Micrasim® 40,000 units

Instructions for Use of Micrasim® 40,000 units

Trade name: Mikrazim^®

International Nonproprietary Name: pancreatin

Dosage form: capsules

Composition per 1 capsule:

Excipients included in the enteric coating of the pellets: Methacrylic acid and ethyl acrylate copolymer [1:1] (as a

30% dispersion, additionally containing polysorbate-80, sodium lauryl sulfate)  - 103.20 mg,   triethyl citrate - 20.64 mg,  simethicone emulsion 30% dry mass (32.6%) including: dimethicone – 27.8 %, precipitated colloidal silicon – 1.3 %, suspended colloidal silicon – 0.9 %, methylcellulose – 2.5 %, sorbic acid – 0.1 %, water – 67.4 %)    -   0.62 mg, talc – 51.70 mg.

Capsule shell composition: Body: gelatin – up to 100 %, water - 14-15 %.

Cap: gelatin – up to 100 %, water - 14-15 %,  Sunset Yellow dye - 0.5500%, titanium dioxide - 1.7998%.

Description

Hard gelatin capsules No. 00 with a transparent body and orange cap. The capsule contents are cylindrical, spherical, or irregularly shaped pellets ranging from light brown to brown in color, with a characteristic odor.

Pharmacotherapeutic group: digestive enzyme preparation

ATC code: A09AA02

Pharmacological properties

Mikrazim^® - pancreatin pellets in capsules. The preparation contains enzymes - protease, lipase and amylase, which ensure the digestion of dietary proteins, fats, and carbohydrates. After taking Mikrazim^®, the gelatin capsule dissolves in the stomach within 1-2 minutes, releasing pancreatin pellets coated with an enteric coating. In the stomach, the pellets rapidly and uniformly mix with food and, due to their small size, easily enter the duodenum together with the food bolus. This reproduces the natural digestive process and ensures the maximum speed of onset of action.

The acid-resistant coating of the pellets preserves the enzymes completely intact until they begin working in the intestine, ensuring their maximum digestive activity.

In the small intestine at pH > 5.5   the pellet coating dissolves and at least 97% of the enzymes are released from the pellets within 30 minutes.

Pharmacodynamics

An enzyme preparation that improves food digestion processes in adults and children, thereby significantly reducing the symptoms of pancreatic enzyme deficiency, including abdominal pain, flatulence, changes in stool frequency and consistency. The pancreatic enzymes in the preparation facilitate the digestion of proteins, fats, and carbohydrates, leading to their complete absorption in the small intestine. Mikrazim^® 40000 contains porcine pancreatin in the form of microgranules coated with an enteric (acid-resistant) coating, in gelatin capsules. The capsules dissolve quickly in the stomach, releasing hundreds of microgranules. This principle is designed to ensure the simultaneous passage (entry) of microgranules with food from the stomach into the intestine and thorough mixing of the microgranules with the intestinal contents, and, ultimately, better distribution of the enzymes after their release within the intestinal contents.

When the microgranules reach the small intestine, the enteric coating rapidly disintegrates (at pH > 5.5), releasing enzymes with lipolytic, amylolytic, and proteolytic activity, leading to the breakdown of fats, carbohydrates, and proteins. The resulting breakdown products are then either absorbed directly or undergo further breakdown by intestinal enzymes.

Pharmacokinetics

Animal studies have demonstrated the absence of absorption of intact enzymes, and consequently, classical pharmacokinetic studies have not been performed. Preparations containing pancreatic enzymes do not require absorption to exert their effects. On the contrary, the full therapeutic activity of these preparations is realized in the lumen of the gastrointestinal tract. Moreover, by their chemical structure, they are proteins and, therefore, during passage through the gastrointestinal tract, enzyme preparations are broken down until they are absorbed as peptides and amino acids.

