These Highlights Do Not Include All The Information Needed To Use prucalopride Tablets Safely And Effectively. See Full Prescribing Information For Prucalopride Tablets.

Common Adverse Reactions

Table 2 below summarizes the incidence (%) of common adverse reactions occurring in at least 2% of patients with CIC receiving either 2 mg of prucalopride once daily or placebo and at an incidence greater than in the placebo group from the six double-blind placebo-controlled trials described above.

Store prucalopride tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store prucalopride tablets in the original container to protect from moisture.

An overdose may result in appearance of symptoms from an exaggeration of the known pharmacodynamic effects of prucalopride and includes headache, nausea, and diarrhea. Specific treatment is not available for prucalopride overdose. Should an overdose occur, treat symptomatically and institute supportive measures, as required. Extensive fluid loss from diarrhea or vomiting may require correction of electrolyte disturbances.

Prucalopride tablets for oral use contain prucalopride succinate, a dihydrobenzofurancarboxamide that is a serotonin type 4 (5-HT₄) receptor agonist. The IUPAC name is: 4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydrobenzofuran-7-carboxamide succinate.

The molecular formula is C₁₈H₂₆ClN₃O₃.C₄H₆O₄ and the molecular weight is 485.96 g/mol. The structural formula is:

Prucalopride succinate is a white to almost white powder. It is sparingly soluble in dimethyl sulphoxide, methanol and soluble in water.

Each 1 mg film-coated tablet of prucalopride contains 1 mg of prucalopride (equivalent to 1.32 mg prucalopride succinate), and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose. The coating for the 1 mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, and triacetin.

Each 2 mg film-coated tablet of prucalopride contains 2 mg of prucalopride (equivalent to 2.64 mg prucalopride succinate), and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose. The coating for the 2 mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, triacetin, red iron oxide, and yellow iron oxide.

The safety and effectiveness of prucalopride have not been established in pediatric patients.

Of the 2,484 patients treated with prucalopride 1 mg or 2 mg once daily in 6 controlled trials of at least 12-week duration in patients with CIC, 15% were 65 years of age and over, and 5% were 75 years of age and over [see Clinical Studies (14)]. No overall differences in safety and effectiveness were observed between elderly and younger patients.

In an additional 4-week double-blind, placebo-controlled dose escalation study in 89 elderly nursing home residents with CIC (PRU-USA-26, NCT00627692), no unanticipated safety issues were identified.

Elderly subjects had higher prucalopride exposure compared to younger subjects. However, the effect of age on the pharmacokinetics of prucalopride appeared to be related to decreased renal function [see Clinical Pharmacology (12.3)]. Adjust the dosage in elderly patients based on renal function [see Dosage and Administration (2), Use in Specific Populations (8.6)].

The efficacy of prucalopride for the treatment of CIC was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical trials in 2,484 adult patients (Studies 1 to 6; see Table 3). Studies 1 through 5 were 12-week treatment duration and Study 6 included 24 weeks of treatment. Patients less than 65 years were dosed with prucalopride 2 mg once daily. In Studies 2 and 6, the geriatric patients started on prucalopride 1 mg once daily and, if necessary, the dose was increased to 2 mg after 2 weeks or 4 weeks of treatment in the event of insufficient response at 1 mg; of these patients 81% increased to 2 mg. Overall, the majority of patients were female (76%) and white (76%), and also included Asian (19%) and black (3%). The mean adult age was 47 years ± 16 years (range 17 years to 95 years) and the mean duration of constipation was 16 years ± 15 years with 28% of patients having chronic constipation for at least 20 years.

Eligible patients required a history of chronic constipation defined as having fewer than 3 spontaneous bowel movements (SBMs) per week that resulted in a feeling of complete evacuation (complete, spontaneous bowel movement [CSBM]) and 1 or more of the following symptoms for greater than 25% of bowel movements in the preceding 3 months, with symptoms onset more than 6 months prior to screening:

• Lumpy or hard stools
• Sensation of incomplete evacuation
• Straining at defecation

Patients who never had SBMs were eligible. In Study 1, eligibility also included sensation of ano-rectal obstruction or blockade or the need for digital manipulation in more than 25% of bowel movements. In all studies, patients were excluded if constipation was due to secondary causes or suspected to be drug-induced.

Efficacy was assessed using information provided by patients in a daily diary.

Prucalopride is contraindicated in patients with:

• A history of hypersensitivity to prucalopride. Reactions including dyspnea, rash, pruritus, urticaria, and facial edema have been observed [see Adverse Reactions (6.2)].
• 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, ulcerative colitis, and toxic megacolon/megarectum.

Most common adverse reactions (≥ 2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact SKG Pharma Inc. at 1-866-495-2621 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dosage adjustment is required for patients with mild and moderate renal impairment (creatinine clearance at least 30 mL/min, as determined from a 24-hour urine collection in the clinical trial).

Prucalopride is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. A decreased dosage is recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min, as determined from a 24-hour urine collection in the clinical trial) [see Dosage and Administration (2)].

Avoid prucalopride in patients with end-stage renal disease requiring dialysis [see Clinical Pharmacology (12.3)].

The pharmacokinetics of prucalopride has been evaluated in healthy subjects and is dose-proportional within and beyond the therapeutic range (tested up to 20 mg, 10 times the maximum approved recommended dose). Prucalopride administered once daily displays time-independent kinetics during prolonged treatment. With once daily administration of 2 mg prucalopride, pharmacokinetic steady-state is attained within 3 days to 4 days, and steady-state plasma concentrations fluctuate between trough and peak values of 2.5 ng/mL and 7 ng/mL, respectively, with mean plasma AUC_0-24h of 109 ng∙h/mL. The accumulation ratio after once daily dosing ranged from 1.9 to 2.3. The terminal half-life is approximately 1 day.

Pharmacokinetic parameters in patients with CIC are similar to those seen in healthy subjects.

Prucalopride tablets are indicated for the treatment of chronic idiopathic constipation (CIC) in adults.

Prucalopride, a selective serotonin type 4 (5-HT₄) receptor agonist, is a gastrointestinal (GI) prokinetic agent that stimulates colonic peristalsis (high-amplitude propagating contractions [HAPCs]), which increases bowel motility.

Prucalopride was devoid of effects mediated via 5-HT_2A, 5-HT_2B, 5-HT₃, motilin or CCK-A receptors in vitro at concentrations exceeding 5-HT₄ receptor affinity by 150-fold or greater. In isolated GI tissues from various animal species, prucalopride facilitated acetylcholine release to enhance the amplitude of contractions and stimulate peristalsis. In rats and dogs, prucalopride stimulated gastrointestinal motility with contractions starting from the proximal colon to the anal sphincter.

Suicidal Ideation and Behavior: Monitor patients for suicidal ideation and behavior as well as self-injurious ideation and new-onset or worsening of depression. Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience any unusual changes in mood or behavior, or they experience emerging suicidal thoughts or behaviors. (5.1)

Prucalopride tablets can be taken with or without food. The recommended dosage by patient population is shown in Table 1.

Prucalopride Tablets:

• 1 mg prucalopride: White to off-white, round, biconvex film-coated tablets debossed with “P1” on one side and plain on other side.
• 2 mg prucalopride: Yellow, round, biconvex film-coated tablets debossed with “P2” on one side and plain on the other side.

The following adverse reactions have been identified during post-approval use of prucalopride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions: dyspnea, rash, pruritus, urticaria, and facial edema [see Contraindications (4)].

Psychiatric disorders: Suicide, suicide attempts, suicidal ideation, self-injurious ideation, depression, anxiety, insomnia, nightmares, and visual hallucinations [see Warnings and Precautions (5.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below represent 2,530 patients (1,251 received prucalopride 2 mg once daily and 1,279 received placebo) with CIC from 6 double-blind, placebo-controlled clinical trials of 12 weeks to 24 weeks in duration. In these trials overall, patients were primarily female (76%) and white (76%). The mean age was 47 years (range 17 years to 95 years) [see Clinical Studies (14)].

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Suicidal Ideation and Behavior: Inform patients, their caregivers, and family members that suicidal ideation and behavior, self-injurious ideation as well as new onset or worsening depression have been reported in patients treated with prucalopride tablets. Advise them to be aware of any unusual changes in mood or behavior, new onset or worsening of depression, or the emergence of suicidal thoughts or behavior. Instruct patients, caregivers, and family members to discontinue prucalopride tablets immediately and contact their healthcare provider if any of these symptoms occur [see Warnings and Precautions (5.1)].

In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. Postmarketing cases of suicidal ideation and behavior as well as self-injurious ideation and new onset or worsening of depression have been reported within the first few weeks of starting prucalopride [see Adverse Reactions (6.1, 6.2)].

A causal association between treatment with prucalopride and an increased risk of suicidal ideation and behavior has not been established.

