Sulfasalazine krka

Patient Information Leaflet

Sulfasalazin Krka, 500 mg, coated tablets
Sulfasalazinum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Sulfasalazin Krka is and what it is used for
2. Important information before taking Sulfasalazin Krka
3. How to take Sulfasalazin Krka
4. Possible side effects
5. How to store Sulfasalazin Krka
6. Contents of the pack and other information

1. What Sulfasalazin Krka is and what it is used for

Sulfasalazin Krka is an anti-inflammatory medicine.
Sulfasalazin Krka is a compound of 5-aminosalicylic acid and sulfapyridine. A smaller portion of sulfasalazine is absorbed in the colon and mainly deposited in connective tissue. The majority of the drug is broken down into 5-aminosalicylic acid and sulfapyridine, which reduce inflammation.
Sulfapyridine reduces systemic inflammatory response; the anti-inflammatory effect of 5-aminosalicylic acid occurs only in the colon due to its poor absorption. Sulfasalazin Krka does not have analgesic effect.
Sulfasalazin Krka is used in the treatment of:

• Rheumatoid arthritis resistant to treatment with non-steroidal anti-inflammatory drugs,
• Inflammatory bowel diseases (e.g. ulcerative colitis, Crohn's disease).

2. Important information before using Sulfasalazin Krka

Inform your doctor about any chronic diseases, metabolic disorders,
hypersensitivity (allergy) to other medicines, and about any other medicines you are taking.

When not to use Sulfasalazin Krka:

• if the patient is allergic to sulfasalazine or to any of the other ingredients of this medicine (listed in section 6),
• if the patient is allergic to sulfonamides and salicylates,
• if the patient has acute intermittent porphyria or mixed porphyria,
• if the patient has urinary or intestinal obstruction,
• in children under 2 years of age.

Warnings and precautions

Before starting treatment with Sulfasalazin Krka, discuss this with your doctor or pharmacist if:

• the patient suffers from severe allergy and/or bronchial asthma;
• the patient has glucose-6-phosphate dehydrogenase deficiency, as this may lead to hemolytic anemia;
• the patient has impaired kidney or liver function, or abnormal blood counts.

During treatment, drink plenty of fluids due to the risk of kidney stone formation.
Inform your doctor if you are taking or have recently taken Sulfasalazin Krka or other medicines containing sulfasalazine, as they may affect blood and urine test results.
Before starting treatment, your doctor may recommend baseline blood tests, including white blood cell differential and liver function tests, and then repeat these tests every 2 weeks during the first 3 months of treatment.
For the next 3 months, monitoring should be performed every 4 weeks, and thereafter every 3 months or whenever clinically indicated.
Kidney function assessment (including urine analysis) should be performed in all patients at the beginning of treatment and at least once a month during the first 3 months. Subsequently, monitoring should be performed when clinically indicated.
The appearance of clinical symptoms such as sore throat, fever, pallor, purpura, or jaundice during sulfasalazine treatment may indicate bone marrow suppression, hemolysis, or hepatotoxicity. Treatment with sulfasalazine should be discontinued while awaiting blood test results.
During treatment with Sulfasalazin Krka, potentially life-threatening skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been observed. These initially appear as red, target-like lesions or circular spots, often with centrally located blisters. Additional symptoms may include ulceration of the mouth, throat, nose, or genital organs, and conjunctivitis (red, swollen eyes). These life-threatening skin reactions are often accompanied by influenza-like symptoms. As the condition progresses, extensive blisters or shedding of large areas of skin may develop.
The highest risk of serious skin reactions occurs during the first weeks of treatment.
If the patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking Sulfasalazin Krka, treatment with this medicine must never be resumed.
If the patient develops a rash, mucosal lesions, other hypersensitivity symptoms, or any of the mentioned skin symptoms, immediate medical consultation is required, and the doctor must be informed about the use of this medicine.
During treatment with Sulfasalazin Krka, severe, life-threatening systemic hypersensitivity reactions have been reported, such as drug rash with eosinophilia and systemic symptoms (DRESS).
Note that early signs of hypersensitivity may appear even in the absence of a rash.

Sulfasalazin Krka and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Sulfasalazin Krka may:

• reduce the absorption of digoxin (used in the treatment of heart failure and atrial fibrillation);
• reduce the absorption of folic acid (recommended by a doctor as a dietary supplement), leading to folic acid deficiency.

Concomitant oral administration of sulfasalazine and mercaptopurine (used in the treatment of certain leukemias and autoimmune diseases, i.e. conditions in which the immune system attacks the body's own tissues) or azathioprine (used in transplantation and autoimmune disease treatment) may cause bone marrow dysfunction and leukopenia (decreased white blood cell count).

Sulfasalazin Krka with food and drink

Take tablets during meals, with a glass of water. Swallow the tablets whole; do not crush or break them.
During treatment, drink large amounts of fluids.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Since the risk associated with using this medicine during pregnancy cannot be excluded, sulfasalazine should be used in pregnant women only if absolutely necessary.
The medicine may reduce sperm count and motility, which may affect fertility. This effect is usually reversible after discontinuation of treatment.
Sulfasalazine and sulfapyridine pass into breast milk in small amounts. This is not expected to pose a risk to a healthy infant.
Caution is advised in preterm infants and newborns with physiological jaundice. Bloody stools or diarrhea have been reported in infants breastfed by mothers taking sulfasalazine. In these cases, bloody stools or diarrhea in infants resolved after the mother discontinued sulfasalazine.

Driving and operating machinery

No effect of Sulfasalazin Krka on the ability to drive or operate machinery has been observed.

3. How to use Sulfasalazin Krka

This medicine should always be taken exactly as directed by your doctor. If in doubt, consult your
doctor or pharmacist. Do not change the dose or stop treatment without
consulting your doctor.
The tablets should be swallowed whole; do not chew or crush them. This helps to
reduce gastrointestinal side effects. The tablets should be taken during meals with a
glass of water.
Rheumatoid arthritis
Adults and elderly patients
The recommended dose is from 1 g to 3 g per day. The most commonly used dose is 2 tablets twice
daily. Treatment is started at lower doses, which are gradually increased according to the scheme
shown in the table below.

If after 2-3 months the doctor determines that the patient's response to treatment is unsatisfactory, the daily dose of sulfasalazine may be increased up to a maximum of 3 g.
In patients who have experienced adverse effects, the dose may be temporarily reduced.

Inflammatory bowel diseases (i.e. ulcerative colitis, Crohn's disease)
The doctor will recommend an appropriate dose depending on the clinical condition, the patient's tolerance to the medication, and response to treatment.
It is recommended that in patients who have never previously been treated with sulfasalazine, the dose should be gradually increased (over several weeks). The daily dose should be evenly divided into multiple doses.

Acute phase of the disease
Adults and elderly patients
Severe exacerbations: 2 to 4 tablets 3 to 4 times daily (3 g to 8 g daily).
Mild and moderate flare-ups: 2 tablets 3 to 4 times daily.

Children
40–60 mg/kg body weight/day in 3 to 6 divided doses.

Maintenance treatment
Adults and elderly patients
The recommended maintenance dose for patients with ulcerative colitis or Crohn's disease in remission is 2 tablets 2 to 3 times daily. Treatment with this dose should not be interrupted and should be continued long-term unless adverse reactions occur. In case of disease flare-up, the doctor may decide to increase the dose to 2 to 4 tablets administered 3 to 4 times daily.

Children
20–30 mg/kg body weight/day in 3 to 6 divided doses.

If you feel that the effect of the medicine is too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Sulfasalazin Krka
If you take more medicine than recommended, contact your doctor or pharmacist immediately.
Symptoms of overdose may include: nausea, vomiting, crystalluria (formation of crystals in urine), hematuria, oliguria and anuria, hypoglycemia, methemoglobinemia (loss of hemoglobin's ability to carry oxygen) in rare cases, cyanosis, hepatic symptoms, and sulfhemoglobinemia. Hypersensitivity reactions such as blood count abnormalities (including potentially fatal agranulocytosis—lack of certain white blood cells, granulocytes), urticaria, polyneuritis, and central nervous system symptoms may also occur.
If a higher than recommended dose of Sulfasalazin Krka has been taken, contact your doctor. Depending on the symptoms present, the doctor will initiate appropriate treatment.

Missed dose of Sulfasalazin Krka
Do not take a double dose to make up for a missed dose.
A missed dose should be taken as soon as possible, unless it is almost time for the next scheduled dose. In that case, wait and take only one dose at the correct time.

Discontinuation of Sulfasalazin Krka
The decision to discontinue treatment should be made by the doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Most of the adverse reactions caused by Sulfasalazin Krka are mild in nature.
Adverse reactions usually resolve spontaneously, after dose reduction or discontinuation of treatment.
Adverse reactions of sulfapyridine are primarily related to its blood concentration,
especially in patients in whom its metabolism is slower.

