Mesalazine is a drug for the basic treatment of ulcerative colitis, a mild form of Crohn's disease in some localizations, as well as a number of other diseases.
According to its chemical structure,
mesalazine is 5-aminosalicylic acid (5-ASA) , which has a local anti-inflammatory effect.
The drug affects the synthesis of pro-inflammatory prostaglandins and leukotrienes, slows down the migration, degranulation and phagocytosis of neutrophils, reducing the severity of inflammatory processes. Mesalazine has an antioxidant effect due to the binding of its molecules to free radicals. The drug is taken orally (orally) in the form of tablets, MMX tablets or granules, used in the form of an aerosol (rectal foam), suspension (microenemas) and suppositories. The anti-inflammatory effect of mesalazine is predominantly local (on the intestinal mucosa), so the concentration of the drug in contact with the intestinal wall and the time of this contact are important. Concentrations of the drug in the blood are usually minimal and do not affect its effectiveness.
The active ingredient in all these drugs is the same, but mesalazine is released in the intestinal lumen in different ways. This depends on the form of the drug, its shell and structure.
Below is a description of the main mesalazines registered in the Russian Federation.
Brief characteristics of mesalazine preparations
"Salofalk"
Production (Germany). In Russia it is presented in the form of tablets, granules, rectal foam, rectal suspension and suppositories.
A. Salofalk tablets
Salofalk tablets are coated with a protective enteric coating of Eudragit L, which provides pH-controlled release of mesalazine. The shell does not dissolve in gastric juice. But when it enters the intestine, where the pH level is ≥6.0, it is destroyed, and the active substance of the drug ends up in the intestinal lumen. In the terminal ileum, 15-30% of the drug is released, in the colon - 60-75%.
The release of mesalazine from Salofalk tablets begins in the terminal ileum 110-170 minutes after taking the drug, and after 4-5 hours, dissolution is completed in the descending colon. The release of mesalazine is not affected by changes in pH due to other medications or food intake.
About 10% of mesalazine is absorbed into the bloodstream, where it is quickly transformed into an inactive form and excreted from the body by the kidneys.
Forms of release and method of application
Salofalk tablets are available in doses of 250 mg and 500 mg. Take them in the morning, afternoon and evening 1 hour before meals. The tablets are swallowed without chewing and washed down with a sufficient amount of liquid.
b. Granules "Salofalk"
Salofalk granules are a two-component dosage form that combines pH-controlled release of mesalazine with long-term continuous release of the drug from a core based on an original polymer matrix. The enteric protective coating provides a pH-dependent release (at pH values ≥6.0) of the active substance, starting in the terminal ileum and continuing in the underlying intestine. The loss of the active substance to the ileum is minimal. The polymer matrix core ensures long-term continuous release of the active substance throughout the colon, right down to the rectum.
A large number of granules (3 g of Salofalk contain about 3500 granules) ensures a uniform and effective distribution of the active substance and, due to the very large surface area, maintains the effect even with diarrhea.
The drug reaches the ileocecal region after about 3 hours, and the ascending colon after 4 hours (faster than when taking Salofalk tablets). Approximately 80% of the oral dose reaches the colon, sigmoid and rectum. The amount of the drug that enters the blood and is excreted in the urine as a metabolite is less than when using Salofalk tablets.
Forms of release and method of application
Salofalk granules are available in doses of 500 mg and 1000 mg. The granules should be placed on the tongue and swallowed without chewing, with plenty of liquid. The prescribed dose of Salofalk in granules should be taken once a day, regardless of food intake.
V. Rectal foam (aerosol) “Salofalk”
Rectal foam (aerosol) “Salofalk” is a dosage form for rectal use, which allows for optimal contact of the active substance with the surface of the intestinal mucosa. Highly effective for active ulcerative colitis localized in the rectum, as well as for left-sided and widespread ulcerative colitis as part of combination therapy. When foam is administered through the rectum, mesalazine acts directly on the mucous membrane of the final sections of the colon. Due to the high adhesive ability of Salofalk foam, the drug can “stick” to the mucous membrane, which ensures long-term contact of mesalazine with the inflamed area of the intestine. And the duration of contact (exposure) increases the effectiveness of the drug.
