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Drug Details
Resolor 2mg film-coated tablets
- Presentation
Film-coated tablet (tablet). Pink, round, biconvex tablets marked “PRU 2” on one side. - Description
Each filmcoated tablet contains 2 mg prucalopride (as prucalopride succinate). Excipients: Each film-coated tablet contains 165 mg lactose monohydrate. - Indications
Resolor is indicated for symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief.
- Adult Dosage
Posology
Adults: 2 mg once daily.
Elderly (>65 years): Start with one 1 mg once daily; if needed the dose can be increased to 2 mg once daily.
Children and adolescents: Resolor is not recommended in children and adolescents younger than 18 years until further data become available.
Patients with renal impairment: The dose for patients with severe renal impairment (GFR < 30 ml/min/1.73 m2) is 1 mg once daily. No dose adjustment is required for patients with mild to moderate renal impairment.
Patients with hepatic impairment: The dose for patients with severe hepatic impairment (ChildPugh class C) is 1 mg once daily. No dose adjustment is required for patients with mild to moderate hepatic impairment.
Due to the specific mode of action of prucalopride (stimulation of propulsive motility) exceeding the daily dose of 2 mg is not expected to increase efficacy.
If the intake of once daily prucalopride is not effective after 4 weeks of treatment, the patient should be re-examined and the benefit of continuing treatment reconsidered.
The efficacy of prucalopride has been established in double blind placebo controlled studies for up to 3 months. In case of prolonged treatment the benefit should be reassessed at regular intervals.
Method of administration
Resolor film-coated tablets are for oral use and can be taken with or without food, at any time of the day.
- Contra Indications
- Hypersensitivity to the active substance or to any of the excipients.
- Renal impairment requiring dialysis.
- Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract, such as Crohn's disease, and ulcerative colitis and toxic megacolon/megarectum
- Special Precautions
Renal excretion is the main route of elimination of prucalopride. A dose of 1 mg is recommended in subjects with severe renal impairment.
Patients with severe and clinically unstable concomitant disease (e.g. liver, cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders) have not been studied. Caution should be exercised when prescribing Resolor to patients with these conditions. In particular Resolor should be used with caution in patients with a history of arrhythmias or ischaemic cardiovascular disease.
In case of severe diarrhoea, the efficacy of oral contraceptives may be reduced and the use of an additional contraceptive method is recommended to prevent possible failure of oral contraception (see the prescribing information of the oral contraceptive).
It is unlikely that hepatic impairment will affect prucalopride metabolism and exposure in man to a clinically relevant extent. No data are available in patients with mild, moderate or severe hepatic impairment, and therefore a lower dose is recommended for patients with severe hepatic impairment .
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption must not take this medicinal product.
- Interactions
In vitro data indicate that prucalopride has a low interaction potential, and therapeutic concentrations of prucalopride are not expected to affect the CYP-mediated metabolism of co-medicated medicinal products. Although prucalopride may be a weak substrate for P-glycoprotein (Pgp), it is not an inhibitor of Pgp at clinically relevant concentrations.
Ketoconazole (200 mg b.i.d.), a potent inhibitor of CYP3A4 and of Pgp, increased the area under the curve (AUC) of prucalopride by approximately 40%. This effect is too small to be clinically relevant and is likely attributable to inhibition of P-gp mediated renal transport. Interactions of similar magnitude as observed with ketoconazole may also occur with other potent inhibitors of Pgp such as verapamil, cyclosporine A and quinidine. Prucalopride is likely also secreted via another renal transporter(s). Inhibition of all transporters involved in the active secretion of prucalopride (including Pgp) may theoretically increase the exposure by up to 75%.
Studies in healthy subjects showed that there were no clinically relevant effects of prucalopride on the pharmacokinetics of warfarin, digoxin, alcohol and paroxetine. A 30% increase in the plasma concentrations of erythromycin was found during prucalopride co-treatment. The mechanism for this interaction is not fully known, but the available data support that this is the consequence of the high intrinsic variability in erythromycin kinetics, rather than a direct effect of prucalopride.
Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of prucalopride.
Resolor should be used with caution in patients receiving concomitant drugs known to cause QTc prolongation.
Because of the mechanism of action, the use of atropine-like substances may reduce the 5HT4 receptor mediated effects of prucalopride.
Interactions with food have not been observed.
- Adverse Drug Reactions
Resolor has been given orally to approximately 2,700 patients with chronic constipation in controlled clinical studies. Of these patients, almost 1,000 patients received Resolor at the recommended dose of 2 mg per day, while about 1,300 patients were treated with 4 mg prucalopride daily. Total exposure in the clinical development plan exceeded 2,600 patient years. The most frequently reported adverse reactions associated with Resolor therapy are headache and gastrointestinal symptoms (abdominal pain, nausea or diarrhoea) occurring in approximately 20% of patients each. The adverse reactions occur predominantly at the start of therapy and usually disappear within a few days with continued treatment. Other adverse reactions have been reported occasionally. The majority of adverse events were mild to moderate in intensity.
The following adverse reactions were reported in controlled clinical studies at the recommended dose of 2 mg with frequencies corresponding to Very common ( 1/10), Common ( 1/100 to < 1/10), Uncommon (> 1/1,000 to < 1/100), Rare (> 1/10,000 to < 1/1,000) and Very rare ( 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are calculated based on the placebo-controlled clinical study data.
Metabolism and nutrition disorders
Uncommon: anorexia
Nervous system disorders
Very common: headache
Common: dizziness
Uncommon: tremors
Cardiac disorders
Uncommon: palpitations
Gastrointestinal disorders
Very common: nausea, diarrhoea, abdominal pain
Common: vomiting, dyspepsia, rectal haemorrhage, flatulence, abnormal bowel sounds
Renal and urinary disorders
Common: pollakiuria
General disorders and administration site conditions
Common: fatigue
Uncommon: fever, malaise
After the first day of treatment, the most common adverse reactions were reported in similar frequencies (incidence less than 1% different between prucalopride and placebo) during Resolor therapy as during placebo, with the exception of nausea and diarrhoea that still occurred more frequently during Resolor therapy, but less pronounced (difference in incidence between prucalopride and placebo between 1 and 3%).Palpitations were reported in 0.7% of the placebo patients, 1.0% of the 1 mg prucalopride patients, 0.7% of the 2 mg prucalopride patients and 1.9% of the 4 mg prucalopride patients. The majority of patients continued using prucalopride. As with any new symptom, patients should discuss the new onset of palpitations with their physician.