Aspazmin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASPAZMIN (ASPAZMIN)

Composition:

Active substance: 1 capsule contains 200 mg of mebeverine hydrochloride;

Excipients: microcrystalline cellulose, mannitol (E 421), spherical sugar, povidone, sodium lauryl sulfate, ethylcellulose, hypromellose phthalate (hydroxypropylmethylcellulose phthalate), cetyl alcohol;

capsule shell composition: gelatin, titanium dioxide (E 171).

Pharmaceutical form. Solid modified-release capsules.

Main physicochemical properties: white hard gelatin capsules with white cap and body. The capsule contents are white or almost white pellets.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders. Synthetic anticholinergic agents, esterified tertiary amines.

ATC code A03A A04.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action and pharmacodynamic effects.

Mebeverine is a myotropic spasmolytic agent with selective action on the smooth muscles of the gastrointestinal tract. Mebeverine relieves spasms without suppressing normal intestinal motility. Since this action is not mediated through the autonomic nervous system, typical anticholinergic adverse effects do not occur.

Clinical efficacy and safety.

Significant relief of predominant symptoms of irritable bowel syndrome (such as abdominal pain, altered bowel habits) has generally been observed in reference and controlled clinical studies based on primary endpoints.

All dosage forms of mebeverine have been generally safe and well tolerated at the recommended dosage regimen.

Children.

Clinical studies with mebeverine have been conducted only in adults. However, data on the clinical efficacy and safety of mebeverine in patients aged 3 years and older have demonstrated that mebeverine is an effective and safe medicinal product which is well tolerated.

Mebeverine-containing preparations are effective in relieving symptoms of irritable bowel syndrome in children.

The dosage regimen for the medicinal product in tablet or capsule form has been established based on the safety and tolerability of mebeverine.

Pharmacokinetics.

Absorption.

Mebeverine is rapidly and completely absorbed after oral administration. Due to the prolonged release of the drug from the capsule, it can be administered twice daily.

Distribution.

With repeated administration of mebeverine, no significant accumulation occurs.

Biotransformation.

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

Elimination.

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

Children.

Pharmacokinetic studies in children have not been conducted.

Clinical characteristics.

Indications.

Aspazmin is used in adults and children aged 10 years and older for:

• symptomatic treatment of abdominal pain and spasms, intestinal disorders and discomfort in the intestinal region associated with irritable bowel syndrome;
• treatment of secondary gastrointestinal spasms caused by organic diseases.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the section "Composition".

Interaction with other medicinal products and other forms of interaction.

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

Special precautions for use

If you have an intolerance to certain sugars, consult your doctor before taking this medicinal product.

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. Aspazmin is not recommended during pregnancy.

Breastfeeding

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

Fertility

There are no clinical data on the effect on male or female fertility; however, available animal studies do not indicate any harmful effect of Aspazmin on fertility.

Ability to affect reaction speed when driving or operating machinery.

Studies on the influence of mebeverine on the ability to drive vehicles or operate machinery have not been conducted. However, the pharmacodynamic and pharmacokinetic profile, as well as post-marketing experience, do not indicate any harmful effect of mebeverine on the ability to drive vehicles or operate machinery.

Dosage and Administration

For oral use.

Capsules should be taken with sufficient amount of water (not less than 100 ml). Chewing is not recommended due to the capsule coating designed to ensure a prolonged-release mechanism.

Adults and children aged 10 years and older: 1 capsule twice daily (in the morning and evening).

Duration of use is not limited. If one or more doses are missed, the patient should take the next dose as prescribed. Missed dose(s) should not be taken additionally to the regular dose.

Special patient groups

Dosage studies in elderly patients or patients with renal and/or hepatic impairment have not been conducted. However, based on available post-marketing data, no specific risk has been identified in elderly patients or patients with renal and/or hepatic impairment. Dose adjustment in the above-mentioned patient groups is not considered necessary.

Children

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

Overdose

Symptoms: Theoretically, central nervous system stimulation may occur in case of overdose. In reported cases of overdose, symptoms were either absent or mild and generally resolved quickly. Observed overdose symptoms were of neurological or cardiovascular origin.

Treatment: No specific antidote is known. Symptomatic treatment is recommended. Gastric lavage is recommended only in cases of multi-drug intoxication diagnosed within 1 hour after drug intake. Measures to reduce absorption are not necessary.

Side effects

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

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

Disorders of the skin and subcutaneous tissue:

urticaria, angioneurotic edema, facial swelling, rash.

Immune system disorders:

hypersensitivity (anaphylactic reactions).

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product by regulatory authorities is an important procedure. It enables ongoing monitoring of the benefit-risk balance of the use of this medicinal product. Healthcare professionals are requested to report any suspected adverse reactions through national reporting systems.

Shelf life. 2 years.

Storage conditions.

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

Keep out of the reach of children.

Packaging.

10 capsules in a blister; 3 blisters per carton.

Prescription category. Prescription only.

Manufacturer.

JSC "KYIV VITAMIN PLANT"

Manufacturer's address and location of its business activity.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua