Salofalk enteric-coated tablets 500 mg No. 100

Instructions for Salofalk enteric-coated tablets 500 mg No. 100

Composition

active ingredient: mesalazine;

1 tablet contains 250 mg of mesalazine (5-aminosalicylic acid);

excipients: sodium carbonate anhydrous, glycine, povidone (K25), microcrystalline cellulose, colloidal anhydrous silica, calcium stearate, hypromellose, methacrylate copolymer (type A), talc, titanium dioxide (E 171), iron hydroxide yellow (E 172), macrogol 6000, acrylate copolymer.

1 tablet contains 500 mg of mesalazine (5-aminosalicylic acid);

excipients: sodium carbonate anhydrous, glycine, povidone (K25), microcrystalline cellulose, colloidal anhydrous silica, calcium stearate, croscarmellose sodium, hypromellose, methacrylate copolymer (type A), talc, titanium dioxide (E 171), iron hydroxide yellow (E 172), macrogol 6000, acrylate copolymer.

Dosage form

The film-coated tablets are enteric-coated.

Main physicochemical properties:

250 mg: butter-yellow to ochre-colored, smooth, round tablets with an unpolished surface;

500 mg: oil-yellow to ocher-colored, non-glossy tablets, oblong in shape, with a smooth surface without noticeable cracks.

Pharmacotherapeutic group

Gastrointestinal tract and metabolism. Antidiarrheals, intestinal anti-inflammatory/antimicrobial drugs. Intestinal anti-inflammatory drugs. Aminosalicylic acid and similar agents. Mesalazine.

ATX code A07ES02.

Pharmacological properties

Pharmacodynamics

The mechanism of anti-inflammatory action is unknown. In vitro studies suggest that inhibition of lipoxygenase may play a role.

An effect on prostaglandin concentrations in the intestinal mucosa has also been demonstrated.

Mesalazine (5-aminosalicylic acid/5-ASA) can bind free radicals.

Mesalazine, when taken orally, acts predominantly locally on the intestinal mucosa and submucosal tissue from the intestinal cavity. It is therefore important that mesalazine is available in areas of inflammation. Systemic bioavailability and plasma concentrations are therefore not essential for the therapeutic effect, but rather are factors of safety. Salofalk tablets are resistant to gastric juice, and mesalazine is released from them depending on the pH of the environment due to the Eudragit L coating.

Preclinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, genotoxicity, carcinogenicity (in rats) or toxicity to reproduction.

Renal toxicity (renal papillary necrosis and epithelial damage in the proximal tubule (Pars convoluta) or the entire nephron) has been observed in toxicity studies with repeated high oral doses of mesalazine. The clinical significance of these findings is unknown.

Pharmacokinetics

General properties of mesalazine

Absorption

Absorption of mesalazine is highest in the proximal part of the intestine and lowest in its distal part.

Biotransformation

Mesalazine is metabolized both presystemically in the intestinal mucosa and in the liver to the pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Acetyl-5-aminosalicylic acid). Acetylation is apparently independent of the acetylation phenotype of the patient. Some acetylation also occurs by the action of bacteria in the large intestine. The protein binding of mesalazine and N-Acetyl-5-aminosalicylic acid is 43% and 78%, respectively.

Excretion

Mesalazine and its metabolite N-Ac-5-ASA are excreted in the faeces (major part), renally (varying between 20 and 50% depending on the type of administration, pharmaceutical form and route of release of mesalazine) and biliary (minor part). Renal excretion occurs mainly in the form of N-Ac-5-ASA. About 1% of the total orally administered dose of mesalazine is excreted in breast milk, mainly in the form of N-Ac-5-ASA.

Features of Salofalk 250 mg tablets

Distribution

A combined pharmaco-scintigraphic/pharmacokinetic study showed that Salofalk 250 mg tablets dissolve in the ileum after approximately 3-4 hours when taken with food. The mean residence time in the stomach is approximately 3 hours. The tablets reach the colon after approximately 7 hours.

In a subsequent study in volunteers, the duodeno-ileal transit time was approximately 3 hours, while the maximum concentration of 5-ASA in the ileal lumen was measured 7-8 hours after taking the tablets with food. Approximately 75% of the mesalazine dose reaches the large intestine in an unmetabolized form.

Absorption

The release of mesalazine from Salofalk 250 mg tablets begins after a lag phase of about 3-4 hours. Peak plasma concentrations are reached after about 5 hours (ileocecal region) and are 2.1 ± 1.7 μg/ml for mesalazine and 2.8 ± 1.7 μg/ml for the metabolite N-Ac-5-ASA at steady state with 3 × 500 mg mesalazine per day (3 × 2 tablets of Salofalk 250 mg).

During long-term treatment with Salofalk 250 mg tablets with a dose of 500 mg mesalazine three times a day (under steady-state conditions), the total renal excretion rate of mesalazine and N-Ac-5-ASA was approximately 55% (24 hours after the last dose). The fraction of unmetabolized mesalazine was approximately 5%. The elimination half-life was 0.7-2.4 hours (mean 1.4 ± 0.6 hours) at a dose of 500 mg mesalazine three times a day.

Features of Salofalk 500 mg tablets

Distribution

A combined pharmaco-scintigraphic/pharmacokinetic study showed that Salofalk 500 mg tablets dissolve in the ileum after approximately 3-4 hours and in the descending colon after approximately 4-5 hours. The total transit time through the large intestine is approximately 17 hours.

Absorption

The release of mesalazine from Salofalk 500 mg enteric-coated tablets begins after a lag phase of about 3-4 hours. Peak plasma concentrations are reached after about 5 hours (ileocecal region) and are 3.0 ± 1.6 μg/ml for mesalazine and 3.0 ± 1.6 μg/ml for mesalazine at steady state with 3 × 500 mg mesalazine per day (3 × 1 tablet of Salofalk 500 mg).

3.4 ± 1.6 μg/ml for the metabolite N-Ac-5-ASA.

Breeding

With multiple administration (3 × 1 tablet of Salofalk 500 mg for 2 days; 1 enteric-coated tablet on the third day = study day), the total renal excretion rate of mesalazine and N-Ac-5-ASA over 24 hours was approximately 60%. The fraction of unmetabolized mesalazine after oral administration was approximately 10%.

Indication

Ulcerative colitis: treatment of exacerbations and prevention of relapses.

Crohn's disease: treatment of exacerbations.

Contraindication

Hypersensitivity to mesalazine, to any of the components of the drug or to salicylates, gastric and duodenal ulcer in the acute stage, severe hepatic and/or renal failure, hemorrhagic diathesis.

Interaction with other medicinal products and other types of interactions

No specific drug interaction studies have been conducted.

During complex treatment with Salofalk and azathioprine, 6-mercaptopurine or thioguanine, some studies have shown a higher frequency of myelosuppressive effects, which supposedly indicates the presence of an interaction, but the mechanism of interaction is not fully established. It is recommended to regularly monitor the level of leukocytes, and the dosage regimen of thiopurines should be adjusted.

There is evidence that mesalazine may reduce the anticoagulant effect of warfarin.

Possible enhancement of the hypoglycemic effect of sulfonylurea derivatives, toxic effects of methotrexate. The activity of furosemide, spironolactone, sulfonamides, rifampicin, uricosuric drugs (probenecid and sulfinpyrazone) may be weakened. Mesalazine may potentiate the undesirable effect of glucocorticoids on the gastric mucosa, reduce the absorption of digoxin.

Application features

Before and during treatment, blood tests (complete blood count; liver function tests such as ALT or AST; serum creatinine) and urine tests (test strips, sediment) should be performed at the discretion of the physician. It is recommended to perform monitoring 14 days after the start of treatment, then two to three times at 4-week intervals.

If the test results are normal, routine checkups every 3 months are sufficient. If other additional symptoms develop, tests should be done urgently.

It should be used with caution in patients with impaired liver function.

Salofalk should be used with caution in patients with impaired renal function. It is necessary to regularly monitor renal function, namely, measure the level of blood urea nitrogen, creatinine in patients with proteinuria.

Cases of nephrolithiasis, including the formation of stones with a 100% mesalazine content, have been reported with the use of mesalazine. It is recommended to ensure adequate fluid intake during treatment.

If renal function deteriorates during treatment, mesalazine-induced renal toxicity should be considered.

Patients with lung diseases, in particular asthma, should be under the supervision of a doctor during the course of treatment with Salofalk tablets.

Adverse severe skin reactions

Severe skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment. Mesalazine should be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions or any other signs of hypersensitivity.

Patients who have had hypersensitivity reactions, including convulsions, acute abdominal pain, fever, severe headache and rash, to sulfasalazine-containing products should be observed from the start of treatment with Salofalk tablets. If acute intolerance reactions, such as convulsions, acute abdominal pain, fever, severe headache and rash, occur, therapy should be discontinued immediately.

Salofalk 250 mg tablets. 1 Salofalk enteric-coated tablet contains 48 mg sodium, equivalent to 2.4% of the WHO recommended maximum daily intake of sodium. The maximum daily dose of this medicine is equivalent to 42.9% of the WHO recommended maximum daily intake of sodium. Salofalk tablets are considered to be high in sodium. This should be taken into account by patients on a controlled sodium diet (low-salt diet).

There is no need to reduce the dosage for elderly patients.

Salofalk 500 mg tablets. 1 Salofalk enteric-coated tablet contains 2.1 mmol 49 mg sodium, equivalent to 2.5% of the WHO recommended maximum daily intake of sodium. The maximum daily dose of this medicine is equivalent to 22% of the WHO recommended maximum daily intake of sodium. Salofalk tablets are considered to be high in sodium. This should be taken into account by patients on a controlled sodium diet (low-salt diet).

Use during pregnancy or breastfeeding

There are no adequate data from the use of Salofalk enteric-coated tablets in pregnant women. However, data on the use of mesalazine in a limited number of pregnant women indicate no adverse effects on the course of pregnancy or on the health of the foetus and/or newborn. No other epidemiological data are available to date. Only one case of renal failure in the newborn has been reported after prolonged use of mesalazine in high doses (2-4 g orally) during pregnancy. There have been reports of blood disorders (leukopenia, thrombocytopenia, anaemia) in newborns whose mothers used mesalazine.

Animal studies with oral administration of mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.

Salofalk 250 mg and 500 mg tablets should only be taken during pregnancy if the potential benefit outweighs the possible risk.

N-acetyl-5-aminosalicylic acid and, to a lesser extent, mesalazine are excreted in breast milk. There is currently only limited experience of the use of the drug in women during breastfeeding. Hypersensitivity reactions, such as diarrhea, in the breastfed infant cannot be excluded. Therefore, Salofalk tablets should be used during breastfeeding only if the potential benefit outweighs the possible risk. If the breastfed infant develops diarrhea, breastfeeding should be discontinued.

Ability to influence reaction speed when driving vehicles or other mechanisms

No effect on the ability to drive or use machines has been observed. If dizziness occurs during treatment with the drug, you should refrain from driving or using other machines.

Method of administration and doses

Salofalk, 250 mg

Adults and elderly patients

For the treatment of chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis), both Salofalk 250 mg and Salofalk 500 mg tablets can be used.

If a dosage exceeding 1.5 g of mesalazine per day is required, it is recommended to use Salofalk 500 mg tablets.

Depending on the clinical need in each individual case, the following daily doses are recommended for the treatment of adults:

Children under 6 years old

Salofalk tablets should not be used in children under 6 years of age. There is limited data on the use of the drug in children aged 6 to 18 years.

Children aged 6 and over

In acute attacks, depending on the severity of the disease, a dose of 30-50 mg mesalazine/kg body weight/day is prescribed, which is divided into 3 doses. The maximum dose is 75 mg mesalazine/kg body weight/day. The total daily dose should not exceed the maximum dose for adults.

For the prevention of relapses (non-specific ulcerative colitis), the drug is prescribed individually, starting with a dose of 15-30 mg mesalazine/kg body weight/day, divided into 2-3 doses. The total daily dose should not exceed the maximum dose for adults.

Children weighing up to 40 kg are recommended to take half the adult dose, children weighing over 40 kg are recommended to take the usual adult dose.

For the treatment of children aged 6 years and over, the following daily doses are recommended:

Salofalk, 500 mg

If the recommended dose exceeds 1.5 g of mesalazine per day, Salofalk 500 mg tablets are usually used.

Adults and elderly patients

Depending on the clinical need in each individual case, the following daily doses are recommended:

Children under 6 years old

Salofalk tablets should not be used in children under 6 years of age. There is limited data on the use of the drug in children aged 6 to 18 years.

Children aged 6 and over

In acute attacks, depending on the severity of the disease, a dose of 30-50 mg mesalazine/kg body weight/day is prescribed, which is divided into 3 doses. The maximum dose is 75 mg mesalazine/kg body weight/day. The total daily dose should not exceed the maximum dose for adults.

For the prevention of relapses (non-specific ulcerative colitis), the drug is prescribed individually, starting with a dose of 15-30 mg mesalazine/kg body weight/day, divided into 2-3 doses. The total daily dose should not exceed the maximum dose for adults.

Children weighing up to 40 kg are recommended to take half the adult dose, children weighing over 40 kg are recommended to take the usual adult dose.

Depending on the clinical needs and body weight (up to 40 kg) of the child, a decision should be made as to which type of tablet should be used: Salofalk, 250 mg, or Salofalk, 500 mg.

General recommendations for use

Salofalk tablets should be taken in the morning, at lunchtime and in the evening 1 hour before meals. The tablets should be swallowed whole, without chewing, with sufficient liquid.

Both in acute inflammatory conditions and with long-term use, Salofalk tablets must be taken regularly and continuously to achieve the desired therapeutic effect.

The duration of use is determined by the doctor.

To maintain remission in ulcerative colitis, the dose can be reduced to 1.5 g mesalazine per day (adults and children weighing more than 40 kg) to 0.75 mg mesalazine per day (children/adolescents).

Children

Salofalk tablets should not be used in children under 6 years of age. There is limited data on the use of the drug in children aged 6 to 18 years.

Overdose

To date, no cases of intoxication and specific antidotes have been reported.

There are reports of cases of overdose (e.g., intentional suicide by taking a high oral dose of mesalazine) that do not indicate renal or hepatic toxicity. There is no specific antidote; treatment should be symptomatic and supportive. If necessary, intravenous electrolyte infusion (forced diuresis) should be used.

Adverse reactions

*See the section "Features of use".

Fatigue, paresthesias, methemoglobinemia, prolonged diarrhea, and worsening of colitis symptoms are also possible.

The mechanism of myocarditis, pericarditis, pancreatitis, nephritis and hepatitis associated with mesalazine is unknown; it may have an allergic etiology.

It should be noted that some of these disorders can be explained by intestinal inflammation itself.

Severe skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see section 4.4).

Photosensitivity

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product has been authorised is very important. This allows the benefit/risk balance of the medicinal product to be monitored continuously. Healthcare professionals are asked to report any suspected adverse reactions via the Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Medicines and Medical Devices) Pharmacovigilance Division Kurt-Georg-Kiesinger-Allee 3 53175 Bonn www.bfarm.de

Expiration date

3 years. Do not use after the expiry date stated on the packaging.

Storage conditions

Keep out of the reach of children. Store at a temperature not exceeding 25 °C.

Packaging

10 tablets in a blister; 5 or 10 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Dr. Falk Pharma GmbH / Dr. Falk Pharma GmbH.

Location of the manufacturer and address of its place of business

Leinenweberstrasse 5, 79108 Freiburg, Germany.