Resolor

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

 2 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 1 mg film-coated tablets. 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 1 mg prucalopride (as succinate). 

 

Excipients with known effect: Each film-coated tablet contains 142.5 mg lactose (as monohydrate). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet). 

 

White to off-white, round, biconvex tablets marked “PRU 1” on one side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail 

to provide adequate relief. 

 

4.2 Posology and method of administration 
 
Posology 

Adults: 2 mg once daily with or without food, at any time of the day. 

 

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. Efficacy beyond three months has not been demonstrated in placebo-controlled studies (see 

Section 5.1). In case of prolonged treatment, the benefit should be reassessed at regular intervals. 

 

Special populations 

Older people (>65 years): Start with 1 mg once daily (see section 5.2); if needed the dose can be 

increased to 2 mg once daily. 
 

Patients with renal impairment: The dose for patients with severe renal impairment 

(GFR <30 ml/min/1.73 m2) is 1 mg once daily (see sections 4.3 and 5.2). No dose adjustment is 

required for patients with mild to moderate renal impairment. 
 

Patients with hepatic impairment: Patients with severe hepatic impairment (Child-Pugh class C) start 

with 1 mg once daily which may be increased to 2 mg if required to improve efficacy and if the 1 mg 

dose is well tolerated (see sections 4.4 and 5.2). No dose adjustment is required for patients with mild 

to moderate hepatic impairment. 

 



 

 3 

Paediatric population: Resolor should not be used in children and adolescents younger than 18 years 

(see section 5.1). 

 

Method of administration 

Oral use 

 

4.3 Contraindications 

 

- 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. 

 

4.4 Special warnings and precautions for use 
 

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. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

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. 



 

 4 

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. 

 

4.6 Fertility, pregnancy and lactation 

 

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. 

 

4.7 Effects on ability to drive and use machines 

 

Resolor may have a minor influence on the ability to drive and use machines, since dizziness and 

fatigue have been observed in clinical studies, particularly during the first day of treatment (see 

section 4.8). 

 

4.8 Undesirable effects 
 

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. 

 



 

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Table 1: Adverse Drug Reactions (ADRs) Associated with Resolor 

System/Organ Class Incidence Category Adverse Drug Reaction 

Metabolism and nutrition 

disorders 

Common Decreased appetite 

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 abnormal 

Uncommon Rectal haemorrhage 

Renal and urinary disorders Uncommon Pollakiuria 

General disorders and 

administration site conditions 

Common Fatigue 

Uncommon Pyrexia, malaise 

 

Description of selected adverse reactions 

After the first day of treatment, the most common adverse reactions were reported in similar 

frequencies (incidence no more 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 (differences in incidence between Resolor and 

placebo of 1.3% and 3.4%, respectively). 

 

Palpitations were reported in 0.7% of the placebo patients, 0.9% of the 1 mg prucalopride patients, 

0.9% 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.  

 

Reporting of suspected adverse reactions  

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V 

 

4.9 Overdose 

 

In a study in healthy volunteers, treatment with prucalopride was well tolerated when given in an 

up-titrating scheme up to 20 mg once daily (10 times the recommended therapeutic dose). An 

overdose may result in symptoms resulting from an exaggeration of prucalopride’s known 

pharmacodynamic effects and include headache, nausea and diarrhoea. Specific treatment is not 

available for Resolor overdose. Should an overdose occur, the patient should be treated 

symptomatically and supportive measures instituted, as required. Extensive fluid loss by diarrhoea or 

vomiting may require correction of electrolyte disturbances. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

 6 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties  

 

Pharmacotherapeutic group: Other drugs for constipation, ATC code: A06AX05.  

 

Mechanism of action 

Prucalopride is a dihydrobenzofurancarboxamide with gastrointestinal prokinetic activities. 

Prucalopride is a selective, high affinity serotonin (5-HT4) receptor agonist, which is likely to explain 

its prokinetic effects. In vitro, only at concentrations exceeding its 5-HT4 receptor affinity by at least 

150-fold, affinity for other receptors was detected. In rats, prucalopride in vivo, at doses above 

5 mg/kg (at and above 30-70 times the clinical exposure), induced hyperprolactinaemia caused by an 

antagonistic action at the D2 receptor.  

 

In dogs, prucalopride alters colonic motility patterns via serotonin 5-HT4 receptor stimulation: it 

stimulates proximal colonic motility, enhances gastroduodenal motility and accelerates delayed gastric 

emptying. Furthermore, giant migrating contractions are induced by prucalopride. These are 

equivalent to the colonic mass movements in humans, and provide the main propulsive force to 

defaecation. In dogs, the effects observed in the gastrointestinal tract are sensitive to blockade with 

selective 5-HT4 receptor antagonists illustrating that the observed effects are exerted via selective 

action on 5-HT4 receptors. 

 

These pharmacodynamic effects of prucalopride have been confirmed in human subjects with chronic 

constipation using manometry in an open-label, randomised, crossover, reader-blinded study 

investigating the effect of prucalopride 2 mg and an osmotic laxative on colon motility as determined 

by the number of colonic high-amplitude propagating contractions (HAPCs, also known as giant 

migrating contractions). Compared with a constipation treatment working through osmotic action, 

prokinetic stimulation with prucalopride increased colonic motility as measured by the number of 

HAPCs during the first 12 hours after intake of the investigational product. The clinical significance or 

benefit of this mechanism of action when compared with other laxatives has not been investigated. 

 

Clinical efficacy and safety 

 

Adult population 

The efficacy of Resolor was established in three multicentre, randomised, double-blind, 12-week 

placebo-controlled studies in subjects with chronic constipation (n=1,279 on Resolor, 1,124 females, 

155 males). The Resolor doses studied in each of these three studies included 2 mg and 4 mg once 

daily. The primary efficacy endpoint was the proportion (%) of subjects that reached normalisation of 

bowel movements defined as an average of three or more spontaneous, complete bowel movements 

(SCBM) per week over the 12-week treatment period. 

 

The proportion of female patients in whom laxatives fail to provide adequate relief treated with the 

recommended dose of 2 mg Resolor (n=458) that reached an average of ≥3 SCBM per week was 

31.0% (week 4) and 24.7% (week 12), versus 8.6% (week 4) and 9.2% (week 12) on placebo. A 

clinically meaningful improvement of ≥1 SCBM per week, the most important secondary efficacy 

endpoint, was achieved in 51.0% (week 4) and 44.2% (week 12) treated with 2 mg Resolor versus 

21.7% (week 4) and 22.6% (week 12) of placebo patients. 

 

The effect of Resolor on spontaneous bowel movements (SBM) also proved to be statistically superior 

to placebo for the portion of patients that had an increase of ≥1 SBM/week over the 12-week treatment 

period. At week 12, 68.3% of patients treated with 2 mg prucalopride had an average increase of 

≥1 SBM/week versus 37.0% of placebo patients (p<0.001 vs placebo). 

 

In all three studies, treatment with Resolor also resulted in significant improvements in a validated and 

disease specific set of symptom measures (PAC-SYM), including abdominal (bloating, discomfort, 

pain and cramps), stool (incomplete bowel movements, false alarm, straining, too hard, too small) and 



 

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rectal symptoms (painful bowel movements, burning, bleeding/tearing), determined at week 4 and 

week 12. At week 4, the proportion of patients with an improvement of ≥1 versus baseline in the 

PAC-SYM abdominal, stool, and rectal symptom subscales was 41.3%, 41.6%, and 31.3% 

respectively in patients treated with prucalopride 2 mg compared with 26.9%, 24.4% and 22.9% in 

patients on placebo. Similar results were observed at Week 12: 43.4%, 42.9%, and 31.7% respectively 

in 2 mg Resolor patients versus 26.9%, 27.2%, and 23.4% in placebo patients (p<0.001 vs placebo). 

 

A significant benefit on a number of Quality of Life measures, such as degree of satisfaction with 

treatment and with bowel habits, physical and psychosocial discomfort and worries and concerns, was 

also observed at both the 4 and 12 week assessment time points. At Week 4, the proportion of patients 

with an improvement of ≥1 versus baseline in the Patient Assessment of Constipation-Quality of Life 

satisfaction subscale (PAC-QOL) was 47.7% in patients treated with Resolor 2 mg compared with 

20.2% in patients on placebo. Similar results were observed at Week 12: 46.9% in 2 mg Resolor 

patients versus 19.0% in placebo patients (p<0.001 vs placebo). 

 

In addition, the efficacy, safety and tolerability of Resolor in male patients with chronic constipation 

were evaluated in a 12-week, multi-centre, randomised, double-blind, placebo–controlled study 

(N=370). The primary endpoint of the study was met: a statistically significantly higher percentage of 

subjects in the Resolor group (37.9%) had an average of ≥3 SCBMs/week compared with subjects in 

the placebo treatment group (17.7%) (p<0.0001) over the 12-week double-blind treatment period. The 

safety profile of Resolor was consistent with that seen in female patients. 

 

Long-term study 

The efficacy and safety of Resolor in patients (aged ≥18 or older) with chronic constipation, were 

evaluated in a 24 week multicentre, randomised, double-blind, placebo controlled study (N=361). The 

proportion of patients with an average weekly frequency of ≥3 Spontaneous Complete Bowel 

Movements (SCBMs) per week (i.e., responders) over the 24-week double-blind treatment phase was 

not statistically different (p=0.367) between the Resolor (25.1%) and placebo (20.7%) treatment 

groups. The difference between treatment groups in the average weekly frequency of ≥3 SCBMs per 

week was not statistically significant over Weeks 1-12 which is inconsistent with the 5 other 

multicentre, randomised, double-blind, 12-week placebo controlled studies demonstrating efficacy at 

this timepoint in adult patients. The study is therefore considered to be inconclusive with respect to 

efficacy. However, the totality of the data including the other double-blind placebo controlled 12 week 

studies support the efficacy of Resolor. The safety profile of prucalopride in this 24 week study was 

consistent with that seen in the previous 12 week studies. 

 

Resolor has been shown not to cause rebound phenomena, nor to induce dependency. 

 

TQT study 

A thorough QT study was performed to evaluate the effects of Resolor on the QT interval at 

therapeutic (2 mg) and supratherapeutic doses (10 mg) and compared with the effects of placebo and a 

positive control. This study did not show significant differences between Resolor and placebo at either 

dose, based on mean QT measurements and outlier analysis. This confirmed the results of two placebo 

controlled QT studies. In double-blind clinical studies, the incidence of QT-related adverse events and 

ventricular arrhythmias was low and comparable to placebo. 

