Pentasa side effects. Pentasa - anti-inflammatory and antimicrobial intestinal drug

P N010197

Tradename: Pentasa ®

INN: mesalazine

Dosage form:

extended-release tablets

Composition for 1 tablet:
active substance- mesalazine 500 mg,
Excipients- microcrystalline cellulose 207 mg, povidone 25 mg, talc 9 mg, ethyl cellulose 6-9 mg, magnesium stearate 1 mg.

Description
The tablets are round, white with a grayish shade of color, with numerous blotches of light brown color with beveled, scored and engraved "500 mg" on one side and "Pentasa" on the other.

Pharmacoteraeutic group: anti-inflammatory and antimicrobial intestinal agent.

ATX code: A07EC02

Pharmacological properties
Pharmacodynamics
Mesalazine - 5-aminosalic acid - is the active component of sulfasalazine. The therapeutic effect of mesalazine after oral or rectal administration is more due to the local effect on the inflamed intestinal tissue than to the systemic effect.
The therapeutic effect of mesalazine is manifested by local contact with the affected intestinal mucosa.
Mesalazine inhibits leukocyte chemotaxis, reduces the production of cytokines and leukotriene, and reduces the formation of free radicals in inflamed intestinal tissue. But the exact mechanism of action of mesalazine is not fully understood.
Pharmacokinetics
Suction: after taking the tablet of Pentasa ® disintegrates into microgranules, which act as independent forms of the drug with sustained release. This ensures the therapeutic effect of Pentasa ® along the entire length from the duodenum to the rectum at any pH value. Microgranules reach the duodenum within an hour after taking the tablet. The transit time of the drug through the small intestine is on average 3-4 hours.
Distribution: about 30-50% of the dose taken is absorbed mainly in the small intestine. The maximum concentration of mesalazine in plasma is reached 1 hour after administration and lasts up to 4 hours, gradually decreasing.
Metabolism: Mesalazine undergoes acetylation in the intestinal mucosa and in the liver, and also, to a small extent, by enterobacteria, forming the main metabolite of N-acetyl-5-aminosalicylic acid. 43% of mesalazine and 73–83% of the metabolite binds to plasma proteins. Mesalazine and its metabolite do not cross the blood-brain barrier, but do pass into breast milk. Mesalazine clearance is 18 l / h. When taking high doses (up to 1500 mg / day), a cumulative effect may be observed.
Derivation: the half-life of mesalazine from plasma is about 40 minutes, the metabolite is about 70 minutes. Mesalazine and its metabolites are excreted in the urine and feces.

Indications for use

Ulcerative colitis (exacerbation of mild to moderate ulcerative colitis, maintenance of remission and / or long-term therapy of ulcerative colitis),

Crohn's disease. Contraindications

Hypersensitivity to mesalazine and other components of the drug,

Severe liver and / or kidney damage

Peptic ulcer of the stomach or duodenum,

Hemorrhagic diathesis

The last 2-4 weeks of pregnancy and lactation,

Children under 2 years of age.
If you have one of the listed diseases, be sure to consult your doctor before taking the drug. Carefully
With caution, the drug should be prescribed to patients who are allergic to salicylates, since hypersensitivity reactions to sulfasalazine are possible, as well as to patients with impaired lung function, in particular, with bronchial asthma.
Care must be taken when prescribing Pentasa ® to patients with mild to moderate renal / hepatic insufficiency, since a decrease in the rate of elimination and an increase in the systemic concentration of mesalazine increases the risk of kidney damage. Application during pregnancy and during breastfeeding
The drug is allowed to be used during pregnancy when the potential benefit of its use to the mother outweighs the possible risk of adverse effects to the fetus. In the last 2-4 weeks of pregnancy, the drug should be discontinued.
Mesalazine crosses the placental barrier and is excreted in breast milk. Therefore, breastfeeding should be discontinued while taking Pentasa ®. Method of administration and dosage
The tablets are recommended to be taken without chewing after meals. To facilitate swallowing, the tablet can be divided into several parts or dissolved in water or juice immediately before taking.
Ulcerative colitis
Acute period: 2 tablets 2–4 times a day.
Supportive therapy: 1 tablet 2-3 times a day.
Crohn's disease
Acute period: 2-4 tablets 4 times a day.
Supportive therapy: 2-4 tablets 2 times a day or 2-3 tablets 3 times a day.
Children
The dose is selected individually, usually 20-30 mg mesalazine per 1 kg of body weight per day in several doses. Side effect Diarrhea (3%), nausea (3%), abdominal pain (3%), headache (3%), vomiting (1%) and skin rashes (1%) are most often observed when using Pentasa ®.

