Resolor, pills 2mg, 28pcs

Composition

1 tablet contains:

Active ingredients:

prucalopride succinate 2,642 mg, which corresponds to the content of prucalopride 2 mg.

Auxiliary substances:

pill core:

lactose monohydrate – 165.458 mg,

microcrystalline cellulose-30 mg,

colloidal silicon dioxide-0.4 mg,

magnesium stearate-1.5 mg,

pink film coating-7 mg.

Composition of the pink film coating as a percentage by weight:

hypromellose 6 cP – 40%,

dye iron oxide red (E 172) – 0,09%,

titanium dioxide – 23,88%,

macrogol 3000 – 8%,

triacetin – 6%,

lactose monohydrate – 22%,

Indigo Carmine (E 132) – 0,02%,

dye iron oxide yellow (E 172) – 0,01%.

The blister contains 7 tablets.

The package contains 2 blisters.

Pharmacological action

Pharmacodynamics

Mechanism of action

Prucalopride is a dihydrobenzofurancarboxamide that enhances intestinal motility. Prucalopride is a selective, high-affinity agonist of 5HT4-serotonin receptors, which most likely explains its effect on intestinal motility. Binding to other types of receptors in vitro was observed only at concentrations of the substance exceeding its affinity for HT4 receptors by at least 150 times.

Pharmacokinetics

Suction

Prucalopride is rapidly absorbed; after a single oral dose of 2 mg, the maximum concentration (Cmax) is reached in 2-3 hours. Absolute bioavailability after oral use exceeds 90%. Taking the drug with a meal does not affect bioavailability.

Distribution

Prucalopride is distributed throughout the body, the volume of distribution at steady state (Vdss ) is 567 liters. Binding to plasma proteins is approximately 30%.

Metabolism

The metabolism of the drug in the human liver in vitro is very slow, and only a small number of metabolites are formed. After oral use of 14C-labeled prucalopride to humans,8 metabolites are detected in small amounts in the urine and feces. The main metabolite (R107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to carboxyacid) is less than 4% of the administered dose of the drug. Radiolabeled studies have shown that about 85% of the drug remains unchanged; the R107504 metabolite is present in plasma in small amounts.

Deduction

Most of the oral dose of the active ingredient is excreted unchanged (approximately 60% by the kidneys and at least 6% in the faeces). Renal elimination of unchanged prucalopride involves passive filtration and active secretion. The average plasma clearance of prucalopride is 317 ml / min, with a final T1 / 2 of approximately 1 day. The equilibrium state is reached after 3-4 days of taking the drug, and when taking prucalopride at a dose of 2 mg 1 time a day, the minimum and maximum plasma concentrations at steady state are 2.5 and 7 ng / ml, respectively. When taken once a day, the k-factor of the drug ranges from 1.9 to 2.3. The pharmacokinetics of prucalopride linearly depend on the dose in the range of up to 20 mg/day. With prolonged use of the drug 1 time a day, its pharmacokinetics do not depend on the duration of use.

Special categories of patients

Population pharmacokinetics

A population pharmacokinetic analysis showed that the total clearance of prucalopride correlates with creatinine clearance (CC) and does not depend on the age, body weight, gender or race of patients.

Elderly patients

When taking the drug in elderly patients at a dose of 1 mg once a day, the Cmax of prucalopride in blood plasma and the area under the concentration-time curve (AUC) were 26% and 28%, respectively, higher than in young patients. This difference may be due to the weakening of kidney function in the elderly.

Impaired renal function

Compared with patients with normal renal function, in patients with mild (creatinine clearance 50-79 ml/min) and moderate (creatinine clearance 25-49 ml/min) renal impairment, the concentration of prucalopride in blood plasma after a single dose of 2 mg was increased by 25% and 51%, respectively. In patients with severe renal impairment (creatinine clearance less than 24 ml/min), the concentration of prucalopride in blood plasma was 2.3 times higher than in healthy people.

Impaired liver function

About 35% of prucalopride is excreted extrarenally, so impaired liver function is unlikely to clinically significantly change the pharmacokinetics of the drug.

Children

After a single oral use of prucalopride at a dose of 0.03 mg/kg in children aged 4-12 years, the Cmax of the drug was the same as after taking the drug in adults at a dose of 2 mg, and the AUC of the unbound fraction of the drug was 30-40% less than in adults, and did not depend on the age of children. The average T1 / 2 of the drug in the terminal phase in children is approximately 19 hours (range 11.6-26.8 hours).

Indications

Resolor is intended for the symptomatic treatment of chronic constipation in women whose laxatives have not provided sufficient effect in eliminating symptoms.

Use during pregnancy and lactation

Pregnancy

Experience with prucalopride during pregnancy is limited. Cases of miscarriage have been reported in clinical trials, although, given the presence of other risk factors, the association of these events with the use of prucalopride remains unproven. Animal studies have shown no direct or indirect adverse effects on pregnancy, embryo/fetus development, delivery, or postnatal development of offspring. The drug Resolor is not recommended for use during pregnancy. During treatment with prucaloprid, women who are capable of childbearing should use adequate methods of contraception.

Lactation period

Prucalopride is excreted in breast milk, but when used in therapeutic doses, the drug is unlikely to affect newborns/infants. Due to the lack of data on use in nursing mothers, the drug is not recommended for use during breastfeeding.

Ability to conceive

Animal studies have not shown any effect of the drug on the fertility of male and female individuals.

Contraindications

• Hypersensitivity to the Active ingredient or to any accessory ingredient;
• the impairment of renal function requiring dialysis;
• perforation, or obstruction of the intestine due to anatomical or functional disorders of the intestine, mechanical intestinal obstruction, severe inflammatory bowel disease, e. g. Crohn’s disease, ulcerative colitis and toxic megacolon/megarectum;
• congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution: the use of the drug in patients with severe and clinically unstable concomitant diseases (liver, lung, cardiovascular, neurological, endocrine diseases, mental disorders, cancer, AIDS) has not been studied. Caution should be exercised when prescribing Resolor to patients with such diseases. In particular, the drug should be used with caution in patients with a history of cardiac arrhythmia or coronary heart disease.

Side effects

The most common adverse reactions when using Resolor were headache and gastrointestinal adverse reactions (abdominal pain, nausea, diarrhea), each of which was observed in approximately 20% of patients. Adverse reactions developed mainly at the beginning of treatment and usually disappeared after a few days, without requiring discontinuation of treatment. Other adverse reactions were observed sporadically. Most of the adverse reactions were mild to moderate in severity.

At the recommended dose of prucalopride 2 mg, the following adverse reactions have been reported in clinical studies, the frequency of which is indicated as:

• very common (> 1/10);>
• common ( > 1/100, > < 1/10);
• infrequent ( > 1/1000, >< 1/100);
• rare ( > 1/10000, >< 1/1000);
• very rare (

From the central nervous system: very often – headache; often-dizziness; infrequently-tremor.

From the cardiovascular system: infrequently-palpitations.

From the gastrointestinal tract: very often-nausea, diarrhea, abdominal pain; often-vomiting, dyspepsia, rectal bleeding, flatulence, pathological intestinal noises; infrequently-anorexia.

From the genitourinary system: often-pollakiuria.

General: often-weakness; infrequently-fever, poor health.

Interaction

In vitro data indicate a weak ability of prucalopride to interact, and at therapeutic concentrations it is unlikely to affect the metabolism of simultaneously used drugs carried out by cytochrome enzymes. Although prucalopride may bind weakly to P-glycoprotein (P-GP), it does not inhibit P-GP activity at clinically significant concentrations.

A potent CYP3A4 and P-glycoprotein inhibitor, ketoconazole 200 mg twice daily, increased the AUC (area under the concentration-time curve) of prucalopride by approximately 40%. This effect is too small to be clinically significant, and is most likely associated with the suppression of active P-glycoprotein transport of prucalopride in the kidneys. The same interaction as with ketoconazole can be observed with other active P-glycoprotein inhibitors, for example, verapamil, cyclosporine A and quinidine. Prucalopride is most likely also transported in the kidneys and other vectors.Theoretically, suppression of the activity of all transporters involved in the active secretion of prucalopride in the kidneys (including P-glycoprotein) can increase the level of its systemic exposure by 75%.