 

Paediatric population 

The efficacy and safety of Resolor in paediatric patients (aged 6 months to 18 years) with functional 

constipation, were evaluated in an 8-week double-blind, placebo-controlled trial (N=213), followed by 

a 16 week open-label comparator-controlled (Polyethylene glycol 4000) study of up to 24 weeks 

(N=197). The starting dose administered was 0.04 mg/kg/day titrated between 0.02 and 

0.06 mg/kg/day (to a maximum of 2 mg daily) for children weighing ≤50 kg given as an oral solution 

of Resolor or matching placebo. Children weighing >50 kg received 2 mg/day Resolor tablets or 

matching placebo. 

 

Response to the treatment was defined as having an average of ≥3 spontaneous bowel movements 

(SBMs) per week and an average number of faecal incontinence episodes of ≤1 per 2 weeks. The 



 

 8 

results of the study showed no difference in efficacy between Resolor and placebo with response rates 

of 17% and 17.8% respectively (P=0.9002). Resolor was generally well tolerated. The incidence of 

subjects with at least 1 treatment-emergent adverse event (TEAE) was similar between the Resolor 

treatment group (69.8%) and the placebo treatment group (60.7%). Overall, the safety profile of 

Resolor in children was the same as in adults. 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Prucalopride is rapidly absorbed; after a single oral dose of 2 mg in healthy subjects, Cmax was attained 

in 2-3 hours. The absolute oral bioavailability is >90%. Concomitant intake of food does not influence 

the oral bioavailability of prucalopride. 

 

Distribution 

Prucalopride is extensively distributed, and has a steady-state volume of distribution (Vdss) of 

567 litres. The plasma protein binding of prucalopride is about 30%. 

 

Biotransformation 

Metabolism is not the major route of elimination of prucalopride. In vitro, human liver metabolism is 

very slow and only minor amounts of metabolites are found. In an oral dose study with radiolabelled 

prucalopride in man, small amounts of seven metabolites were recovered in urine and faeces. The 

quantitatively most important metabolite in excreta, R107504, accounted for 3.2% and 3.1% of the 

dose in urine and faeces, respectively. Other metabolites identified and quantified in urine and faeces 

were R084536 (formed by N-dealkylation) accounting for 3% of the dose and products of 

hydroxylation (3% of the dose) and N-oxidation (2% of the dose). Unchanged active substance made 

up about 92-94% of the total radioactivity in plasma. R107504, R084536 and R104065 (formed by 

O-demethylation) were identified as minor plasma metabolites. 

 

Elimination 

A large fraction of the active substance is excreted unchanged (60-65% of the administered dose in 

urine and about 5% in faeces). Renal excretion of unchanged prucalopride involves both passive 

filtration and active secretion. The plasma clearance of prucalopride averages 317 ml/min. Its terminal 

half-life is about one day. Steady-state is reached within three to four days. On once daily treatment 

with 2 mg prucalopride, steady-state plasma concentrations fluctuate between trough and peak values 

of 2.5 and 7 ng/ml, respectively. The accumulation ratio after once daily dosing ranged from 1.9 

to 2.3. The pharmacokinetics of prucalopride is dose-proportional within and beyond the therapeutic 

range (tested up to 20 mg). Prucalopride o.d. displays time-independent kinetics during prolonged 

treatment. 

 

Special populations 

 

Population pharmacokinetics 

A population pharmacokinetic analysis showed that the apparent total clearance of prucalopride was 

correlated with creatinine clearance, but that age, body weight, sex or race had no influence. 

 

Older people 

After once daily dosing of 1 mg, peak plasma concentrations and AUC of prucalopride in older people 

were 26% to 28% higher than in young adults. This effect can be attributed to a diminished renal 

function in older people. 

 

Renal impairment 

Compared to subjects with normal renal function, plasma concentrations of prucalopride after a single 

2 mg dose were on average 25% and 51% higher in subjects with mild (ClCR 50-79 ml/min) and 

moderate (ClCR 25-49 ml/min) renal impairment, respectively. In subjects with severe renal 

impairment (ClCR ≤24 ml/min), plasma concentrations were 2.3 times the levels in healthy subjects 

(see section 4.2 and 4.4). 

 



 

 9 

Hepatic impairment 

Non-renal elimination contributes to about 35% of total elimination. In a small pharmacokinetic study, 

the Cmax and AUC of prucalopride were, on average, 10-20% higher in patients with moderate to 

severe hepatic impairment compared with healthy subjects (see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to 

reproduction and development. An extended series of safety pharmacology studies with special 

emphasis on cardiovascular parameters showed no relevant changes in haemodynamic and ECG 

derived parameters (QTc) with the exception of a modest increase in heart rate and blood pressure 

observed in anaesthetised pigs after intravenous administration, and an increase in blood pressure in 

conscious dogs after bolus intravenous administration, which was not observed either in anaesthetised 

dogs or after oral administration in dogs reaching similar plasma levels. A subcutaneous 

neonatal/juvenile toxicity study performed in rats 7-55 days of age resulted in a NOAEL of 

10 mg/kg/day. The AUC0-24h exposure ratios at the NOAEL versus human children (dosed at 

approximately 0.04 mg/kg daily) ranged between 21 and 71 providing adequate safety margins for the 

clinical dose. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core 

Lactose monohydrate 

Microcrystalline cellulose 

Colloidal silicon dioxide 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Lactose monohydrate 

Triacetin 

Titanium dioxide (E171) 

Macrogol 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

4 years. 

