Prucalopride

Prucalopride™ is indicated for the treatment of chronic idiopathic constipation (CIC) in adults.

Prucalopride is used to treat chronic idiopathic (unknown cause) constipation (CIC). It works by increasing peristalsis (contractions) in the colon, leading to an increase in the number of bowel movements.

Prucalopride is available only with your doctor's prescription.

Adults: 2 mg once daily.

Elderly (>65 years): Start with one 1 mg once daily; if needed the dose can be increased to 2 mg once daily.

Children and Adolescents: Prucalopride is not recommended in children and adolescents <18 years until further data become available. Currently available data are described in Pharmacokinetics under Actions.

Renal Impairment: The dose for patients with severe renal impairment (GFR <30 mL/min/1.73 m²) is 1 mg once daily. No dose adjustment is required for patients with mild to moderate renal impairment.

Hepatic Impairment: The dose for patients with severe hepatic impairment (Child-Pugh class C) is 1 mg once daily. No dose adjustment is required for patients with mild to moderate hepatic impairment.

Men: The safety and efficacy of Prucalopride for use in men has not been established in controlled clinical trials, therefore, Prucalopride is not recommended for use in men until further data becomes available.

Due to the specific mode of action of Prucalopride (stimulation of propulsive motility) exceeding the daily dose of 2 mg is not expected to increase efficacy.

If the intake of once daily Prucalopride is not effective after 4 weeks of treatment, the patient should be re-examined and the benefit of continuing treatment reconsidered.

The efficacy of Prucalopride has been established in double-blind placebo controlled studies for up to 3 months. In case of prolonged treatment, the benefit should be reassessed at regular intervals.

Administration: Prucalopride film-coated tablets are for oral use and can be taken with or without food, at any time of the day.

See also:
What is the most important information I should know about Prucalopride?

Hypersensitivity to Prucalopride or to any of the excipients of Prucalopride.

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 eg, Crohn's disease, and ulcerative colitis and toxic megacolon/megarectum.

The tablet contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption must not take Prucalopride.

Use: Labeled Indications

Chronic idiopathic constipation: Treatment of chronic idiopathic constipation in adults

Off Label Uses

Opioid-induced constipation in patients with chronic pain (noncancer)

Data from a phase II, randomized, double-blind, placebo-controlled study support the use of Prucalopride in the treatment of opioid-induced constipation in noncancer, chronic pain patients. Prucalopride improved patient-rated severity of constipation and effectiveness of treatment. Additional trials may be necessary to further define the role of Prucalopride in this condition.

See also:
What other drugs will affect Prucalopride?

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 twice daily), 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 eg, 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%.

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.

Prucalopride 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-HT₄ receptor mediated effects of Prucalopride.

Interactions with food have not been observed.

Incompatibilities: None.

See also:
What are the possible side effects of Prucalopride?

Prucalopride has been given orally to approximately 2700 patients with chronic constipation in controlled clinical studies. Of these patients, almost 1000 received Prucalopride at the recommended dose of 2 mg/day, while about 1300 were treated with Prucalopride 4 mg daily. Total exposure in the clinical development plan exceeded 2600 patient-years. The most frequently reported adverse reactions associated with Prucalopride therapy are headache and gastrointestinal symptoms (abdominal pain, nausea or diarrhea) occurring in approximately 20% of each patient. 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 intensity.

The following adverse reactions were reported in controlled clinical studies at the recommended dose of 2 mg with frequencies corresponding to: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000) and very rare (≤1/10,000). Within each frequency grouping, adverse effects are presented in order of decreasing seriousness. Frequencies are calculated based on the placebo-controlled clinical study data.

Metabolism and Nutrition disorders: Uncommon: Anorexia.

Nervous System Disorders: Very Common: Headache. Common: Dizziness. Uncommon: Tremors.

Cardiac Disorders: Uncommon: Palpitations.

Gastrointestinal Disorders: Very Common: Nausea, diarrhea, abdominal pain. Common: Vomiting, dyspepsia, rectal haemorrhage, flatulence, abnormal bowel sounds.

Renal and Urinary Disorders: Common: Pollakiuria.

General Disorders and Administration Site Conditions: Common: Fatigue. Uncommon: Fever, malaise.

After the 1st day of treatment, the most common adverse reactions were reported in similar frequencies (incidence <1% different between Prucalopride and placebo) during Prucalopride therapy as during placebo, with the exception of nausea and diarrhea that still occurred more frequently during Prucalopride 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% of the Prucalopride 1 mg patients, 0.7% of the Prucalopride 2 mg patients and 1.9% of the Prucalopride 4 mg patients. The majority of patients continued using Prucalopride. As with any new symptom, patients should discuss the new onset of palpitations with their physician.

Each 1-mg film-coated tablet contains Prucalopride 1 mg equivalent to Prucalopride succinate 1.321 mg.

Each 2-mg film-coated tablet contains Prucalopride 2 mg equivalent to Prucalopride succinate 2.642 mg.

Prucalopride also contains the following excipients: Tablet Core: Lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate. Coating: Hypromellose (E464), lactose monohydrate, triacetin, titanium dioxide (E171), macrogol 3000, red iron oxide (E172)*, yellow iron oxide (E172)*, FD&C blue no. 2 aluminum lake (E132)** 2 mg.