ROZUVASTATIN KRKA

INSTRUCTIONS for medical use of the medicinal product DUSPATALIN® RETARD 200

Composition

active substance: mebeverine hydrochloride; 1 capsule contains mebeverine hydrochloride 200 mg; excipients: magnesium stearate, methacrylic acid copolymer dispersion, talc, hypromellose, polyacrylate dispersion, glycerol triacetate; solid gelatin capsule (size No. 1): titanium dioxide (E 171), gelatin.

Pharmaceutical form

Prolonged-release capsules, hard.

Main physical and chemical properties

Opaque white hard gelatin capsules, size No. 1, with corresponding marking 245, containing granules from white to almost white color.

Pharmacotherapeutic group

Drugs used for functional gastrointestinal disorders. Synthetic anticholinergic drugs, esterified tertiary amines. Mebeverine. ATC code A03AA04.

Pharmacological properties

Pharmacodynamics

Mechanism of action and pharmacodynamic effects

Mebeverine is a myotropic spasmolytic with selective action on the smooth muscles of the gastrointestinal tract. It eliminates spasms without suppressing normal intestinal motility. Since this action is not mediated by the autonomic nervous system, typical anticholinergic side effects are absent.

Clinical efficacy and safety

The clinical efficacy and safety of various mebeverine formulations have been studied in over 1,500 patients. Significant relief of predominant symptoms of irritable bowel syndrome (such as abdominal pain, bowel habits) was usually observed in reference and controlled clinical trials.

All mebeverine formulations were generally safe and well-tolerated at the recommended dosage regimen.

Children

Clinical trials of tablet or capsule administration were conducted only in adults. Data on clinical efficacy and safety obtained from clinical trials and post-marketing experience with mebeverine suspension in patients aged 3 years and older demonstrated that mebeverine is an effective and safe medicinal product, well-tolerated.

Clinical trials of mebeverine suspension showed that the drug is effective in relieving symptoms of irritable bowel syndrome in children. Further open-controlled clinical trials of mebeverine suspension confirmed the efficacy of the drug.

Pharmacokinetics

Absorption

Mebeverine is rapidly and completely absorbed after oral administration in tablet form. Due to the prolonged release of the drug from the capsule, it can be taken twice a day.

Distribution

With repeated use of Duspatalin® Retard 200, no significant accumulation occurs.

Metabolism

Mebeverine hydrochloride is mainly metabolized by esterases, which in the first stage of metabolism cleave the ether bonds to form veratric acid and mebeverine alcohol. In plasma, demethylcarboxylic acid (DMCA) is the main metabolite. The half-life of DMCA at steady state is 5.77 hours. With repeated use of capsules (200 mg twice daily), Cmax for DMCA was 804 ng/mL, and tmax was approximately 3 hours. The relative bioavailability of prolonged-release capsules was optimal, with a mean ratio of 97%.

Excretion

Mebeverine is not excreted unchanged; it is completely metabolized, and its metabolites are excreted almost entirely. Veratric acid is excreted in the urine. Mebeverine alcohol is also excreted by the kidneys, partly as the corresponding carboxylic acid (CA) and partly as demethylcarboxylic acid (DMCA).

Children

Pharmacokinetic studies in children have not been conducted.

Clinical characteristics

Indications

Adults and children aged 10 years and older:

• Symptomatic treatment of abdominal pain and spasms, bowel disorders, and discomfort in the bowel area in irritable bowel syndrome;
• Treatment of gastrointestinal spasms of secondary genesis caused by organic diseases.

Contraindications

Hypersensitivity to the active substance or to any of the excipients of the drug, as specified in the "Composition" section.

Interactions with other medicinal products and other types of interactions

Interaction studies have not been conducted, except for the interaction with alcohol. In vitro and in vivo studies in animals have demonstrated the absence of any interaction between Duspatalin® Retard 200 and ethanol.

Special warnings and precautions for use

None.

Use during pregnancy or breastfeeding

Pregnancy

There are only very limited data on the use of mebeverine in pregnant women. Reproductive toxicity studies conducted in animals are insufficient. Duspatalin® Retard 200 is not recommended during pregnancy.

Breastfeeding

It is unknown whether mebeverine or its metabolites are excreted in human breast milk. Excretion of mebeverine in breast milk of animals has not been studied. Duspatalin® Retard 200 should not be used during breastfeeding.

Fertility

Clinical data on the effect on male or female fertility are not available; however, available animal studies do not indicate a harmful effect of Duspatalin® Retard 200.

Ability to influence the reaction rate when driving vehicles or operating machinery

Studies on the effect on the ability to drive a car and work with mechanical devices have not been conducted. The pharmacodynamic and pharmacokinetic profile, as well as post-marketing experience, do not indicate any harmful effect of mebeverine on the ability to drive a car and work with mechanical devices.

Method of administration and dosage

For oral administration.

Capsules should be taken with a sufficient amount of water (at least 100 mL). It is not recommended to chew, as the capsule coating is designed to ensure a prolonged release mechanism.

Adults and children aged 10 years and older should take 1 capsule twice a day (in the morning and evening).

The duration of use is not limited. If one or more doses are missed, the patient should take the next dose as scheduled. The missed dose(s) should not be taken in addition to the regular dose.

Special populations

Dosing studies in elderly patients, patients with impaired renal and/or hepatic function have not been conducted. Based on available post-marketing data, no specific risk has been identified for elderly patients, patients with impaired renal and/or hepatic function. Dose adjustment for these patient groups is not considered necessary.

Children

Duspatalin® Retard 200 should not be used in children under 3 years of age due to the lack of clinical data for this age group. Duspatalin® Retard 200, 200 mg capsules, should not be used in children aged 3 to 10 years due to the high content of the active substance.

Overdose

Symptoms. Theoretically, in case of overdose, central nervous system stimulation is possible. In cases of overdose, symptoms were absent or mild and usually resolved quickly. Overdose symptoms observed were of neurological or cardiovascular origin.

Treatment. A specific antidote is unknown. Symptomatic treatment is recommended. Gastric lavage is recommended only in case of intoxication with multiple drugs diagnosed within 1 hour of taking the medicinal product. Measures to reduce absorption are not necessary.

Adverse reactions

The following adverse reactions have been reported spontaneously during post-marketing use. The frequency cannot be accurately determined from the available data.

Allergic reactions were observed mainly, but not exclusively, on the skin.

Disorders of the skin and subcutaneous tissue:

• urticaria, angioedema, facial edema, rash.

Disorders of the immune system:

• hypersensitivity (anaphylactic reactions).

Shelf life

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C. Do not store at a temperature below 5 °C. Store in a place inaccessible to children.

Packaging

10 capsules in a blister pack, 3 blister packs in a carton, or 15 capsules in a blister pack, 1, 2, or 4 blister packs in a carton.

Release category

Prescription only.

Manufacturer

Mylan Laboratoires SAS/Mylan Laboratories SAS.

Manufacturer's location and address

Route de Belleville, Lieu dit Maillard, 01400, Chatillon-sur-Chalaronne, France.