| AMERICAN DRUGS | ANATOMY | HEALTH TOPICS | HIV/AIDS GLOSSARY | DISEASES | HEALTH ARTICLES | GENOME | OCCUPATIONS |

Resolor

Spanish Simplified Chinese French German Russian Hindi Arabic Portuguese
















Summary for the public


What is Resolor?

Resolor is a medicine that contains the active substance prucalopride. It is available as round tablets (white: 1 mg and pink: 2 mg).


What is Resolor used for?

Resolor is used to treat symptoms of chronic (long-term) constipation in women for whom laxatives (medicines that trigger bowel movements) do not work well enough.

The medicine can only be obtained with a prescription.


How is Resolor used?

The recommended dose of Resolor is 2 mg taken once a day. Women aged over 65 years should start with a 1 mg dose once a day, and this can be increased to 2 mg once a day if needed.

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


How does Resolor work?

The active substance in Resolor, prucalopride, is a ‘5-HT4 receptor agonist’. This means that it works like a substance in the body called 5-hydroxytryptamine (5HT, also known as serotonin) and attaches to the same receptors in the gut called ‘5-HT4 receptors’. When it binds to these receptors, 5HT normally stimulates movement in the gut. In the same way, when prucalopride attaches to and stimulates these receptors, it increases this movement and allows the bowels to empty faster.


How has Resolor been studied?

The effects of Resolor were first tested in experimental models before being studied in humans.

In three main studies involving 1999 patients with chronic constipation 88% of whom were women, Resolor (2 or 4 mg once a day) was compared with placebo (a dummy treatment). The patients had not responded well enough to previous treatment with laxatives. The main measure of effectiveness was the number of patients who completely emptied their bowels at least three times a week over a 12-week period without the help of laxatives.


What benefit has Resolor shown during the studies?

Resolor was more effective than placebo at treating chronic constipation. Over the 12-week period, 24% (151 out of 640) of patients who received Resolor 2 mg completely emptied their bowels at least three times a week, compared with 11% (73 out of 645) of patients who received placebo. The result from patients who received Resolor at the higher dose of 4 mg was similar to those who took the 2 mg dose.


What is the risk associated with Resolor?

The most common side effects with Resolor (seen in more than 1 patient in 10) are headache, nausea (feeling sick), diarrhoea and abdominal (tummy) pain. For the full list of all side effects reported with Resolor, see the Package Leaflet.

Resolor should not be used in people who may be hypersensitive (allergic) to prucalopride or any of the other ingredients. It must not be used in patients with kidney problems requiring dialysis (a blood clearance technique). It must also not be used in patients with intestinal perforation or obstruction, severe inflammatory conditions of the intestines such as Crohn’s disease, ulcerative colitis (inflammation of the large intestine causing ulceration and bleeding) and toxic megacolon and megarectum (very serious complications of colitis).


Why has Resolor been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that almost all the patients in the main study were women and that new data is required to understand how the medicine works in men. Based on the available data, the CHMP decided that Resolor’s benefits are greater than its risks for the treatment of the symptoms of chronic constipation in women for whom laxatives fail to provide adequate relief. The Committee recommended that Resolor be given marketing authorisation.


Other information about Resolor

The European Commission granted a marketing authorisation valid throughout the European Union for Resolor to Movetis NV on 15 October 2009.

Authorisation details
Name: Resolor
EMEA Product number: EMEA/H/C/001012
Active substance: prucalopride
INN or common name: prucalopride
Therapeutic area: Constipation
ATC Code: A03AE04
Marketing Authorisation Holder: Movetis NV
Revision: 2
Date of issue of Market Authorisation valid throughout the European Union: 15/10/2009
Contact address:
Movetis NV
Veedijk 58
B-2300 Turnhout
Belgium