 

6.4 Special precautions for storage 

 

Store in the original blister in order to protect from moisture. 

 

6.5 Nature and contents of container 
 

Aluminium/aluminium perforated unit dose blisters (calendar marked) containing 7 tablets. Each pack 

contains 7 x 1, 14 x 1, 28 x 1 or 84 x 1 film-coated tablet. 

 

Not all pack sizes may be marketed. 

 



 

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6.6 Special precautions for disposal 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/581/001 (28 tablets) 

EU/1/09/581/003 (7 tablets) 

EU/1/09/581/005 (14 tablets) 

EU/1/09/581/007 (84 tablets) 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 15 October 2009 

Date of latest renewal: 06 June 2014 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu/. 

http://www.ema.europa.eu/


 

 11 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 2 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 2 mg prucalopride (as succinate). 

 

Excipients with known effect: 

Each film-coated tablet contains 156.75 mg lactose (as monohydrate). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet). 

 

Pink, round, biconvex tablets marked “PRU 2” on one side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail 

to provide adequate relief. 

 

4.2 Posology and method of administration 
 
Posology 

Adults: 2 mg once daily with or without food, at any time of day. 

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. Efficacy beyond three months has not been demonstrated in placebo-controlled studies (see 

Section 5.1). In case of prolonged treatment, the benefit should be reassessed at regular intervals. 

 

Special populations 

Older people (>65 years): Start with 1 mg once daily (see section 5.2); if needed the dose can be 

increased to 2 mg once daily. 
 

Patients with renal impairment: The dose for patients with severe renal impairment 

(GFR <30 ml/min/1.73 m2) is 1 mg once daily (see sections 4.3 and 5.2). No dose adjustment is 

required for patients with mild to moderate renal impairment. 
 

Patients with hepatic impairment: Patients with severe hepatic impairment (Child-Pugh class C) start 

with 1 mg once daily which may be increased to 2 mg if required to improve efficacy and if the 1 mg 

dose is well tolerated (see sections 4.4 and 5.2). No dose adjustment is required for patients with mild 

to moderate hepatic impairment. 

 



 

 12 

Paediatric population: Resolor should not be used in children and adolescents younger than 18 years 
(see section 5.1). 

 

Method of administration 

Oral use 

 

4.3 Contraindications 

 

- 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. 

 

4.4 Special warnings and precautions for use 
 

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. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

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. 



 

 13 

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. 

 

4.6 Fertility, pregnancy and lactation 

 

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. 

 

4.7 Effects on ability to drive and use machines 

 

Resolor may have a minor influence on the ability to drive and use machines, since dizziness and 

fatigue have been observed in clinical studies, particularly during the first day of treatment (see 

section 4.8). 

 

4.8 Undesirable effects 
 

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. 

 



 

 14 

Table 1: Adverse Drug Reactions (ADRs) Associated with Resolor 

System/Organ Class Incidence Category Adverse Drug Reaction 

Metabolism and nutrition 

disorders 

Common Decreased appetite 

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 

abnormal 

Uncommon Rectal haemorrhage 

Renal and urinary disorders Uncommon Pollakiuria 

General disorders and 

administration site conditions 

Common Fatigue 

Uncommon Pyrexia, malaise 

 

Description of selected adverse reactions 

After the first day of treatment, the most common adverse reactions were reported in similar 

frequencies (incidence no more 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 (differences in incidence between Resolor and 

placebo of 1.3% and 3.4%, respectively). 

 

Palpitations were reported in 0.7% of the placebo patients, 0.9% of the 1 mg prucalopride patients, 

0.9% 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. 

 

Reporting of suspected adverse reactions  

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V 

 

4.9 Overdose 

 

In a study in healthy volunteers, treatment with prucalopride was well tolerated when given in an 

up-titrating scheme up to 20 mg once daily (10 times the recommended therapeutic dose). An 

overdose may result in symptoms resulting from an exaggeration of prucalopride’s known 

pharmacodynamic effects and include headache, nausea and diarrhoea. Specific treatment is not 

available for Resolor overdose. Should an overdose occur, the patient should be treated 

symptomatically and supportive measures instituted, as required. Extensive fluid loss by diarrhoea or 

vomiting may require correction of electrolyte disturbances. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

 15 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties  

 

Pharmacotherapeutic group: Other drugs for constipation, ATC code: A06AX05. 

 

Mechanism of action 

Prucalopride is a dihydrobenzofurancarboxamide with gastrointestinal prokinetic activities. 

Prucalopride is a selective, high affinity serotonin (5-HT4) receptor agonist, which is likely to explain 

its prokinetic effects. In vitro, only at concentrations exceeding its 5-HT4 receptor affinity by at least 

150-fold, affinity for other receptors was detected. In rats, prucalopride in vivo, at doses above 

5 mg/kg (at and above 30-70 times the clinical exposure), induced hyperprolactinaemia caused by an 

antagonistic action at the D2 receptor.  

 

In dogs, prucalopride alters colonic motility patterns via serotonin 5-HT4 receptor stimulation: it 

stimulates proximal colonic motility, enhances gastroduodenal motility and accelerates delayed gastric 

emptying. Furthermore, giant migrating contractions are induced by prucalopride. These are 

equivalent to the colonic mass movements in humans, and provide the main propulsive force to 

defaecation. In dogs, the effects observed in the gastrointestinal tract are sensitive to blockade with 

selective 5-HT4 receptor antagonists illustrating that the observed effects are exerted via selective 

action on 5-HT4 receptors. 

 

These pharmacodynamic effects of prucalopride have been confirmed in human subjects with chronic 

constipation using manometry in an open-label, randomised, crossover, reader-blinded study 

investigating the effect of prucalopride 2 mg and an osmotic laxative on colon motility as determined 

by the number of colonic high-amplitude propagating contractions (HAPCs, also known as giant 

migrating contractions). Compared with a constipation treatment working through osmotic action, 

prokinetic stimulation with prucalopride increased colonic motility as measured by the number of 

HAPCs during the first 12 hours after intake of the investigational product. The clinical significance or 

benefit of this mechanism of action when compared with other laxatives has not been investigated. 

 

Clinical efficacy and safety 

 

Adult population 

The efficacy of Resolor was established in three multicentre, randomised, double-blind, 12-week 

placebo-controlled studies in subjects with chronic constipation (n=1,279 on Resolor, 1,124 females, 

155 males). The Resolor doses studied in each of these three studies included 2 mg and 4 mg once 

daily. The primary efficacy endpoint was the proportion (%) of subjects that reached normalisation of 

bowel movements defined as an average of three or more spontaneous, complete bowel movements 

(SCBM) per week over the 12-week treatment period. 

 

The proportion of female patients in whom laxatives fail to provide adequate relief treated with the 

recommended dose of 2 mg Resolor (n=458) that reached an average of ≥3 SCBM per week was 

31.0% (week 4) and 24.7% (week 12), versus 8.6% (week 4) and 9.2% (week 12) on placebo. A 

clinically meaningful improvement of ≥1 SCBM per week, the most important secondary efficacy 

endpoint, was achieved in 51.0% (week 4) and 44.2% (week 12) treated with 2 mg Resolor versus 

21.7% (week 4) and 22.6% (week 12) of placebo patients. 

 

The effect of Resolor on spontaneous bowel movements (SBM) also proved to be statistically superior 

to placebo for the portion of patients that had an increase of ≥1 SBM/week over the 12-week treatment 

period. At week 12, 68.3% of patients treated with 2 mg Resolor had an average increase of 

≥1 SBM/week versus 37.0% of placebo patients (p<0.001 vs placebo). 

 

In all three studies, treatment with Resolor also resulted in significant improvements in a validated and 

disease specific set of symptom measures (PAC-SYM), including abdominal (bloating, discomfort, 

pain and cramps), stool (incomplete bowel movements, false alarm, straining, too hard, too small) and 



 

 16 

rectal symptoms (painful bowel movements, burning, bleeding/tearing), determined at week 4 and 

week 12. At week 4, the proportion of patients with an improvement of ≥1 versus baseline in the 

PAC-SYM abdominal, stool, and rectal symptom subscales was 41.3%, 41.6%, and 31.3% 

respectively in patients treated with Resolor 2 mg compared with 26.9%, 24.4% and 22.9% in patients 

on placebo. Similar results were observed at Week 12: 43.4%, 42.9%, and 31.7% respectively in 2 mg 

Resolor patients versus 26.9%, 27.2%, and 23.4% in placebo patients (p<0.001 vs placebo). 

 

A significant benefit on a number of Quality of Life measures, such as degree of satisfaction with 

treatment and with bowel habits, physical and psychosocial discomfort and worries and concerns, was 

also observed at both the 4 and 12 week assessment time points. At Week 4, the proportion of patients 

with an improvement of ≥1 versus baseline in the Patient Assessment of Constipation-Quality of Life 

satisfaction subscale (PAC-QOL) was 47.7% in patients treated with Resolor 2 mg compared with 

20.2% in patients on placebo. Similar results were observed at Week 12: 46.9% in 2 mg Resolor 

patients versus 19.0% in placebo patients (p<0.001 vs placebo). 

 

In addition, the efficacy, safety and tolerability of Resolor in male patients with chronic constipation 

were evaluated in a 12-week, multi-centre, randomised, double-blind, placebo–controlled study 

(N=370). The primary endpoint of the study was met: a statistically significantly higher percentage of 

subjects in the Resolor group (37.9%) had an average of ≥3 SCBMs/week compared with subjects in 

the placebo treatment group (17.7%) (p<0.0001) over the 12-week double-blind treatment period. The 

safety profile of Resolor was consistent with that seen in female patients. 

 

Long-term study 

The efficacy and safety of Resolor in patients (aged ≥18 or older) with chronic constipation, were 

evaluated in a 24 week multicentre, randomised, double-blind, placebo controlled study (N=361). The 

proportion of patients with an average weekly frequency of ≥3 Spontaneous Complete Bowel 

Movements (SCBMs) per week (i.e., responders) over the 24-week double-blind treatment phase was 

not statistically different (p=0.367) between the prucalopride (25.1%) and placebo (20.7%) treatment 

groups. The difference between treatment groups in the average weekly frequency of ≥3 SCBMs per 

week was not statistically significant over Weeks 1-12 which is inconsistent with the 5 other 

multicentre, randomised, double-blind, 12-week placebo controlled studies demonstrating efficacy at 

this timepoint in adult patients. The study is therefore considered to be inconclusive with respect to 

efficacy. However, the totality of the data including the other double-blind placebo controlled 12 week 

studies support the efficacy of Resolor. The safety profile of Resolor in this 24 week study was 

consistent with that seen in the previous 12 week studies. 

 

Resolor has been shown not to cause rebound phenomena, nor to induce dependency. 

 

TQT study 

A thorough QT study was performed to evaluate the effects of Resolor on the QT interval at 

therapeutic (2 mg) and supratherapeutic doses (10 mg) and compared with the effects of placebo and a 

positive control. This study did not show significant differences between Resolor and placebo at either 

dose, based on mean QT measurements and outlier analysis. This confirmed the results of two placebo 

controlled QT studies. In double-blind clinical studies, the incidence of QT-related adverse events and 

ventricular arrhythmias was low and comparable to placebo. 

 

Paediatric population 

The efficacy and safety of Resolor in paediatric patients (aged 6 months to 18 years) with functional 

constipation, were evaluated in an 8-week double-blind, placebo-controlled trial (N=213), followed by 

a 16 week open-label comparator-controlled (Polyethylene glycol 4000) study of up to 24 weeks 

(N=197). The starting dose administered was 0.04 mg/kg/day titrated between 0.02 and 

0.06 mg/kg/day (to a maximum of 2 mg daily) for children weighing ≤50 kg given as an oral solution 

of Resolor or matching placebo. Children weighing >50 kg received 2 mg/day Resolor tablets or 

matching placebo. 

 

Response to the treatment was defined as having an average of ≥3 spontaneous bowel movements 

(SBMs) per week and an average number of faecal incontinence episodes of ≤1 per 2 weeks. The 



 

 17 

results of the study showed no difference in efficacy between Resolor and placebo with response rates 

of 17% and 17.8% respectively (P=0.9002). Resolor was generally well tolerated. The incidence of 

subjects with at least 1 treatment-emergent adverse event (TEAE) was similar between the Resolor 

treatment group (69.8%) and the placebo treatment group (60.7%). Overall, the safety profile of 

Resolor in children was the same as in adults. 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Prucalopride is rapidly absorbed; after a single oral dose of 2 mg in healthy subjects, Cmax was attained 

in 2-3 hours. The absolute oral bioavailability is >90%. Concomitant intake of food does not influence 

the oral bioavailability of prucalopride. 

 

Distribution 

Prucalopride is extensively distributed, and has a steady-state volume of distribution (Vdss) of 

567 litres. The plasma protein binding of prucalopride is about 30%. 

 

Biotransformation 

Metabolism is not the major route of elimination of prucalopride. In vitro, human liver metabolism is 

very slow and only minor amounts of metabolites are found. In an oral dose study with radiolabelled 

prucalopride in man, small amounts of seven metabolites were recovered in urine and faeces. The 

quantitatively most important metabolite in excreta, R107504, accounted for 3.2% and 3.1% of the 

dose in urine and faeces, respectively. Other metabolites identified and quantified in urine and faeces 

were R084536 (formed by N-dealkylation) accounting for 3% of the dose and products of 

hydroxylation (3% of the dose) and N-oxidation (2% of the dose). Unchanged active substance made 

up about 92-94% of the total radioactivity in plasma. R107504, R084536 and R104065 (formed by 

O-demethylation) were identified as minor plasma metabolites. 

 

Elimination 

A large fraction of the active substance is excreted unchanged (60-65% of the administered dose in 

urine and about 5% in faeces). Renal excretion of unchanged prucalopride involves both passive 

filtration and active secretion. The plasma clearance of prucalopride averages 317 ml/min. Its terminal 

half-life is about one day. Steady-state is reached within three to four days. On once daily treatment 

with 2 mg prucalopride, steady-state plasma concentrations fluctuate between trough and peak values 

of 2.5 and 7 ng/ml, respectively. The accumulation ratio after once daily dosing ranged from 1.9 

to 2.3. The pharmacokinetics of prucalopride is dose-proportional within and beyond the therapeutic 

range (tested up to 20 mg). Prucalopride o.d. displays time-independent kinetics during prolonged 

treatment. 

 

Special populations 

 

Population pharmacokinetics 

A population pharmacokinetic analysis showed that the apparent total clearance of prucalopride was 

correlated with creatinine clearance, but that age, body weight, sex or race had no influence. 

 

Older people 

After once daily dosing of 1 mg, peak plasma concentrations and AUC of prucalopride in older people 

were 26% to 28% higher than in young adults. This effect can be attributed to a diminished renal 

function in older people. 

 

Renal impairment 

Compared to subjects with normal renal function, plasma concentrations of prucalopride after a single 

2 mg dose were on average 25% and 51% higher in subjects with mild (ClCR 50-79 ml/min) and 

moderate (ClCR 25-49 ml/min) renal impairment, respectively. In subjects with severe renal 

impairment (ClCR ≤24 ml/min), plasma concentrations were 2.3 times the levels in healthy subjects 

(see section 4.2 and 4.4).  

 



 

 18 

Hepatic impairment 

Non-renal elimination contributes to about 35% of total elimination. In a small pharmacokinetic study, 

the Cmax and AUC of prucalopride were, on average, 10-20% higher in patients with moderate to 

severe hepatic impairment compared with healthy subjects (see sections 4.2 and 4.4). 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to 

reproduction and development. An extended series of safety pharmacology studies with special 

emphasis on cardiovascular parameters showed no relevant changes in haemodynamic and ECG 

derived parameters (QTc) with the exception of a modest increase in heart rate and blood pressure 

observed in anaesthetised pigs after intravenous administration, and an increase in blood pressure in 

conscious dogs after bolus intravenous administration, which was not observed either in anaesthetised 

dogs or after oral administration in dogs reaching similar plasma levels. A subcutaneous 

neonatal/juvenile toxicity study performed in rats 7-55 days of age resulted in a NOAEL of 

10 mg/kg/day. The AUC0-24h exposure ratios at the NOAEL versus human children (dosed at 

approximately 0.04 mg/kg daily) ranged between 21 and 71 providing adequate safety margins for the 

clinical dose. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Lactose monohydrate 

Microcrystalline cellulose 

Colloidal silicon dioxide 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Lactose monohydrate 

Triacetin 

Titanium dioxide (E171) 

Macrogol 

Iron oxide red (E172) 

Iron oxide yellow (E172) 

Indigo carmine aluminium lake (E132) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

4 years. 

 

6.4 Special precautions for storage 

 

Store in the original blister in order to protect from moisture. 

 



 

 19 

6.5 Nature and contents of container 

 

Aluminium/aluminium perforated unit dose blisters (calendar marked) containing 7 tablets. Each pack 

contains 7 x 1, 14 x 1, 28 x 1 or 84 x 1 film-coated tablet. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/581/002 (28 tablets) 

EU/1/09/581/004 (7 tablets) 

EU/1/09/581/006 (14 tablets) 

EU/1/09/581/008 (84 tablets) 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation:15 October 2009 

Date of latest renewal: 06 June 2014 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu/. 

http://www.ema.europa.eu/


 

 20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 



 

 21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Sanico N.V. 

Veedijk 59 

B-2300 Turnhout 

Belgium 

 

Janssen Cilag S.P.A. 

Via C. Janssen 

I-04010 Borgo San Michele (Latina) 

Italy 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports 

 

The marketing authorisation holder shall submit periodic safety update reports for this product in 

accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 

under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal.  

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP shall be submitted annually until renewal. 

  

An updated RMP should be submitted: 

• At the request of the European Medicines Agency;  

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted 

at the same time. 

 

 

 

 

 



 

 22 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

 23 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 

 24 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 1 mg film-coated tablets 

prucalopride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 1 mg prucalopride (as succinate) 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 x 1 film-coated tablets  

14 x 1 film-coated tablets 

28 x 1 film-coated tablets 

84 x 1 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP.: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original blister in order to protect from moisture.  

 

 



 

 25 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/581/003 (7 tablets) 

EU/1/09/581/005 (14 tablets) 

EU/1/09/581/001 (28 tablets) 

EU/1/09/581/007 (84 tablets) 

 

 

13. BATCH NUMBER 

 

Lot:  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Resolor 1 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  



 

 26 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 2 mg film-coated tablets 

prucalopride 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 2 mg prucalopride (as succinate) 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 x 1 film-coated tablets  

14 x 1 film-coated tablets 

28 x 1 film-coated tablets 

84 x 1 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP.: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original blister in order to protect from moisture.  

 

 



 

 27 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/581/004 (7 tablets) 

EU/1/09/581/006 (14 tablets) 

EU/1/09/581/002 (28 tablets) 

EU/1/09/581/008 (84 tablets) 

 

 

13. BATCH NUMBER 

 

Lot:  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Resolor 2 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN:  

NN: 



 

 28 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 1 mg tablets 

prucalopride 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Mon Tue Wed Thu Fri Sat Sun 



 

 29 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Resolor 2 mg tablets 

prucalopride 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Mon Tue Wed Thu Fri Sat Sun 



 

 30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



 

 31 

Package leaflet: Information for the user 

 

Resolor 1 mg film-coated tablets 

Resolor 2 mg film-coated tablets 

prucalopride 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Resolor is and what it is used for 

2. What you need to know before you take Resolor 

3. How to take Resolor 

4. Possible side effects 

5. How to store Resolor 

6. Contents of the pack and other information 

 

 

1. What Resolor is and what it is used for 
 

Resolor contains the active substance prucalopride. 

 

Resolor belongs to a group of gut motility enhancing medicines (gastrointestinal prokinetics). It acts 

on the muscle wall of the gut, helping to restore the normal functioning of the bowel. Resolor is used 

for the treatment of chronic constipation in adults in whom laxatives do not work well enough. 

 

Not for use in children and adolescents younger than 18 years. 

 

2. What you need to know before you take Resolor 
 

Do not take Resolor: 

- if you are allergic to prucalopride or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are on renal dialysis, 

- if you suffer from perforation or obstruction of the gut wall, severe inflammation of the 

intestinal tract, such as Crohn’s disease, ulcerative colitis or toxic megacolon/megarectum. 

 

Warnings and precautions 

Talk to your doctor before taking Resolor. 

 

Take special care with Resolor and tell your doctor if you: 

- suffer from severe kidney disease, 

- suffer from severe liver disease, 

- are currently under supervision by a doctor for a serious medical problem such as lung or heart 

disease, nervous system or mental health problems, cancer, AIDS or a hormonal disorder. 

 

If you have very bad diarrhoea, the contraceptive pill may not work properly and the use of an extra 

method of contraception is recommended. See the instructions in the patient leaflet of the 

contraceptive pill you are taking. 

 



 

 32 

Other medicines and Resolor 

Tell your doctor if you are taking, or have recently taken, or might take any other medicines. 

 

Resolor with food and drink 

Resolor can be taken with or without food and drinks, at any time of the day. 

 

Pregnancy and breast-feeding 

Resolor is not recommended for use during pregnancy. 

- Tell your doctor if you are pregnant or planning to become pregnant. 
- Use a reliable method of contraception while you’re taking Resolor, to prevent pregnancy. 
- If you do become pregnant during treatment with Resolor, tell your doctor. 
 

When breast-feeding, prucalopride can pass into breast milk. Breast-feeding is not recommended 

during treatment with Resolor. Talk to your doctor about this. 

 

Ask your doctor for advice before taking any medicine. 

 

Driving and using machines 

Resolor is unlikely to affect your ability to drive or use machines. However, sometimes Resolor may 

cause dizziness and tiredness, especially on the first day of treatment, and this may have an effect on 

driving and use of machines. 

 

Resolor contains lactose  

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 

before taking this medicine. 

 

 

3. How to take Resolor 
 

Always take this medicine exactly as described in this leaflet or as your doctor has told you. Check 

with your doctor or pharmacist if you are not sure. Take Resolor every day for as long as your doctor 

prescribes it. 

 

The doctor may want to reassess your condition and the benefit of continued treatment after the first 

4 weeks and thereafter at regular intervals. 

 

The usual dose of Resolor for most patients is one 2 mg tablet once a day. 

 

If you are older than 65 years or have severe liver disease, the starting dose is one 1 mg tablet once a 

day, which your doctor may increase to 2 mg once a day if needed. 

 

Your doctor may also recommend a lower dose of one 1 mg tablet daily if you have severe kidney 

disease. 

 

Taking a higher dose than recommended will not make the product work better. 

 

Resolor is only for adults and should not be taken by children and adolescents up to 18 years. 

 

If you take more Resolor than you should 

It is important to keep to the dose as prescribed by your doctor. If you have taken more Resolor than 

you should, it is possible that you will get diarrhoea, headache and/or nausea. In case of diarrhoea, 

make sure that you drink enough water. 

 

If you forget to take Resolor 

Do not take a double dose to make up for a forgotten tablet. Just take your next dose at the usual time. 

 



 

 33 

If you stop taking Resolor 

If you stop taking Resolor, your constipation symptoms may come back again. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 

effects mostly occur at the start of treatment and usually disappear within a few days with continued 

treatment. 

 

The following side effects have been reported very commonly (may affect more than 1 in 10 people): 

headache, feeling sick, diarrhoea and abdominal pain. 

 

The following side effects have been reported commonly (may affect up to 1  in 10 people): decreased 

appetite, dizziness, vomiting, disturbed digestion (dyspepsia), windiness, abnormal bowel sounds, 

tiredness. 

 

The following uncommon side effects have also been seen (may affect up to 1 in 100 people): tremors, 

pounding heart, rectal bleeding, increase in frequency of passing urine (pollakiuria), fever and feeling 

unwell. If pounding heart occurs, please tell your doctor. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Resolor 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The 

expiry date refers to the last day of that month. 

 

Store in the original blister package in order to protect from moisture. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Resolor contains 

The active substance is prucalopride. 

One film-coated tablet of Resolor 1 mg contains 1 mg prucalopride (as succinate). 

One film-coated tablet of Resolor 2 mg contains 2 mg prucalopride (as succinate). 

 

The other ingredients are: 

Lactose monohydrate (see section 2), microcrystalline cellulose, colloidal silicon dioxide, magnesium 

stearate, hypromellose, triacetin, titanium dioxide (E171), macrogol. The 2 mg tablet also contains 

iron oxide red (E172), iron oxide yellow (E172), indigo carmine aluminium lake (E132). 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

 34 

What Resolor looks like and contents of the pack 

Resolor 1 mg film-coated tablets are white to off-white round shaped tablets marked “PRU 1” on one 

side. 

Resolor 2 mg film-coated tablets are pink round shaped tablets marked “PRU 2” on one side. 

 

Resolor is provided in aluminium/aluminium perforated unit dose blister (calendar marked) containing 

7 tablets. Each pack contains 7x1, 14x1, 28x1 or 84x1 film-coated tablets. 

 

Not all pack sizes may be marketed in your country. 

 

Marketing authorisation holder 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

Tel: +44(0)1256 894 959 

E-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Sanico NV 

Veedijk 59 

B-2300 Turnhout 

Belgium 

 

Janssen Cilag S.P.A. 

Via C. Janssen 

I-04010 Borgo San Michele (Latina) 

Italy 

 

This leaflet was last revised in 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu/.  

 

mailto:medinfoEMEA@shire.com
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET