SULFASALAZIN EN 50CPR 500MG Produttore: KRKA FARMACEUTICI MILANO SRL

DENOMINAZIONE

SULFASALAZIN KRKA 500 MG

CATEGORIA FARMACOTERAPEUTICA

Antidiarrheals, intestinal anti-inflammatory/anti-infective agents, aminosalicylic acid and similar agents.

PRINCIPI ATTIVI

Each film-coated tablet contains 500 mg sulfasalazine. Each gastro-resistant tablet contains 500 mg sulfasalazine.

ECCIPIENTI

Film-coated tablets. Tablet core: povidone (E1201), pregelatinised starch, magnesium stearate (E470b), colloidal anhydrous silica (E551). Film coating: hypromellose (E464), propylene glycol (E1520). Gastro-resistant tablets. Tablet core: povidone (E1201), pregelatinised starch, magnesium stearate (E470b), colloidal anhydrous silica (E551). Coating: methacrylic acid - ethyl acrylate copolymer (1:1), talc (E553b), titanium dioxide (E171), yellow iron oxide (E172), triethyl citrate (E1505), carmellose sodium (E466), macrogol 6000.

INDICAZIONI

The drug is indicated for: treatment of acute onsets and exacerbations of Crohn's disease, ulcerative colitis and proctitis, maintenance ofremission of ulcerative colitis and proctitis, treatment of rheumatoid arthritis and juvenile idiopathic chronic polyarthritis which have failed to sufficiently respond to nonsteroidal anti-inflammatory drugs.This drug can be combined with corticosteroids and metronidazole.

CONTROINDICAZIONI/EFF.SECONDAR

Hypersensitivity to the active substance, sulphonamides, salicylates or to any of the excipients. The drug should not be taken by patients with acute porphyria and patients with granulocytopenia. The drug is not recommended for use in children under 2 years of age with chronic inflammatory bowel disease and children under 6 years of age with juvenile idiopathic chronic polyarthritis because the safety and efficacy of treatment have not been established. It is also not recommended in the systemic form of juvenile idiopathic chronic polyarthritis because it may often cause undesirable effects, including serum sickness-like condition.

POSOLOGIA

Posology: dosage should be adjusted according to the severity of the disease and possible undesirable effects. Acute onset of ulcerative colitis and proctitis, and Crohn's disease: adults and children over 16 years of age should take 2 to 4 tablets (1 g to 2 g) 4 times a day. Children over 2 years of age can be given 40 mg to 60 mg of the drug perkg body weight a day. With the induction of remission, the dose should be gradually reduced. Maintenance of remission of ulcerative colitisand proctitis: the recommended maintenance dose for adults and children over 16 years of age is 1 tablet (500 mg) 4 times a day. Children over 2 years of age can be given 20 mg to 30 mg sulfasalazine per kg body weight a day. The duration of maintenance treatment is not limited.Rheumatoid arthritis and juvenile idiopathic chronic polyarthritis: the recommended dose for adults and children over 16 years of age is 2 g to 3 g a day. Treatment should be started with 1 tablet (500 mg) of sulfasalazine a day. The dose should be increased gradually, at weeklyintervals, so that after 4 weeks 2 tablets (1 g) are taken 2 to 3 times a day. The clinical effect will presumably be seen in 6 to 10 weeksof treatment. The drug should be taken for at least 6 months. Children over 6 years of age can be given 30 mg to 50 mg sulfasalazine per kgbody weight a day in two or three divided doses. Treatment should be started with 1/3 or 1/4 of the recommended maintenance dose, e.g. with1 tablet in the evening. The dose of sulfasalazine should be increased gradually, at weekly intervals, until the recommended dose is achieved. The maximum daily dose must not exceed 2 g (4 tablets). Special patient groups. Use in elderly patients: normal adult doses of sulfasalazine are recommended. Use in patients with renal insufficiency: caution should be used in patients with renal insufficiency (creatinine clearance less than 60 ml/min). Normal adult doses of sulfasalazine are recommended. Prior to treatment and occasionally during the treatment, aurine test is recommended. Good hydration of the patient should be provided during the treatment. Use in patients with hepatic insufficiency: caution should be used in patients with hepatic insufficiency. Normal adult doses of sulfasalazine are recommended. Method of administration: the tablets should be taken during a meal with a glass of liquid.The gastro-resistant tablets should be swallowed whole as their coating reduces gastrointestinal undesirable effects. A missed dose should be taken as soon as possible unless it is nearly time for the next dose. In this case, only the next dose should be taken at the usual time.

CONSERVAZIONE

Do not store above 25 degrees C.

AVVERTENZE

Prior to treatment with sulfasalazine and occasionally during the treatment (once to twice monthly at the beginning, then every 3 to 6 months), blood tests (complete blood count) and urine tests are recommended. Good hydration of the patient should be provided during the treatment. During treatment with sulfasalazine, special attention should be paid to patients with renal insufficiency (creatinine clearance less than 60 ml/min) or hepatic insufficiency, bronchial asthma and allergy (cross hypersensitivity to furosemide, thiazide diuretics, sulfonylureaderivatives and carbon anhydrase inhibitors is possible). In milder forms of allergy to sulfasalazine, the patient can be desensitised. Life-threatening skin reactions, i.e. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported during the use ofthis drug. Patients should be advised of the signs and symptoms of SJS and TEN and closely monitored for skin reactions. The highest risk for the occurrence of SJS or TEN is within the first weeks of treatment. If symptoms or signs of SJS or TEN (e.g. progressive skin rash oftenwith blisters or mucosal lesions) occur, treatment with this drug should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. If a patient has developed SJS or TEN with the use of this drug, this drug must not be re-started in this patient at any time. Interference with laboratorytesting: sulfasalazine or its metabolites may interfere with ultraviolet absorbance, particularly at 340 nm, and may cause interference with some laboratory assays that use NAD(H) or NADP(H) to measure ultraviolet absorbance around that wavelength. Examples of such assays may include urea, ammonia, LDH, alfa-HBDH and glucose. It is possible that alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK-MB), glutamate dehydrogenase (GLDH), or thyroxine may also show interference when sulfasalazine treatment is given at high doses. Consult with the testing laboratory regarding the methodology used. Caution should be exercised in the interpretation of these laboratory results in patients who are receiving sulfasalazine. Results should be interpreted in conjunction with clinical findings. Sodium: this medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

INTERAZIONI

Sulfasalazine reduces the absorption of folic acid and digoxin. When administered concomitantly with anticoagulants or sulphonamide hypoglycaemics, it potentiates their effect.

EFFETTI INDESIDERATI

Undesirable effects of sulfasalazine are mainly associated with high concentrations of sulfapyridine in the blood, especially in people in whom its degradation is slower (slow acetylators). Undesirable effectsare more common in patients with rheumatoid arthritis. Undesirable effects that may occur during treatment with sulfasalazine are classified into the following groups in order of frequency: 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, undesirable effects are presented in order of decreasing seriousness. Frequency of undesirable effects listed by individual organ systems. Blood and lymphatic system disorders. Common: leukopenia, neutropenia, macrocytosis; uncommon: megaloblastic anaemia, haemolytic anaemia, agranulocytosis, thrombocytopenia; very rare: aplastic anaemia, methaemoglobinaemia, heinz body anaemia, hypoprothrombinaemia, lymphadenopathy, eosinophilia. Immune system disorders. Very rare: serum sickness, generalised skin rash, exanthema multiforme, exfoliative dermatitis, photosensitivity reactions, drug-induced fever, periorbital oedema, polyarteritis nodosa of the conjunctiva or cornea, urticaria, pruritus, redness. Metabolism and nutrition disorders. Common: anorexia; uncommon: in patients with porphyria, sulfasalazine may cause an acute outbreak of the disease. Psychiatric disorders. Uncommon: depression, insomnia; rare: hallucinations. Nervous system disorders. Common: headache; rare: peripheral neuropathy, vertigo, convulsions, ataxia; very rare: aseptic meningitis. Ear and labyrinth disorders. Uncommon: tinnitus. Respiratory, thoracic and mediastinal disorders. Rare: pulmonary infiltrates, dyspnoea, cough; very rare: fibrosing alveolitis. Gastrointestinal disorders. Common: nausea, vomiting; uncommon: diarrhoea, stomatitis, parotitis; rare: pancreatitis. Hepatobiliary disorders. Rare: hepatitis; the urine, skin or soft contact lenses may become orange-yellow.Renal and urinary disorders. Rare: nephrotic syndrome, haematuria, proteinuria, crystalluria. Skin and subcutaneous tissue disorders. Very rare: severe cutaneous adverse reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported. Reproductive system and breast disorders. Uncommon: reversible oligospermia, reversible male infertility. Investigations. Uncommon: increased levels of serum amylase, bilirubin, alkaline phosphatase and hepatic transaminases. If severe undesirable effects occur, treatment should be discontinued. 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 to: Javna agencija Republike Slovenije za zdravila in medicinske pripomocke Sektor za farmakovigilanco Nacionalni center za farmakovigilanco Slovenceva ulica 22 SI-1000 Ljubljana.

GRAVIDANZA E ALLATTAMENTO

Pregnancy: data on a limited number of exposed pregnancies indicate no adverse effects of sulfasalazine on pregnancy or on the health of the foetus/newborn child. To date, there are no other relevant epidemiological data available. The drug should be prescribed to pregnant womenwith caution. Sulfasalazine should be used during pregnancy only if clearly needed and at the lowest effective dose. Sulfasalazine is not recommended for use in the last trimester of pregnancy; in the newborn,it can compete with bilirubin for binding sites on the plasma proteins and cause kernicterus. In newborns with glucose-6-phosphate dehydrogenase deficiency, it can cause haemolytic anaemia. Breast-feeding: a very small quantity of sulfasalazine is excreted into breast milk; therefore, the possibility of kernicterus in a healthy newborn is negligible, which is also confirmed by experience. Difficulties could arise inpremature infants or other newborns at risk. The situation with sulfapyridine is different. Its concentrations achieved in milk are about 40% of plasma concentrations; however, sulfapyridine is only moderatelybound to plasma proteins. Since the effects of sulfasalazine on breast-fed infants have not been sufficiently investigated, concomitant breast-feeding and treatment is not recommended.