Monitor all patients treated with prucalopride for new onset or worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience any of these symptoms.

Prucalopride tablets containing 1 mg prucalopride are white to off-white, round, biconvex film-coated tablets debossed with “P1” on one side and plain on other side. They are supplied as:

• NDC 83085-005-30: HDPE bottle of 30 tablets, with child-resistant closure.

Prucalopride tablets containing 2 mg prucalopride are yellow, round, biconvex film-coated tablets debossed with “P2” on one side and plain on other side. They are supplied as:

• NDC 83085-006-30: HDPE bottle of 30 tablets, with child-resistant closure.

In safety pharmacology studies, no relevant effects were observed in any of the cardiovascular studies at concentrations at least 50 times the human therapeutic C_max. Prucalopride had no effect on potassium current in hERG-transfected HEK cells at concentrations up to 1 micromolar (50 times the human therapeutic C_max). At concentrations ≥ 3 micromolar, concentration-dependent inhibition of the current was observed (IC₅₀ = 22 micromolar; 1,100 times the human therapeutic C_max). In studies in pigs, minor and transient increases in heart rate and blood pressure were noted upon first exposure to prucalopride, at plasma levels at least 10 times the human therapeutic C_max.

In repeated-dose toxicology studies in male rats, increases in heart weight (up to 9%) were observed at doses of 20 mg/kg/day or higher (at least 75 times the human therapeutic AUC). Cardiac histology revealed an increase in focal infiltration of chronic inflammatory cells in the heart at a dose of 80 mg/kg/day (at least 785 times the human therapeutic AUC). In dogs, no changes in heart rate, blood pressure, electrocardiogram parameters, heart weight, or cardiac histology were observed at any dose tested (the highest dose of 30 mg/kg/day was 572 times the human therapeutic AUC).

In vitro studies demonstrated no effect of prucalopride on either contractile responses in human, canine, and porcine coronary arteries at concentrations up to 10 micromolar (500 times the human clinical C_max) or on platelet aggregation at concentrations up to 200 nanomolar (10 times the human clinical C_max).

NDC 83085-005-30

Prucalopride Tablets

1 mg

Usual Dose: One tablet once daily.

Rx only

30 Tablets

NDC 83085-006-30

Prucalopride  Tablets

2 mg

Usual Dose: One tablet once daily.

Rx only

30 Tablets

Common Adverse Reactions

Table 2 below summarizes the incidence (%) of common adverse reactions occurring in at least 2% of patients with CIC receiving either 2 mg of prucalopride once daily or placebo and at an incidence greater than in the placebo group from the six double-blind placebo-controlled trials described above.

Store prucalopride tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store prucalopride tablets in the original container to protect from moisture.

An overdose may result in appearance of symptoms from an exaggeration of the known pharmacodynamic effects of prucalopride and includes headache, nausea, and diarrhea. Specific treatment is not available for prucalopride overdose. Should an overdose occur, treat symptomatically and institute supportive measures, as required. Extensive fluid loss from diarrhea or vomiting may require correction of electrolyte disturbances.

Prucalopride tablets for oral use contain prucalopride succinate, a dihydrobenzofurancarboxamide that is a serotonin type 4 (5-HT₄) receptor agonist. The IUPAC name is: 4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydrobenzofuran-7-carboxamide succinate.

The molecular formula is C₁₈H₂₆ClN₃O₃.C₄H₆O₄ and the molecular weight is 485.96 g/mol. The structural formula is:

Prucalopride succinate is a white to almost white powder. It is sparingly soluble in dimethyl sulphoxide, methanol and soluble in water.

Each 1 mg film-coated tablet of prucalopride contains 1 mg of prucalopride (equivalent to 1.32 mg prucalopride succinate), and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose. The coating for the 1 mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, and triacetin.

Each 2 mg film-coated tablet of prucalopride contains 2 mg of prucalopride (equivalent to 2.64 mg prucalopride succinate), and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose. The coating for the 2 mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, triacetin, red iron oxide, and yellow iron oxide.

The safety and effectiveness of prucalopride have not been established in pediatric patients.

Of the 2,484 patients treated with prucalopride 1 mg or 2 mg once daily in 6 controlled trials of at least 12-week duration in patients with CIC, 15% were 65 years of age and over, and 5% were 75 years of age and over [see Clinical Studies (14)]. No overall differences in safety and effectiveness were observed between elderly and younger patients.

In an additional 4-week double-blind, placebo-controlled dose escalation study in 89 elderly nursing home residents with CIC (PRU-USA-26, NCT00627692), no unanticipated safety issues were identified.

Elderly subjects had higher prucalopride exposure compared to younger subjects. However, the effect of age on the pharmacokinetics of prucalopride appeared to be related to decreased renal function [see Clinical Pharmacology (12.3)]. Adjust the dosage in elderly patients based on renal function [see Dosage and Administration (2), Use in Specific Populations (8.6)].

The efficacy of prucalopride for the treatment of CIC was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical trials in 2,484 adult patients (Studies 1 to 6; see Table 3). Studies 1 through 5 were 12-week treatment duration and Study 6 included 24 weeks of treatment. Patients less than 65 years were dosed with prucalopride 2 mg once daily. In Studies 2 and 6, the geriatric patients started on prucalopride 1 mg once daily and, if necessary, the dose was increased to 2 mg after 2 weeks or 4 weeks of treatment in the event of insufficient response at 1 mg; of these patients 81% increased to 2 mg. Overall, the majority of patients were female (76%) and white (76%), and also included Asian (19%) and black (3%). The mean adult age was 47 years ± 16 years (range 17 years to 95 years) and the mean duration of constipation was 16 years ± 15 years with 28% of patients having chronic constipation for at least 20 years.

Eligible patients required a history of chronic constipation defined as having fewer than 3 spontaneous bowel movements (SBMs) per week that resulted in a feeling of complete evacuation (complete, spontaneous bowel movement [CSBM]) and 1 or more of the following symptoms for greater than 25% of bowel movements in the preceding 3 months, with symptoms onset more than 6 months prior to screening:

• Lumpy or hard stools
• Sensation of incomplete evacuation
• Straining at defecation

Patients who never had SBMs were eligible. In Study 1, eligibility also included sensation of ano-rectal obstruction or blockade or the need for digital manipulation in more than 25% of bowel movements. In all studies, patients were excluded if constipation was due to secondary causes or suspected to be drug-induced.

Efficacy was assessed using information provided by patients in a daily diary.

Prucalopride is contraindicated in patients with:

• A history of hypersensitivity to prucalopride. Reactions including dyspnea, rash, pruritus, urticaria, and facial edema have been observed [see Adverse Reactions (6.2)].
• 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, ulcerative colitis, and toxic megacolon/megarectum.

Most common adverse reactions (≥ 2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact SKG Pharma Inc. at 1-866-495-2621 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dosage adjustment is required for patients with mild and moderate renal impairment (creatinine clearance at least 30 mL/min, as determined from a 24-hour urine collection in the clinical trial).

Prucalopride is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. A decreased dosage is recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min, as determined from a 24-hour urine collection in the clinical trial) [see Dosage and Administration (2)].

Avoid prucalopride in patients with end-stage renal disease requiring dialysis [see Clinical Pharmacology (12.3)].

The pharmacokinetics of prucalopride has been evaluated in healthy subjects and is dose-proportional within and beyond the therapeutic range (tested up to 20 mg, 10 times the maximum approved recommended dose). Prucalopride administered once daily displays time-independent kinetics during prolonged treatment. With once daily administration of 2 mg prucalopride, pharmacokinetic steady-state is attained within 3 days to 4 days, and steady-state plasma concentrations fluctuate between trough and peak values of 2.5 ng/mL and 7 ng/mL, respectively, with mean plasma AUC_0-24h of 109 ng∙h/mL. The accumulation ratio after once daily dosing ranged from 1.9 to 2.3. The terminal half-life is approximately 1 day.

Pharmacokinetic parameters in patients with CIC are similar to those seen in healthy subjects.

Prucalopride tablets are indicated for the treatment of chronic idiopathic constipation (CIC) in adults.

Prucalopride, a selective serotonin type 4 (5-HT₄) receptor agonist, is a gastrointestinal (GI) prokinetic agent that stimulates colonic peristalsis (high-amplitude propagating contractions [HAPCs]), which increases bowel motility.

Prucalopride was devoid of effects mediated via 5-HT_2A, 5-HT_2B, 5-HT₃, motilin or CCK-A receptors in vitro at concentrations exceeding 5-HT₄ receptor affinity by 150-fold or greater. In isolated GI tissues from various animal species, prucalopride facilitated acetylcholine release to enhance the amplitude of contractions and stimulate peristalsis. In rats and dogs, prucalopride stimulated gastrointestinal motility with contractions starting from the proximal colon to the anal sphincter.

Suicidal Ideation and Behavior: Monitor patients for suicidal ideation and behavior as well as self-injurious ideation and new-onset or worsening of depression. Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience any unusual changes in mood or behavior, or they experience emerging suicidal thoughts or behaviors. (5.1)

Prucalopride tablets can be taken with or without food. The recommended dosage by patient population is shown in Table 1.

Prucalopride Tablets:

• 1 mg prucalopride: White to off-white, round, biconvex film-coated tablets debossed with “P1” on one side and plain on other side.
• 2 mg prucalopride: Yellow, round, biconvex film-coated tablets debossed with “P2” on one side and plain on the other side.

The following adverse reactions have been identified during post-approval use of prucalopride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions: dyspnea, rash, pruritus, urticaria, and facial edema [see Contraindications (4)].

Psychiatric disorders: Suicide, suicide attempts, suicidal ideation, self-injurious ideation, depression, anxiety, insomnia, nightmares, and visual hallucinations [see Warnings and Precautions (5.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below represent 2,530 patients (1,251 received prucalopride 2 mg once daily and 1,279 received placebo) with CIC from 6 double-blind, placebo-controlled clinical trials of 12 weeks to 24 weeks in duration. In these trials overall, patients were primarily female (76%) and white (76%). The mean age was 47 years (range 17 years to 95 years) [see Clinical Studies (14)].

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Suicidal Ideation and Behavior: Inform patients, their caregivers, and family members that suicidal ideation and behavior, self-injurious ideation as well as new onset or worsening depression have been reported in patients treated with prucalopride tablets. Advise them to be aware of any unusual changes in mood or behavior, new onset or worsening of depression, or the emergence of suicidal thoughts or behavior. Instruct patients, caregivers, and family members to discontinue prucalopride tablets immediately and contact their healthcare provider if any of these symptoms occur [see Warnings and Precautions (5.1)].

In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. Postmarketing cases of suicidal ideation and behavior as well as self-injurious ideation and new onset or worsening of depression have been reported within the first few weeks of starting prucalopride [see Adverse Reactions (6.1, 6.2)].

A causal association between treatment with prucalopride and an increased risk of suicidal ideation and behavior has not been established.

Monitor all patients treated with prucalopride for new onset or worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience any of these symptoms.

Prucalopride tablets containing 1 mg prucalopride are white to off-white, round, biconvex film-coated tablets debossed with “P1” on one side and plain on other side. They are supplied as:

• NDC 83085-005-30: HDPE bottle of 30 tablets, with child-resistant closure.

Prucalopride tablets containing 2 mg prucalopride are yellow, round, biconvex film-coated tablets debossed with “P2” on one side and plain on other side. They are supplied as:

• NDC 83085-006-30: HDPE bottle of 30 tablets, with child-resistant closure.

In safety pharmacology studies, no relevant effects were observed in any of the cardiovascular studies at concentrations at least 50 times the human therapeutic C_max. Prucalopride had no effect on potassium current in hERG-transfected HEK cells at concentrations up to 1 micromolar (50 times the human therapeutic C_max). At concentrations ≥ 3 micromolar, concentration-dependent inhibition of the current was observed (IC₅₀ = 22 micromolar; 1,100 times the human therapeutic C_max). In studies in pigs, minor and transient increases in heart rate and blood pressure were noted upon first exposure to prucalopride, at plasma levels at least 10 times the human therapeutic C_max.

In repeated-dose toxicology studies in male rats, increases in heart weight (up to 9%) were observed at doses of 20 mg/kg/day or higher (at least 75 times the human therapeutic AUC). Cardiac histology revealed an increase in focal infiltration of chronic inflammatory cells in the heart at a dose of 80 mg/kg/day (at least 785 times the human therapeutic AUC). In dogs, no changes in heart rate, blood pressure, electrocardiogram parameters, heart weight, or cardiac histology were observed at any dose tested (the highest dose of 30 mg/kg/day was 572 times the human therapeutic AUC).

In vitro studies demonstrated no effect of prucalopride on either contractile responses in human, canine, and porcine coronary arteries at concentrations up to 10 micromolar (500 times the human clinical C_max) or on platelet aggregation at concentrations up to 200 nanomolar (10 times the human clinical C_max).

NDC 83085-005-30

Prucalopride Tablets

1 mg

Usual Dose: One tablet once daily.

Rx only

30 Tablets

NDC 83085-006-30

Prucalopride  Tablets

2 mg

Usual Dose: One tablet once daily.

Rx only

30 Tablets