the blood brain barrier in patients unless the meninges are inflamed, when the 
concentration of para-aminosalicylic acid in cerebrospinal fluid is about 10 to 50% of the plasma. It is 
unknown whether it passes through the placental barrier. Small amounts of this agent are distributed in 
the milk and bile. 
Plasma protein binding is about 50 to 60%, the kinetic distribution has a half-life of 0.94 hours and a 
volume of distribution of 1.001 L/kg. 
 
Biotransformation 
 
Para-aminosalicylic acid is acetylated in the liver and converted into the inactive metabolite, N-acetyl-
para-aminosalicylic acid which is devoid of bacteriostatic activity. The plasma half-life of this agent is 
about 1 hour, the concentration is not substantially altered in hepatic dysfunction. The concentration of 
the metabolite may be increased in cases of renal failure. 
 
The major metabolites of PAS are produced by conjugation to glycine in para-aminosalicyluric acid 
(PASU) for up to 25% of the dose and to N-acetyl in N-acetyl para-aminosalicylic acid (Ac-PAS) for 
up to 70% of the dose. Together they constitute more than 90% of the total metabolites of PAS found 
in urine. 
 
Elimination 
 
In a single dose study the plasma half-life of para-aminosalicylic acid administered as GRANUPAS 
was 1.62 ± 0.85 h. 
Para-aminosalicylic acid and its metabolites are excreted by glomerular filtration and tubular secretion. 
The cumulative excretion of para-aminosalicylic after 24 hours is 84% of an oral dose of 4 g, 21% as 
para-aminosalicylic acid and 63% as the acetylated form. The acetylation process is not genetically 
determined as is the case for isoniazid. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology and repeated dose toxicity. 
The data available from a rat embryofoetal development study, where animals were given sodium 
aminosalicylate (3.85 to 385 mg/kg) were limited. Bone defects were observed at 77 mg/kg only.and 
increased foetal weight was noted at the other doses. Other malformations were observed; however, 
the exact nature of these findings is unknown. The lack of a dose-response relationship suggests that 
the findings are not of clinical relevance, but it is noted that the findings were observed at doses below 
those proposed clinically. In the rabbit, sodium aminosalicylate had no effects on embryofoetal 
development; however, the doses evaluated were below those proposed clinically. 
 
Sodium aminosalicylic acid was not mutagenic in Ames test strain TA 100. In human lymphocyte 
cultures in-vitro clastogenic effects of achromatic, chromatid, isochromatic breaks or chromatid 
translocations were not seen at 153 or 600 µg /mL but at 1500 and 3000 µg /mL there was a dose 



related increase in chromatid aberrations. An in vivo genotoxicity study (micronucleus test) has been 
conducted with para-aminosalicylic acid. Results indicate that para-aminosalicylic acid was considered 
not to have produced any clastogenic effect in mice treated at non-toxic dose levels (examined 
24 hours after 2 daily administrations of 312.5 to 1250 mg/kg). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Silica, colloidal hydrated 
Dibutyl sebacate 
Methacrylic acid – Ethyl acrylate copolymer (1:1) Dispersion 30 per cent 
Hypromellose 
Cellulose, microcrystalline 
Talc 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
The sachets can be stored below 25°C up to 24 hours after first opening. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Sachets consisting of paper/low density polyethylene/aluminium foil/primer/low density polyethylene.  
 
Pack size of 30 sachets. A calibrated measuring spoon is provided. 
 
6.6 Special precautions for disposal and other handling 
 
The sachet should not be used if it is swollen or if the granules have lost their light brown colour, and 
are turning dark brown or purple. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
7. MARKETING AUTHORISATION HOLDER 
 
Eurocept International BV 
Trapgans 5 
1244 RL Ankeveen 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/896/001 



 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 07 April 2014. 
Date of latest renewal: 18 December 2018. 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu. 
 
 
  



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer responsible for batch release  

Lucane Pharma 
172 rue de Charonne  
75011 Paris 
France 
 
Eurocept International BV 
Trapgans 5 
1244 RL Ankeveen 
The Netherlands 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set  
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile 
or as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 
• Additional risk minimisation measures 
 

None 
 



• Obligation to conduct post-authorisation measures 
 

None 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
GRANUPAS 4 g gastro-resistant granules  
para-aminosalicylic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sachet contains 4 g of para-aminosalicylic acid 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Gastro-resistant granules  
30 sachets 
Calibrated measuring spoon 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
Do not chew or crush. 
Warning: Do not use if sachet is swollen or the granules have lost their light brown colour and are dark 
brown or purple 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 
 



10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eurocept International BV (Lucane Pharma) 
Trapgans 5 
1244 RL Ankeveen 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/896/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
GRANUPAS 4 g 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
  



MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
GRANUPAS 4g gastro-resistant granules  
para aminosalicylic acid 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Do not chew or crush. 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4 g 
 
 
6. OTHER 
 
Warning: Do not use if sachet is swollen or the granules have lost their light brown colour and are dark 
brown or purple. 
  



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



Package leaflet: Information for the patient 
 

GRANUPAS 4 g gastro-resistant granules 
para-aminosalicylic acid 

 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What GRANUPAS is and what it is used for 
2. What you need to know before you take GRANUPAS 
3. How to take GRANUPAS 
4. Possible side effects 
5. How to store GRANUPAS 
6. Contents of the pack and other information 
 
 
1. What GRANUPAS is and what it is used for 
 
GRANUPAS contains para-aminosalicylic acid which is used in adults and children aged 28 days and 
older to treat resistant tuberculosis in combination with other medicines, in cases of resistance or 
intolerability with other treatments. 
 
 
2. What you need to know before you take GRANUPAS  

Do not take GRANUPAS 
• if you are allergic to para-aminosalicylic acid or any of the other ingredients of this 

medicine (listed in section 6). 
• if you have severe kidney disease. 
If you are not sure, talk to your doctor or pharmacist before taking GRANUPAS. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking GRANUPAS 
• if you have liver problems or mild or moderate kidney disease 
• if you have a stomach ulcer 
• if you are infected with HIV 
 
Children  
Use of GRANUPAS is not recommended in newborn babies (under 28 days of age). 
 
Other medicines and GRANUPAS 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
It is especially important to tell your doctor if you are taking any of the following: 
• Antituberculosis medicines or ethionamide (other treatments against tuberculosis) 
• Vitamin B12 
• Digoxin (for heart disease) 



 

20 
 
 
 
 
 

• Diphenylhydramine (for allergic reactions) 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
GRANUPAS is not recommended during pregnancy and should only be used if advised by your 
physician. 
Do not breastfeed whilst taking GRANUPAS. This is because small amounts of the medicine can 
pass into mother’s milk. 
 
Driving and using machines 
GRANUPAS is unlikely to affect your ability to drive any vehicle and use machines. 
In case it does, please report it to your doctor or pharmacist. 
 
 
3. How to take GRANUPAS 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
Adults 
The recommended dose for adults is 1 sachet three times a day, with a schedule of 1 sachet every 
8 hours. Your physician may need to start with a lower dose to prevent possible side effects. 
Do not take more than 3 sachets per day. Treatment is usually given for two years (24 months). 
 
• Add the contents of the sachet to a drink of tomato or orange juice. 
• Drink straight away 
• If some granules are left in the glass, add some more juice and drink straight away. 
 
Use in infants, children and adolescents 
The dose in infants, children and adolescents will be calculated by your doctor based on the patient’s 
body weight. The recommended total dose per day is 150 mg for each kg of body weight. This daily 
amount is divided into two doses spread out through the day. 
 
• Use the spoon that comes with the medicine to measure the dose. 
• To measure the dose: 

o Lines on the spoon indicate the amount (in milligrams of para-aminosalicylic acid). 
Take the correct amount as prescribed by your doctor. 

o Put granules directly into the spoon. 
o Tap the spoon once on a table to give a horizontal level of granules and 

continue filling if necessary. 
• Sprinkle the granules onto apple sauce or yogurt. 
• Make your child eat it straight away. 
 
Taking this medicine 
• Do not crush or chew the granules. Swallow the granules whole. It is important that you do not 

dissolve, crush or chew the granules as they may not absorb properly and may cause stomach 
ache or bleeding. 

• Do not use the sachet if it is swollen or the granules have lost their light brown colour. 
• You may notice granules appearing in your stools; this is normal. 
 



 

21 
 

If you take more GRANUPAS than you should 
Speak to a doctor or pharmacist. 
 
If you forget to take a dose of GRANUPAS 
Do not take a double dose to make up for a forgotten dose. Wait until the next dose is due, then take 
your normal dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
During the first 3 months of your treatment with GRANUPAS, you must be attentive to any sign of 
allergic reaction (for example skin eruption, itchy red spots on the skin, itching, rash, watery or itchy 
eyes or stuffy nose) or hepatitis (for example fever, fatigue, dark urine, pale stool, abdominal pain, 
yellow skin and eyes). If you experience any of these symptoms, you must contact to your doctor 
immediately. 
 
Common side effects (may affect more than 1 in 100 people):  
• giddiness,  
• stomach ache (abdominal pain),  
• vomiting,  
• nausea,  
• bloating,  
• diarrhoea,  
• soft stools,  
• skin redness or rash,  
• disturbance of gait and equilibrium. 
 
Uncommon side effects (may affect more than 1 in 1,000 people):  
• loss of appetite (anorexia). 
 
Rare side effects (may affect more than 1 in 10,000 people):  
• thyroid gland problems*,  
• reduced ability to absorb nutrients from food ulcer,  
• bleeding in the gut,  
• yellowing of skin or eyes (jaundice),  
• metallic taste,  
• itchy rash. 
 