Common adverse reactions (may occur in up to 1 in 10 patients):

• leukopenia (reduced number of white blood cells in peripheral blood),
• loss of appetite,
• dizziness, headache, taste disturbances,
• tinnitus,
• cough,
• abdominal pain, diarrhoea, flatulence, vomiting,
• itching,
• joint pain,
• proteinuria (presence of protein in urine),
• fever.

Uncommon adverse reactions (may occur in up to 1 in 100 patients):

• thrombocytopenia (reduced number of platelets in the blood),
• depression,
• dyspnoea (difficulty breathing),
• alopecia, urticaria,
• facial swelling,
• increased liver enzyme activity.

Rare adverse reactions (may occur in up to 1 in 1,000 patients):

• nail changes,
• jaundice.

Very rare adverse reactions (may occur in up to 1 in 10,000 patients):

• potentially life-threatening skin rashes: toxic epidermal necrolysis (Lyell's syndrome) – a condition characterized by large flaccid blisters on erythematous areas (especially in pressure-prone areas), which quickly rupture, resulting in extensive erosions;
  bullous erythema multiforme (Stevens-Johnson syndrome, fever, severe rash with blistering of mucous membranes) (see section 2).

Adverse reactions with unknown frequency (cannot be estimated from the available data):

• aseptic meningitis, pseudomembranous colitis,
• agranulocytosis (complete or near-complete absence of granulocytes in the blood), aplastic anaemia (failure of the bone marrow to produce new red or white blood cells), haemolytic anaemia (abnormal premature destruction of red blood cells), macrocytosis (excessive enlargement of red blood cells), megaloblastic anaemia (anaemia due to vitamin B12 or folic acid deficiency), pancytopenia (reduction in the number of all cellular blood components: red blood cells, white blood cells and platelets),
• anaphylactic shock (severe allergic reaction)* (symptoms of anaphylactic shock include: rapidly worsening general condition, itching, urticaria, pale and clammy skin, rapid and shallow breathing, dyspnoea, tachycardia, significant drop in blood pressure, vomiting, diarrhoea, swelling of the throat and tongue, disturbances of consciousness), serum sickness (allergic systemic reaction to intravenously administered heterologous serum or medication),
• encephalopathy (brain function disturbances), peripheral neuropathy (peripheral nerve disorders), disturbances of smell,
• pericarditis, cyanosis,
• fibrosing alveolitis, interstitial lung disease*, eosinophilic infiltrates,
• exacerbation of symptoms in ulcerative colitis, pancreatitis,
• liver failure*, fulminant hepatitis*, hepatitis,
• drug-induced eosinophilia with systemic symptoms*, angioedema*, toxic pustular dermatitis, erythema, rash, exfoliative dermatitis, lichen planus, photosensitivity,
• systemic lupus erythematosus (chronic autoimmune disease leading to damage of various organs, particularly skin, joints, blood and kidneys), Sjögren's syndrome,
• nephrotic syndrome (syndrome of symptoms caused by excessive loss of protein in urine), interstitial nephritis, crystals in urine, haematuria,
• transient oligospermia (low sperm count in male semen),
• yellow discoloration of skin and body fluids*,
• induction of autoantibodies.

*Adverse reactions identified after marketing.
Severe adverse reactions occur very rarely, but may be serious enough for the physician to recommend discontinuation of treatment.
If any of the following symptoms occur: itching, rash, difficulty breathing or swallowing, swelling of eyelids, face or other body parts, unexplained fever or chills, sore throat, cough, unusual fatigue, pallor, severe abdominal pain, jaundice, skin bleeding, unusual bruising, or central nervous system disturbances (dizziness, tinnitus, uncoordinated movements, seizures, insomnia and hallucinations), contact your doctor immediately.

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected].
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Sulfasalazin Krka

Keep the medicine out of the sight and reach of children.
Store below 25 °C.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This helps protect the environment.

6. Contents of the pack and other information

What Sulfasalazin Krka contains

• The active substance is sulfasalazine. Each coated tablet contains sulfasalazine in the form of granules with povidone, equivalent to 500 mg of sulfasalazine.
• Other ingredients are: maize starch gelatinised, magnesium stearate, colloidal anhydrous silica, hypromellose, propylene glycol.

What Sulfasalazin Krka looks like and contents of the pack
Round, slightly biconvex coated tablets, brownish-yellow in colour.
Pack: 50 coated tablets in blisters, packed in a cardboard box.
Marketing Authorisation Holder and Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For further information, contact the local representative of the Marketing Authorisation Holder:
Krka Polska Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Poland
telephone: + 48 22 573 75 00