Ukrenzym 10000

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT UKRENZYME® 10000 (UKRENZYME® 10000)

Composition:

Active substance: pancreatin;

1 hard capsule contains 150 mg of pancreatin in gastroresistant granules, which have enzymatic activity: lipase 10,000 IU Ph. Eur., amylase 8,000 IU Ph. Eur., protease 600 IU Ph. Eur.;

Excipients: macrogol 8000, hypromellose, hypromellose phthalate, triethyl citrate, dimethicone;

hard capsule: gelatin, purified water, iron oxide yellow (E 172), iron oxide red (E 172), iron oxide black (E 172), titanium dioxide (E 171), sodium lauryl sulfate.

Pharmaceutical form. Hard capsules with gastroresistant granules.

Main physicochemical characteristics: hard gelatin capsule size 1 with an opaque brown cap and a transparent colorless body, containing brownish gastroresistant granules.

Pharmacotherapeutic group. Digestive enzymes and other agents used to improve digestion. Pancreatic enzyme preparations.

ATC code A09AA02.

Pharmacological Properties

Pharmacodynamics

UKRENZYM 10000 contains porcine-derived pancreatin in the form of enteric-coated (acid-resistant) granules in gelatin capsules. The capsules dissolve rapidly in the stomach, releasing a large number of granules according to the multi-dose principle, ensuring good mixing with gastric contents, transport from the stomach together with its contents, and favorable distribution of enzymes within intestinal contents after release. When the granules reach the small intestine, the coating dissolves rapidly (at pH > 5.5), releasing enzymes with lipolytic, amylolytic, and proteolytic activity, which enables the breakdown of fats, carbohydrates, and proteins. The products of pancreatic digestion are subsequently absorbed either directly or after further hydrolysis by intestinal enzymes.

Clinical efficacy

Treatment with pancreatin has been shown to significantly reduce symptoms associated with impaired exocrine pancreatic function, including stool consistency, abdominal pain, meteorism, and frequency of defecation, regardless of the underlying disease in patients with exocrine pancreatic insufficiency.

Preclinical safety data

Preclinical studies have not revealed evidence of relevant acute, subchronic, or chronic toxicity. Studies on genotoxicity, carcinogenicity, or toxic effects on reproduction have not been conducted.

Pharmacokinetics

Animal studies have not shown evidence of absorption of enzymes in unchanged form; therefore, classical pharmacokinetic studies have not been performed. Medicinal products containing pancreatic enzymes do not require systemic absorption to achieve their therapeutic effect. On the contrary, their full therapeutic action occurs within the lumen of the gastrointestinal tract. Moreover, as proteins, they undergo proteolytic digestion in the gastrointestinal tract before being absorbed as peptides and amino acids.

Clinical Characteristics

Indications

Treatment of exocrine pancreatic insufficiency in adults and children caused by various diseases and conditions, including but not limited to the following:

• Chronic pancreatitis;
• Pancreatectomy;
• Gastrectomy;
• Gastrointestinal anastomosis surgery (e.g., Billroth II gastroenteroanastomosis);
• Shwachman-Diamond syndrome;
• Condition following an acute pancreatitis attack and restoration of enteral or oral nutrition.

Contraindications

Hypersensitivity to the active substance, to pork (pork allergy), or to any other component of the medicinal product.

Acute hepatitis.

Mechanical jaundice.

Obstructive intestinal obstruction.

Interaction with other medicinal products and other forms of interaction

Iron. Concomitant use of pancreatin with iron preparations may reduce iron absorption.

Folic acid. Absorption of folic acid may be reduced in patients taking pancreatin; therefore, monitoring of folic acid levels is recommended when used concomitantly.

Acarbose, miglitol. Pancreatin may reduce the effectiveness of acarbose and miglitol. Therefore, blood glucose levels should be monitored during concomitant use.

Special precautions for use

During administration of high doses of pancreatin, narrowing of the ileocecal region of the intestine and colon (fibrosing colonopathy) has been observed. Therefore, if unusual abdominal symptoms occur or if there is a change in the nature of abdominal symptoms, medical advice should be sought to exclude fibrosing colonopathy, especially if the patient is receiving more than 10,000 IU E.U. of lipase/kg/day (see section "Adverse reactions").

There is a theoretical risk of transmission of porcine viral infections, including infections caused by new or undefined viruses. The possibility of porcine viruses capable of infecting humans cannot be completely ruled out. However, to date, no cases of transmission of infectious diseases due to the use of porcine pancreatin preparations have been reported.

Caution should be exercised when administering to patients with renal insufficiency or hyperuricemia.

Should not be used in acute or chronic pancreatitis during the exacerbation phase until the patient is switched to enteral nutrition.

Excipients

This medicinal product contains sodium in the amount of 0.00022 mmol/capsule, i.e. practically sodium-free.

Use during pregnancy or breast-feeding

Data on the use of pancreatin in pregnant women are lacking. Animal studies are insufficient to determine the impact of pancreatin on pregnancy, embryonal/foetal development, delivery, and postnatal development of the child. The potential risk for humans is unknown. Therefore, the medicinal product UKRENZYM 10000 should not be used during pregnancy and lactation, except in individual cases where, in the opinion of the physician, the benefit of its use outweighs the potential risks.

Ability to affect driving performance and use of machinery

The effect of the medicinal product on the ability to drive vehicles or operate machinery is absent or negligible.

Method of Administration and Dosage

Method of Administration

The medicinal product should be taken during or immediately after a meal.

Capsules and granules should be swallowed whole, without breaking or chewing, and taken with sufficient fluid during or immediately after a meal, particularly a light snack.

If a patient is unable to swallow the capsule whole (e.g., children or elderly patients), it may be carefully opened and the granules mixed with soft food with an acidic environment (pH < 5.5) that does not require chewing, or with a liquid with an acidic environment (pH < 5.5). Suitable options include apple puree, yogurt, or fruit juice with pH < 5.5, such as apple, orange, or pineapple juice.

When mixing granules with food or liquid, it is important to consume the mixture immediately. Such mixtures must not be stored.

Breaking or chewing the granules, or mixing them with food or liquids with pH > 5.5, may damage their protective enteric coating. This may lead to premature release of enzymes in the oral cavity, reduced efficacy of the medicinal product, and irritation of the mucous membranes.

Care must be taken to ensure that no residue of the medicinal product remains in the oral cavity.

Adequate fluid intake during pancreatin therapy is very important, especially during periods of increased fluid loss. Fluid deficiency may worsen constipation.

Any mixture of granules with food or liquid should be taken immediately and must not be stored.

Dosage

Dosage of the medicinal product is based on individual patient needs and depends on the severity of the disease and dietary composition.

Treatment should be initiated at the lowest recommended dose, gradually increasing while carefully monitoring the patient's response to therapy, disease symptoms, and nutritional status. Patients should be warned against self-adjusting the dose. Dose adjustment may require several days.

Adults

The usual starting dose is 10,000 to 25,000 IU of lipase activity per main meal. However, some patients may require higher doses to control steatorrhea and maintain adequate nutritional status. According to standard clinical practice, a minimum of 20,000 to 50,000 IU of lipase activity should be taken with each meal. The dose for main meals (breakfast, lunch, or dinner) may range from 25,000 to 80,000 IU of lipase activity, while for light snacks between main meals, the dose should be half the individual main-meal dose.

Children (from birth to 18 years of age)

Dosage and duration of treatment for children are determined individually by the physician.

Duration of Treatment

The duration of treatment is determined by the physician based on the nature and course of the disease.

Children

The medicinal product UKRENZYM 10000 may be used in children (see section "Method of Administration and Dosage").

Overdose

Cases of hyperuricosuria and hyperuricemia have been reported following ingestion of extremely high doses of pancreatin.

Supportive measures are recommended, including discontinuation of enzyme therapy and ensuring adequate rehydration.

Adverse Reactions

Gastrointestinal disorders were most frequently reported, mostly of mild or moderate severity, primarily associated with the underlying disease.

The frequency categories of adverse reactions are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data).

Gastrointestinal disorders:

Very common — abdominal pain*;

Common — nausea, vomiting, constipation, bloating, diarrhea*;

Very rare — changes in stool characteristics, irritation of the skin around the mouth or anus, particularly after high-dose administration;

Frequency not known — narrowing of the ileocecal region and ascending colon (fibrosing colonopathy)**.

Skin and subcutaneous tissue disorders:

Uncommon — rash;

Frequency not known — pruritus, urticaria.

Immune system disorders:

Frequency not known — immediate-type allergic reactions***, hypersensitivity (anaphylactic reactions and gastrointestinal-localized reactions).

Effects on laboratory and instrumental test results:

Frequency not known — hyperuricemia, hyperuricosuria, folate deficiency.

* Frequency was similar to or lower than with placebo.

** Narrowing of the ileocecal region and colon (fibrosing colonopathy) has been reported in patients receiving high doses of pancreatin-containing products (see section "Dosage and Administration").

*** Allergic reactions were predominantly skin-related (rash, urticaria); other manifestations included sneezing, lacrimation, bronchospasm, and dyspnea.

Children

No specific adverse reactions have been identified in pediatric patients. The frequency, type, and severity of adverse reactions in children are similar to those in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions

Store at temperatures not exceeding 25°C in the original packaging.

Keep out of reach and sight of children.

Packaging. 10 capsules per blister, 2 or 10 blisters per cardboard pack.

Prescription status. Over-the-counter (OTC).

Manufacturer. Kusum Healthcare Pvt Ltd.