Studies in healthy volunteers showed no clinically significant effect of prucalopride on the pharmacokinetics of warfarin, digoxin, ethyl alcohol, and paroxetine. With simultaneous use of prucalopride and erythromycin, the concentration of the latter in blood plasma increases by 30%. The mechanism of this interaction is not fully understood, but the available data indicate that it is most likely not the result of the direct action of prucalopride, but a consequence of the high variability in the pharmacokinetics of erythromycin itself.

Probenecid, cimetidine, erythromycin, and paroxetine at therapeutic doses did not affect the pharmacokinetics of prucalopride.

The drug Resolor should be used with caution simultaneously with drugs that can prolong the QTc interval.

Atropine-like substances can attenuate the effects of prucalopride mediated through HT4 receptors.

No interaction with food was detected.

How to take, course of use and dosage

The drug is taken orally, regardless of food intake, at any time of the day.

• For adults: 2 mg once a day.
• Elderly (over 65 years of age): start with 1 mg once a day, if necessary, increase the dose to 2 mg once a day.
• Children and adolescents: Resolor is not recommended for use in children and adolescents under 18 years of age.

In patients with impaired renal function and severe renal impairment (glomerular filtration rate less than 30 ml / min /1.73 m), the dose is 1 mg once a day. No dose adjustment is required in patients with mild to moderate renal impairment.

Patients with hepatic impairment: in severe hepatic impairment (Child-Pugh class C), the dose is 1 mg once a day. No dose adjustment is required for patients with mild to moderate hepatic impairment.

Due to the specific mechanism of action of prucalopride (stimulation of intestinal motility), an increase in the daily dose of more than 2 mg is unlikely to lead to an increased effect. If taking prucalopride once a day for 4 weeks does not work, the patient should be re-examined and determine whether to continue treatment.

Overdose

A study involving healthy volunteers showed that prucalopride is well tolerated when the dose is increased to 20 mg once a day (10 times the recommended therapeutic dose).

Overdose can lead to symptoms due to an increase in the known side effects of the drug, including headache, nausea and diarrhea.

There is no specific antidote for Resolor. In case of overdose, symptomatic and supportive therapy should be performed if necessary. A large loss of fluid due to diarrhea or vomiting may require correction of electrolyte disturbances.

Special instructions

The main route of elimination of prucalopride is through the kidneys. For patients with severe renal impairment, the recommended dose is 1 mg.

In severe diarrhea, the effectiveness of oral contraceptives may decrease, and it is recommended to use additional methods of contraception to prevent the effectiveness of oral contraceptives from decreasing. Impaired liver function is unlikely to have a clinically significant effect on the metabolism and level of systemic exposure to prucalopride in humans. There are no data on the use of the drug in patients with mild, moderate or severe hepatic impairment, so a lower dose is recommended for patients with severe hepatic impairment.

The drug contains lactose monohydrate, so the drug should not be taken in patients with congenital lactase deficiency, lactose intolerance or glucose-galactose malabsorption.

For prucalopride, neither the rebound phenomenon nor the development of addiction were detected. A study of the effect of prucalopride on the QT interval in therapeutic (2 mg) and supratherapeutic (10 mg) dosages did not show significant differences in terms of QT interval values compared to placebo.

The frequency of QT-related adverse events and ventricular arrhythmias was low and comparable to that of placebo.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Studies of the effect of prucalopride on the ability to drive a car and moving mechanisms have not been conducted. In some cases, the use of Resolor has been associated with the development of dizziness and weakness, especially in the first days of treatment, which may affect the ability to drive a car and move mechanisms.

Form of production

Film-coated tablets.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging

Shelf life

3 years

Active ingredient

Prucalopride

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Constipation