Indications for use

Replacement therapy for exocrine (enzyme) pancreatic insufficiency in children and adults, caused by reduced pancreatic enzyme activity due to impaired production, regulation of secretion, delivery of pancreatic enzymes, or their increased destruction in the intestinal lumen. This is caused by various gastrointestinal diseases, most commonly:

• cystic fibrosis;
• chronic pancreatitis;
• status after pancreatic surgery;
• status after gastrectomy;
• pancreatic cancer;
• partial gastrectomy (e.g., Billroth II);
• obstruction of pancreatic ducts or common bile duct (e.g., due to neoplasm);
• Shwachman-Diamond syndrome;
• status after an acute pancreatitis attack and upon refeeding.

To avoid complications, use only after consultation with a doctor.

Contraindications

• Hypersensitivity to any component of the drug.
• Use during pregnancy and breastfeeding
• Pregnancy

Clinical data on the treatment of pregnant women with preparations containing pancreatic enzymes are lacking. Animal studies have not revealed absorption of porcine pancreatic enzymes, so toxic effects on reproductive function and fetal development are not expected. The drug should be prescribed to pregnant women with caution.

Breastfeeding period

Animal studies have not revealed systemic negative effects of pancreatic enzymes during lactation, so no harmful effects of the drug on the breastfed infant are expected. Pancreatic enzymes can be taken during breastfeeding.

If intake during pregnancy or breastfeeding is necessary, the drug should be taken in doses sufficient to maintain an adequate nutritional status.

Dosage and administration

Mikrazim^® can be prescribed to patients of any age, including infants and elderly people, due to the possibility of individual dose selection by combining preparations with different dosages, as well as the possibility of using the contents of the gelatin capsules (pellets) directly.

Capsules are taken orally, during or after meals, without chewing, with a sufficient amount of fluid (water, juices). If a single dose is more than 1 capsule, half of the total number of capsules should be taken immediately before the meal, and the other half during the meal. If a single dose is 1 capsule, it should be taken during the meal.

If swallowing is difficult (e.g., in young children or elderly persons), the capsule is opened and the preparation is taken directly as pellets, after mixing them with a slightly acidic (pH<5.0) liquid or soft food that does not require chewing (pH<5.0). Any mixture of pellets with food or liquid must be taken immediately after preparation.

When treating with Mikrazim^®  to prevent increased constipation, it is important to ensure adequate water intake, especially with increased fluid loss.

The dose of the drug is selected individually based on age and severity of symptoms. To achieve an adequate individual dose, besides Mikrazim^® 40000 IU capsules, it is possible to use Mikrazim^® with dosages of 10000 IU  or 25000 IU.

Cystic fibrosis

For children over 4 years  of age  the average dose is  500 IU of lipase per kilogram of body weight with each meal. For children under  4 years  of age  the initial calculated dose is 1000 IU of lipase per kilogram of body weight with each feeding (it is recommended to use Mikrazim^® 10000 IU or 25000 IU)   

The dose should be selected individually, depending on the severity of the disease, steatorrhea severity, and nutritional status. The maintenance dose for most patients should not exceed 10000 IU of lipase per kilogram of body weight per day.

For other conditions accompanied by exocrine pancreatic insufficiency, the dose is set individually  taking into account the degree of digestive insufficiency, fat content in the food, individual dietary habits, and the patient's age. The lipase dose required by the patient during a main meal (breakfast, lunch, or dinner) varies from 20000 IU to 75000 IU. 

When treating with Mikrazim^® the average initial lipase dose is 10000 - 25000 IU during a main meal (ensured by using Mikrazim 10000 IU or Mikrazim 25000 IU), but higher doses may be required to achieve a therapeutic effect. Usually, the patient should receive at least 20000 IU- 50,000 IU  of lipase with food.

For severe steatorrhea (more than 15 g of fat in stool per day), with  the presence of diarrhea, weight loss, and lack of effect from dietary therapy, treatment is started with a dosage of 25000 IU of lipase with each meal, but if necessary and well tolerated, the dose is increased to 35000 IU - 40000 IU of lipase per single dose. A further dose increase, in most cases, does not improve treatment results and requires review of the diagnosis, reduction of dietary fat content, and/or additional prescription of proton pump inhibitors.

The average pancreatin dose for adults is 150,000 IU/day; with complete blockade of the exocrine function of the pancreas - 400,000 IU/day, which corresponds to the daily lipase requirement of an adult.

The maximum daily dose is 15000 IU-20000 IU/kg. The permissible dose for children under 1.5 years is 50,000 IU/day; over 1.5 years - 100,000 IU/day.

The duration of pancreatin administration can vary from several days (digestive disorders) to several months or years (long-term replacement therapy).

Side effects

Gastrointestinal disorders

Very common (≥1/10): abdominal pain.

Common (≥1/100, <1/10): nausea, vomiting, constipation, abdominal distension, steatorrhea, diarrhea.

Frequency unknown: strictures of the ileum, cecum, and colon (fibrosing colonopathy). Weight loss.
Gastrointestinal disorders are mainly related to the underlying disease. The frequency of such adverse reactions as abdominal pain and diarrhea was lower or similar to that with placebo.

Strictures of the ileum, cecum, and colon (fibrosing colonopathy) have been observed in patients with cystic fibrosis receiving high doses of pancreatin preparations (see "Special Instructions" section).

Skin and subcutaneous tissue disorders

Uncommon (>1/1000, <1/100): rash.

Frequency unknown: pruritus, urticaria.

Immune system disorders

Frequency unknown: hypersensitivity (anaphylactic reactions, including angioedema).

Allergic reactions were observed predominantly in the skin, but other manifestations of allergy were also noted. Reports of these side effects were obtained during post-marketing use and were spontaneous. For an accurate assessment of frequency, available data are insufficient.

No specific adverse reactions were noted in children. The frequency, type, and severity of adverse reactions in children with cystic fibrosis were similar to those in adults.

Overdose

Symptoms with extremely high doses: hyperuricosuria and hyperuricemia.
Treatment: drug withdrawal, symptomatic therapy.

Interaction with other medicinal products

Interaction studies have not been conducted.

Special instructions

In patients with cystic fibrosis receiving high doses of pancreatin preparations, strictures of the ileum, cecum, and colon (fibrosing colonopathy) have been described. As a precaution, if unusual abdominal symptoms or changes appear, a medical examination is necessary to exclude fibrosing colonopathy, especially in patients taking the drug at a dose exceeding 10000  lipase units/kg per day.

Effect on ability to drive and use machines

The use of Mikrazim^® 40000 has no or negligible influence on the ability to drive and use machines.

Packaging

Capsules 40,000 IU

3, 5, or 10 capsules in a blister pack made of polyvinyl chloride film and printed lacquered aluminum foil.

20, 30, 40, or 50 capsules in a polymer jar (made of high-density polyethylene) with a screw cap.

1 jar, or 1, 2, 3, 4, 6, 8, or 10 blister packs of 3 or 5 capsules, or 1, 2, 3, 4, 5, 6, 8, or 10 blister packs of 10 capsules are placed in a cardboard carton together with the instructions for use.

Storage conditions

Store in a dry place, protected from light and moisture, at a temperature not above 25 °C.  Keep out of reach of children.

Shelf life

3 years.  Do not use after the expiration date.

Supply terms

Over-the-counter.

Name and Address of the Legal Entity in whose name the Marketing Authorization is issued / Organization handling complaints:

JSC "AVVA RUS", Russia 121614, Moscow, ul. Krylatskie Kholmy, 30, building 9.

Tel./Fax: +7 (495) 956-75-54.

avva.com.ru

micrazim.com

Manufactured by:

JSC "AVVA RUS",

Russia, 610044, Kirov region, Kirov, ul. Luganskaya, 53a.

Tel.: +7 (8332) 25-12-29, +7 (495) 956-75-54.

When distributed by JSC "Otisi farm", the instructions state:

Manufactured by order of: JSC "Otisi farm"

Russia, 123112, Moscow, ul. Testovskaya, 10, floor 12, room II, room 29.

Tel.: +7 (495) 221-18-00

www.otcpharm.ru