Hidrasec (Capsules) Instructions for Use

Marketing Authorization Holder

Abbott Laboratories, GmbH (Germany)

Manufactured By

Sophartex (France)

ATC Code

A07XA04 (Racecadotril)

Active Substance

Racecadotril (Rec.INN registered by WHO)

Dosage Form

Hidrasec

Capsules 100 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 2, light yellow in color; capsule contents – white powder with a characteristic odor.

Excipients : lactose monohydrate – 41 mg, pregelatinized corn starch – 78 mg, magnesium stearate – 4 mg, colloidal silicon dioxide – 2 mg.

Composition of the hard gelatin capsule iron oxide yellow dye (E172) – 0.061 mg, titanium dioxide (E171) – 1.22 mg, gelatin – up to 61 mg.

10 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Antidiarrheal drug

Pharmacotherapeutic Group

Antidiarrheal agent

Pharmacological Action

Antidiarrheal agent. Racecadotril is a prodrug that is hydrolyzed to the active metabolite – thiorphan, which is an enkephalinase inhibitor, a surface peptidase (located on the cell membrane) localized in various tissues, especially in the epithelium of the small intestine.

This enzyme is responsible for both the hydrolysis of exogenous peptides and the breakdown of endogenous peptides, such as enkephalins. As a result, Racecadotril protects endogenous enkephalins, which exhibit physiological activity at the level of the digestive tract, prolonging their antisecretory action.

It is an intestinal antisecretory substance. It reduces intestinal hypersecretion of water and electrolytes caused by cholera enterotoxin or inflammation and does not affect basal intestinal secretion.

Racecadotril has a rapid antidiarrheal effect without changing the transit time of intestinal contents through the intestine. It does not cause bloating.

Pharmacokinetics

After oral administration, Racecadotril is rapidly absorbed. The time to onset of plasma enkephalinase inhibition is 30 min. C_max is reached 2.5 h after administration. Food intake does not affect the bioavailability of racecadotril, but after a meal, the drug’s activity is delayed by approximately 1.5 h.

In blood plasma after administration of racecadotril labeled with the radioactive isotope ¹⁴C, the content of radiocarbon was many times higher than in blood cells and 3 times higher than in whole blood. Thus, the drug binds insignificantly to blood cells. Radiocarbon is moderately distributed in other body tissues, as evidenced by an apparent V_d in plasma of 66.4 kg. 90% of the active metabolite of racecadotril (thiorphan) ((RS)-N(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine) binds to plasma proteins, predominantly albumin.

When taking racecadotril at a dose of 100 mg, the time to peak plasma enkephalinase inhibition is approximately 2 h and corresponds to 75% inhibition. The duration and efficacy of racecadotril’s action are dose-dependent. In adults, the time to peak plasma enkephalinase inhibition is approximately 2 h and corresponds to 75% inhibition when taking a 100 mg dose. The duration of plasma enkephalinase inhibition is approximately 8 h.

Racecadotril is rapidly hydrolyzed to thiorphan, the active metabolite, which, in turn, is transformed into inactive metabolites. Repeated doses of racecadotril do not lead to its accumulation in the body. Data from in vitro studies show that Racecadotril/thiorphan and four main inactive metabolites do not inhibit CYP enzyme isoforms (3A4, 2D6, 2C9, 1F2, and 2C19) to an extent that may be clinically significant. Data from in vitro studies show that Racecadotril/thiorphan and four main inactive metabolites do not induce CYP enzyme isoforms (3A, 2A6, 2B6 2C9/2C19, 1A, 2E1) and conjugated uridine glucuronosyltransferase (UGT) enzymes to an extent that may be clinically significant.

The biological T_1/2 of racecadotril, measured as the time of plasma enkephalinase inhibition, is approximately 3 h. Racecadotril is eliminated from the body in the form of active and inactive metabolites, predominantly by the kidneys, and to a much lesser extent – with feces. Elimination through the lungs is insignificant.

In patients with hepatic insufficiency (Child-Pugh class B), the kinetic profile of the active metabolite of racecadotril demonstrated similar T_max and T_1/2 values and lower C_max (-65%) and AUC (-29%) values compared to those in healthy individuals.

In patients with severe renal failure (CrCl 11-39 ml/min), the kinetic profile of the active metabolite of racecadotril demonstrated a lower C_max (-49%) and higher AUC (+16%) and T_1/2 values compared to healthy volunteers (CrCl >70 ml/min).

Indications

Symptomatic treatment of acute diarrhea in adults.

ICD codes

Dosage Regimen

Administer orally.

The single dose is 100 mg.

Take the first dose immediately at the onset of symptoms, regardless of the time of day.

Continue with 100 mg three times daily.

Take each dose before meals.

Continue treatment until normal stool consistency is achieved, defined as the appearance of formed stools up to two times.

Do not exceed a maximum treatment duration of 7 days.

Avoid long-term use.

In cases of repeated vomiting, drug absorption may be reduced.

Concurrent oral rehydration therapy is recommended if indicated.

For acute bacterial diarrhea, this product may be used as an adjunctive therapy in combination with antibiotics.

Discontinue use and consult a physician if bloody or purulent stools or high fever are present.

Use with caution in patients with hepatic impairment or renal impairment due to limited data.

Adverse Reactions

Nervous system disorders common – headache.

Skin and subcutaneous tissue disorders: uncommon – skin rash, erythema; frequency not known (cannot be estimated from the available data) – erythema multiforme, tongue edema, facial edema, lip edema, eyelid edema, angioedema, urticaria, erythema nodosum, papular rash, prurigo, skin itching, toxic dermatitis.

Contraindications

Pregnancy; breastfeeding period; age under 18 years; hypersensitivity to racecadotril.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Due to insufficient data, the drug should be used with caution in patients with renal and hepatic insufficiency.

Use in Renal Impairment

Due to insufficient data, the drug should be used with caution in patients with renal and hepatic insufficiency.

Geriatric Use

The drug is approved for use in elderly patients.

Special Precautions

The use of racecadotril does not preclude oral rehydration in cases where it is necessary.

The presence of bloody or purulent discharge in the stool and high fever may be symptoms of an invasive bacterial infection causing the diarrhea or another serious illness, which is grounds for etiotropic therapy (e.g., with antibiotics) or further investigation. Monotherapy with racecadotril for these conditions is contraindicated. As an adjunctive therapy for acute bacterial diarrhea, Racecadotril can be used in combination with antibiotics.

The bioavailability of racecadotril may be reduced with repeated vomiting.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.