	Often (> 1% and	Rarely (> 0.01% and	Very rarely (
On the part of the hematopoietic organs			Eosinophilia, anemia, leukopenia, granulocytopenia, agranulocytosis, thrombocytopenia, pancytopenia
From the immune system			Hypersensitivity reactions, drug fever, Quincke's edema
From the nervous system		Dizziness	Peripheral neuropathy, benign intracranial hypertension
On the part of the cardiovascular system *		Myocarditis, pericarditis
From the respiratory system *			Shortness of breath, cough, allergic alveolitis, pulmonary eosinophilia, lung infiltration, pneumonia, bronchospasm
From the digestive system	Diarrhea, abdominal pain, nausea, vomiting, flatulence	Increased amylase content, pancreatitis *	Worsening of colitis symptoms
From the hepato-biliary system			Increased levels of liver enzymes and bilirubin, hepatotoxicity * (hepatitis, hepatosis, cirrhosis, liver failure)
From the skin	Hives, eczema		Photosensitivity, reversible alopecia
From the musculoskeletal system			Myalgia, arthralgia
From the urinary excretory system			Interstitial nephritis *, nephrotic syndrome, urine discoloration, transient renal failure
Other	Headache, fever

(*) The mechanism of the development of adverse reactions, presumably, is of an allergic nature.
If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects that are not indicated in the instructions, tell your doctor about it. Overdose
Cases of overdose with Pentasa ® are rare. There are no specific antidotes.
It is recommended to flush the stomach and take measures to increase urine output. In the case of the development of acidosis, alkalosis or dehydration, it is necessary to restore the acid-base and water-electrolyte balance. In case of signs of hypoglycemia, administration of dextrose is recommended. Interaction with other medicinal products
With the simultaneous administration of Pentasa ® with azathioprine or mercaptopurine, the risk of bone marrow suppression (leukopenia, thrombocytopenia, erythrocytopenia / anemia or pancytopenia) increases. The simultaneous administration of Pentasa ® and other drugs with nephrotoxicity, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) and azathioprine, increases the risk of side effects, slows down the absorption of cyanocobalamin (vitamin B 12), enhances the hypoglycemic effect of sulfonylurea derivatives, weakens ulcerogenicity, glucocorticosteroids the activity of furosemide, spironolactone, sulfonamides, rifampicin, enhances the effect of anticoagulants, increases the effectiveness of uricosuric drugs (tubular secretion blockers). special instructions
In case of acute symptoms of drug intolerance (muscle cramps, abdominal pain, fever, severe headache and skin rashes) or signs of liver and / or kidney dysfunction, Pentasa ® should be discontinued!
During the entire course of treatment with Pentasa ®, the creatinine level in the blood should be monitored regularly.
In the event of side effects (dizziness, nausea), it is not recommended to drive a car and other mechanisms that require increased concentration of attention and speed of psychomotor reactions. Release form
Extended-release tablets 500 mg. 10 tablets in an aluminum foil blister.
5 or 10 blisters with instructions for use in a cardboard box. Storage conditions
At a temperature not higher than 25 ° C.
Keep out of the reach of children. Shelf life
3 years.
Do not use after the expiration date. Vacation conditions
On prescription. Manufacturer
Ferring A / S,
Indertoften 10, 2720 Vanlose, Denmark
or
Ferring International Center S.A.,
Chemin de la Vergognasaz 50, 1162 Sant Pré, Switzerland For complaints and additional information, please contact:
Ferring Pharmaceuticals LLC
115054, Moscow, Kosmodamianskaya nab., 52 bld. 4.

Pharmacodynamics... Mesalazine has an anti-inflammatory effect by inhibiting the activity of neutrophilic lipoxygenase and the synthesis of prostaglandins and leukotrienes. Slows down the migration, degranulation and phagocytosis of neutrophilic granulocytes, as well as the secretion of immunoglobulins by lymphocytes, binds free radicals. It has an antibacterial effect (manifested in the large intestine) against Escherichia coli and some cocci. Reduces the risk of recurrence of Crohn's disease, especially in patients with ileitis for a long period of time. The therapeutic properties of mesalazine when administered orally and rectally are due to a greater extent to its local action on the inflamed areas of the intestine than to its systemic action.
Prolonged-release pentasa in tablets is mesalazine microgranules coated with ethylcellulose. After application and dissolution, mesalazine is gradually released from each microgranule during the passage of the tablet through the gastrointestinal tract (from the duodenum to the rectum) at any pH of the intestinal medium. After 1 hour after oral administration of the drug, microgranules are in the duodenum, regardless of food intake. The average intestinal passage time in healthy volunteers is 3-4 hours.
Pharmacokinetics... Biotransformation: mesalazine is converted to N-acetyl-mesalazine both first-pass in the intestinal mucosa and systemically in the liver. Minor acetylation is carried out with the participation of bacteria in the large intestine, resulting in the formation of acetyl-5-aminosalicylic acid. Acetylation of mesalazine is obviously not associated with the individual characteristics of the patient's phenotype. It is also believed that acetyl-mesalazine is clinically and toxicologically inactive.
Absorption: from 30 to 50% of the drug when administered orally is absorbed in the small intestine. Already 15 minutes after the administration of mesalazine is determined in the blood plasma. The maximum concentration of mesalazine in the blood plasma is achieved within 1-4 hours after the application of the drug; the concentration of mesalazine decreases gradually and already 12 hours after application is not determined. The concentration curve of acetyl-mesalazine in blood plasma has the same character, but in general it is characterized by higher concentrations and slower elimination. The metabolic ratio in blood plasma of acetyl-mesalazine to mesalazine is 3.5: 1.3 after oral administration of 500 mg 3 times a day and 2 g 3 times a day, respectively, which reflects the dependence of acetylation on the dose.
Average stable concentrations of mesalazine in blood plasma are 2, 8 and 12 mmol / l after 1.5, 4 and 6 g per day, respectively. For acetyl-mesalazine, these concentrations are 6, 13, and 16 mmol / L, respectively. The passage and release of mesalazine after oral administration does not depend on food intake, systemic absorption is reduced.
When administered rectally, the drug is absorbed slowly, although the intensity depends on the dose used. About 30-50% of the dose is absorbed mainly in the rectum. Absorption, determined by the restored composition of urine in healthy volunteers who received 2 g of the drug per day, is about 10%.
Distribution: mesalazine and acetyl-mesalazine do not penetrate the BBB. The binding of mesalazine to blood plasma proteins is about 50%, and that of acetyl-mesalazine is about 80%.
Excretion: the half-life of mesalazine from blood plasma is about 40 minutes (clearance after application of 500 mg - 18.0 l / h), and acetyl-mesalazine is about 70 minutes. Cumulative properties are also determined in healthy volunteers after using 1500 mg / day, and they are 1.1-1.8 mg / l. Since mesalazine is constantly released as it passes through the gastrointestinal tract, it is impossible to determine the half-life after oral administration of the drug. The results of the experiments showed that mesalazine reaches a stable concentration after oral administration of the drug for 5 days.
After oral and rectal administration, mesalazine and acetyl-mesalazine are excreted in the urine and feces (mainly acetyl-mesalazine is excreted in the urine).
The oral bioavailability of mesalazine is slightly impaired due to pathophysiological processes in acute inflammatory bowel diseases such as diarrhea and hyperacidity of the intestine. In patients with increased intestinal peristalsis, systemic absorption is reduced to 20-25% of the daily dose of the drug. The elimination rates of the substance in urine and feces are likely to increase.
In patients with impaired liver and kidney function, a decrease in the rate of elimination and an increase in the systemic concentration of a substance may increase the risk of developing nephrotoxic side effects.
Impaired liver and kidney function
In patients with impaired liver and kidney function, an insufficient rate of excretion of the drug may increase the risk of side nephrotoxic effects.