Release form and method of application
Salofalk foam is produced in an aerosol can containing 14 applications of the drug, 1 g each, the set is equipped with 14 disposable soft applicators for insertion into the rectum. It is recommended to administer the drug before bedtime (preferably after a bowel movement), however, if there are frequent nighttime bowel movements, the attending physician may prescribe a different time.
Excerpt from the instructions for use of Salofalk rectal foam:
- At the time of administration, the drug should be at room temperature (20–25 °C)
- Place the applicator firmly on the cylinder head
- Shake the can for 20 seconds
- When using for the first time, remove the protective tab from the base of the dosing head.
- Turn the cap so that the semicircular cutout on the safety ring is in line with the nozzle. Place your index finger on the cap and turn the can upside down.
- Insert the applicator into the rectum as deeply as possible. It is best to place your foot on a chair or stool. In order to administer the first part of the dose of the drug, press the cap all the way and slowly release it. To administer the second dose of the drug, press the cap again and release slowly. Wait 10–15 seconds, then slowly remove the applicator from the rectum
- After introducing the foam, remove the applicator and throw it away in a plastic bag. For each new dose of the drug, a new applicator should be used.
- After the procedure, wash your hands. Try not to have a bowel movement until the next morning.
g. Rectal suspension "Salofalk" (microenema)
Rectal suspension "Salofalk" (microenema) is a ready-made suspension in a bottle with disposable applicators. The drug reaches the left (splenic) corner of the colon. In some patients, the drug reaches the transverse colon and even the ascending colon. When mesalazine is used in microenemas, low absorption of the drug is observed.
Forms of release and method of application
Microclysters "Salofalk" are available in doses of 2 g/30 ml and 4 g/60 ml. Smaller volume microenemas are suitable for patients who find it difficult to hold large volumes of suspension. The entire volume of microenemas is injected into the rectum at night (preferably after bowel movements), however, if there are frequent nighttime bowel movements, the attending physician may prescribe a different time.
d. Rectal suppositories "Salofalk"
Rectal suppositories "Salofalk" are suppositories intended for insertion into the rectum. They are used to achieve the highest concentration of mesalazine in this section of the intestine.
Forms of release and method of application
Rectal suppositories "Salofalk" are available in doses of 250 mg, 500 mg and 1000 mg (this dose is not registered in Russia). Suppositories are inserted into the rectum 1-2 times a day as prescribed by a doctor (preferably after bowel movements). It is usually recommended to administer the suppository at night, however, depending on the prescribed frequency of administration, combination with other local forms of therapy, as well as for nighttime bowel movements, the attending physician may prescribe a different time.
Due to the small size of the granules (about 1 mm), which facilitates unhindered passage through the stomach, they can be taken regardless of meals.
"Pentasa"
Production (Denmark). Presented in the Russian Federation in the form of tablets, granules and suppositories.
A. Pentasa tablets
Pentas tablets are enteric-coated. After administration, it disintegrates into microgranules coated with ethylcellulose. Microgranules act as independent forms of the drug with a slow release. This provides a therapeutic effect throughout the duodenum to the rectum, regardless of pH. The microgranules reach the duodenum within an hour after taking the tablet, regardless of food intake. The average passage time for the drug through the small intestine is 3-4 hours. About 30-50% of the dose taken is absorbed in the small intestine.
Release form and method of application
Pentasa tablets are available in doses of 500 mg. It is recommended to take after meals without chewing in 2-3 doses. The tablet can be split into several pieces or dissolved in water to make it easier to swallow.
b. Pentas granules
Pentas granules are microgranules coated with ethylcellulose. They act as independent forms of the drug with a slow release, which provides a therapeutic effect throughout the entire length from the duodenum to the rectum, regardless of pH. Microgranules reach the duodenum within an hour, regardless of food intake. The passage time of the drug through the small intestine is on average 3-4 hours.