Manufacturer's address and location of operations

Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India.

INSTRUCTIONS

for medical use of the medicinal product

UKRENZYM 10000

(UKRENZYME® 10000)

Composition:

Active substance: pancreatin;

1 hard capsule contains 150 mg of pancreatin in gastroresistant granules, which have enzymatic activity: lipase 10,000 IU Ph.Eur., amylase 8,000 IU Ph.Eur., protease 600 IU Ph.Eur.;

Excipients: macrogol 8000, hypromellose, hypromellose phthalate, triethyl citrate, simethicone;

hard capsule: gelatin, purified water, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172), titanium dioxide (E 171), sodium lauryl sulfate.

Dosage form. Hard capsules with gastroresistant granules.

Main physicochemical properties: hard gelatin capsule size 1 with an opaque brown cap and a transparent colorless body, containing brownish gastroresistant granules.

Pharmacotherapeutic group. Digestive enzymes. Pancreatic enzyme preparations.

ATC code A09AA02.

Pharmacological Properties

Pharmacodynamics

UKRENZYM 10000 contains porcine-derived pancreatin in the form of enteric-coated (acid-resistant) granules in gelatin capsules. The capsules dissolve rapidly in the stomach, releasing a large number of granules according to the multi-dose principle, ensuring good mixing with gastric contents, transport from the stomach along with its contents, and even distribution of enzymes within the intestinal contents after release. When the granules reach the small intestine, the coating dissolves rapidly (at pH > 5.5), releasing enzymes with lipolytic, amylolytic, and proteolytic activity, which enables the breakdown of fats, carbohydrates, and proteins. The products of pancreatic digestion are then absorbed either directly or after further hydrolysis by intestinal enzymes.

Clinical efficacy

Treatment with pancreatin has been shown to significantly reduce symptoms associated with impaired exocrine pancreatic function, including stool consistency, abdominal pain, meteorism, and frequency of defecation, regardless of the underlying disease in patients with exocrine pancreatic insufficiency.

Preclinical safety data

Preclinical studies have not indicated relevant acute, subchronic, or chronic toxicity. Studies on genotoxicity, carcinogenicity, or toxic effects on reproduction have not been performed.

Pharmacokinetics

Animal studies have not shown evidence of absorption of unchanged enzymes; therefore, classical pharmacokinetic studies have not been conducted. Medicinal products containing pancreatic enzymes do not require absorption to achieve their therapeutic effect. On the contrary, their full therapeutic action occurs within the lumen of the gastrointestinal tract. Moreover, as proteins, they undergo proteolytic digestion in the gastrointestinal tract before being absorbed as peptides and amino acids.

Clinical characteristics

Indications

Treatment of exocrine pancreatic insufficiency in adults and children caused by various diseases and conditions, including but not limited to those listed below:

• Chronic pancreatitis;
• Pancreatectomy;
• Gastrectomy;
• Gastrointestinal anastomosis surgery (e.g., gastroenterostomy according to Billroth II);
• Shwachman-Diamond syndrome;
• Condition following an acute pancreatitis attack and restoration of enteral or oral feeding.

Contraindications

Hypersensitivity to the active substance, to pork (pork allergy), or to any other component of the medicinal product.

Acute hepatitis.

Mechanical jaundice.

Obstructive intestinal obstruction.

Interaction with other medicinal products and other forms of interaction

Iron. Concomitant use of pancreatin with iron preparations may reduce iron absorption.

Folic acid. Absorption of folic acid may be reduced in patients taking pancreatin; therefore, monitoring of folic acid levels is recommended when used concomitantly.

Acarbose, miglitol. Pancreatin may reduce the effectiveness of acarbose and miglitol. Therefore, blood glucose levels should be monitored in patients during concomitant use.

Special precautions for use

During the use of high doses of pancreatin, narrowing of the ileocecal region of the intestine and the colon (fibrosing colonopathy) has been observed. Therefore, if unusual abdominal symptoms occur or if there is a change in the nature of existing abdominal symptoms, it is recommended to consult a physician to rule out fibrosing colonopathy, especially in patients receiving more than 10,000 IU/kg/day of lipase (see section "Adverse reactions").

There is a theoretical risk of transmission of porcine viral infections, including infections caused by novel or undefined viruses. The possibility of porcine viruses infecting humans cannot be completely excluded. However, to date, no cases of infectious disease transmission due to the use of porcine pancreatin preparations have been reported.

Caution should be exercised when administering to patients with renal insufficiency or hyperuricemia.

Should not be used in acute or chronic pancreatitis during the exacerbation phase until the patient is switched to enteral nutrition.

Excipients

This medicinal product contains sodium in the amount of 0.00022 mmol/capsule, i.e. practically sodium-free.

Use during pregnancy or breastfeeding

There are no data on the use of pancreatin in pregnant women. Animal studies are insufficient to determine the impact of pancreatin on pregnancy course, embryonic/fetal development, labor, and postnatal development of the child. The potential risk for humans is unknown. Therefore, the medicinal product UKRENZYM 10000 should not be used during pregnancy and breastfeeding, except in individual cases where, in the opinion of the physician, the benefit of its use outweighs the possible risks.

Ability to influence the speed of reactions when driving or operating machinery

The effect of the medicinal product on the ability to drive vehicles or operate machinery is absent or negligible.

Dosage and Administration

Administration

The medicinal product should be taken during or immediately after a meal.

Capsules and granules must be swallowed whole, without breaking or chewing, and taken with sufficient liquid during or immediately after meals, particularly with a light snack.

If a patient is unable to swallow the capsule whole (e.g., children or elderly patients), it may be carefully opened and the granules mixed with soft food or liquid with an acidic environment (pH < 5.5) that does not require chewing. Suitable options include apple puree, yogurt, or fruit juice with pH < 5.5, such as apple, orange, or pineapple juice.

When mixing granules with liquid or food, it is essential to consume the mixture immediately. The mixture must not be stored.

Breaking or chewing the granules, or mixing them with food or liquid with pH > 5.5, may damage their protective enteric coating. This could lead to premature release of enzymes in the oral cavity, reduced efficacy of the medicinal product, and irritation of the mucous membranes.

Care must be taken to ensure that no residue of the medicinal product remains in the oral cavity.

Adequate fluid intake during pancreatin therapy is very important, especially during periods of increased fluid loss. Fluid deficiency may exacerbate constipation.

Any mixture of granules with food or liquid must be taken immediately and must not be stored.

Dosage

The dosage of the medicinal product is based on individual patient needs and depends on the severity of the disease and dietary composition.

Treatment should be initiated at the lowest recommended dose, gradually increasing while carefully monitoring the patient's response to therapy, disease symptoms, and nutritional status. Patients should be warned against self-adjusting the dose. Dose adjustments may require several days to take effect.

Adults

The usual initial dose is 10,000 to 25,000 IU of lipase per main meal. However, some patients may require higher doses to control steatorrhea and maintain adequate nutritional status. According to standard clinical practice, at least 20,000 to 50,000 IU of lipase should be taken with food. The dose for each main meal (breakfast, lunch, or dinner) may range from 25,000 to 80,000 IU of lipase, and for snacks between main meals, half the individual main-meal dose should be administered.

Children (from birth to 18 years of age)

Dosage and duration of treatment for children are determined individually by the physician.

Duration of treatment

The duration of treatment is determined by the physician according to the nature and course of the disease.

Children

The medicinal product UKRENZYM 10000 may be used in children (see section "Dosage and Administration").

Overdose

Cases of hyperuricosuria and hyperuricemia have been reported following the ingestion of extremely high doses of pancreatin.

Supportive measures are recommended, including discontinuation of enzyme therapy and ensuring adequate rehydration.

Side effects

Gastrointestinal disorders, mostly of mild or moderate severity, have been reported most frequently and were mainly associated with the underlying disease.

The frequency categories of adverse reactions are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Gastrointestinal disorders:

Very common — abdominal pain*;

Common — nausea, vomiting, constipation, bloating, diarrhea*;

Very rare — changes in stool characteristics, perianal or perioral skin irritation, particularly after high-dose administration;

Frequency not known — narrowing of the ileocecal region and ascending colon (fibrosing colonopathy)**.

Skin and subcutaneous tissue disorders:

Uncommon — rash;

Frequency not known — pruritus, urticaria.

Immune system disorders:

Frequency not known — immediate-type allergic reactions***, hypersensitivity (anaphylactic reactions and gastrointestinal tract-localized reactions).

Effects on laboratory and instrumental test results:

Frequency not known — hyperuricemia, hyperuricosuria, folate deficiency.

* Incidence was similar to or lower than that observed with placebo.

** Cases of narrowing of the ileocecal region and colon (fibrosing colonopathy) have been reported in patients receiving high doses of pancreatin-containing products (see section "Special precautions").

*** Allergic reactions were predominantly cutaneous (rash, urticaria); other manifestations included sneezing, lacrimation, bronchospasm, and dyspnea.

Children

No specific adverse reactions have been identified in pediatric patients. The frequency, type, and severity of adverse reactions in children are similar to those observed in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, and patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions

Store at temperatures not exceeding 25°C in the original packaging.

Keep out of reach of children.

Packaging. 10 capsules in a blister, 2 or 10 blisters per cardboard pack.

Supply category. Over-the-counter (without prescription).

Manufacturer. GLEDFARM LTD LLC.

Manufacturer's address and location of its business activity

54 Davydovskoho Hryhoriia Street, Sumy, Sumy Oblast, 40020, Ukraine.