Product Characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS


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 prucalopride succinate).
Excipients: Each film-coated tablet contains 150 mg lactose monohydrate.
For a 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 women in whom laxatives
fail to provide adequate relief.
4.2 Posology and method of administration
Posology
Women : 2 mg once daily.
Men : The safety and efficacy of Resolor for use in men has not been established in controlled clinical
trials therefore Resolor is not recommended for use in men until further data becomes available.
Elderly (>65 years) : Start with one 1 mg once daily (see section 5.2); 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. Currently available data are described in section 5.2.
Patients with renal impairment : The dose for patients with severe renal impairment
(GFR < 30 ml/min/1.73 m 2 ) 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 : The dose for patients with severe hepatic impairment (Child-Pugh
class C) is 1 mg once daily (see sections 4.4 and 5.2). 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.
2
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.
4.3 Contraindications
-
Hypersensitivity to the active substance or to any of the excipients.
-
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).
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
(see section 4.2).
Men: The safety and efficacy of Resolor for use in men has not been established in controlled clinical
trials therefore Resolor is not recommended for use in men until further data becomes available.
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption must not take this
medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
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 (P-gp), it is not an
inhibitor of P-gp at clinically relevant concentrations.
Ketoconazole (200 mg b.i.d.), a potent inhibitor of CYP3A4 and of P-gp, 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 P-gp 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
P-gp) may theoretically increase the exposure by up to 75%.
3
-
Renal impairment requiring dialysis.
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 5-HT 4
receptor mediated effects of prucalopride.
Interactions with food have not been observed.
4.6 Pregnancy and lactation
Pregnancy
Experience with prucalopride during pregnancy is limited. 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 pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Resolor is not recommended during pregnancy. Women of childbearing potential should use effective
contraception during treatment with prucalopride.
Lactation
Prucalopride is excreted in breast milk. However, at therapeutic doses of Resolor no effects on the
breastfed newborns/infants are anticipated. In the absence of human data, it is not recommended to use
Resolor during breast-feeding.
Fertility
Animal studies indicate that there is no effect on male or female fertility.
4.7 Effects on ability to drive and use machines
No studies on the effects of prucalopride on the ability to drive and use machines have been
performed. Resolor has been associated with dizziness and fatigue particularly during the first day of
treatment which may have an effect on driving and using machines (see section 4.8).
4.8 Undesirable effects
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.
4
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
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.
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 the medicinal product’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.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs acting on serotonin receptors, ATC code: A03AE04.
5
Very common: nausea, diarrhoea, abdominal pain
Mechanism of action
Prucalopride is a dihydrobenzofurancarboxamide with enterokinetic activities. Prucalopride is a
selective, high affinity serotonin (5-HT 4 ) receptor agonist, which is likely to explain its enterokinetic
effects. In vitro , only at concentrations exceeding its 5-HT 4 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-HT 4 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
defecation. In dogs, the effects observed in the gastrointestinal tract are sensitive to blockade with
selective 5-HT 4 receptor antagonists illustrating that the observed effects are exerted via selective
action on 5-HT 4 receptors.
Clinical experience
The efficacy of prucalopride was established in three multicentre, randomised, double-blind, 12-week
placebo-controlled studies in subjects with chronic constipation (n=1,279 on prucalopride, 1,124
females, 155 males). The prucalopride 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. Both doses were statistically
superior (p<0.001) to placebo at the primary endpoint in each of the three studies, with no incremental
benefit of the 4 mg over the 2 mg dose. The proportion of patients treated with the recommended dose
of 2 mg prucalopride that reached an average of ≥ 3 SCBM per week was 27.8% (week 4) and 23.6%
(week 12), versus 10.5% (week 4) and 11.3% (week 12) on placebo. A clinically meaningful
improvement of ≥ 1 SCBM per week, the most important secondary efficacy endpoint, was achieved
in 48.1% (week 4) and 43.1% (week 12) of patients treated with 2 mg prucalopride versus 23.4%
(week 4) and 24.6% (week 12) of placebo patients.
In all three studies, treatment with prucalopride also resulted in significant improvements in a
validated and disease specific set of symptom measures (PAC SYM), including abdominal, stool and
rectal symptoms, determined at week 4 and week 12. 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.
Prucalopride has been shown not to cause rebound phenomena, nor to induce dependency.
A thorough QT study was performed to evaluate the effects of prucalopride 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 prucalopride 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.
Data from open label studies up to 2.6 years offer some evidence for longer-term safety and efficacy;
however, no placebo controlled efficacy data for treatments longer than 12 weeks duration are
available.
5.2 Pharmacokinetic properties
Absorption
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg C max was attained in 2-3 hours. The
absolute oral bioavailability is >90%. Concomitant intake of food does not influence the oral
bioavailability of prucalopride.
6
Distribution
Prucalopride is extensively distributed, and has a steady-state volume of distribution (Vd ss ) of
567 litre. The plasma protein binding of prucalopride is about 30%.
Metabolism
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 eight metabolites were recovered in urine and faeces. The major
metabolite (R107504, formed by O-demethylation and oxidation of the resulting alcohol function to a
carboxylic acid) accounted for less than 4% of the dose. Unchanged active substance made up about
85% of the total radioactivity in plasma and only R107504 was a minor plasma metabolite.
Elimination
A large fraction of the active substance is excreted unchanged (about 60% of the administered dose in
urine and at least 6% 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.
Elderly
After once daily dosing of 1 mg, peak plasma concentrations and AUC of prucalopride in elderly
subjects were 26% to 28% higher than in young adults. This effect can be attributed to a diminished
renal function in elderly.
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 (Cl CR 50-79 ml/min) and
moderate (Cl CR 25-49 ml/min) renal impairment, respectively. In subjects with severe renal
impairment (Cl CR ≤ 24 ml/min), plasma concentrations were 2.3 times the levels in healthy subjects
(see section 4.2 and 4.4).
Hepatic impairment
Non-renal elimination contributes to about 35% of total elimination, and hepatic impairment is
unlikely to affect the pharmacokinetics of prucalopride to a clinically relevant extent (see section 4.2
and 4.4).
Paediatric population
After a single oral dose of 0.03 mg/kg in paediatric patients aged between 4 and 12 years , C max of
prucalopride was comparable to the C max in adults after a single 2 mg dose, while unbound AUC was
30-40% lower than after 2 mg in adults. Unbound exposure was similar over the whole age-range
(4-12 years).The average terminal half life in the paediatric subjects was about 19 hours (range 11.6 to
26.8 hours) (see section 4.2).
7
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 anaesthesized pigs after intravenous administration, and an increase in blood pressure in
conscious dogs after bolus intravenous administration, which was not observed either in anaesthetized
dogs or after oral administration in dogs reaching similar plasma levels.
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core
Lactose monohydrate
Microcrystalline cellulose
Colloidal silicon dioxide
Magnesium stearate
Coating
Hypromellose
Lactose monohydrate
Triacetin
Titanium dioxide (E171)
Macrogol 3000
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 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.
6.6 Special precautions for disposal
No special requirements.
8
7.
MARKETING AUTHORISATION HOLDER
Shire-Movetis NV
Veedijk 58
B-2300 Turnhout
Belgium
Tel.: 008006683 8470
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
15/10/09
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu/.
9
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 prucalopride succinate).
Excipients: Each film-coated tablet contains 165 mg lactose monohydrate.
For a 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 women in whom laxatives
fail to provide adequate relief.
4.2 Posology and method of administration
Posology
Women : 2 mg once daily.
Men : The safety and efficacy of Resolor for use in men has not been established in controlled clinical
trials therefore Resolor is not recommended for use in men until further data becomes available.
Elderly (>65 years) : Start with one 1 mg once daily (see section 5.2); 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. Currently available data are described in section 5.2.
Patients with renal impairment : The dose for patients with severe renal impairment
(GFR < 30 ml/min/1.73 m 2 ) 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 : The dose for patients with severe hepatic impairment (Child-Pugh
class C) is 1 mg once daily (see sections 4.4 and 5.2). 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.
10
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.
4.3 Contraindications
-
Hypersensitivity to the active substance or to any of the excipients.
-
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).
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
(see section 4.2).
Men: The safety and efficacy of Resolor for use in men has not been established in controlled clinical
trials therefore Resolor is not recommended for use in men until further data becomes available.
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption must not take this
medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
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 (P-gp), it is not an
inhibitor of P-gp at clinically relevant concentrations.
Ketoconazole (200 mg b.i.d.), a potent inhibitor of CYP3A4 and of P-gp, 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 P-gp 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
P-gp) may theoretically increase the exposure by up to 75%.
11
-
Renal impairment requiring dialysis.
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 5-HT 4
receptor mediated effects of prucalopride.
Interactions with food have not been observed.
4.6 Pregnancy and lactation
Pregnancy
Experience with prucalopride during pregnancy is limited. 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 pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Resolor is not recommended during pregnancy. Women of childbearing potential should use effective
contraception during treatment with prucalopride.
Lactation
Prucalopride is excreted in breast milk. However, at therapeutic doses of Resolor no effects on the
breastfed newborns/infants are anticipated. In the absence of human data, it is not recommended to use
Resolor during breast-feeding.
Fertility
Animal studies indicate that there is no effect on male or female fertility.
4.7 Effects on ability to drive and use machines
No studies on the effects of prucalopride on the ability to drive and use machines have been
performed. Resolor has been associated with dizziness and fatigue particularly during the first day of
treatment which may have an effect on driving and using machines (see section 4.8).
4.8 Undesirable effects
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.
12
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
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.
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 the medicinal product’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.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs acting on serotonin receptors, ATC code: A03AE04.
13
Very common: nausea, diarrhoea, abdominal pain
Mechanism of action
Prucalopride is a dihydrobenzofurancarboxamide with enterokinetic activities. Prucalopride is a
selective, high affinity serotonin (5-HT 4 ) receptor agonist, which is likely to explain its enterokinetic
effects. In vitro , only at concentrations exceeding its 5-HT 4 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-HT 4 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
defecation. In dogs, the effects observed in the gastrointestinal tract are sensitive to blockade with
selective 5-HT 4 receptor antagonists illustrating that the observed effects are exerted via selective
action on 5-HT 4 receptors.
Clinical experience
The efficacy of prucalopride was established in three multicentre, randomised, double-blind, 12-week
placebo-controlled studies in subjects with chronic constipation (n=1,279 on prucalopride, 1,124
females, 155 males). The prucalopride 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. Both doses were statistically
superior (p<0.001) to placebo at the primary endpoint in each of the three studies, with no incremental
benefit of the 4 mg over the 2 mg dose. The proportion of patients treated with the recommended dose
of 2 mg prucalopride that reached an average of ≥ 3 SCBM per week was 27.8% (week 4) and 23.6%
(week 12), versus 10.5% (week 4) and 11.3% (week 12) on placebo. A clinically meaningful
improvement of ≥ 1 SCBM per week, the most important secondary efficacy endpoint, was achieved
in 48.1% (week 4) and 43.1% (week 12) of patients treated with 2 mg prucalopride versus 23.4%
(week 4) and 24.6% (week 12) of placebo patients.
In all three studies, treatment with prucalopride also resulted in significant improvements in a
validated and disease specific set of symptom measures (PAC SYM), including abdominal, stool and
rectal symptoms, determined at week 4 and week 12. 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.
Prucalopride has been shown not to cause rebound phenomena, nor to induce dependency.
A thorough QT study was performed to evaluate the effects of prucalopride 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 prucalopride 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.
Data from open label studies up to 2.6 years offer some evidence for longer-term safety and efficacy;
however, no placebo controlled efficacy data for treatments longer than 12 weeks duration are
available.
5.2 Pharmacokinetic properties
Absorption
Prucalopride is rapidly absorbed; after a single oral dose of 2 mg C max was attained in 2-3 hours. The
absolute oral bioavailability is >90%. Concomitant intake of food does not influence the oral
bioavailability of prucalopride.
14
Distribution
Prucalopride is extensively distributed, and has a steady-state volume of distribution (Vd ss ) of
567 litre. The plasma protein binding of prucalopride is about 30%.
Metabolism
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 eight metabolites were recovered in urine and faeces. The major
metabolite (R107504, formed by O-demethylation and oxidation of the resulting alcohol function to a
carboxylic acid) accounted for less than 4% of the dose. Unchanged active substance made up about
85% of the total radioactivity in plasma and only R107504 was a minor plasma metabolite.
Elimination
A large fraction of the active substance is excreted unchanged (about 60% of the administered dose in
urine and at least 6% 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.
Elderly
After once daily dosing of 1 mg, peak plasma concentrations and AUC of prucalopride in elderly
subjects were 26% to 28% higher than in young adults. This effect can be attributed to a diminished
renal function in elderly.
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 (Cl CR 50-79 ml/min) and
moderate (Cl CR 25-49 ml/min) renal impairment, respectively. In subjects with severe renal
impairment (Cl CR ≤ 24 ml/min), plasma concentrations were 2.3 times the levels in healthy subjects
(see section 4.2 and 4.4).
Hepatic impairment
Non-renal elimination contributes to about 35% of total elimination, and hepatic impairment is
unlikely to affect the pharmacokinetics of prucalopride to a clinically relevant extent (see section 4.2
and 4.4).
Paediatric population
After a single oral dose of 0.03 mg/kg in paediatric patients aged between 4 and 12 years , C max of
prucalopride was comparable to the C max in adults after a single 2 mg dose, while unbound AUC was
30-40% lower than after 2 mg in adults. Unbound exposure was similar over the whole age-range
(4-12 years).The average terminal half life in the paediatric subjects was about 19 hours (range 11.6 to
26.8 hours) (see section 4.2).
15
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 anaesthesized pigs after intravenous administration, and an increase in blood pressure in
conscious dogs after bolus intravenous administration, which was not observed either in anaesthetized
dogs or after oral administration in dogs reaching similar plasma levels.
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core
Lactose monohydrate
Microcrystalline cellulose
Colloidal silicon dioxide
Magnesium stearate
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
3 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.
6.6 Special precautions for disposal
No special requirements.
16
7.
MARKETING AUTHORISATION HOLDER
Shire-Movetis NV
Veedijk 58
B-2300 Turnhout
Belgium
Tel.: 008006683 8470
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
15/10/09
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu/.
17
ANNEX II
A. MANUFACTURINGAUTHORISATIONHOLDER
RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
18
A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer 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
manufacturers responsible for the release of the concerned batch.
B. CONDITIONS OF THE MARKETING AUTHORISATION
CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON
THE MARKETING AUTHORISATION HOLDER
Medicinal product subject to medical prescription.
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as presented in Module 1.8.1. of the
Marketing Authorisation Application, is in place and functioning before and whilst the product is on
the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 3.0 of the Risk Management Plan (RMP) presented
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
At the request of the EMEA
19
ANNEX III
LABELLING AND PACKAGE LEAFLET
20
A. LABELLING
21
 
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 prucalopride succinate)
3.
LIST OF EXCIPIENTS
Contains lactose monohydrate. See leaflet for further information.
4.
PHARMACEUTICAL FORM AND CONTENTS
7 x 1 film-coated tablet
14 x 1 film-coated tablet
28 x 1 film-coated tablet
84 x 1 film-coated tablet
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 REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight 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.
22
 
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-Movetis NV
Veedijk 58 (1004)
B-2300 Turnhout, Belgium
Tel.: 008006683 8470
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
23
 
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 prucalopride succinate)
3.
LIST OF EXCIPIENTS
Contains lactose monohydrate. See leaflet for further information.
4.
PHARMACEUTICAL FORM AND CONTENTS
7 x 1 film-coated tablet
14 x 1 film-coated tablet
28 x 1 film-coated tablet
84 x 1 film-coated tablet
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 REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight 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.
24
 
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-Movetis NV
Veedijk 58 (1004)
B-2300 Turnhout, Belgium
Tel.: 008006683 8470
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
25
 
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-Movetis
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
Lot:
5.
OTHER
Mon Tue Wed Thu Fri Sat Sun
26
 
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-Movetis
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
Lot:
5.
OTHER
Mon Tue Wed Thu Fri Sat Sun
27
 
B. PACKAGE LEAFLET
28
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.
-
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. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet :
1. What Resolor is and what it is used for
2. Before you take Resolor
3. How to take Resolor
4. Possible side effects
5. How to store Resolor
6. Further information
1. WHAT RESOLOR IS AND WHAT IT IS USED FOR
Resolor belongs to a group of gut motility enhancing medicines (enterokinetics). It acts on the muscle
wall of the gut, helping to restore the normal functioning of the bowel. The tablets are used for the
treatment of chronic constipation in women in whom laxatives do not work well enough.
Not for use in men, children and adolescents younger than 18 years as Resolor has been insufficiently
studied in these populations.
2. BEFORE YOU TAKE RESOLOR
Do not take Resolor if you:
-
are allergic (hypersensitive) to prucalopride or any of the other ingredients of Resolor,
-
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.
Take special care with Resolor if you:
-
suffer from severe kidney disease,
-
are currently under supervision by your doctor for a serious medical problem such as lung or
heart disease, cancer or AIDS.
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.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription.
Taking Resolor with food and drink
Resolor can be taken with or without food and drinks, at any time of the day.
29
-
are on renal dialysis,
-
suffer from severe liver disease,
Pregnancy and breast-feeding
Do not take Resolor if you are pregnant or if you intend to become pregnant unless your doctor
advises you to do so.
When breast-feeding, prucalopride can pass into breast milk. Do not use Resolor while breastfeeding
unless your doctor advises you to do so .
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.
Important information about some of the ingredients of Resolor
Resolor contains lactose monohydrate. 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 Resolor exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure. You must 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, 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 or
liver disease.
Taking a higher dose than recommended will not make the product work better.
Resolor is only for adult women 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.
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.
30
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Resolor 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 frequency of possible side effects listed below is defined using the following convention:
-
very common (affects more than 1 user in 10)
-
common (affects 1 to 10 users in 100)
-
uncommon (affects 1 to 10 users in 1,000)
-
rare (affects 1 to 10 users in 10,000)
-
very rare (affects less than 1 user in 10,000)
-
not known (frequency cannot be estimated from the available data).
The following side effects have been reported very commonly: headache, feeling sick, diarrhoea and
abdominal pain.
The following side effects have been reported commonly: dizziness, vomiting, disturbed digestion
(dyspepsia), rectal bleeding, windiness, abnormal bowel sounds, increase in frequency of passing urine
(pollakiuria), tiredness.
The following uncommon side effects have also been seen: loss of appetite, tremors, pounding heart,
fever and weakness. If pounding heart occurs, please tell your doctor.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE RESOLOR
Keep out of the reach and sight of children.
Do not use Resolor 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.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Resolor contains
The active substance is prucalopride.
One film-coated tablet of Resolor 1 mg contains 1 mg prucalopride (as prucalopride succinate).
One film-coated tablet of Resolor 2 mg contains 2 mg prucalopride (as prucalopride succinate).
The other ingredients are:
Lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate,
hypromellose, triacetin, titanium dioxide (E171), macrogol 3000. The 2 mg tablet also contains iron
oxide red (E172), iron oxide yellow (E172), indigo carmine aluminium lake (E132).
31
What Resolor looks like and contents of the pack
Resolor 1 mg film-coated tablets are white to off-white, biconvex, round shaped tablets marked
“PRU 1” on one side.
Resolor 2 mg film-coated tablets are pink, biconvex, 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 tablet.
Not all pack sizes may be marketed in your country.
Marketing authorisation holder
Shire-Movetis NV
Veedijk 58
B-2300 Turnhout
Belgium
Tel.: 008006683 8470
Manufacturer
Sanico NV
Veedijk 59
B-2300 Turnhout
Belgium
Janssen Cilag S.P.A.
Via C. Janssen
I-04010 Borgo San Michele (Latina)
Italy
32
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Luxembourg/Luxemburg
Nederland
Shire Belgium BVBA
Lambroekstraat 5C
B-1831 Diegem
België/Belgique
Tél/Tel: +32 2 711 02 30
Ísland
Shire Sweden AB
Svärdvägen. 11D
SE-182 33 Danderyd
Svíþjóð
Tel: +46 8 544 964 00
България, Česká Republika, Eesti, Ελλάδα,
Kύπρος, Latvija, Lietuva,
Magyarország, Malta, Österreich, Polska,
România,
Slovenija, Slovenská republika.
Shire-Movetis NV
Veedijk 58 (1004)
2300 Turnhout
Белгия, Belgie, Βέλγιο, Beļģija, Belgija,
Belgium, Il-Belġju, Belgicko
Teл/Tel/Τηλ: 008006683 8470
Italia
Shire Italia S.p.A
Corso Italia, 29
I-50123, Firenze
Tel: +39 055 288860
Danmark
Shire Sweden AB
Svärdvägen. 11D
SE-182 33 Danderyd
Sverige
Tlf: +46 8 544 964 00
Norge
Shire Sweden AB
Svärdvägen. 11D
SE-182 33 Danderyd
Sverige
Tel: +46 8 544 964 00
Deutschland
Shire Deutschland GmbH
Friedrichstrasse 149
D-10117 Berlin
Tel: +49 30 206 582 0
Portugal
Shire Pharmaceuticals Portugal Lda
Avenida João Crisóstomo, 30-1º
1050-127 Lisboa
Tel: +351 213 303 730
España
Shire Pharmaceuticals Ibérica, S.L.
Paseo Pintor Rosales, 44 Bajo Izda.
E-28008 Madrid
Tel: +34 915 500 691
Suomi/Finland
Shire Sweden AB
Svärdvägen. 11D
SE-182 33 Danderyd
Ruotsi
Tel: +46 8 544 964 00
France
Shire France S.A.
88, rue du Dôme
F-92514 Boulogne-Billancourt Cedex
Tél: +33 1 46 10 90 00
Sverige
Shire Sweden AB
Svärdvägen. 11D
SE-182 33 Danderyd
Tel: +46 8 544 964 00
Ireland
Shire Pharmaceuticals Ltd
Hampshire International Business Park
Chineham, Basingstoke
Hampshire, RG24 8EP
United Kingdom
Tel: 1800 818 016
United Kingdom
Shire Pharmaceuticals Ltd
Hampshire International Business Park
Chineham, Basingstoke
Hampshire, RG24 8EP
Tel: 0800 055 6614
33
This leaflet was last approved in {MM/YYYY}
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
site: http://www.emea.europa.eu /.
34


Source: European Medicines Agency



- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.



http://www.theodora.com/drugs/eu/resolor.html

Copyright © 1995-2011 ITA all rights reserved.