Release form and method of application
Pentasa granules are available in doses of 1000 mg and 2000 mg. It is recommended to take the granules after meals without chewing. Pour the contents of one sachet onto your tongue and wash it down with water or juice.
V. Rectal suppositories "Pentas"
Pentasa rectal suppositories are suppositories intended for insertion into the rectum. They are used to achieve the highest concentration of mesalazine in this section of the intestine.
Release form and method of application
Rectal suppositories "Pentasa" are available in doses of 1000 mg. Externally they look like oblong tablets. Suppositories are inserted into the rectum 1-2 times a day as prescribed by a doctor, preferably after bowel movements. It is usually recommended to administer the suppository at night, however, depending on the prescribed frequency of administration, combination with other local forms of therapy, as well as in case of frequent nighttime bowel movements, the attending physician may prescribe a different time.
The drug can be moistened with water for easier administration.
"Mezavant"
Production (USA). Presented in the Russian Federation in the form of MMX tablets. MMX Mezavant tablets have a core containing mesalazine in a multicomponent matrix. The core is surrounded by a shell of methacrylic acid copolymers of types A and B. Mesalazine is released in the intestine only when the pH reaches >7. Scintigraphy studies have shown that after a single dose of 1.2 g of the drug on an empty stomach to healthy volunteers, mesalazine quickly and unchanged passes through the upper gastrointestinal tract. Traces of 14C-labeled mesalazine were detected throughout the colon. Complete disintegration of the tablet and release of mesalazine was observed after approximately 17.4 hours. After a single dose of 2.4 or 4.8 g to healthy volunteers for 14 days, mesalazine absorption was 21–22% of the dose taken.
Release form and method of application
MMX Mezavant tablets are available in a dose of 1.2 g (1200 mg). The entire recommended dose is taken 1 time per day with meals. The tablets should not be crushed or chewed and should be swallowed whole.
"Mesakol"
Manufacturing (India). Presented in the Russian Federation in the form of tablets. Mesacol tablets are coated with an enteric coating of Eudragit-L and Eudragit-S, which dissolves at pH>7. The bulk of mesalazine (60-79%) is released in the colon.
Forms of release and method of application
Mesacol tablets are available in a dose of 400 mg. The recommended dose of the drug is taken in 2-3 doses. The tablets should be taken before meals without chewing.
"Asakol"
Production (Switzerland). Presented in the Russian Federation in the form of tablets. Asakol tablets are coated with an enteric coating of Eudragit-S. Drug release begins in the colon at pH>7.
Forms of release and method of application
Asakol tablets are available in doses of 400 mg and 800 mg. The recommended dose of the drug is taken in 2-3 doses. The tablets should be taken before meals without chewing.
"Kansalazin"
Manufactured by Canonpharma Production CJSC (Russia). Presented in the Russian Federation in the form of tablets. The results of a study of the bioequivalence of the drug Cansalazine to the original drug mesalazine (manufactured by Danish) confirmed the full correspondence of the dynamics and concentration of mesalazine in the intestines when taking Kansalazine and the original drug. Thus, the manufacturer considers Kansalazine tablets to be a drug that has the same effect as Pentasa tablets.
Release form and method of application
Kansalazine tablets are available in doses of 500 mg. The recommended dose of the drug is taken in 2-3 doses. It is recommended to take the tablets after meals without chewing.
Instructions for use SALOFALK® tablets
General properties of mesalazine
Suction
Mesalazine is absorbed most efficiently in the proximal intestine and least efficiently in the distal intestine.
Distribution
Plasma protein binding of mesalazine and N-Ac-5-ASA is 43% and 78%, respectively. Approximately 1% of an oral dose of mesalazine is excreted in breast milk, mainly as N-Ac-5-ASA.
Metabolism
Mesalazine undergoes first-pass metabolism to form inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), both in the intestinal mucosa and in the liver. The pattern of acetylation is independent of the patient's acetylation phenotype. Part of mesalazine is also acetylated due to the action of bacterial microflora of the large intestine.
Removal
Mesalazine and its metabolite N-Ac-5-ASA are excreted in excrement (most of it), kidneys (the amount varies from 20% to 50% depending on the route of administration, dosage form and mechanism of release of the active substance) and bile (minor part) . It is excreted by the kidneys mainly in the form of N-Ac-5-ASA.
Specific features of the drug Salofalk® in the form of tablets 250 mg
Distribution
A combined pharmacoscintigraphic/pharmacokinetic study demonstrated that when taken with food (breakfast test), enteric film-coated tablets dissolve in approximately 3-4 hours in the ileum. The average time for evacuation of gastric contents was approximately 3 hours. After approximately 7 hours, the tablets reached the colon. In a subsequent study in volunteers, the evacuation time from the duodenum to the ileum was approximately 3 hours, with the highest concentration of 5-ASA in the intestinal lumen observed 7-8 hours after co-administration of the tablets with a test breakfast. Approximately 75% of the mesalazine dose reaches the large intestine unmetabolized.
Suction
The release of mesalazine from Salofalk® 250 mg enteric film-coated tablets begins after a lag phase of approximately 3-4 hours. The highest plasma concentration is achieved after approximately 5 hours (in the ileum) and with the administration of mesalazine at a dose of 500 mg 3 times/day (3×2 tablets. Salofalk® 250 mg) under the condition of steady-state equilibrium is 2.1±1.7 µg/ml for mesalazine and 2.8±1.7 µg/ml for its metabolite, N-A4-5-ACK.
Removal
During long-term treatment with Salofalk® 250 mg enteric film-coated tablets at a daily dose of 500 mg mesalazine 3 times a day (assuming steady state), the total rate of renal excretion of mesalazine and N-A4-5-ACK was approximately 55% (value obtained within 24 hours after the last dose). The proportion of unmetabolized mesalazine was approximately 5%. T1/2 is 0.7-2.4 hours (on average 1.4±0.6 hours) when using mesalazine at a dose of 500 mg 3 times a day.
Specific features of the drug Salofalk® in the form of tablets 500 mg
Distribution
A combined pharmacoscintigraphic/pharmacokinetic study demonstrated that when taken with food (breakfast test), enteric film-coated tablets dissolve in approximately 3-4 hours in the ileum. After approximately 4-5 hours, the tablets reach the colon. The total transit time in the large intestine is about 17 hours.
Suction
The release of mesalazine from Salofalk® 500 mg enteric film-coated tablets begins after a lag phase of approximately 3-4 hours. The highest plasma concentration is achieved after approximately 5 hours (in the ileum) and with the administration of mesalazine at a dose of 500 mg 3 times/day, subject to steady state equilibrium, is 3±1.6 µg/ml for mesalazine and 3.4±1.6 µg/ml for its metabolite, N-Ac-5-ASA.
Removal
The total rate of renal excretion of mesalazine and N-Ac-5-ASA within 24 hours with repeated doses (1 tablet 500 mg 3 times a day for 2 days; and 1 tablet on the third control day) was approximately 60% ( value obtained within 24 hours after the last dose). The proportion of unmetabolized mesalazine was approximately 10%.
Indications for the use of mesalazine
Many patients with ulcerative colitis and Crohn's disease are familiar with this drug under various commercial names (Salofalk, Pentasa, Mezavant, Mesacol, Asacol, etc.).
Most often, these drugs are prescribed for inflammatory bowel diseases (IBD), primarily ulcerative colitis .
Mesalazine and ulcerative colitis
According to the Russian and European recommendations of 2022, mesalazine is a drug for the basic treatment of ulcerative colitis of any localization. Clinical studies have shown that all commercial forms of mesalazine are equally effective in the treatment of ulcerative colitis.
Then what is their difference? Why do some patients benefit from pH-dependent release mesalazine granules, others from slow-release tablets, and some do not get better at all?
Undoubtedly, there are differences in the drugs. In the section with general characteristics of mesalazines, the mechanisms of release of the active substance from tablets and granules are discussed in sufficient detail. Sometimes the release and uniform distribution of the drug throughout the intestine is affected by the acidity (i.e., the same pH) in the intestine. In other cases, the release of mesalazine is independent of pH but is dependent on intestinal transit time. In pathological conditions, pH values can vary greatly and differ from the norm. Thus, according to the results of one study (on a limited group of healthy individuals), pH values did not reach 7 in any part of the gastrointestinal tract in 25% of cases. In 90% of cases (again, not in all study participants), the pH exceeded 6. That is, there is a possibility that in a number of patients with ulcerative colitis and Crohn's disease, mesalazines with a pH-dependent release system (Salofalk, Mesacol, Asacol, Mezavant) may be less effective than expected. When using pH-independent mesalazines (Pentasa, Canasalazine), researchers note that most of the drug begins to be released in the small intestine, which means there is a possibility that the concentration of mesalazine in the colon will be less than necessary to achieve an effect. In some cases, this probability can be reduced by increasing the dose of the drug.
The dose of mesalazine prescribed is another factor in the success or failure of IBD treatment. An insufficient dose of the drug leads to a poor response to therapy.
It is important to correctly assess the location of intestinal damage. It is this (proctitis, left-sided or widespread/total ulcerative colitis) that determines the choice of the dosage form of mesalazine (tablets, granules, foam, microenemas or suppositories). For example, suppositories can be used in first-line therapy for ulcerative colitis affecting the rectum.
Finally, mesalamines may not have the expected benefit due to high disease activity. In this case, they are combined with other drugs (including hormonal agents and immunosuppressants).
Summarizing the above, we can conclude:
Good knowledge of the mechanism of action of drugs and the capabilities of various dosage forms allows a gastroenterologist to select an individual treatment regimen for the patient.
Mesalazine and Crohn's disease
A few words about Crohn's disease and the effectiveness of mesalazine in its treatment. Until 2016, when the update of the European consensus on the diagnosis and treatment of Crohn's disease (3rd revision) was published, mesalazine was recommended for mild forms of the disease affecting the large intestine (Crohn's colitis) and small intestine (Crohn's ileitis). In the first case, the use of large doses of mesalazine (3-4 g per day) with a pH-dependent release system was recommended, in the second - mesalazine with a pH independent release system (Pentasa) at a dose of 4 g per day. Changes to the treatment strategy were made after publication of the consensus. This also influenced Russian recommendations related to the diagnosis and treatment of Crohn's disease. Mesalazine is found to be ineffective compared to placebo. However, clinical practice shows that for patients with mild disease, taking mesalazine helps, up to the healing of the mucous membrane.
Mesalazine can also be prescribed for chronic colitis of unknown or unspecified origin, radiation (radiation) colitis, diverticular disease of the intestine, etc.
Salofalk rectal suspension
INSTRUCTIONS for medical use of the drug SALOFALK®
INN: Mesalazine
General characteristics Homogeneous rectal suspension from light brown to brown color, does not contain foreign particles.
Composition of the medicinal product Each bottle (= 60 ml of rectal suspension) contains the active substance: mesalazine (5-aminosalicylic acid) 4 g; excipients: potassium metabisulfite (E 224), sodium benzoate (E 211), carbomer 934P (carbopol 974P), disodium edetate (in the form of disodium edetate dihydrate), potassium acetate (E 261), xanthan gum (E 415), purified water .
Dosage form Rectal suspension
Pharmacotherapeutic group: intestinal anti-inflammatory drugs, aminosalicylic acid and similar active ingredients ATC code: A07EC02
Pharmacological properties Pharmacodynamics The mechanism of anti-inflammatory action is unknown. In vitro studies have demonstrated that inhibition of the enzyme lipoxygenase may play a role. An effect on prostaglandin concentrations in the intestinal mucosa has also been demonstrated. Mesalazine (5-aminosalicylic acid/5-ASA) may also act as a radical scavenger of reactive oxygen species. When administered rectally into the intestinal lumen, mesalazine has a significant local effect on the intestinal mucosa and submucosal layers. Pharmacokinetics General properties of mesalazine: Absorption Mesalazine is absorbed most effectively in the proximal parts of the intestine and least effectively in the distal parts of the intestine. Biotransformation Mesalazine undergoes first-pass metabolism with the formation of inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) both in the intestinal mucosa and in the liver. Acetylation appears to be independent of the patient's acetylation phenotype. Some mesalazine is also acetylated by colonic bacteria. Plasma protein binding is 43% for mesalazine and 78% for N-Ac-5-ASA. Excretion/excretion Mesalazine and its metabolite N-Ac-5-ASA are excreted in feces (most of them), kidneys (the amount varies from 20 to 50% depending on the route of administration, dosage form and mechanism of release of the active substance) and along with bile ( smaller part). It is excreted by the kidneys mainly in the form of N-Ac-5-ASA. Approximately 1% of an oral dose of mesalazine is excreted in breast milk, mainly as N-Ac-5-ASA.
Specific features of the drug Salofalk® rectal suspension 4 g/60 ml: Distribution: Radiological studies have established that when used in patients with mild or moderate ulcerative colitis, the suspension at the beginning of treatment and during remission after 12 weeks of treatment is distributed mainly according to the rectum and sigmoid colon, and to a lesser extent in the descending colon. Absorption and excretion: It was found that when used in patients with ulcerative colitis in remission, the highest plasma concentration was 0.92 μg/ml 5-ASA and 1.62 μg/ml N-Ac-5-ASA, it was achieved approximately after 11–12 hours under equilibrium conditions. The elimination rate was approximately 13% (45-hour value), with the majority (about 85%) of the administered dose excreted as the metabolite N-Ac-5-ASA. The plasma concentrations of 5-ASA and N-Ac-5-ASA in children with chronic inflammatory bowel disease treated with Salofalk® rectal suspension 4 g/60 ml were 0.5–2.8 μg/ml and 0.9 –4.1 µg/ml, respectively, under equilibrium conditions. Preclinical Safety Data: Preclinical data from standard pharmacological safety, genotoxicity, carcinogenicity (in rats) and reproductive toxicity studies did not indicate any particular hazard to humans. In toxicity studies, nephrotoxicity (medullary necrosis of the kidney and damage to the epithelium of the proximal convoluted tubule (pars convoluta) or the entire nephron) was observed with repeated oral administration of high doses of mesalazine. The clinical significance of the findings is unclear.
Indications for use Treatment of acute attacks of inflammatory disease of the large intestine, known in medicine as ulcerative colitis.
Directions for use and dosage Adults and elderly people When used to treat patients with an acute attack of inflammation, the contents of one bottle (= 60 ml of rectal suspension) are administered into the intestines as an enema once a day before bedtime.
Children and adolescents There is little experience with the drug in children and limited literature on the effectiveness of the drug in children.
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General information for all patients Salofalk® rectal suspension 4 g/60 ml should be used once a day before bedtime. The drug Salofalk® rectal suspension 4 g/60 ml should be used regularly and systematically, since only in this case can a positive result be achieved. The duration of treatment is determined by the attending physician.
Route of administration: Apply rectally. The best results will be achieved if the patient has a bowel movement before using Salofalk® rectal suspension 4 g/60 ml.
Preparation for administration: Shake the bottle for 30 seconds. Remove the protective cap of the applicator. Hold the bottle at the top and bottom.
Correct posture when administering a rectal suspension: The patient should lie on his left side, with his left leg extended and his right leg bent at the knee. This position makes it easier to administer the enema and allows you to achieve greater effect. Administration of the rectal suspension: Insert the tip of the applicator deep into the rectum. Point the tip of the applicator slightly downward, then squeeze the bottle slowly and evenly. When the bottle is empty, slowly remove the applicator tip from your rectum. The patient should remain in a horizontal position for at least 30 minutes after administration to ensure even distribution of the drug throughout the rectum. If possible, the enema should be left overnight.
Side effects The following side effects have been reported in connection with the use of mesalazine:
Organ system/organ/category Frequency in accordance with the medical dictionary of regulatory activities Rarely (≥1/10,000, <1/1,000) Very rarely (<1/10,000) Disorders of the circulatory and lymphatic systems Changes in the blood formula ( aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leukopenia, thrombocytopenia) Nervous system disorders Headaches, dizziness Peripheral neuropathies Cardiovascular system disorders Myocarditis, pericarditis Respiratory tract and mediastinal disorders Allergic and fibrous pulmonary reactions (including shortness of breath, cough, bronchospasm, alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonitis) Gastrointestinal disorders Abdominal pain, diarrhea, bloating, nausea and vomiting Acute pancreatitis Renal disorders Renal dysfunction, including acute and chronic interstitial nephritis and renal deficiency Skin and subcutaneous tissue disorders Photosensitivity (increased sensitivity of the skin to light)
Alopecia (hair loss) Musculoskeletal and connective tissue disorders Myalgia, arthralgia Immune system disorders Hypersensitivity reactions such as allergic exanthema, drug fever, drug-induced lupus erythematosus syndrome, pancolitis Liver and biliary disorders Changes in functional parameters liver (increased levels of transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis Disorders of the reproductive system Oligospermia (reversible)
Photosensitivity (increased sensitivity of the skin to light) More severe reactions have been reported in patients with underlying skin conditions such as atopic dermatitis and atopic eczema.
Contraindications The drug Salofalk® rectal suspension 4 g/60 ml is contraindicated in patients with: - known hypersensitivity to salicylic acid and its derivatives or to any of the excipients included in the drug; - severe liver or kidney dysfunction.
Overdose There is very limited information on mesalazine overdose (for example, when ingesting high doses for suicidal purposes), which does not indicate nephro- or hepatotoxicity of the drug. No specific antidote is known. Treatment is symptomatic and supportive.
Precautions At the discretion of the physician, a blood test (blood test with differential leukocyte count), determination of indicators of the functional state of the liver (levels of ALT or AST enzymes, plasma creatinine levels) and a urine test (test strips) should be performed before starting treatment and during treatment. . It is recommended to conduct these studies 14 days after the start of treatment and then 2-3 times with an interval of 4 weeks. If the results obtained are normal, then it is sufficient to carry out these tests every three months. If additional manifestations of the disease appear, additional studies should be performed immediately. Use with caution when treating patients with reduced liver function. Salofalk® rectal suspension 4 g/60 ml should not be used in the treatment of patients with reduced renal function. If a decrease in renal function occurs during treatment, mesalazine-related nephrotoxicity should be considered. Careful monitoring of patients with respiratory system disorders, especially asthma, is necessary when prescribing Salofalk® rectal suspension 4 g/60 ml. Patients with known hypersensitivity to drugs containing sulfasalazine should only be treated under close medical supervision. If symptoms of acute intolerance appear, such as cramps, acute abdominal pain, fever, severe headaches and skin rash, treatment should be stopped immediately. Due to the content of potassium metabisulfite as an excipient, allergic reactions with symptoms of anaphylaxis and bronchoconstriction (bronchospasm) may occur in sensitive patients, especially those suffering from asthma or other allergies. Due to the content of sodium benzoate as an excipient, hypersensitivity reactions may occur in susceptible patients in the form of irritation of the skin, eyes and mucous membranes.
Period of pregnancy and lactation Pregnancy At the moment, there is insufficient data on the use of the drug Salofalk® rectal suspension 4 g/60 ml for pregnant women. However, no adverse effects on pregnancy or fetal/newborn health were observed. There is no other information available at this time. There is one case of renal failure in a newborn born to a woman who received high doses of mesalazine for a long time during pregnancy (2-4 g per day orally). Animal studies of the oral route of mesalazine have demonstrated no direct or indirect adverse effects on gestation, embryo/fetal development, parturition or postnatal development. Salofalk® rectal suspension 4 g/60 ml should be prescribed during pregnancy only if the expected benefit outweighs the potential risk. Breastfeeding N-acetyl-5-aminosalicylic acid and small amounts of mesalazine are secreted into breast milk. To date, there is limited experience with the use of mesalazine during breastfeeding. The development of hypersensitivity reactions in infants cannot be ruled out, one of the manifestations of which may be diarrhea. Thus, the drug Salofalk® rectal suspension 4 g/60 ml should be prescribed during breastfeeding only if the expected benefit outweighs the potential risk. If the baby develops diarrhea, breastfeeding should be stopped.
Effect on the ability to drive a car and operate complex equipment The use of the drug Salofalk® rectal suspension 4 g/60 ml either has no effect or has an insignificant effect on the ability to drive a car and operate complex equipment.
Interaction with other medicinal products No specific interaction studies have been conducted. The possibility of increasing the suppressive effect of azathioprine, 6-mercaptopurine or thioguanine on the bone marrow should be taken into account during treatment with simultaneous use of the drug Salofalk® rectal suspension 4 g/60 ml. There is weak evidence that mesalazine may reduce the effect of the anticoagulant warfarin.
Storage conditions and shelf life Does not require special storage conditions. Keep out of the reach of children. Store in sealed contour packaging in a dark place. Shelf life – 2 years. Do not use after the expiration date stated on the packaging.
Dispensing conditions Prescription
Packaging Rectal suspension 4 g/60 ml: 60 ml in white, round, compressible low-density polyethylene bottles, closed with a lubricated rectal applicator tip and a green protective cap. The bottle is placed in a contour package made of heat-sealable polyvinyl chloride film and laminated paper with aluminum coating. 7 bottles each, placed in contour packaging, with instructions for use in a cardboard pack.
Applicant/manufacturer Dr. Falk Pharma GmbH Leinenweberstr. 5 79108 Freiburg Germany
Vifor AG Brüchlstrasse 50 4107 Oettingen Switzerland
Representative in the Republic of Belarus Representative office of Alpen Pharma AG JSC in the Republic of Belarus 220053, Minsk, st. Parkhomenko 3, office 1-B Tel./fax: (+375 17) 3350644
Side effects when using mesalazine
The side effects of mesalazine are described in sufficient detail in the official instructions for the drug, however, in general, the drug is well tolerated even in large doses and with long-term use (in 93-98% of patients).
Immediate allergic reactions (soft tissue swelling, Quincke's edema, anaphylaxis) when taking mesalazine range from 0.07 to 0.1% of cases.
The risk of allergic reactions generally increases in patients with bronchial asthma.
The drug is toxic to the liver, pancreas and bone marrow. Drug-induced liver damage and clinically insignificant changes in liver tests (increased ALT and/or AST) when taking mesalazine occur in 2.6-4% of cases. Toxic pancreatitis (inflammation of the pancreas) is observed even less frequently - less than 1% of cases.
Mesalazine, pregnancy and breastfeeding
In the article “Frequently Asked Questions on IBD,” we looked at the problem of conception, pregnancy and delivery in ulcerative colitis and Crohn’s disease.
These diagnoses are not a death sentence at all; patients with IBD can become pregnant and give birth. At the same time, the patient may need to continue taking mesalazine even during pregnancy.
The effect of mesalazine on conception
There is no data on the effect of mesalazine on the ability of men to conceive (unlike, for example, sulfasalazine).