Indications for the use of the drug Pentasa

Ulcerative colitis, Crohn's disease, ulcerative proctitis (suppositories).

Application of the drug Pentasa

Tablets and granules(doses are selected individually).
Ulcerative colitis.
Exacerbation stage
Adults: The recommended dose is up to 4 g of mesalazine per day, divided into 2-4 doses.

Supportive therapy
Adults: The recommended dose is 2 g of mesalazine per day.
Children over the age of 2: The recommended dose is 20-30 mg of mesalazine per 1 kg of body weight per day.
With left-sided ulcerative colitis, additional administration of local forms of Pentasa is possible to achieve the required concentration of the drug in the distal colon.
Crohn's disease.
Exacerbation stage and supportive therapy
Adults: the recommended dose (selected by the doctor individually) is up to 4 g of mesalazine per day, divided into 2-4 doses.
Children: The recommended dose is 20-30 mg of mesalazine per 1 kg of body weight per day.
The tablets are taken without chewing inside. To facilitate swallowing, the tablet can be divided into several parts or dissolved in water (juice) immediately before use. The contents of the sachet are poured into the mouth, do not chew, and washed down with water. It is important to take the drug regularly for optimal results.
Suppositories.
Adults: 1 suppository 1-2 times a day. Immediately before the introduction of the suppository, it is recommended to cleanse the intestines. To ensure hygienic handling, a rubber fingertip should be used. The suppository is injected into the rectum until the muscle resistance disappears. If the suppository falls out within 10 minutes after administration, a second should be introduced. The suppository can be moistened with water to facilitate administration. The maximum daily dose is 3-4 g.
Children: not for use in children under 2 years of age. There are limited clinical data on the use of the drug in children, therefore, mesalazine is used in pediatric practice only if the expected benefit outweighs the possible risk.
The average duration of treatment is 8-12 weeks. The criterion for the effectiveness of treatment is the achievement of clinical and endoscopic remission. For the prevention of relapses, the drug is prescribed 1.5 g per day (using if necessary for several years) or tablets (1 g per day) are combined with suppositories.

Contraindications to the use of the drug Pentasa

Hypersensitivity to mesalazine, any other component of the drug or salicylates; liver disease and / or renal failure; diseases of the blood system; age up to 2 years.
In addition, contraindications to the use of the drug in the form of tablets and granules are: stomach and duodenal ulcers, bleeding, deficiency of glucose-6-phosphate dehydrogenase, pregnancy and lactation.

Side effects of the drug Pentasa

From the digestive system: nausea, vomiting, heartburn, diarrhea, flatulence, loss of appetite, abdominal pain, dry mouth; rarely - stomatitis, increased levels of liver transaminases, hepatitis, cirrhosis, pancreatitis, exacerbation of colitis symptoms.
On the part of the cardiovascular system: palpitations, increase or decrease in blood pressure, chest pain, shortness of breath, pericarditis, myocarditis.
From the nervous system: headache, tinnitus, dizziness, polyneuropathy, tremor, depression, intracranial hypertension.
From the respiratory system: shortness of breath, cough, allergic alveolitis, pulmonary infiltration, pulmonary eosinophilia, bronchospasm, pneumonia.
From the urinary systems: proteinuria, hematuria, oliguria, anuria, crystalluria, nephrotic syndrome.
Allergic reactions: manifestations of hypersensitivity to the components of the drug (do not depend on the dose), skin rashes, itching, dermatoses (pseudoerythromatosis), bronchospasm, drug disease. Patients who are allergic to salicylates react in the same way when using mesalazine.
On the part of the hematopoietic organs: eosinophilia, anemia (hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, hypoprothrombinemia, pancytopenia.
Other: weakness, mumps, photosensitivity, lupus erythematosus-like syndrome, oligospermia, alopecia, decreased production of lacrimal fluid.

Special instructions for the use of the drug Pentasa

The drug Pentasa (5-aminosalicylic acid) can be prescribed to most patients with allergic reactions to sulfasalazine or at risk of developing an allergy to salicylates, but during the period of treatment such patients need constant monitoring. However, if seizures, abdominal pain, fever, severe headache or rash develop, treatment is stopped immediately.
The drug is used with caution in case of impaired liver function. It is not recommended to use the drug in patients with renal insufficiency. Renal function should be monitored regularly, for example by measuring serum creatinine levels (especially in the initial phase of treatment). Disruption of normal renal function in a patient during treatment may be caused by the nephrotoxic effect of mesalazine. If you suspect the development of myocarditis or pericarditis, or if the composition of the blood changes, treatment should be discontinued. The manifestations of the above adverse reactions can be: in the case of pronounced changes in the composition of the blood - increased bleeding, subcutaneous hemorrhage, sore throat and fever, and in the case of pericarditis or myocarditis - fever, chest pain and shortness of breath. Patients whose acetylation process is slow have an increased risk of side effects. They may notice yellow-orange staining of urine and lacrimal fluid, staining of contact lenses. Changes in blood composition have very rarely been reported. If such reactions are suspected, treatment should be discontinued.
When used in elderly patients, there is no need to reduce the dose.
During pregnancy and breastfeeding. It is known that mesalazine penetrates the placental barrier. Limited information on the use of this substance during pregnancy does not allow assessing the possible toxic effects. Mesalazine passes into breast milk in lower concentrations than in the mother's blood, while the metabolite of acetyl-mesalazine is determined in breast milk at the same or higher concentrations. In infants whose mothers used the drug Pentasa, no adverse effects were noted, however, the available information is limited. During pregnancy and lactation, the drug should be used with caution and only if the possible benefits of the drug outweigh the possible risk.
In the event of the development of side effects from the central nervous system, one should refrain from driving vehicles and working with mechanisms.

Interactions of the drug Pentasa

Enhances the hypoglycemic effect of sulfonylurea derivatives, ulcerogenicity of GCS, toxicity of methotrexate. Weakens the activity of furosemide, spironolactone, sulfonamides, rifampicin. Enhances the effect of anticoagulants. Increases the effectiveness of uricosuric drugs (tubular secretion blockers). Slows down the absorption of cyanocobalamin. May decrease absorption of digoxin.

Overdose of the drug Pentasa, symptoms and treatment

Tablets and granules.
Considering the unique dosage form in the form of prolonged-release granules and the specific pharmacokinetic properties of mesalazine, only a small part of the active substance has a systemic effect, therefore one should not expect the development of overdose symptoms even when the drug is used in high doses.
Symptoms: nausea, vomiting, gastralgia, weakness, drowsiness.
Treatment symptomatic: gastric lavage, use of laxatives; restoration of CRC depending on the clinical situation and replacement of electrolyte loss in mixed alkalosis / acidosis; replenishment of fluid volume in case of hyperhidrosis, vomiting; with hypoglycemia - the introduction of glucose. Control of kidney function.
Suppositories.
There is no experience in studying overdose.

Storage conditions of the drug Pentasa

In a dark place at a temperature not exceeding 25 ° C.

List of pharmacies where you can buy Pentasa:

• St. Petersburg

Ulcerative colitis of mild to moderate severity; Crohn's disease.

Contraindications Pentasa 500mg tablets

Hypersensitivity to salicylates and other components of the drug; Severe hepatic or renal impairment; Children under 6 years of age. If you have one of the listed diseases, be sure to consult your doctor before taking the drug. With caution: with caution, the drug should be prescribed to patients with impaired lung function, in particular, with bronchial asthma, gastric ulcer or duodenal ulcer in the acute stage, hemorrhagic diathesis. Care must be taken when prescribing the drug to patients with renal / hepatic insufficiency of mild to moderate severity, since a decrease in the rate of elimination and an increase in the systemic concentration of mesalazine increases the risk of kidney damage. Application during pregnancy and during breastfeeding: the drug is allowed to be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Inflammatory bowel disease can increase your risk of adverse effects during pregnancy. Pregnancy: mesalazine penetrates the placental barrier, its concentration in the blood of the umbilical cord is lower than in the mother's blood plasma. Acetyl mesalazine is present in the umbilical cord and in the mother's blood plasma at the same concentration. There are no reliable, clearly stated results of studies of the use of mesalazine in pregnant women. According to published data, no increase in the incidence of congenital malformations was found with the use of mesalazine. Some data point to an increase in preterm birth, fetal death and low birth weight. However, the above complications may be due to active inflammatory bowel disease. There have been cases of blood and lymphatic system disorders (leukopenia, thrombocytopenia, anemia) in newborns whose mothers took the drug. There was a single case of impaired renal function in a newborn whose mother had taken mesalazine in a high dose (2-4 g, orally) for a long time during pregnancy. Preclinical studies have not shown the presence of embryo- or fetotoxicity in the drug, the possibility of influencing childbirth and postnatal development. Lactation: mesalazine is excreted in breast milk. The concentration of mesalazine in milk is lower than in the mother's blood plasma, and the metabolite is present in milk at the same or higher concentration. A controlled clinical study of the use of the drug during breastfeeding has not been conducted. Experience with the drug in this group is limited. Children may develop hypersensitivity reactions (eg, diarrhea), in which case breastfeeding should be discontinued. Fertility: According to the results of preclinical studies, no effect of mesalazine on fertility was found.

