Mesacol

An anti-inflammatory drug for the treatment of intestinal diseases, known in the international registry of pharmacological drugs under the name mesalazine, can be found on the shelves of our pharmacies as Mesacol. This is the drug that will be discussed in this article. Its pharmacological characteristics, indications and contraindications for use, as well as the method of administration and recommended dosages will be considered.

Proctological diseases not only bring many unpleasant hours and days, but sometimes even months. For some reason, problems related to the intestines - the small and large intestines - make many people blush. They are ashamed to go to the clinic with their problems. And as a result, when it is already "bad enough" or the ambulance has taken the patient away, the proctologist has to solve much more difficult problems, bringing the patient out of a serious condition. Sometimes it is not always possible to restore the patient's former health.

Mesacol, a convenient modern anti-inflammatory drug specially developed to relieve intestinal diseases, helps to solve many proctological problems. Therefore, in order for the treatment to be easier and without complications, it is necessary to seek advice from a qualified specialist when unpleasant symptoms have just appeared, then a quick and favorable result can be expected. You should not just make a diagnosis and prescribe medications on your own. Such an approach to treatment will not lead to anything good. In this case, the situation will only worsen, and time will be lost.

[ 1 ], [ 2 ]

Indications Mesacola

Due to its medicinal properties and form of release, indications for the use of Mesacol are limited to the following diseases:

1. Therapy and preventive treatment of nonspecific ulcerative colitis.
2. Pathological changes of an ulcerative nature affecting the intestinal mucosa with damage to the rectum (ulcerative proctitis).
3. Crohn's disease.
4. Non-specific ulcerative colitis, accompanied by damage to the distal parts of the large intestine and rectum.

[ 3 ]

Mesalazine's ability to prevent colorectal cancer

In recent years, there has been considerable interest in the potential for mesalazine to chemoprevent colorectal cancer (CRC) associated with inflammatory bowel disease (IBD). Given the difficulty of conducting double-blind, placebo-controlled, randomized clinical trials in patients, researchers have turned to experimental cancer models, and indeed, existing data suggest that mesalazine may reduce the risk of colorectal cancer by directly influencing CRC cell biology beyond simply controlling inflammation. However, definitive conclusions from experimental results are not always entirely valid, and future studies will therefore be needed to establish whether data from studies with cultured cells or animal models of CRC can be generalized to IBD- or CRC-associated dysplasia.

Another important issue that requires further study concerns the dosage/concentration of mesalazine required to interfere with the growth and survival of CRC cells. In vitro studies have shown that the antitumor effect of mesalazine occurs at relatively high doses of the drug (e.g. 10-50 mmol/L), which are not always achieved in colon tissue with standard oral treatment. In this context, it is also relevant to take into account the metabolism of mesalazine, such as oxidation and acetylation of mesalazine, which may differ significantly between in vitro and in vivo conditions and limit the amount of biologically active compound. [ 4 ]

Release form

Depending on the characteristics of the lesion of the intestinal mucosa and its accompanying pathologies, the release form of the drug in question may vary somewhat.

1. Mesacol is available in the form of tablets, which are coated with a special shell that can dissolve only in the intestine, which makes it possible to "deliver" the drug directly to the pathologically affected area. The tablet form of the drug is produced with a concentration of the active ingredient mesalazine (5-ASA) of 400 mg or 800 mg. The shell of the drug has a brownish-reddish tint, allowing for inclusions. Mesacol itself is a light gray mass. Auxiliary chemical compounds that help maintain a high level of pharmacodynamics of Mesacol: sodium carboxymethyl, sodium lauryl sulfate, macrogol 6000, povidone, talc, starch, magnesium stearate, methacrylic acid copolymer, maltodextrin, triethyl acetate, sodium hydroxide, titanium dioxide. The tablets have a prolonged effect.
2. The second type of release is a rectal suppository, which has a grayish-cream shade. The dosage of one unit of the drug is 500 mg of mesalazine (5-ASA). The accompanying substance is solid fat.
3. Another form of the drug can be called a rectal suspension. This is a homogeneous cream-colored liquid, 1 ml of which contains 40 mg of mesalazine (5-ASA). Associated chemical compounds of this release form are: sodium edetate, sodium metabisulfite, tragacanth, distilled water, sodium benzoate, sodium acetate, xanthan gum. Mesacol is packaged in seven containers, which have a volume of 50 ml (2 g of mesalazine) or 100 ml (4 g of mesalazine). Together with the drug in the cardboard package there is also an applicator.

Pharmacodynamics

In addition to the clinical efficacy of masalazine on various symptoms, three trials also showed whether mesalazine could reduce immune cells and proinflammatory cytokines compared with placebo. [ 5 ], [ 6 ] R. Corinaldesi et al. found that mesalazine could significantly reduce the total mucosal immune cells compared with placebo (P = 0.0082). It could significantly reduce the number of mast cells (P = 0.0014), but not T cells, B cells or macrophages. The proinflammatory cytokine IL-1b (P = 0.047) and mast cell mediators tryptase (P = 0.030) and histamine (P = 0.016) were also significantly reduced in the mesalazine group compared with placebo. Ghadir et al and Ching Lam et al showed that there were no significant differences in total immune cell counts in patients with irritable bowel syndrome after treatment with mesalazine compared with placebo.

[ 7 ], [ 8 ]

Pharmacokinetics

Any form of the drug in question makes it possible to “deliver” therapeutic volumes of mesalazine directly to the site of the pathological focus. Namely, these are the mucous layers of the rectum and sigmoid colon, descending colon, right up to the splenic zone.

Mesacol has an anti-inflammatory component (5-ASA). The sulfonamide moiety acts as a carrier to deliver the active component 5-ASA to the colon where it is released by bacterial action. Mesacol is metabolized by bacterial enzymes in the colon to form two active by-products. Sulfapyradine is metabolized in the liver and excreted in the urine, while the 5-ASA component is acetylated by the colonic epithelium (Rochester and Abreu 2005).

The pharmacokinetics of Mesacol show an average level of absorption. About a third to half of the drug is adsorbed by the intestinal mucosa, namely in the small intestine. The metabolites of mesalazine are N-acetyl-5-aminosalicylic acid.

The active substance undergoes acetylation (replacement of hydrogen atoms in organic compounds with acetic acid residues), which occurs in the mucous layers of the intestine and liver.

The level of binding capacity of N-acetyl-5-aminosalicylic acid with protein components of blood plasma corresponds to 85%, while mesalazine shows a relationship of only 43%.

The active ingredient Mesacola is not only able to pass through the blood-brain barrier, but is also consistently detected in breast milk during breastfeeding.

This drug is eliminated from the patient's body, mostly in unchanged form, as well as in the form of metabolites, both in urine and together with feces.

The half-life of mesalazine (T _1/2 ) is determined by a figure from half an hour to one and a half hours, everything depends on the individual characteristics of the human body. The same parameter for the metabolite N-acetyl-5-aminosalicylate is somewhat longer and ranges from five to ten hours.

[ 9 ]

Dosing and administration

The choice of dosage form is determined by the location and scale of the affected area of the intestine. Only the attending physician can determine the form of administration, method of administration and dose of the prescribed drug. When using Mesacol in the form of a rectal suspension in therapeutic therapy, the doctor can simultaneously introduce the administration of this drug in the form of tablets. Naturally, in this situation, the total amount of the drug entering the patient's body should be taken into account. If this fact is not taken into account, the dosage is exceeded, which invariably leads to an overdose of mesalazine and an increased likelihood of toxic effects on kidney function.

The doctor prescribes the therapeutic dosage strictly individually for each patient, based on the clinical picture of the disease and his general health condition. If the therapeutic effectiveness is not observed during a month of drug therapy, the drug in question should be replaced with its analogue.

During the treatment period, it is necessary to maintain the required hydration. If there is a medical need, mesalazine can be taken in parallel with metronidazole or drugs belonging to the corticosteroid group.

For children whose body weight has already reached 40 kg and adult patients, Mesacol in the form of a rectal suspension, in order to achieve the expected effectiveness, is recommended to be administered to the patient's body immediately after bowel movement - eat after the defecation process.