(*) in subjects also infected with HIV thyroid gland problems and specifically underactive thyroid or 
low levels of thyroid hormones, are a very common side effect that may affect more than 1 in 10 
people. Regular monitoring of the thyroid function is indicated for all people living with HIV. 
 
Very rare side effects (may affect less than 1 in 10,000 people):  
• reduction in blood platelets, 
• red spots on the skin,  
• reduction in numbers of white blood cells,  
• reduction in numbers of red blood cells,  
• reduction of the ability of red blood cells to release oxygen  
• low levels of blood sugar,  
• tendon pain,  
• headache,  



 

22 
 

• visual abnormalities,  
• nerve damage in the hands and feet,  
• dizziness,  
• crystals in urine. 
• prolonged bleeding time, 
• destruction of liver cells  
• elevated liver enzymes,  
• weight loss.  
 
Not known side effects (frequency cannot be estimated from the available data):  
• Hepatitis. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store GRANUPAS 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and sachet after EXP. The 
expiry date refers to the last day of the month. 
 
Do not store above 25°C. The sachets can be stored below 25°C up to 24 hours after opening. 
 
Do not use this medicine if you notice the sachets are swollen or if the granules are dark brown or 
purple. 
 
Do not throw away any medicines via wastewater or household waste.  
Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment. 
 
 
6. Contents of the pack and other information 
 
What GRANUPAS contains  
The active substance is para-aminosalicylic acid. 
Each sachet of gastro-resistant granules contains 4 g of para-aminosalicylic acid. 
The other ingredients are silica, colloidal hydrated, dibutyl sebacate, methacrylic acid – ethyl acrylate 
copolymer (1:1) dispersion 30 per cent, hypromellose, cellulose, microcrystalline, talc. 
 
What GRANUPAS looks like and contents of the pack 
This medicine is presented as light brown gastro-resistant granules in sachets.  
Each box contains 30 sachets. A calibrated measuring spoon is provided. 
 
Marketing Authorisation Holder 
Eurocept International BV 
Trapgans 5 
1244 RL Ankeveen 
The Netherlands 
 
Manufacturer 
Lucane Pharma 



 

23 
 

172 rue de Charonne 
75011 Paris 
France 
 
Eurocept International BV 
Trapgans 5 
1244 RL Ankeveen 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Lucane Pharma 
Tél/Tel: + 33 153 868 750 
info@lucanepharma.com 

Lietuva  
FrostPharma AB 
Tel: +46 775 86 80 02 
info@frostpharma.com 

България 
Lucane Pharma 
Teл.: + 33 153 868 750 
info@lucanepharma.com 

Luxembourg/Luxemburg 
Lucane Pharma 
Tél/Tel: + 33 153 868 750 
info@lucanepharma.com 

Česká republika 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Magyarország 
Lucane Pharma 

                 Tel.: + 33 153 868 750 
info@lucanepharma.com 

Danmark 
FrostPharma AB 
Tlf: +45 808 20 101 
info@frostpharma.com 

Malta 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Deutschland 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Nederland 
Eurocept International BV 
Tel: +31 35 528 39 57 
info@eurocept.nl 

Eesti 
FrostPharma AB 
Tel: +46 775 86 80 02 
info@frostpharma.com 

Norge 
FrostPharma AB 
Tlf: +47 815 03 175 
info@frostpharma.com 
 

Ελλάδα 
Lucane Pharma 
Τηλ: + 33 153 868 750 
info@lucanepharma.com 

Österreich 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

 
España 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

 
Polska 

                  Lucane Pharma 
Tel.: + 33 153 868 750 
info@lucanepharma.com 



 

24 
 

France 
Lucane Pharma 
Tél: + 33 153 868 750 
info@lucanepharma.com 

Portugal 
Overpharma 
Tel: +351 214 307 760 
info@overpharma.pt 

Hrvatska 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

România 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Ireland 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Slovenija 
                  Lucane Pharma 

Tel: + 33 153 868 750 
info@lucanepharma.com 

Ísland 
FrostPharma AB 
Sími: +46 775 86 80 02 
E-mail: info@frostpharma.com 

Slovenská republika  
                      Lucane Pharma 

    Tel: + 33 153 868 750 
info@lucanepharma.com 

Italia 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

Suomi/Finland 
FrostPharma AB 
Puh/Tel: +35 875 32 51 209 
info@frostpharma.com 
 

Κύπρος 
Lucane Pharma 
Τηλ: + 33 153 868 750 
info@lucanepharma.com 

Sverige 
FrostPharma AB  
Tel: +46 775 86 80 02 
info@medicalneed.com 

Latvija 
FrostPharma AB 
Tel: +46 775 86 80 02 
info@frostpharma.com 

United Kingdom 
Lucane Pharma 
Tel: + 33 153 868 750 
info@lucanepharma.com 

 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
There are also links to other websites about rare diseases and treatments. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET