- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 3. PHARMACEUTICAL FORM
- 4. CLINICAL PARTICULARS
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. PHARMACOLOGICAL PROPERTIES
- 6. PHARMACEUTICAL PARTICULARS
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBER(S)
- 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
- 10. DATE OF REVISION OF THE TEXT
1.NAME OF THE MEDICINAL PRODUCT
GRANUPAS 4 g
2.QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains 4 g of
For the full list of excipients, see section 6.1.
The granules are small off white/ light brown coloured approximately 1.5mm diameter.
GRANUPAS is indicated for use as part of an appropriate combination regimen for
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2Posology and method of administration
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.
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 4g for young children.
The safety and efficacy of GRANUPAS in neonates have not been established. No data are available.
Desensitization can be accomplished by starting with 10 mg
Method of administration
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
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.
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 GRANUPAS. Patients with severe renal disease will accumulate the inactive acetyl metabolite of
4.4Special warnings and precautions for use
Mild to moderate renal impairment
Given that the metabolites of
GRANUPAS should be used with caution in patients with peptic ulcer.
GRANUPAS should be used with caution in patients with hepatic impairment.
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 adjustements for desensitization.
Hypothyroidism in HIV
Patients should be advised that the skeletons of the granules may be seen in the stools.
4.5Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with GRANUPAS.
Results from literature suggest the following:
Vitamin B12 absorption may be reduced by
A malabsorption syndrome can develop in patients on
This medicinal product decreases the gastrointestinal absorption of
No drug interaction studies have been conducted in patients with HIV infection taking antiretroviral agents and
4.6Fertility, pregnancy and lactation
There are no or limited data from the use of
Literature reports on para- aminosalicylic acid in pregnant women always report
There is no evidence available on the effect of
4.7Effects on ability to drive and use machines
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 availabledata). Within each frequency grouping, adverse reactions are presented in order of decreasingseriousness.
System Organ Class
Blood and lymphatic system
Thrombocytopenia, purpura, leukopenia,
anemia, methemoglobinemia, agranulocytosis
Metabolism and nutrition
Tendon pain, headache, visual abnormalities,
Nervous system disorders
peripheral neuropathy, dizziness
Giddiness, vestibular syndrome
abdominal pain, vomiting, nausea, bloating,
diarrhea, soft stools,
Malabsorption syndrome, peptic ulcer,
gastrointestinal bleeding, jaundice, metallic
Skin and subcutaneous tissue
Cutaneous hypersensitivity, skin rash
Renal and urinary disorders
Decreased prothrombine level, hepatocytolysis.
Increased blood alkaline phosphatase,
transaminases. weight loss
*Description of selected adverse reactions
Hypothyroidism in HIV
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.
No case of overdose in adults or paediatrics has been reported. Treatment is symptomatic and supportive.
Pharmacotherapeutic group: Antimycobacterials, drugs for treatment of tuberculosis ATC code:
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
GRANUPAS is a
Care must be taken in the administration of these granules to protect the
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 2µg/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.
Plasma protein binding is about 50 to 60%, the kinetic distribution has a
The major metabolites of PAS are produced by conjugation to glycine in
In a single dose study the plasma
The cumulative excretion of
5.3Preclinical safety data
The data available from a rat embrofetal 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 fetal weight was noted at the other doses. Other malformations were observed; however, the exact nature of these findings is unknown. The lack of a
Sodium aminosalicylic acid was not mutagenic in Ames test strain TA 100. In human lymphocyte cultures
6.1List of excipients
Colloidal silicon dioxide
Methacrylic acid – Ethyl acrylate Copolymer (1:1) Dispersion 30%
6.4Special precautions for storage
Do not store above 25°C.
The sachets can be stored below 25°C up to 24 hours after first opening.
6.5Nature 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.
6.6Special precautions for disposal and other handling
The granules should not be crushed or chewed.
DO NOT USE if sachet is swollen or if the granules have lost their light brown colour, and are turning dark brown or purple.
Any unused product or waste material should be disposed in accordance with local requirements.
7.MARKETING AUTHORISATION HOLDER
Lucane Pharma, 172 rue de Charonne 75011 Paris
8.MARKETING AUTHORISATION NUMBER(S)
9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 07 April 2014.
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.