Instructions Salofalk gastro-resistant granules prolonged 1.5 g Granu-Stix sachet No. 35
Composition
active ingredient: mesalazine (5-aminosalicylic acid);
1 packet (2.79 g of granules) contains 1.5 g of mesalazine or 1 packet (5.58 g of granules) contains 3 g of mesalazine;
excipients: microcrystalline cellulose, hypromellose, colloidal anhydrous silicon dioxide, polyacrylate dispersion, magnesium stearate, simethicone emulsion.
Coating I: methacrylic acid - methyl methacrylate copolymer (1:1), triethyl citrate, talc, titanium dioxide (E 171), magnesium stearate.
Coating II: hypromellose, talc.
Final coating: sodium carboxymethylcellulose, titanium dioxide (E 171), aspartame (E 951), anhydrous citric acid, sweet vanilla flavor, talc, povidone.
Dosage form
Gastro-resistant granules, prolonged action.
Main physicochemical properties: rounded particles of elongated or rounded shape, grayish-white in color, packaged in composite aluminum foil bags.
Pharmacotherapeutic group
Anti-inflammatory drugs used to treat intestinal diseases. ATC code A07E C02.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
The mechanism of anti-inflammatory action is unknown. In vitro studies suggest that inhibition of lipoxygenase may play a role.
It has also been shown to have an effect on the concentration of prostaglandins in the intestinal mucosa. Mesalazine (5-aminosalicylic acid/5-ASA) binds free radicals.
Pharmacodynamic effect
Mesalazine, when administered orally, acts predominantly locally on the intestinal mucosa and on the submucosal tissue on the luminal side of the intestine. It is therefore important that mesalazine is available in areas of inflammation. Systemic bioavailability and plasma concentrations are therefore not essential for determining the therapeutic effect, but rather are factors for determining the degree of safety. To achieve this effect, Salofalk granules are resistant to gastric juice, and mesalazine is released from them depending on the pH of the medium due to the coating with Eudragit L (coating I); prolonged release is ensured by the structure of the granule matrix.
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 due to the action of colonic bacteria. 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 passes into breast milk, mainly in the form of N-Ac-5-ASA.
Features of Salofalk granules
Distribution
Due to the size of the granules (about 1 mm), they quickly pass from the stomach to the duodenum.
A combined pharmaco-scintigraphic/pharmacokinetic study showed that the compound reaches the ileocecal region within 3 hours and the ascending colon after approximately 4 hours. The total transit time through the large intestine is approximately 20 hours.
About 80% of an administered oral dose is available in the colon, sigmoid colon, and rectum.
Absorption
The release of mesalazine from Salofalk granules begins after a lag phase lasting about 2-3 hours. Peak plasma concentrations are reached after about 4-5 hours. The systemic bioavailability of mesalazine after oral administration is approximately 15-25%.
Food intake delays absorption by 1–2 hours, but does not alter its rate or extent.
Breeding
When mesalazine was administered at a daily dose of 3 × 500 mg, the total renal excretion rate of mesalazine and N-Ac-5-ASA under steady-state conditions was approximately 25%. The fraction of unmetabolized mesalazine was approximately 1% of the oral dose. The elimination half-life in this study was 4.4 hours.
Indication
Treatment of exacerbations and prevention of relapses of ulcerative colitis (maintenance of remission of ulcerative colitis).
Contraindication
Salofalk granules should not be used in patients with:
hypersensitivity to salicylic acid and its derivatives or to any substance included in the composition of the medicinal product;
severe liver or kidney dysfunction.
Interaction with other medicinal products and other types of interactions
No specific interaction studies have been conducted.
Interactions may occur during treatment with Salofalk granules with the simultaneous use of the following medicinal products (most of these possible interactions are expected based on theoretical considerations):
Glucocorticoids: possible increase in adverse gastric events.
Sulfonylurea: possible enhancement of blood sugar-lowering effects.
Methotrexate: possible increase in the toxic effects of methotrexate.
Probenecid/sulfinpyrazone: possible weakening of the uricosuric effect.
Spironolactone/furosemide: possible reduction of the diuretic effect.
Rifampicin: possible weakening of the tuberculostatic effect.
Lactulose or similar drugs may reduce the release of mesalazine from the granules due to a decrease in stool pH: pH caused by bacterial metabolism.
Patients who are concomitantly taking azathioprine, 6-mercaptopurine or thioguanine should be aware of the possible enhancement of the myelosuppressive effect of azathioprine, 6-mercaptopurine or thioguanine.
Application features
At the discretion of the physician, blood tests (formed elements; liver function parameters such as ALT or AST; serum creatinine) and urine tests (test strips, sediment) should be performed during and after treatment. It is recommended that tests be performed approximately 14 days after the start of treatment and then 2–3 times at 4-week intervals. If the test results are normal, preventive checks can be performed every three months. If other additional symptoms appear, tests should be performed urgently.
It should be used with caution in patients with impaired liver function.
Salofalk granules are not recommended for use in patients with impaired kidney function.
Cases of nephrolithiasis, including the formation of stones with a 100% mesalazine content, have been reported with the use of mesalazine. Adequate fluid intake is recommended during treatment.
If renal function deteriorates during treatment, mesalazine-induced renal toxicity should be considered.
Patients with lung diseases, in particular asthma, should be monitored during treatment with Salofalk granules.
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 adverse reactions to sulfasalazine-containing drugs should be under medical supervision from the very beginning of treatment with Salofalk granules. In the event of acute symptoms of intolerance, such as cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.
Each sachet of Salofalk granules 500 mg/1000 mg/1500 mg/3000 mg contains 1 mg/2 mg/3 mg/6 mg aspartame. Aspartame is a source of phenylalanine. This may be harmful for people with phenylketonuria (PKU).
Salofalk granules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose/galactose malabsorption or sucrase/isomaltase insufficiency should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per sachet, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
There are no adequate data from the use of Salofalk prolonged-release enteric-coated granules in pregnant women, but data from a limited number of exposed pregnancies indicate no adverse effects of mesalazine on pregnancy or on the health of the foetus and/or newborn. No other epidemiological data are available to date. In a single case, renal failure in the newborn has been reported following prolonged use of high-dose mesalazine (2-4 g orally) during pregnancy.
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 granules should only be taken during pregnancy if the expected benefit outweighs the risk.
N-acetyl-5-aminosalicylic acid and, to a lesser extent, mesalazine pass into breast milk. There is currently only limited experience of use in women during breastfeeding. Hypersensitivity reactions such as diarrhoea in infants cannot be excluded. Therefore, Salofalk granules should only be used during breastfeeding if the expected benefit outweighs the risk. If diarrhoea develops in the breastfed infant, breastfeeding should be discontinued.
The ability to influence the reaction speed when driving or working with other mechanisms
In general, 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 machines.
Method of administration and doses
Adults and elderly patients
Take 1 sachet of Salofalk 3 g, 1–2 sachets of Salofalk 1.5 g once a day (equivalent to 1.5–3.0 g of mesalazine daily), preferably in the morning, according to individual clinical need.
To prevent relapses of ulcerative colitis (maintenance of remission)
1 sachet of Salofalk 1.5 g once a day, which is equivalent to 1.5 g of mesalazine per day.
For patients at high risk of relapse, the dosage regimen can be changed to 3.0 g mesalazine as a single daily dose, preferably in the morning.
Children under 6 years old
Salofalk granules should not be used in children under 6 years of age due to lack of experience with the drug in this age group.
Children aged 6 and over
Depending on the severity of the disease, during an exacerbation, 30–50 mg mesalazine/kg body weight should be given once daily, preferably in the morning, or divided into 3 doses. The total dose should not exceed the maximum adult dose.
For relapse prevention (maintenance treatment), 15–30 mg mesalazine/kg body weight/day should be given in several doses.
Children weighing up to 40 kg are recommended to take half the adult dose, and children weighing more than 40 kg are recommended to take the usual adult dose.
Salofalk granules should not be chewed. The contents of the Granu-Stix sachet should be poured onto the tongue and swallowed with a sufficient amount of liquid, without chewing.
Both in the treatment of exacerbations of inflammation and during long-term treatment, Salofalk granules should be used regularly and continuously to achieve the desired therapeutic effect.
Ulcerative colitis flares usually resolve within 8–12 weeks; for most patients, the dosage can be reduced to a maintenance dose.
Children
Salofalk granules should not be used in children under 6 years of age due to lack of experience in this age group. There are limited data on use in children aged 6–18 years.
Overdose
To date, no cases of intoxication and specific antidotes have been reported.
If necessary, intravenous infusion of electrolytes (forced diuresis) should be used.
Side effects
| Organ system classification | Frequency according to MedDRA convention |
Frequent (≥ 1/100, but < 1/10) | Infrequent (≥ 1/1000, but < 1/100) | Rare (≥ 1/10,000 but < 1/1,000) | Very rare (< 1/10,000) | Frequency unknown (cannot be estimated from available data) |
| Blood and lymphatic system disorders | | | | Changes in blood count (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leukopenia, thrombocytopenia) | |
| Immune system disorders | | | | Hypersensitivity reactions such as allergic rash, drug fever, lupus erythematosus syndrome, pancolitis | |
| Nervous system disorders | Headache | | Dizziness | Peripheral neuropathy | |
| Cardiac disorders | | | Myocarditis, pericarditis | | |
| Respiratory, thoracic and mediastinal disorders | | | | Allergic and fibrotic pulmonary reactions (including dyspnea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonitis) | |
| Gastrointestinal disorders | | Abdominal pain, diarrhea, dyspepsia, flatulence, nausea, vomiting, acute pancreatitis | | | |
| Hepatobiliary disorders | | | Cholestatic hepatitis | Hepatitis | |
| Skin and subcutaneous tissue disorders | | | Increased skin sensitivity to sunlight and ultraviolet rays (photosensitivity) | Alopecia | Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) |
| Musculoskeletal and connective tissue disorders | | | Arthralgia | Myalgia | |
| Renal and urinary disorders | | | | Renal impairment, including acute and chronic interstitial nephritis and renal failure | Nephrolithiasis* |
| Disorders of the reproductive system and mammary glands | | | | Oligospermia (reversible) | |
| General violations | | | Asthenia, fatigue | | |
| Research results | | Changes in liver function tests (increased transaminases and markers of cholestasis), changes in pancreatic enzymes (increased lipase and amylase), increased eosinophil count | | | |
*For more detailed information, see the "Application Features" section.
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
There have been reports of severe reactions in patients with skin conditions such as atopic dermatitis and atopic eczema.
Expiration date
4 years. Do not use after the expiry date stated on the packaging.
Storage conditions
Does not require any special storage conditions. Keep out of the reach of children.
Packaging
5.58 g of granules in a Granu-Stix bag; 50 bags in a cardboard box for Salofalk granules, 3 g each.
2.79 g of granules in a Granu-Stix package; 35 packages in a cardboard box for Salofalk granules of 1.5 g.
Vacation category
According to the recipe.
Producer
Dr. Falk Pharma GmbH / Dr. Falk Pharma GmbH.
Address
Leinenweberstrasse 5, 79108 Freiburg, Germany.