1. To make the procedure more comfortable, the patient should lie on his left side and bend his legs slightly.
2. Before use, shake the bottle with the medicinal liquid well, then insert the applicator into the anus as far as possible.
3. Very carefully and slowly squeeze the suspension out of the tube.
4. After the administration of the drug, you must lie down for half an hour without changing your previously adopted position.
5. After the time has elapsed, turn to the right side and back several times. This is necessary for better distribution of mesalazine throughout the intestine.

The recommended dosage, for example, during the acute phase of ulcerative colitis is the administration of 100 ml of Mesacol with an active substance concentration of 4 g per 100 ml, taken once a day. This form of administration is most effective if the administration occurs in the evening, immediately before going to bed.

If for some reason the patient finds it difficult to retain a “large” volume of medicine in the intestine, in such a situation it is advisable to spread the intake of this dose over two procedures of 50 ml each. In this case, a 50 ml package with an active substance content of 2 g will be more convenient to use. Pharmacists recommend the time of administration, with such a schedule: the first procedure - immediately before bedtime, the second - preferably at night, after a preliminary bowel movement.

The duration of the treatment course is usually from six to eight weeks.

As a preventive measure for recurrent ulcerative colitis, doctors recommend using a dosage of 50 ml (active substance concentration 2 g), once a day. In this case, it is advisable to do the procedure after bowel movement and at night. This approach to treatment is more effective, since the medicine works on the affected area all night.

The duration of preventive treatment also ranges from six to eight weeks.

For small patients whose weight has not yet reached 40 kg, the amount of Mesacol prescribed by the attending physician is based on the activity of the inflammatory process and the place of its progression, as well as based on the baby's body weight.

In case of diagnosis of acute ulcerative lesions of the intestinal mucosa, as well as Crohn's disease, the recommended amount of mesalazine for children is calculated according to the formula 30 - 50 mg per kilogram of the child's weight, divided into three procedures.

To prevent recurrence of the disease, this therapeutic dosage corresponds to values of 15 - 30 mg per kilogram of the baby's weight, divided into two or three procedures.

The method of carrying out the treatment procedure is similar to what was described earlier. As a rule, therapy of the pathology during the period of exacerbation takes from eight to twelve weeks (two to three months).

Mesacol in tablets is mainly prescribed by the attending physician if distal proctosigmoiditis or proctitis is diagnosed.

If the disease has worsened, the recommended dose is 0.4 - 0.8 g, taken three times a day. The duration of the treatment course is usually from eight to twelve weeks.

As a preventive measure to prevent relapses of the disease, a slightly smaller dose is prescribed - 0.4 - 0.5 g three times a day (in the case of ulcerative colitis) or 1 g four times a day (in the case of Crohn's disease).

For small patients who are already two years old, the daily amount of the drug is calculated using the formula 20-30 mg per kilogram of the baby's weight, divided into several doses. Such a graph of therapy can be maintained for several years. If the disease is severe, accompanied by complications, the daily amount of the administered drug can be increased to 3-4 g. But these numerical indicators should not be exceeded. Also, the maximum dosage should not be taken for more than 8-12 weeks.

The tablet form of Mesacol is administered orally, whole, without chewing. The recommended time of administration is after a meal with a large volume of water, or an hour before the expected meal.

Mesacol in the form of rectal suppositories (candles) is prescribed at 0.5 g (one suppository) three times a day - for adult patients. For children, the daily administration of a rectal suppository is calculated as follows: in the case of an acute phase of the disease as 40 - 60 mg per kilogram of the baby's weight, in the case of preventive measures, the daily amount of the drug is 20 - 30 mg per kilogram of the child's weight.

During mesalazine drug therapy, the main blood parameters should be constantly monitored by conducting a general blood test. Urine parameters, which are a characteristic of the kidney condition, are regularly monitored.

If one of the doses was missed, it is necessary to carry out the procedure at any convenient time, if it does not work, then the missed amount is administered to the patient together with the next dose. If more than one dose was not taken, then the medication should be taken according to the prescribed schedule, but it is necessary to consult with your doctor.

If a specialist begins to suspect that the patient is developing acute intolerance to mesalazine, he or she will stop taking Mesacol.

[ 13 ]

Use Mesacola during pregnancy

You may be advised to continue using mesalazine during pregnancy to control inflammatory bowel disease. There is no evidence that taking mesalazine during pregnancy harms your baby.

If you become pregnant while taking mesalazine, talk to your doctor. Do not stop taking the medicine until your doctor tells you to.

Your doctor can explain the risks and benefits of taking mesalazine and help you choose the best treatment for you and your baby.

Mesalazine and breastfeeding

If your doctor or health visitor says your baby is healthy, it is usually safe to take mesalazine while breastfeeding.

Small amounts of mesalazine pass into breast milk and are unlikely to cause any side effects in your baby. Many people have taken mesalazine while breastfeeding without problems, although there have been rare cases of diarrhea in infants.

Tell your midwife, health visitor, pharmacist or doctor as soon as possible if you notice that your baby is not feeding as well as usual, or has diarrhoea, or if you have any other concerns about your baby. [ 10 ]

Contraindications

Contraindications to the use of Mesacol, which are reduced to the following pathological changes:

• Increased individual intolerance of the patient's body to the active substance and/or other components of the drug, including propylparabens and methylparabens.
• Deficiency of glucose-6-phosphate dehydrogenase in the patient's body.
• Hypersensitivity of the mucous membrane to the enema procedure, when using the suspension form of the drug.
• Severe liver and/or kidney dysfunction in the patient's history.
• Hemorrhagic diathesis.
• Ulcerative and erosive pathology affecting the mucous membrane of the duodenum and stomach.
• Pregnancy, especially the first and last weeks of gestation.
• The period of breastfeeding a newborn.
• For children under two years of age.
• Rectal suspension is not recommended for use by patients with a history of bronchial asthma.

There is currently no data available regarding the effect of Mesacol on the patient's ability to adequately react when driving a vehicle or other potentially dangerous machinery.

Adults and children aged 5 years and older can take mesalazine.

Side effects Mesacola

Mostly, most medicines are capable of causing accompanying pathological symptoms, which manifest themselves with greater or lesser intensity. The medicine in question is tolerated by the patient's organism quite well, but the side effects of Mesacol are still specified in the instructions attached to it.

• Increased human fatigue.
• Swelling.
• Vomit.
• Painful symptoms in the throat, abdomen, and headaches may appear.
• Exacerbation of asthma.
• Increase in body temperature.
• Symptoms of an allergic nature:
• Skin rashes.
• Itchy sensation.
• Manifestations of lupus erythematosus.
• Burning.
• Dermatosis.
• Quite rarely, eosinophilic or interstitial pneumonia.
• Sinusitis.
• Tachycardia.
• Very rarely myocarditis or pericarditis.
• Vasodilation is an increase in the lumen of blood vessels caused by a decrease in the tone of the muscles of the vascular wall.
• Signs of flatulence.
• Decreased or, on the contrary, increased appetite.
• Diarrhea.
• The following can be observed individually:
  • Increased hair loss on the scalp.
  • Hepatitis.
  • Exacerbation of pancreatitis, gastritis, cholecystitis or gastroenteritis.
  • Dry skin, dry mouth, possible ulcers.
  • Erythema nodosum (inflammation of the blood vessels of the skin and subcutaneous fat).
  • Manifestations of psoriasis and gangrenous pyoderma.
  • Dysuria is a disorder of urination.
  • Tinnitus.
  • Multiple manifestations affecting the urinary system.
  • Ulcerative manifestations.
  • Exacerbation of kidney pathology.
  • Changes in taste sensations.
  • The appearance of shortness of breath.
  • Visual impairment.
  • Dizziness.
• Sudden mood swings.
• Unstable psychological level of the patient.
• Exacerbation of arthrosis manifestations.
• Changes in blood pressure both in the direction of decrease and in the direction of increase.
• Thrombocytopenia, leukopenia and lymphadenopathy.

