Rosol tablets are indicated in:

• Treatment of the acute phase of mild or moderate ulcerative colitis.
• Maintenance treatment of remission in ulcerative colitis (including patients unable to tolerate salazosulphapyridine).
   

Posology
During the acute inflammatory phase and in long-term maintenance therapy, the patient must accurately follow the treatment established by the doctor to ensure the intended
therapeutic effect.
The dosage should be adjusted according to patient response. The following dosage is recommended:
Adults

•  Ulcerative colitis (acute phase): 1,5 – 4 g mesalazine/day, once daily or in divided doses. The dose of 4 g is recommended for patients who do not respond to lower doses of mesalazine. The effect of the treatment should be evaluated 8 weeks after initiation.
• Ulcerative colitis (maintenance of remission): 1,5 – 3 g mesalazine daily, once daily or in divided doses. The dose of 3 g is recommended for patients who do not respond to lower doses of mesalazine and for those who required higher doses during acute phase. In order to adjust the dosage another presentation with a lower dose is available: Rosol 500 mg gastroresistant tablets.

Elderly
Administration of Rosol to elderly patients must be performed with caution and always limited to patients with normal renal function.

Paediatric population
Rosol is not recommended for use in children under 5 years of age due to lack of data on efficacy and safety.

Method of administration
Oral use
The tablets must be administered before meals and must be taken whole with some fluid.
 

Administration of Rosol must be performed with caution in the following cases:

• Patients with severe liver or renal insufficiency. As 5-ASA is eliminated mainly by acetylation and subsequent urinary excretion, patients with impaired liver function or renal failure should be closely monitored, so it is advisable to perform liver and renal function tests before instituting treatment and regularly during it. Treatment should be stopped immediately if there is evidence of renal deterioration. In patients who develop renal impairment during treatment, mesalazine-induced nephrotoxicity should be suspected.
• There have been reports of increases in liver enzyme levels in patients taking preparations with mesalazine. Liver function should be evaluated before and during treatment according to medical criteria. Caution is advised if Rosol is given to patients with hepatic impairment.
• Patients with a history of hypersensitivity to sulfasalazine should be kept under close medical surveillance; In case of acute intolerance reactions, such as abdominal cramps, acute abdominal pain, fever, severe headache and rashes, treatment should be discontinued immediately.
• Patients with pulmonary diseases, particularly asthma, should be carefully monitored during treatment.
• Cardiac hypersensitivity reactions induced by mesalazine (myo- and pericarditis) have been rarely reported. Caution should be exercised when treating mesalazine with patients with conditions that predispose them to myocarditis or pericarditis. If there is a suspicion of a cardiac hypersensitivity reaction, products containing mesalazine should not be re-administered.
• In rare occasions, serious blood dyscrasias have been reported after treatment with mesalazine. Hematological investigations should be performed if patient suffering unexplained haemorrhages, bruises, purpura, anaemia, fever or pharyngolaryngeal pain. Treatment with Rosol should be discontinued in case of suspected blood dyscrasia (see 4.5).
• Caution is recommended when treating patients with active gastric or duodenal ulcer.
• Rosol tablets should not be administered concomitantly with lactose-type laxatives or the like, since it lowers the pH of the faeces and may prevent the release of the active ingredient.

Warnings about excipients
Rosol tablets contain 4.23 mmols (98 mg) of sodium per tablet, which has to be taken
into account by patients under low sodium die
 

In common with other salicylates, mesalazine can:

• Reduce the anticoagulant activity of anticoagulants derived from coumarin, such as warfarin.
• Enhance the glucose-lowering effects of sulfonylureas.
• Antagonize the uricosuric effects of probenecid and sulfinpirazone.
• Express the toxicity of salicylates at lower doses than usual when administered with furosemide due to competition for renal excretion sites.
• Increase the risk of adverse renal reactions with the concomitant use of known nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) and azathioprine.
• Increase the myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine. Caution is advised in patients treated with azathioprine, 6- mercaptopurine or thioguanine and mesalazine since it may increase the possibility of blood dyscrasias. The haematological parameters (especially leukocytes and thrombocytes) should be monitored regularly, especially at the beginning of such a therapeutic combination.
• Decrease the natriuretic effect of spironolactone.
• Mesalazine may delay the excretion of methotrexate.
• Lactose-type laxatives or similar can prevent the release of mesalazine from the tablet, which would reduce its effect (see section 4.4 Special warnings and special precautions for use).
   

No adequate data are available on the use of Rosol during pregnancy or lactation. As mesalazine is a salicylate, its use is not recommended during pregnancy or lactation, unless the benefit of treatment outweighs the possible risks
 

Rosol has no or not significant influence on the ability to drive or use machines.
 

The adverse reactions reported with mesalazine are listed below, classified by organ system MedDRA. The frequencies are defined as follows: Very frequent (1/10); frequent
(1/100, <1/10); low frequency (1/1000, <1/100); rare (1/10.000 and <1/1.000); very rare (<1/10.000) and unknown (it can be determined from the available data).
The following adverse reactions have been described on rare occasions:
Blood and lymphatic system disorders: leukopenia, neutropenia, thrombocytopenia, aplastic anaemia.
Immune system disorders: Hypersensitivity reactions, including pulmonary and cardiac changes: fever, myalgia, arthralgia, alveolitis, myocarditis, pericarditis.
Central nervous system disorders: headache, neuropathy.
Gastrointestinal system disorders: nausea, abdominal pain, diarrhoea, pancreatitis.
Hepatobiliary disorders: transient liver enzyme increases, hepatitis.
Skin and subcutaneous tissue disorders: reddening (including itching and hives), local irritation (rectal forms), photo sensibility*.
With unknown frequency it has been described the appearance of multiform eritema,
Stevens-Johnson syndrome and necrolysis toxic epidermal.
Renal and urinary system disorders: renal disorders, acute and chronic interstitial nephritis, renal failure.
In very rare occasions, exacerbation of symptoms of colitis has been reported.

* More severe reactions have been reported in patients with pre-existing skin
conditions, such as atopic dermatitis and atopic eczema.
 

In case of massive intake of tablets, the treatment includes gastric lavage, inducing vomiting, together with symptomatic treatment and support measures. There is no specific antidote.

To report any side effect (s):
The National Pharmacovigilance and Drug Satefy Centre (NPC):
- Fax: +966-11-205-7662
- SFDA Call Center: 19999
- Toll free phone: 8002490000
- E-mail: npc.drug@sfda.gov.sa
- Website: www.sfda.gov.sa./npc
 

Pharmacotherapeutic group: Aminosalicilic acid and similar, code ATC: A07EC02

Mesalazine is one of the two components of sulfasalazine, the other being sulphapyridine. While mesalazine is the active fraction, sulphapyridine is responsible for most adverse events associated with therapy with sulfasalazine.

Mechanism of action
Although the anti-inflammatory mechanism of action of 5-ASA is unknown, several possibilities are considered:

•  Inhibition of prostaglandin synthesis (cyclooxygenase inhibition pathway), reducing inflammatory prostaglandin output.
•  Inhibition of chemotactic leukotriene synthesis (lipooxygenase inhibition pathway), therefore reducing inflammation.
•  Inhibition of chemotaxis of macrophages and neutrophils in the swollen tissue.

The most recent data suggest that 5-ASA is a biological antioxidant and its activity is based on the uptake of oxygen free radicals. In this activity, 5-ASA differs from sulfasalazine, sulphapyridine, N-acetyl-5-ASA (Ac-5-ASA) and other salicylates.
 

Absorption
The peak plasma levels with the retard release forms are obtained at 5 hours postadministration. Recovery (at the highest dose) in urine (44%) and faeces (35%) shows that 5- ASA is available for its local and systemic action. In fasting healthy subjects, the peak plasma concentration of 1.3 µg/ml and 2.3 µg/ml of 5-ASA and Ac-5-ASA respectively was obtained at 6 hours post-administration.
Acetylation
Acetylation of 5-ASA occurs in the liver and the colon wall, regardless of the acetylator status. It appears that the acetylation process is saturable; however, at therapeutic doses (250-500 mg) neither the peak plasma concentration nor the area under the curve of plasma concentration vs. time for 5-ASA evidenced any deviation from linearity of the dose in the steady state.
Clearence
After oral administration, 5-ASA is cleared at a high percentage as Ac-5-ASA both in urine and in faeces. In fact, over 90% of the drug identified in urine is in metabolite form. After rectal administration, 5-ASA is cleared mainly unchanged in faeces.
 

Non clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenic and toxicity to reproduction and development.
 

Sodium carbonate, anhydrous
Glycine
Povidone
Cellulose, microcrystalline
Croscarmellose sodium
Silica, colloidal anhydrous
Calcium stearate
Copolymer Methacrylic acid - ethyl acrylate (1:1) (Eudragit L 30D)
Copolymer Methacrylic acid - methyl methacrylate (1:1) (Eudragit L 12.5 P)
Copolymer Methacrylic acid - methyl methacrylate (1:2) (Eudragit S 12.5 P)
Dibutyl sebacate
Talc
Titanium dioxide (E-171)
Polyethylenglycol 6000
Yellow iron oxide (E-172)
Red iron oxide (E-172)
Isopropilic alcoo
 

Not applicable
 

Store Below 30^oC
 

Rosol 1 g is presented in blisters of AquaBa® 130/AL, containing 100 gastroresistant tablets.
 

Disposal of this medicinal product not used and all the materials in contact with it, must be performed according to local regulations