Resolor · 4.4 Special warnings and precautions for use · 2

HOS-095304 · has-adverse-reaction-information · PDF-Seite 4

Summary of the safety profile In an integrated analysis of 17 double-blind placebo-controlled studies, Resolor was given orally to approximately 3,300 patients with chronic constipation. Of these, over 1,500 patients received Resolor at the recommended dose of 2 mg per day, while approximately 1,360 patients were treated with 4 mg prucalopride daily. The most frequently reported adverse reactions associated with Resolor 2 mg therapy are headache (17.8%) and gastrointestinal symptoms (abdominal pain (13.7%), nausea (13.7%) and diarrhoea (12.0%)). 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. Tabulated list of adverse reactions 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), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are calculated based on the integrated analysis of 17 double-blind placebo-controlled clinical studies. 4  Table 1: Adverse Drug Reactions (ADRs) Associated with Resolor System/Organ Class Incidence Category Adverse Drug Reaction Metabolism and nutrition Common Decreased appetite disorders Nervous system disorders Very common Headache Common Dizziness Uncommon Tremors, migraine Cardiac disorders Uncommon Palpitations Ear and labyrinth disorders Uncommon Vertigo Gastrointestinal disorders Very common Nausea, diarrhoea, abdominal pain Common Vomiting, dyspepsia, flatulence, gastrointestinal

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095310 · has-adverse-reaction-information · PDF-Seite 13

Summary of the safety profile In an integrated analysis of 17 double-blind placebo-controlled studies, Resolor was given orally to approximately 3,300 patients with chronic constipation. Of these, over 1,500 patients received Resolor at the recommended dose of 2 mg per day, while approximately 1,360 patients were treated with 4 mg prucalopride daily. The most frequently reported adverse reactions associated with Resolor 2 mg therapy are headache (17.8%) and gastrointestinal symptoms (abdominal pain (13.7%), nausea (13.7%) and diarrhoea (12.0%)). 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. Tabulated list of adverse reactions 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) and not known (cannot be estimated from available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are calculated based on the integrated analysis of 17 double-blind placebo-controlled clinical studies. 13  Table 1: Adverse Drug Reactions (ADRs) Associated with Resolor System/Organ Class Incidence Category Adverse Drug Reaction Metabolism and nutrition Common Decreased appetite disorders Nervous system disorders Very common Headache Common Dizziness Uncommon Tremors, migraine Cardiac disorders Uncommon Palpitations Ear and labyrinth disorders Uncommon Vertigo Gastrointestinal disorders Very common Nausea, diarrhoea, abdominal pain Common Vomiting, dyspepsia, flatulence, gastrointestinal sounds

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095300 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - 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.

HOS-095306 · has-contraindication-information · PDF-Seite 12

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - 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.

HOS-095305 · has-indication-information · PDF-Seite 11

Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief.

HOS-095299 · has-indication-information · PDF-Seite 2

Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief.

HOS-095302 · has-interaction-information · PDF-Seite 3

Prucalopride has a low pharmacokinetic interaction potential. It is extensively excreted unchanged in urine (approximately 60% of the dose) and in vitro metabolism is very slow. Prucalopride did not inhibit specific CYP450 activities in in vitro studies in human liver microsomes at therapeutically relevant concentrations. Although prucalopride may be a weak substrate for P-glycoprotein (P-gp), it is not an inhibitor of P-gp at clinically relevant concentrations. Effects of prucalopride on pharmacokinetics of other medicinal products A 30% increase in plasma concentrations of erythromycin was found during prucalopride co-administration. The mechanism for this interaction is not clear. Prucalopride had no clinically relevant effects on the pharmacokinetics of warfarin, digoxin, alcohol, paroxetine or oral contraceptives. Effects of other medicinal products on pharmacokinetics of prucalopride Ketoconazole (200 mg twice daily), a potent inhibitor of CYP3A4 and of P-gp, increased the systemic exposure to prucalopride by approximately 40%. This effect is too small to be clinically relevant. 3 Interactions of similar magnitude may be expected with other potent inhibitors of P-gp such as verapamil, cyclosporine A and quinidine. Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of prucalopride.

HOS-095308 · has-interaction-information · PDF-Seite 12

Prucalopride has a low pharmacokinetic interaction potential. It is extensively excreted unchanged in urine (approximately 60% of the dose) and in vitro metabolism is very slow. Prucalopride did not inhibit specific CYP450 activities in in vitro studies in human liver microsomes at therapeutically relevant concentrations. Although prucalopride may be a weak substrate for P-glycoprotein (P-gp), it is not an inhibitor of P-gp at clinically relevant concentrations. Effects of prucalopride on pharmacokinetics of other medicinal products A 30% increase in plasma concentrations of erythromycin was found during prucalopride co-administration. The mechanism for this interaction is not clear. Prucalopride had no clinically relevant effects on the pharmacokinetics of warfarin, digoxin, alcohol, paroxetine or oral contraceptives. Effects of other medicinal products on pharmacokinetics of prucalopride Ketoconazole (200 mg twice daily), a potent inhibitor of CYP3A4 and of P-gp, increased the systemic exposure to prucalopride by approximately 40%. This effect is too small to be clinically relevant. Interactions of similar magnitude may be expected with other potent inhibitors of P-gp such as verapamil, cyclosporine A and quinidine. 12 Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of prucalopride.

HOS-095309 · has-pregnancy-information · PDF-Seite 13

Women of childbearing potential Women of childbearing potential have to use effective contraception during treatment with prucalopride Pregnancy There is a limited amount of data from the use of prucalopride in pregnant women. Cases of spontaneous abortion have been observed during clinical studies, although, in the presence of other risk factors, the relationship to prucalopride is unknown. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (including pregnancy, embryonal/foetal development, parturition or postnatal development) (see section 5.3). Resolor is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding A human study has shown that prucalopride is excreted in breast milk. At therapeutic doses of Resolor, no effects on breast-fed newborns/infants are anticipated. In the absence of human data in women who actively breast-fed while taking Resolor, a decision should be made whether to discontinue breast-feeding or to discontinue Resolor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility Animal studies indicate that there is no effect on male or female fertility.

HOS-095303 · has-pregnancy-information · PDF-Seite 4

Women of childbearing potential Women of childbearing potential have to use effective contraception during treatment with prucalopride Pregnancy There is a limited amount of data from the use of prucalopride in pregnant women. Cases of spontaneous abortion have been observed during clinical studies, although, in the presence of other risk factors, the relationship to prucalopride is unknown. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (including pregnancy, embryonal/foetal development, parturition or postnatal development) (see section 5.3). Resolor is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding A human study has shown that prucalopride is excreted in breast milk. At therapeutic doses of Resolor, no effects on breast-fed newborns/infants are anticipated. In the absence of human data in women who actively breast-fed while taking Resolor, a decision should be made whether to discontinue breast-feeding or to discontinue Resolor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility Animal studies indicate that there is no effect on male or female fertility.

HOS-095307 · has-warning-information · PDF-Seite 12

Renal excretion is the main route of elimination of prucalopride (see section 5.2). A dose of 1 mg is recommended in subjects with severe renal impairment (see section 4.2). Caution should be exercised when prescribing Resolor to patients with severe hepatic impairment (Child-Pugh class C) due to limited data in patients with severe hepatic impairment (see section 4.2). There is limited information on the safety and efficacy of Resolor for use in patients with severe and clinically unstable concomitant disease (e.g. cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders). Caution should be exercised when prescribing Resolor to patients with these conditions especially when used 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). The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

HOS-095301 · has-warning-information · PDF-Seite 3

Renal excretion is the main route of elimination of prucalopride (see section 5.2). A dose of 1 mg is recommended in subjects with severe renal impairment (see section 4.2). Caution should be exercised when prescribing Resolor to patients with severe hepatic impairment (Child-Pugh class C) due to limited data in patients with severe hepatic impairment (see section 4.2). There is limited information on the safety and efficacy of Resolor for use in patients with severe and clinically unstable concomitant disease (e.g. cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders). Caution should be exercised when prescribing Resolor to patients with these conditions especially when used 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). The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.