Most of the above symptoms appear in isolated cases and it is enough to reduce the dosage of Mesacol for the side symptoms to disappear on their own. There are very rare cases when the attending physician has to completely remove this drug from the treatment protocol and introduce symptomatic therapy.

[ 11 ], [ 12 ]

How to manage mesalazine side effects?

What to do with:

• indigestion, stomach pain or wind - try to avoid wind-inducing foods (such as lentils, peas, beans and onions). Eat less, eat and drink slowly. Placing a heating pad or closed hot water bottle on your stomach can also help with stomach pain.
• feeling or nausea - stick to simple meals and avoid fatty or spicy foods. Check the instructions on your medication to see if it can be taken after meals. If you are sick, try drinking water or pumpkin in small, frequent sips to avoid dehydration. Do not take any other anti-vomiting medications without talking to your pharmacist or doctor.
• diarrhea - drink plenty of fluids, such as water or pumpkin, to avoid dehydration. Do not take any other medicines for diarrhea without talking to your pharmacist or doctor.
• headaches, muscle aches and pains - drink plenty of water and ask your pharmacist to recommend a suitable painkiller. Tell your doctor if the pain continues despite taking painkillers or if it lasts for more than a few days.

Overdose

The main amount of the drug is absorbed in the intestines, and only a small amount of it "leaks" into the blood. Therefore, there is a very small probability that an overdose of mesalazine will occur, causing intoxication of the patient's body. But given that each person's body is individual, we will still give the symptoms of an overdose that salicylates show at high doses of intake, which includes the drug in question:

1. Shortness of breath, respiratory depression, increased frequency of diaphragmatic contractions.
2. Increased activity of sweat glands.
3. Redness of the skin.
4. Loss of consciousness.
5. Increased ventilation of the lungs provokes an increase in respiratory alkalosis (an imbalance of acids and alkalis), which, in turn, is transformed into metabolic acidosis (the accumulation of endogenous acids in the body's tissues).

If it does happen that signs of intoxication begin to appear, the attending physician usually prescribes intravenous administration of electrolytic solutions, such as sodium lactate or sodium bicarbonate. This will increase diuresis (the amount of urine excreted over a certain period of time). Thanks to this correction, it is possible to increase the alkaline reserves of the patient's body and improve the situation with the excretion of the components and metabolites of Mesacol by the kidneys, together with urine.

Hemodialysis may also be added to the therapeutic measures. There is currently no specially developed antipode to relieve this situation.

Interactions with other drugs

There are some medicines that affect how mesalazine works. Tell your pharmacist or doctor if you are taking:

• medications that increase the acidity of stool, such as the laxative lactulose;
• medications that affect kidney function, such as azathioprine, mercaptopurine, or thiojuanine, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen;
• certain medications that help prevent blood clots, such as warfarin.

[ 14 ], [ 15 ]

Storage conditions

Depending on how correctly the medicine is stored, its high pharmacological effectiveness throughout the entire period of work of the product considered in this article, permitted by the manufacturer, depends. The storage conditions of Mesacol, described in detail in the instructions attached to the medicine, are not complicated, but their strict adherence is simply necessary.

1. Mesacol, produced in tablet form, should be kept in a cool place where the room temperature does not exceed +30 degrees throughout the entire period of permitted use.
2. Mesacol, produced in the form of a rectal suppository or rectal suspension, should be kept in a cool place where the temperature does not exceed + 25 degrees during the entire period of acceptable use.
3. Mesalazine should be kept out of the reach of small children.
4. The medicine should not be exposed to direct sunlight, this reduces its shelf life and reduces the quality of the medicine itself.

Shelf life

When releasing any medicine to pharmacy shelves, the manufacturer must indicate on the packaging of the drug the date of its production and the final date after which this medicine should not be used in therapeutic and preventive therapy. Since then the drug begins to lose its pharmacological characteristics, and, therefore, one should not expect high efficiency in stopping the disease from such a medicine.

The expected period of effective work of Mesacol varies depending on the form of its release:

• The shelf life of enteric-coated tablets is three years;
• Mesacol in the form of a rectal suspension is suitable for use for two years after release;
• The medicine in the form of rectal suppositories shows high efficiency for three years after the date of manufacture.