Pruvict

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

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

Pruvict 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.

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

Pruvict 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.

Pruvict 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: Pruvict 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 Pruvict for use in men has not been established in controlled clinical trials, therefore, Pruvict is not recommended for use in men until further data becomes available.

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

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

The efficacy of Pruvict 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: Pruvict 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 Pruvict?

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

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 Pruvict.

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 Pruvict in the treatment of opioid-induced constipation in noncancer, chronic pain patients. Pruvict improved patient-rated severity of constipation and effectiveness of treatment. Additional trials may be necessary to further define the role of Pruvict in this condition.

See also:
What other drugs will affect Pruvict?

In vitro data indicate that Pruvict has a low interaction potential, and therapeutic concentrations of Pruvict are not expected to affect the CYP-mediated metabolism of co-medicated medicinal products. Although Pruvict 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 Pruvict 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. Pruvict is likely also secreted via another renal transporter(s). Inhibition of all transporters involved in the active secretion of Pruvict (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 Pruvict on the pharmacokinetics of warfarin, digoxin, alcohol and paroxetine. A 30% increase in the plasma concentrations of erythromycin was found during Pruvict 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 Pruvict.

Therapeutic doses of probenecid, cimetidine, erythromycin and paroxetine did not affect the pharmacokinetics of Pruvict.

Pruvict 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 Pruvict.

Interactions with food have not been observed.

Incompatibilities: None.

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

Pruvict has been given orally to approximately 2700 patients with chronic constipation in controlled clinical studies. Of these patients, almost 1000 received Pruvict at the recommended dose of 2 mg/day, while about 1300 were treated with Pruvict 4 mg daily. Total exposure in the clinical development plan exceeded 2600 patient-years. The most frequently reported adverse reactions associated with Pruvict 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 Pruvict and placebo) during Pruvict therapy as during placebo, with the exception of nausea and diarrhea that still occurred more frequently during Pruvict therapy, but less pronounced (difference in incidence between Pruvict and placebo between 1% and 3%).

Palpitations were reported in 0.7% of the placebo patients, 1% of the Pruvict 1 mg patients, 0.7% of the Pruvict 2 mg patients and 1.9% of the Pruvict 4 mg patients. The majority of patients continued using Pruvict. As with any new symptom, patients should discuss the new onset of palpitations with their physician.