Resolor pills 2 mg №28

Active substance

Prucalopride

Composition

1 pill contains:

Active ingredients: prucaloprid succinate 2.624 mg, which corresponds to the content of prucaloprid 2 mg.

Excipients: 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.

The composition of the film coating of pink in percent by weight: hypromellose 6 cP - 40%, iron dye red oxide (E172) - 0.09%, titanium dioxide - 23.88%, macrogol 3000 - 8%, triacetin - 6%, lactose monohydrate - 22%, indigo carmine (E132) - 0.02%, iron dye yellow oxide (E172) - 0.01%.

In the blister of 7 tablets. In packing 2 blisters.

Mechanism of action

Pharmacodynamics

Mechanism of action

Prukaloprid is dihydrobenzofurancarboxamide, which increases intestinal motility. Prukaloprid 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 a substance greater than its affinity for HT4 receptors at least 150 times.

Pharmacokinetics

Suction

Prukaloprid is rapidly absorbed; after a single oral dose of 2 mg, the maximum concentration (Cmax) is reached in 2-3 hours. The absolute bioavailability after oral administration exceeds 90%. Taking the drug with meals does not affect bioavailability.

Distribution

Prukaloprid is distributed throughout the body, the volume of distribution in the equilibrium state (Vdss) is 567 l. Plasma protein binding is approximately 30%.

Metabolism

Metabolism of the drug in the human liver in vitro is very slow, and only a small number of metabolites are formed. After oral ingestion of 14C-labeled prukaloprid in the urine and feces by humans, 8 metabolites are detected in a small amount. The main metabolite (R107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to carboxylic acid) is less than 4% of the administered dose of the drug. Studies have shown with a radioactive label, about 85% of the drug remains unchanged; the metabolite R107504 is present in plasma in a small amount.

Removal

Most of the orally ingested dose of the active component is excreted unchanged (approximately 60% by the kidneys and at least 6% with feces). The elimination of unchanged prucalopride by the kidneys includes passive filtration and active secretion. The plasma clearance of prucaloprid is on average 317 ml / min, the final T1 / 2 is about 1 day. The equilibrium state is reached after 3-4 days of taking the drug, and when taking prukaloprid at a dose of 2 mg once a day, the minimum and maximum plasma concentrations in the equilibrium state are 2.5 and 7 ng / ml, respectively. When taken once a day, the coefficient k of the drug ranges from 1.9 to 2.3.The pharmacokinetics of prucalopride is linearly dependent on the dose in the range of up to 20 mg / day. With long-term use of the drug 1 time per day, its pharmacokinetics does not depend on the duration of administration.

Special categories of patients

Population pharmacokinetics

A population-based analysis of pharmacokinetics showed that total clearance of prucalopride correlates with creatinine clearance (CK) and is independent of the age, body weight, gender, or race of the patients.

Elderly Sick

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

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

About 35% of prucaloprid is excreted extrarenally, therefore, an abnormal liver function is unlikely to clinically significantly change the pharmacokinetics of the drug.

Children

After a single oral administration of prucaloprid 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 by 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 is approximately 19 hours in children (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 the elimination of symptoms.

Contraindications

• Hypersensitivity to the active ingredient or any excipient;
• impaired renal function requiring dialysis;
• perforation or obstruction of the intestine due to anatomical or functional disorders of the intestinal wall, mechanical intestinal obstruction, severe inflammation of the intestine, for example, Crohn's disease, ulcerative colitis and toxic megacolon / megarectum;
• congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With care: the use of the drug in patients with severe and clinically unstable concomitant diseases (diseases of the liver, lungs, cardiovascular, neurological, endocrine diseases, mental disorders, oncological diseases, AIDS) has not been studied. Caution should be exercised in the appointment of the drug Resolor patients with such diseases. In particular, the drug should be used with caution in patients with cardiac arrhythmias or ischemic heart disease in history.

Side effects

The most frequent adverse reactions in the use of the drug Rezolor were headache and adverse reactions from the gastrointestinal tract (abdominal pain, nausea, diarrhea), each of which was observed in about 20% of patients.Adverse reactions developed predominantly at the beginning of treatment and usually disappeared after a few days, without requiring cancellation of treatment. Other adverse reactions were observed sporadically. Most adverse reactions were mild or moderate.

At the recommended dose of prucaloprid 2 mg, the following adverse reactions were recorded in clinical studies, the frequency of which is indicated as:

• very often (> 1/10);
• often (> 1/100, <1/10);
• infrequently (> 1/1000, <1/100);
• rarely (> 1/10000, <1/1000);
• very rarely (<1/10000), including isolated cases.

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

Cardiovascular: infrequently - the heartbeat.

On the part of the gastrointestinal tract: very often - nausea, diarrhea, abdominal pain; often - vomiting, dyspepsia, rectal bleeding, flatulence, abnormal intestinal noise; infrequently - anorexia.

From the genitourinary system: often - pollakiuria.

General: often - weakness; infrequently - fever, feeling unwell.

Interaction

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

A potent inhibitor of CYP3A4 and P-glycoprotein Ketoconazole at a dose of 200 mg 2 times a day increased the AUC (area under the concentration-time curve) of prucalopride by about 40%. This effect is too small to be clinically significant, and is most likely associated with the suppression of the active transport of prukaloprid in the kidneys by the P-glycoprotein. The same interaction as with ketoconazole can be observed with other active inhibitors of β-glycoprotein, for example, Verapamil, cyclosporin A and quinidine. Prucalopride is also likely transported by kidney and other vectors. Theoretically, the suppression of the activity of all vectors involved in the active secretion of prucaloprid in the kidneys (including P-glycoprotein) can increase the level of its systemic effect by 75%.

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

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

Resolor should be used with caution along with drugs that can lengthen the QTc interval.

Atropin-like substances can weaken the effects of prucalopride mediated through HT4 receptors.

No interaction with food detected.

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

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

Patients with impaired renal function with severe impaired renal function (glomerular filtration rate less than 30 ml / min / 1.73 m), the dose is 1 mg 1 time per day. For patients with mild and moderate renal impairment, dose adjustment is not required.

Patients with impaired liver function: in severe impaired liver function (Child-Pugh class C), the dose is 1 mg 1 time per day. For patients with mild and moderate hepatic impairment, dose adjustment is not required.

Due to the specific mechanism of action of prucaloprid (stimulation of intestinal motility), an increase in the daily dose of more than 2 mg is unlikely to increase the effect. If taking prukaloprid 1 time per day for 4 weeks does not give effect, you should re-examine the patient and determine the feasibility of continuing treatment.

Overdose

A study with healthy volunteers showed that prukaloprid was well tolerated when the dose was increased to 20 mg 1 time per day (10 times the recommended therapeutic dose).

Overdose can lead to symptoms due to increased 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 carried out if necessary. Greater fluid loss due to diarrhea or vomiting may require correction of electrolyte imbalance.

Special instructions

The main route of elimination of prucaloprid is through the kidneys. For patients with severely impaired renal function, 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 a decrease in the effectiveness of oral contraceptives. Impaired liver function is unlikely to have a clinically significant effect on metabolism and the 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 liver dysfunction, therefore, a lower dose is recommended for patients with severe liver dysfunction.

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

For prucalopride, neither the rebound phenomenon nor the development of dependence was identified.The study of the effect of prucalopride on the QT interval in therapeutic (2 mg) and supra-therapeutic (10 mg) dosages showed no significant differences compared with placebo in relation to the values ​​of the QT interval.

The incidence of adverse events associated with the QT interval and ventricular arrhythmias was low and comparable with placebo.

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

Studies of the effect of prucalopride on the ability to drive and moving machinery was not conducted. In some cases, the use of the drug Rezolor was 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 moving machinery.

Tablets, film coated.

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