Dosage and administration of Pentasa tablets 500mg

The tablets are recommended to be taken after meals, without chewing or crushing. To facilitate swallowing, the tablet can be divided into several parts or dissolved in 50 ml of cold water immediately before taking. Adults. Acute period, the dosage is selected individually, the recommended dose during the exacerbation period is up to 4 g per day, divided into 2-4 doses. Maintenance therapy: the dosage is selected individually, the recommended dose is 2 g of mesalazine per day. For the treatment of Crohn's disease, the drug can be prescribed in a daily dose of up to 4 g, divided into several doses. Children over 6 years of age: There are limited data on the use of mesalazine in children aged 6 to 18 years. Acute period: the dosage is selected individually. The recommended dose during the exacerbation period is 30-50 mg mesalazine per kilogram of body weight per day (mg / kg / day) in several doses, the maximum single dose is not more than 75 mg / kg / day, the maximum daily dose is not more than 4 g. Maintenance therapy: the dose is selected individually, the recommended maintenance dose is 15-30 mg / kg / day, divided into several doses, the maximum daily dose is not more than 2 g (4 g - for the treatment of Crohn's disease). For children weighing less than 40 kg, it is recommended to prescribe 1/2 the dose for adults, for children weighing more than 40 kg, it is recommended to prescribe doses for adults. The duration of therapy is determined by the attending physician.

Pentasa: instructions for use and reviews

Latin name: Pentasa

ATX code: A07EC02

Active substance: mesalazine

Manufacturer: Ferring-Lechiva A.S. (Ferring-Leciva, a.s.) (Czech Republic); Ferring International Center S.A. (Ferring International Center S.A.) (Switzerland)

Description and photo update: 09.09.2019

Pentasa is an anti-inflammatory and antimicrobial intestinal drug with localization of action mainly in the intestine upon contact with the affected mucosa.

Release form and composition

• Sustained-release tablets: round, chamfered, white with a grayish tint and numerous light brown blotches, on one side there is an engraving “500 mg” and a dividing line, on the other side there is an engraving “PENTASA” (10 pcs. In aluminum blisters foil, in a pack of cardboard 2, 3, 5, 6, 9 or 10 blisters; 50 pcs. in plastic bottles, in a pack of cardboard 1 bottle);
• Sustained-release granules for oral administration: cylindrical, color from light brown to light gray (in bags of aluminum foil / polyester / low density polyethylene: 1 g each - 50, 60, 100, 120 or 150 pcs. In a cardboard box ; 2 g each - 30, 50, 60 or 120 pcs. in a cardboard box);
• Rectal suppositories: oval, color from white with a yellowish-brown tinge to white, with numerous light gray blotches (5 or 7 pieces in blisters made of aluminum foil, in a package of 1, 2, 3, 4 or 6 blisters, 1 package in a cardboard box, the kit may include rubber hygienic fingertips);
• Rectal suspension: a suspension of white or light yellow color (100 ml in bottles made of low density polyethylene, sealed with a tip with a valve that allows the suspension to flow in one direction, hermetically sealed in a nitrogen atmosphere in aluminum foil bags; 7 bags with bottles in a pack cardboard, the kit may include plastic hygienic bags).

Each pack also contains instructions for the use of Pentasa.

Composition of 1 tablet:

• Active ingredient: mesalazine - 0.5 g;
• Auxiliary components: povidone, talc, microcrystalline cellulose, magnesium stearate, ethyl cellulose.

Composition of 1 sachet of granules:

• Active ingredient: mesalazine - 1 g or 2 g;
• Auxiliary components: ethylcellulose, povidone.

Composition of 1 suppository:

• Auxiliary components: talc, macrogol 6000, magnesium stearate, povidone.

Composition of 100 ml suspension (1 bottle):

• Active ingredient: mesalazine - 1 g;
• Auxiliary components: sodium disulfite, disodium edetate dihydrate, sodium acetate trihydrate, purified water (up to 100 ml), concentrated hydrochloric acid to pH 4.6-5.0.

Pharmacological properties

Pharmacodynamics

Mesalazine is the active component of sulfasalazine (5-aminosalicylic acid). The therapeutic effect of Pentasa after oral or rectal administration is more related to the local effect on the inflamed intestinal tissue than to its systemic effect.

The main effects of mesalazine: inhibition of leukocyte chemotaxis, a decrease in the production of cytokines and leukotriene, and a decrease in the formation of free radicals in the inflamed intestinal tissue. However, the exact mechanism of action of the substance is not fully understood.

The therapeutic effect of mesalazine is manifested by local contact with the affected intestinal mucosa.

Pharmacokinetics

Oral capsules and granules

After oral administration, the tablet and granules disintegrate into microgranules, which act as separate sustained-release forms of the drug. This ensures the therapeutic effect of Pentasa along the entire length from the duodenum to the rectum at any pH value. After taking the drug, microgranules reach the duodenum in 60 minutes. The transit time of mesalazine through the small intestine is approximately 3-4 hours.

Approximately 30-50% of the dose taken is absorbed in the small intestine (mainly). The maximum plasma concentration of mesalazine is reached in 60 minutes and lasts up to 4 hours, gradually decreasing.

Mesalazine in the liver and intestinal mucosa undergoes acetylation (to a small extent - with the participation of enterobacteria), while the formation of the main metabolite, N-acetyl-5-aminosalicylic acid, occurs. Plasma proteins bind 43% of mesalazine and 73–83% of the metabolite. Mesalazine and its metabolite do not pass through the blood-brain barrier, but pass into breast milk. The clearance of the substance is 18 l / h. In the case of taking high doses (up to 1500 mg per day), a cumulative effect may be observed.

T 1/2 (half-life) of mesalazine and metabolite from plasma is about 40 and 70 minutes, respectively. Excretion of the substance and metabolite is carried out with feces and urine.

Rectal suppositories and suspension

Absorption and distribution:

• Suppositories: create a high concentration of mesalazine in the distal part of the intestine, while its minimal systemic absorption (up to 10%) is noted. Plasma proteins bind 43 and 73% of mesalazine and its main metabolite, respectively;
• Suspension: has a therapeutic effect in the distal intestine. Absorbed on average from 15 to 20% of the administered dose. The degree of absorption in ulcerative colitis in the active phase is noticeably lower than in patients in remission. On average, 50 and 80% of mesalazine and its main metabolite bind to proteins, respectively.

Mesalazine and its metabolite do not pass through the blood-brain barrier, but penetrate into breast milk.

Mesalazine in the liver and intestinal mucosa undergoes acetylation (to a small extent - with the participation of enterobacteria), while the formation of the main metabolite, N-acetyl-5-aminosalicylic acid, occurs.

Excretion of the substance and metabolite is carried out with feces and urine.

Indications for use

Pentasa granules and tablets are taken for Crohn's disease and ulcerative colitis.

Rectal suppositories are used in the case of ulcerative proctitis, one of the forms of ulcerative colitis affecting the distal colon.

Contraindications

Absolute:

• Hemorrhagic diathesis;
• Severe renal and / or liver dysfunction;
• A stomach or duodenal ulcer;
• Pregnancy (2-4 weeks before delivery);
• Breastfeeding (lactation) period;
• Children under 2 years of age (for tablets), up to 6 years (for granules); suspension and suppositories of Pentas are contraindicated for use in pediatrics due to insufficient data;
• Hypersensitivity to mesalazine and / or other components.

Relative (Pentasa is used with caution due to the increased risk of complications):

• Allergy to salicylates (hypersensitivity reactions to sulfasalazine are possible);
• Lung function disorders, in particular bronchial asthma;
• Renal / hepatic impairment of mild to moderate severity (an increase in the systemic concentration of mesalazine and a decrease in the rate of elimination increases the risk of kidney damage);
• Pregnancy (except for the period 2-4 weeks before childbirth) (Pentasu is used according to indications, only if the potential benefit to the mother exceeds the possible risk of adverse effects to the fetus).

Pentasa, instructions for use: method and dosage

Extended release tablets

Pentas tablets are taken orally after meals, without chewing. If the patient cannot swallow the pill whole, it is allowed to divide it into several parts, or dissolve it in juice or water immediately before taking it.

• Ulcerative colitis: with exacerbation - 2 pcs. 2-4 times a day; supportive treatment - 1 pc. 2-3 times a day;
• Crohn's disease: with exacerbation - 2-4 pcs. 4 times a day; supportive treatment - 2-4 pcs. 2 times a day or 2-3 pcs. 3 times a day.

For children, an individual dose of mesalazine is selected, usually at the rate of 0.02-0.03 g / kg of body weight per day in several doses.

Sustained release granules

Pentas granules are taken orally after meals, without chewing. The contents of one sachet should be poured onto the tongue, then washed down with juice or water.

The daily dose of mesalazine (selected individually, it should be divided into several doses):

• Adults: with exacerbation - up to 4 g; maintenance treatment - 2-4 g;
• Children from 6 years old and adolescents: in case of exacerbation - 0.02-0.03 g / kg of body weight, but not more than 4 g (the maximum single dose should not exceed 0.075 g / kg); supportive treatment - 0.02-0.03 g / kg, maximum - no more than 2 g.

The duration of the course of therapy is determined by the attending physician.

Rectal suppositories

Pentasa rectal suppositories are intended to be inserted into the rectum.

The manipulation is carried out after bowel movement. A rubber fingertip should be used to ensure the hygiene of the procedure. In order to facilitate administration, the suppository can be moistened with water, and then inserted into the anus until the resistance of the muscle pulp stops. If the candle comes out within 10 minutes after the injection, you need to repeat the procedure using another suppository.

Rectal suspension

The drug is used once a day before bedtime in the form of an enema. It is advisable to empty the bowel before the procedure.

Open the package immediately before use, shake the contents of the bottle. Turn the tip with a valve until it stops, allowing the suspension to flow out in one direction. Lie on your side to perform the procedure and gently insert the tip as deep as possible into the rectum.

The average duration of therapy with rectal forms of Pentasa (suspension, suppositories) is 8-12 weeks, an indicator of its effectiveness is the achievement of clinical and endoscopic remission. The maximum duration of the course, including supportive and anti-relapse therapy, is not limited.

Side effects

Side effects from the use of mesalazine from organs and systems, in accordance with the gradation - often -> 1% -<10%; редко – >0,01%-< 1%; очень редко – <0,01%, в т. ч. единичные случаи:

• Hematopoietic organs: very rarely - anemia, leukopenia, eosinophilia, granulocytopenia, thrombocytopenia, pancytopenia, agranulocytosis;
• Immune system: very rarely - hypersensitivity reactions, Quincke's edema, drug fever;
• Nervous system: rarely - dizziness; very rarely - benign intracranial hypertension, peripheral neuropathy;
• Cardiovascular system: rarely - pericarditis, myocarditis;
• Respiratory system: very rarely - cough, shortness of breath, allergic alveolitis, infiltration in the lungs, pulmonary eosinophilia, pneumonia, bronchospasm;
• Digestive system: often - diarrhea, abdominal pain, nausea, vomiting, flatulence; rarely - pancreatitis, increased amylase content; very rarely - exacerbation of colitis symptoms;
• Hepatobiliary system: very rarely - increased levels of bilirubin and liver enzymes, hepatotoxicity (hepatosis, hepatitis, liver failure, cirrhosis);
• Skin: often - eczema, urticaria; very rarely - reversible alopecia, photosensitivity;
• Musculoskeletal system: very rarely - arthralgia, myalgia;
• Urinary system: very rarely - nephrotic syndrome, interstitial nephritis, transient renal failure, changes in urine color;
• Others: often - fever, headache;
• Reactions at the injection site (suspension, suppositories): rarely - pain and irritation in the anal area.

Most often, due to the use of mesalazine, there are: diarrhea, nausea, abdominal pain, headache - up to 3% of cases; vomiting and skin rashes - up to 1% of cases.

In case of aggravation of any side effects from those indicated in the instructions, or the occurrence of any other reactions not described in the instructions, you need to seek the advice of your doctor.

Overdose

Overdose cases, especially with rectal administration of Pentasa, are rare.

The main symptoms: vomiting, nausea, gastralgia, drowsiness, weakness.

Therapy: symptomatic in combination with control of kidney and liver function. In the case of the development of acidosis, dehydration or alkalosis, restoration of acid-base and water-electrolyte balance is required. With signs of hypoglycemia, glucose is indicated.

There is no specific antidote.

special instructions

If there are acute signs of Pentasa intolerance (such as muscle cramps, abdominal pain, fever, severe headache, skin rash) or symptoms of impaired renal and / or liver function, therapy should be interrupted.

It is required to carry out regular monitoring of the creatinine in the blood throughout the entire time of use of any form of release of the drug Pentasa.

Coloring of soft contact lenses, lacrimal fluid and urine in yellow-orange color is allowed.

Influence on the ability to drive vehicles and complex mechanisms

Patients are advised to be careful when taking tablets, granules and using rectal suspension, driving vehicles and engaging in other potentially hazardous activities that require speed of psychomotor reactions and increased concentration of attention, since they may be influenced by such side effects of Pentasa as nausea, weakness, dizziness, etc.

Application during pregnancy and lactation

• Pregnancy (2-4 weeks before delivery), lactation period: therapy is contraindicated;
• Pregnancy (excluding the period 2-4 weeks before childbirth): Pentasa can only be used after evaluating the ratio of the expected benefit to the possible risk.

Childhood use

Age restrictions for the use of Pentasa in pediatrics, depending on the form of release:

• Tablets: up to 2 years;
• Granules: up to 6 years old;
• Suppositories and suspensions: up to 18 years of age.

With impaired renal function

Mesalazine therapy is contraindicated in patients with severe renal impairment.

In case of impaired renal function of mild to moderate severity, Pentasa should be used with caution.

For violations of liver function

Mesalazine therapy is contraindicated in patients with severe hepatic impairment.

In case of impaired hepatic function of mild to moderate severity, Pentasa should be used with caution.

Drug interactions

With simultaneous use with mesalazine:

• Azathioprine or mercaptopurine - increase the risk of bone marrow suppression (thrombocytopenia, leukopenia, pancytopenia, erythrocytopenia / anemia);
• Non-steroidal anti-inflammatory drugs (NSAIDs), azathioprine and other nephrotoxic drugs - increase the risk of side effects from the kidneys;
• Cyanocobalamin (Vitamin B 12) - absorption slows down;
• Sulfonylurea derivatives - increased hypoglycemic effect;
• Glucocorticosteroids (GCS) - ulcerogenicity increases;
• Methotrexate - increased toxicity;
• Furosemide, spironolactone, sulfonamides, rifampicin - activity is weakened;
• Anticoagulants - the effect is enhanced;
• Tubular secretion blockers (uricosuric drugs) - efficiency increases.

Analogs

The analogues of Pentasa are: Mesakol, Salofalk, Salozinal, Samezil, Mezavant, Asakol, Mesalazin.

Terms and conditions of storage

Keep out of the reach of children, in a dry, dark place at temperatures up to 25 ° C.

Shelf life:

• Granules - 2 years;
• Tablets, suspension, suppositories - 3 years.

An anti-inflammatory drug used to treat Crohn's disease and NUC

Active substance

Mesalazine (5-ASA) (mesalazine)

Release form, composition and packaging

Extended release tablets white with a grayish shade of color, with numerous blotches of light brown color, regular round shape, with a chamfer, a line and the inscription "500 mg" on one side and "Pentasa" - on the other.

Excipients: ethyl cellulose, magnesium stearate, talc, microcrystalline cellulose.

10 pieces. - blisters (5) - cardboard packs.
10 pieces. - blisters (10) - cardboard packs.

pharmachologic effect

An anti-inflammatory drug used to treat Crohn's disease and NUC.

It has an antibacterial effect against Escherichia coli and some cocci (manifested in the colon).

It has an antioxidant effect (due to the ability to bind to free oxygen radicals and destroy them).

Reduces the risk of recurrence in Crohn's disease, especially in patients with ileitis with a long duration of the disease.

The therapeutic effect of mesalazine is manifested as a result of local contact of the drug with the intestinal mucosa. After oral administration, the tablet disintegrates into microgranules, which act as independent forms of the drug with a slow release of mesalazine. This ensures the therapeutic effect of the drug from the duodenum to the rectum at any pH value. Microgranules reach the duodenum within the first hour after taking the tablet. Passage of the drug through the intact small intestine when ingested is carried out within 3-4 hours.

Pharmacokinetics

Absorption and distribution

About 30-50% of the dose taken is absorbed mainly in the small intestine.

The binding of mesalazine to proteins is 43%, and N-acetyl-5-aminosalicylic acid is 73-83%.

Mesalazine and its metabolites do not penetrate the BBB. Cumulative properties occur when using high doses of the drug - 1500 mg / day.

Metabolism and excretion

Mesalazine undergoes acetylation in the intestinal mucosa, in the liver and, to a small extent, by enterobacteria, forming N-acetyl-5-aminosalicylic acid.

The clearance of mesalazine after intravenous administration at a dose of 500 mg is 18.0 l / h.

Mesalazine and its metabolite are excreted in breast milk, urine and feces.

Indications

Contraindications

- blood diseases;

- peptic ulcer of the stomach and duodenum;

- deficiency of glucose-6-phosphate dehydrogenase;

- hemorrhagic diathesis;

- severe renal failure;

- severe liver failure;

- the last 2-4 weeks of pregnancy;

- lactation period;

- children under 2 years old;

- hypersensitivity to the components of the drug.

WITH caution the drug should be used in the first trimester of pregnancy, with hepatic and / or renal failure.

Dosage

The tablets should be swallowed without chewing. To facilitate swallowing, the tablet can be divided into several parts or dissolved in an injection or juice just before taking.

The dose of the drug is selected individually.

The maximum daily dose of the drug is 6-8 g / day.

The average duration of treatment is 8-12 weeks. The maximum duration of treatment, including supportive and anti-relapse therapy, is not limited. The criterion for the effectiveness of the therapy is the achievement of clinical and endoscopic remission.

Side effects

From the digestive system: nausea, vomiting, heartburn, diarrhea, decreased appetite, abdominal pain, dry mouth, stomatitis, increased activity of hepatic transaminases, hepatitis, pancreatitis.

On the part of the cardiovascular system: palpitations, tachycardia, increase or decrease in blood pressure, chest pain, shortness of breath, pericarditis, myocarditis.

From the side of the central nervous system and peripheral nervous system: headache, tinnitus, dizziness, polyneuropathy, tremor, depression.

From the urinary system: proteinuria, hematuria, oliguria, anuria, crystalluria, nephrotic syndrome.

From the hematopoietic system: eosinophilia, anemia (including hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, hypoproteinemia.

Allergic reactions: skin rash, itching, dermatoses (pseudoerythromatosis), bronchospasm.

Others: weakness, mumps, lupus-like syndrome, oligospermia, alopecia, decreased production of tear fluid, photosensitization.

Overdose

Symptoms: nausea, vomiting, gastralgia, weakness, drowsiness.

Treatment: gastric lavage, prescription of laxatives, symptomatic therapy.

Drug interactions

With the simultaneous use of Pentas, it enhances the hypoglycemic effect of sulfonylurea derivatives, the ulcerogenicity of GCS, the toxicity of methotrexate and the effect of anticoagulants.

With the simultaneous use of Pentas, it weakens the activity of furosemide, spironolactone, sulfonamides, rifampicin.

With the simultaneous use of Pentas, it increases the effectiveness of uricosuric drugs.

With the simultaneous use of Pentasa, it slows down the absorption of cyanocobalamin.

special instructions

Treatment of patients with impaired liver or kidney function is possible only after assessing their severity.

During the entire course of treatment, and especially at the beginning, kidney function (level of creatinine in the blood) should be regularly monitored.

If you suspect the development of pericarditis, myocarditis and changes in the blood count, treatment should be interrupted. The manifestations of the above side reactions can serve with pronounced pathological changes in the composition of the blood - increased bleeding, subcutaneous hemorrhage, and fever; with pericarditis and / or myocarditis - fever and chest pain in combination with shortness of breath.

In some cases of an allergic reaction to the possible development of intolerance to the drug Pentasa (risk of allergy to salicylates).

Patients who are "slow acetylators" are at increased risk of side effects.

Possible staining of urine and lacrimal fluid in a yellow-orange color, staining of soft contact lenses.

Influence on the ability to drive vehicles and control mechanisms

The drug does not affect the ability to drive vehicles and control mechanisms.

Pregnancy and lactation

The use of the drug during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

Mesalazine crosses the placental barrier, but limited experience with the drug during pregnancy does not allow assessing possible side effects.

Terms of dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children, at a temperature not exceeding 25C. Shelf life is 3 years.