Pentasa

Pentasa exhibits intense anti-inflammatory activity. The drug does not have a systemic effect, showing its effect within the inflamed areas of the intestine. With maintenance use of the drug, the likelihood of developing colorectal carcinoma is very low.

Individuals with inflammatory bowel disease experience leukocyte migration, abnormal cytokine production, increased production of the metabolic building blocks arachidonic acid (especially leukotrienes type B4), and increased levels of free radicals within inflamed intestinal tissues. [ 1 ]

Indications Pentasa

Granules and tablets are used in the treatment of moderate and mild forms of ulcerative colitis (non-specific).

Suppositories are usually prescribed for the treatment of ulcerative proctitis.

Release form

The medicine is released in tablets - 10 pieces in a cell plate.

The medicine can also be produced in the form of powder granules – inside a paper sachet (volume 1 or 2 g).

Also available in the form of rectal suppositories (complete with rubber finger cots), 28 pieces per pack.

Pharmacodynamics

By suppressing leukocyte chemotaxis, the drug prevents the movement of leukocytes into the inflammation site, which reduces infiltration. The binding of inflammatory conductors, including leukotrienes, PG and other metabolic components of arachidonic acid, is also weakened.

Pentasa reduces the volume of LPO components, slowing down their damaging effect on intestinal tissues. [ 2 ]

Pharmacokinetics

The granules of the medicine have an ethylcellulose coating. Mesalazine, taken orally and dissolved, is then gradually released from all the microgranules while the tablet passes through the gastrointestinal tract (at any intestinal pH values). After 60 minutes from the moment of taking the medicine orally, the microgranules are detected in the duodenum (this does not depend on the consumption of food). The average period of passage of the medicine through the intestine in volunteers is 3-4 hours.

Exchange processes.

Mesalazine is transformed into the element N-acetyl-mesalazine (presystemically in the intestinal mucosa and systemically in the liver). Weak acetylation occurs with the help of colon microbes, which leads to the formation of N-acetyl-5-aminosalicylic acid. Acetyl-mesalazine is considered to have no toxic and therapeutic effects.

Absorption.

Within 30-50% of the drug after oral administration is absorbed in the small intestine. Already after 15 minutes from the moment of administration, mesalazine is registered in the blood plasma. Plasma Cmax values are observed after 1-4 hours from the moment of administration of the drug. Then the plasma level of the substance gradually decreases; after 12 hours it is no longer detectable.

The plasma AUC level has a similar character, but its values are still higher, and elimination is slower. Metabolic intraplasmic proportions of acetyl-mesalazine and mesalazine are within 3.5-1.3 when taken orally at 0.5 g 3 times a day, as well as 2 g 3 times a day. This allows us to conclude that they depend on the intensity of acetylation.

The stable mean values of mesalazine in blood plasma are 2, 8, and 12 μmol/l when administered per day at 1.5, 4, and 6 g, respectively. For acetyl mesalazine, these values are 6, 13, and 16 μmol/l, respectively.

When administered orally, the movement and release of the drug is not affected by food intake, because the substance has poor systemic absorption.

Distribution processes.

The active element of the drug and its metabolite do not cross the blood-brain barrier. Protein synthesis of mesalazine is approximately 50%, and acetyl-mesalazine is approximately 80%.

Excretion.

The half-life of mesalazine is approximately 40 minutes, and that of acetyl-mesalazine is approximately 70 minutes. Although mesalazine is always released during transit through the gastrointestinal tract, its half-life after oral administration cannot be determined. Tests have shown that stable values of mesalazine after oral administration are observed for 5 days.

Both elements of the drug are excreted with feces and urine. In this case, mainly acetyl-mesalazine is excreted with urine.

Dosing and administration

Granules or tablets should be taken orally, without chewing. To facilitate swallowing, the medicine is washed down with juice or plain water. The portion size is selected personally by the attending physician.

An adult with a relapse of UC or Crohn's disease should take 4000 mg of the drug per day. The maintenance dose in case of Crohn's disease is 4 g of the drug, and in case of UC - 2 g. The daily dose can be divided into several doses.

Children are prescribed 30 mg/kg of the medication; the daily dose should also be taken in several doses.

Rectal suppositories are inserted into the anus - 1-2 pieces per day, until the resistance to this procedure from the circular muscle ceases. Before performing the insertion, it is necessary to clean the intestine with an enema. To ensure the required hygiene during the procedure, it is necessary to use rubber finger cots, which come with the medicine. To facilitate the insertion of the suppository, it can be moistened with water.

If the suppository spontaneously falls out of the intestine, the procedure must be repeated within the next 10 minutes.

• Application for children

Should not be administered to persons under 2 years of age.

Use Pentasa during pregnancy

Pentasu is not prescribed to pregnant women. The drug can be used only in the 1st trimester, if there are strict indications. The use of the drug should be stopped a month before childbirth (if the course of the pathology allows it).

During the treatment period, you should stop breastfeeding.

Contraindications

Main contraindications:

• severe intolerance associated with mesalazine and its metabolic components (cross-resistance with salicylates is observed);
• use in individuals with severe hepatic or secretory dysfunction;
• impaired blood clotting;
• ulcerative pathologies.

Side effects Pentasa

Side effects include:

• Gastrointestinal disorders: dyspeptic disorders, abdominalgia, nausea, bowel disorders. Vomiting sometimes occurs. Biochemical tests may also show an increase in the activity of liver enzymes;
• problems with central nervous system function: lack of coordination, tinnitus, dizziness, depression, tremors and tingling in the extremities;
• secretory disorders: hematuria or proteinuria, as well as urinary disorders that can develop into anuria;
• signs of allergy: epidermal burning or itching, as well as exanthema;
• lesions associated with the cardiovascular system: pain in the sternum, subjective sensation of cardiac arrest, increase or decrease in the level of SBP, bradycardia and dyspnea;
• blood test results: immunosuppression, suppression of all hematopoietic germs and coagulation disorder;
• Others: occasionally alopecia appears or the process of lacrimation decreases.

Overdose

There is limited information on Pentasa poisoning. Symptoms are usually similar to those seen with salicylate salts. Dehydration is accompanied by hyperventilation, acid-base imbalances, and hypoglycemia.

Symptomatic actions are carried out, and the victim is hospitalized. The drug has no antidote.

During the first hours after taking the drug orally, gastric lavage is performed. Regular monitoring of electrolyte and acid-base balance indicators, as well as renal function, is also carried out.

Interactions with other drugs

The administration of the drug together with methotrexate, mercaptopurine, and azathioprine causes an increase in the toxic properties of the latter.

The drug weakens the effect of warfarin.

Pentasa enhances the hypoglycemic activity of sulfonylurea derivatives.

The carcinogenic effect of GCS is enhanced when combined with the drug.

The drug potentiates the therapeutic effect of anticoagulants.

The medicinal effect of rifampicin, sulfonamides and thiazide-type diuretics is weakened when combined with the active element of the drug.

Combination with the drug leads to suppression of cyanocobalamin absorption.

Administration together with uricosuric substances increases their medicinal effect.

Storage conditions

Pentasa should be stored at temperatures not exceeding 25°C.

Shelf life

Pentasa can be used within 24 months from the date of manufacture of the therapeutic product.

Analogues

The analogs of the drug are Budenofalk, Tykveol, Medrol and Probifor with Hydrocortisone, St. John's wort with Defenorm, and also Depo-medrol, Acylact and Cortef with Solu-medrol, as well as Bifiliz and Cinquefoil rhizome.