Release form, packaging and composition
Film-coated tablets
white or almost white, round, biconvex, in cross section the core of the tablet is white or almost white.
| 1 tab. | |
| Prucalopride succinate | 1.321 mg, |
| which corresponds to the content of prucalopride | 1 mg |
Excipients
: microcrystalline cellulose - 96 mg, sodium carboxymethyl starch - 1.419 mg, magnesium stearate - 0.9 mg, colloidal silicon dioxide - 0.36 mg.
Tablet weight without coating
- 100 mg.
Shell composition:
hypromellose 6 cP - 1.8 mg, macrogol 6000 - 0.6 mg, titanium dioxide - 0.5 mg, talc - 0.1 mg.
The weight of the coated tablet
is 103 mg.
pharmachologic effect
A drug that increases intestinal motility, dihydrobenzofurancarboxamide. The effect on intestinal motility is most likely due to the selectivity and high affinity of prucalopride for serotonin 5-HT4 receptors.
Pharmacokinetics
After a single oral dose, prucalopride is rapidly absorbed from the gastrointestinal tract. After taking a dose of 2 mg, Cmax is achieved within 2-3 hours. Absolute bioavailability after oral administration exceeds 90%. Taking with food does not affect bioavailability. Prucalopride is widely distributed in the body, Vd at steady state is 567 l. Plasma protein binding is approximately 30%.
An equilibrium state is achieved after 3-4 days of administration, and when taking prucalopride at a dose of 2 mg 1 time / day, Cmin and Cmax in blood plasma at steady state are 2.5 and 7 ng/ml, respectively.
The pharmacokinetics of prucalopride is linearly dependent on the dose in the range of up to 20 mg/day. With long-term administration 1 time/day, pharmacokinetics do not depend on the duration of administration.
The metabolism of prucalopride in the human liver in vitro is very slow and only a small number of metabolites are formed. Following oral administration of 14C-labeled prucalopride in humans, 8 metabolites are found in small amounts in urine and feces. The main metabolite (R107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to a carboxylic acid) accounts for less than 4% of the dose. As studies with a radioactive label have shown, about 85% of the active substance remains unchanged; metabolite R107504 is present in plasma in small quantities.
Most of the orally administered dose is excreted unchanged (approximately 60% via the kidneys and at least 6% via the feces). Excretion of unchanged prucalopride by the kidneys involves passive filtration and active secretion. The clearance of prucalopride from blood plasma averages 317 ml/min, the final T1/2 is approximately 1 day.
Vegaprat, 1 mg, film-coated tablets, 30 pcs.
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg, the maximum concentration (Cmax) is achieved after 2-3 hours. Absolute bioavailability after oral administration exceeds 90%. Taking the drug with food does not affect bioavailability.
Prucalopride is distributed throughout the body, the volume of distribution at steady state is 567 l. Plasma protein binding is approximately 30%.
Metabolism of the drug in the human liver in vitro is very slow, and only a small amount of metabolites is formed. After oral administration of 14C-labeled prucalopride by humans, 8 metabolites are found in small amounts in urine and feces. The main metabolite (R 107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to carboxylic acid) constitutes less than 4% of the administered dose of the drug. As studies with a radioactive label have shown, about 85% of the drug remains unchanged; metabolite R 107504 is present in plasma in small quantities.
Most of the orally administered dose of the active ingredient is excreted unchanged (approximately 60% by the kidneys and at least 6% in the feces). Excretion of unchanged prucalopride by the kidneys involves passive filtration and active secretion. Plasma clearance of prucalopride averages 317 ml/min, with a terminal half-life of approximately 24 hours. An equilibrium state is achieved after 3-4 days of taking the drug, and when taking prucalopride at a dose of 2 mg 1 time per day, the minimum and maximum concentrations in blood plasma at steady state are 2.5 and 7 ng/ml, respectively. When taken once a day, the k coefficient 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 once a day, its pharmacokinetics do not depend on the duration of administration.
Pharmacokinetics in selected patient groups
Population pharmacokinetics
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 the drug was taken by elderly patients at a dose of 1 mg 1 time per day, the maximum plasma concentration of prucalopride (Cmax) 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 decreased renal function in older adults.
Renal dysfunction
Compared with patients with normal renal function, in patients with mild (creatinine clearance 50-79 ml/min) and moderately severe (creatinine clearance 25-49 ml/min) renal impairment, the plasma concentration of prucalopride 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 plasma concentration of prucalopride was 2.3 times higher than in healthy people.
Liver dysfunction
About 35% of prucalopride is eliminated extrarenally, so impairment of liver function is unlikely to clinically significantly alter the pharmacokinetics of the drug.
Children
After a single oral dose of 0.03 mg/kg prucalopride 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 half-life of the drug in the terminal phase is approximately 19 hours in children (range 11.6 - 26.8 hours).
Indications for use
Prucalopride is indicated for the symptomatic treatment of chronic constipation in women in whom laxatives have not been sufficiently effective in relieving symptoms.
Side effect
From the digestive system:
very often - nausea, diarrhea, abdominal pain; often - vomiting, dyspepsia, rectal bleeding, flatulence, abnormal bowel sounds; infrequently - anorexia.
From the nervous system:
very often - headache; often - dizziness; infrequently - tremor.
From the cardiovascular system:
infrequently - palpitations.
From the urinary system:
often - pollakiuria.
General reactions:
often - weakness; infrequently - fever, poor health.
Use during pregnancy and breastfeeding
Use during pregnancy and lactation (breastfeeding) is not recommended.
Cases of miscarriage have been reported in clinical studies, although given the presence of other risk factors, the association of these events with the use of prucalopride remains unproven.
Women of childbearing age should use reliable methods of contraception during treatment.
Prucalopride is excreted in breast milk, however, when used in therapeutic doses, the effect on newborns/infants is unlikely. There are no data on use in nursing mothers.
In preclinical studies
in animals, no direct or indirect adverse effects on the course of pregnancy, development of the embryo/fetus, childbirth and postnatal development of the offspring were detected; any effect on the fertility of males and females.
Vegaprat
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg, the maximum concentration (Cmax) is reached after 2-3 hours. Absolute bioavailability after oral administration exceeds 90%. Taking the drug with food does not affect bioavailability.
Prucalopride is distributed throughout the body, the volume of distribution at steady state is 567 l. Plasma protein binding is approximately 30%.
Metabolism of the drug in the human liver in vitro is very slow, and only a small amount of metabolites is formed. After oral administration of 14C-labeled prucalopride by humans, 8 metabolites are found in small amounts in urine and feces. The main metabolite (R107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to carboxylic acid) constitutes less than 4% of the administered dose of the drug. As studies with a radioactive label have shown, about 85% of the drug remains unchanged; metabolite R107504 is present in plasma in small quantities.
Most of the orally administered dose of the active ingredient is excreted unchanged (approximately 60% by the kidneys and at least 6% in the feces). Excretion of unchanged prucalopride by the kidneys involves passive filtration and active secretion. Plasma clearance of prucalopride averages 317 ml/min, with a terminal half-life of approximately 24 hours.
An equilibrium state is achieved after 3-4 days of taking the drug, and when taking prucalopride at a dose of 2 mg 1 time per day, the minimum and maximum concentrations in blood plasma at steady 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 once a day, its pharmacokinetics do not depend on the duration of administration.
Pharmacokinetics in selected patient groups
Population pharmacokinetics
Population pharmacokinetic analysis showed that the total clearance of prucalopride correlates with creatinine clearance (CC) and is independent of the age, body weight, sex or race of patients.
Elderly patients
When the drug was taken by elderly patients at a dose of 1 mg 1 time per day, the maximum plasma concentration of prucalopride (Cmax) 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 decreased renal function in older adults.
Renal dysfunction
Compared with patients with normal renal function, in patients with mild (creatinine clearance 50-79 ml/min) and moderately severe (creatinine clearance 25-49 ml/min) renal impairment, the plasma concentration of prucalopride 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 plasma concentration of prucalopride was 2.3 times higher than in healthy people.
Liver dysfunction
About 35% of prucalopride is eliminated extrarenally, so impairment of liver function is unlikely to clinically significantly alter the pharmacokinetics of the drug.
Children
After a single oral dose of 0.03 mg/kg prucalopride 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 half-life of the drug in the terminal phase is approximately 19 hours in children (range 11.6-26.8 hours).
special instructions
Use with caution in patients with severe and clinically unstable concomitant diseases (liver, lung, cardiovascular, neurological, endocrine diseases, mental disorders, cancer, AIDS) has not been studied; use with extreme caution in patients with cardiac arrhythmias or coronary artery disease in the anamnesis.
Due to the specific mechanism of action of prucalopride (stimulation of intestinal motility), increasing the daily dose to more than 2 mg is unlikely to increase the effect. If taking prucalopride once a day for 4 weeks does not produce an effect, the patient should be re-examined and the advisability of continuing treatment should be determined.
Severe diarrhea may reduce the effectiveness of oral contraceptives, and the use of additional methods of contraception is recommended to prevent a decrease in the effectiveness of oral contraceptives.
Use in pediatrics
Not recommended for use in children and adolescents under 18 years of age.
Impact on the ability to drive vehicles and operate machinery
In some cases, the use of prucalopride has been associated with the development of dizziness and weakness, especially in the first days of treatment, which may affect the ability to drive vehicles and operate machinery.
Vegaprat, 30 pcs., 2 mg, film-coated tablets
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg, the maximum concentration (Cmax) is achieved after 2-3 hours. Absolute bioavailability after oral administration exceeds 90%. Taking the drug with food does not affect bioavailability.
Prucalopride is distributed throughout the body, the volume of distribution at steady state is 567 l. Plasma protein binding is approximately 30%.
Metabolism of the drug in the human liver in vitro is very slow, and only a small amount of metabolites is formed. After oral administration of 14C-labeled prucalopride by humans, 8 metabolites are found in small amounts in urine and feces. The main metabolite (R 107504, formed by O-demethylation of prucalopride and oxidation of the resulting alcohol to carboxylic acid) constitutes less than 4% of the administered dose of the drug. As studies with a radioactive label have shown, about 85% of the drug remains unchanged; metabolite R 107504 is present in plasma in small quantities.
Most of the orally administered dose of the active ingredient is excreted unchanged (approximately 60% by the kidneys and at least 6% in the feces). Excretion of unchanged prucalopride by the kidneys involves passive filtration and active secretion. Plasma clearance of prucalopride averages 317 ml/min, with a terminal half-life of approximately 24 hours. An equilibrium state is achieved after 3-4 days of taking the drug, and when taking prucalopride at a dose of 2 mg 1 time per day, the minimum and maximum concentrations in blood plasma at steady state are 2.5 and 7 ng/ml, respectively. When taken once a day, the k coefficient 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 once a day, its pharmacokinetics do not depend on the duration of administration.
Pharmacokinetics in selected patient groups
Population pharmacokinetics
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 the drug was taken by elderly patients at a dose of 1 mg 1 time per day, the maximum plasma concentration of prucalopride (Cmax) 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 decreased renal function in older adults.
Renal dysfunction
Compared with patients with normal renal function, in patients with mild (creatinine clearance 50-79 ml/min) and moderately severe (creatinine clearance 25-49 ml/min) renal impairment, the plasma concentration of prucalopride 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 plasma concentration of prucalopride was 2.3 times higher than in healthy people.
Liver dysfunction
About 35% of prucalopride is eliminated extrarenally, so impairment of liver function is unlikely to clinically significantly alter the pharmacokinetics of the drug.
Children
After a single oral dose of 0.03 mg/kg prucalopride 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 half-life of the drug in the terminal phase is approximately 19 hours in children (range 11.6 - 26.8 hours).
Indications for use
Prucalopride is indicated for the symptomatic treatment of chronic constipation in women in whom laxatives have not been sufficiently effective in relieving symptoms.
