Prucalopride Succinate
FDA Drug Information • Also known as: Prucalopride Succinate
- Brand Names
- Prucalopride Succinate
- Dosage Form
- TABLET, FILM COATED
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION Prucalopride tablets for oral use contain prucalopride succinate, a dihydrobenzofurancarboxamide that is a serotonin type 4 (5-HT 4 ) 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 C 18 H 26 ClN 3 O 3 .C 4 H 6 O 4 and the molecular weight is 485.96. The structural formula is: Prucalopride succinate is a white to almost white powder. It is highly soluble in acidic aqueous media and alkaline aqueous media up to a pH of approximately 9. 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: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The coating for the 1-mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol 4000, 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: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The coating for the 2-mg tablet contains hypromellose, lactose monohydrate, polyethylene glycol 4000, titanium dioxide, triacetin, red iron oxide, yellow iron oxide, and FD&C Blue #2 aluminum lake. Image
What Is Prucalopride Succinate Used For?
1 INDICATIONS AND USAGE Prucalopride tablet is indicated for the treatment of chronic idiopathic constipation (CIC) in adults. Prucalopride tablet is a serotonin-4 (5-HT 4 ) receptor agonist indicated for the treatment of chronic idiopathic constipation (CIC) in adults. (1)
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Prucalopride tablets can be taken with or without food. The recommended dosage by patient population is shown in Table 1. Table 1: Recommended Dosage Regimen and Dosage Adjustments by Population Population with CIC Recommended Oral Dose Regimen Adults 2 mg once daily Patients with severe renal impairment (creatinine clearance (CrCL) less than 30 mL/min) [see Use in Specific Populations (8.5 and 8.6)] . 1 mg once daily Take with or without food. (2) Recommended dosage by patient population: Population with CIC Recommended Oral Dose Regimen Adults 2 mg once daily. (2) Patients with severe renal impairment (creatinine clearance (CrCL) less than 30 mL/min 1 mg once daily. (2, 8.5, 8.6)
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 Somerset Therapeutics, LLC at 1- 800-417-9175 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience 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 2530 patients (1251 received prucalopride tablets 2 mg once daily and 1279 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 to 95 years) [see Clinical Studies (14)] . 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 tablets once daily or placebo and at an incidence greater than in the placebo group from the six double-blind placebo-controlled trials described above. Table 2: Common Adverse Reactions* in Double-Blind Placebo-Controlled Trials of CIC of at least 12 Weeks Duration Adverse Reaction PRUCALOPRIDE TABLET 2 mg Once Daily N=1251 † % Placebo N=1279 % Headache 19 9 Abdominal pain ‡ 16 11 Nausea 14 7 Diarrhea 13 5 Abdominal distension 5 4 Dizziness 4 2 Vomiting 3 2 Flatulence 3 2 Fatigue 2 1 *Reported in ≥2% of patients receiving prucalopride tablet and a rate higher than patients receiving placebo. †Includes 93 patients who started on prucalopride tablet 1 mg and increased to prucalopride tablet 2 mg. ǂIncludes abdominal pain, upper abdominal pain, lower abdominal pain, abdominal tenderness, abdominal discomfort, and epigastric discomfort. Less Common Adverse Reactions Less common adverse reactions occurring in <2% of patients receiving prucalopride tablet 2 mg once daily include: Gastrointestinal disorders : abnormal gastrointestinal sounds Metabolism and nutrition disorders : decreased appetite Nervous system disorders : migraine Renal and urinary disorders : pollakiuria Diarrhea Of the patients who reported diarrhea, 70% (110 out of 157) reported it in the first week of treatment. Diarrhea typically resolved within a few days in 73% (80 out of 110) of those patients. Severe diarrhea was reported in 1.8% of patients treated with prucalopride tablets 2 mg compared to 1% of patients in the placebo group, and had a similar onset and duration as diarrhea overall. Headache Of the patients who reported headache, 66% (157 out of 237) treated with prucalopride tablets 2 mg once daily reported onset in the first 2 days of treatment. Symptoms typically resolved within a few days in 65% (102 out of 157) of those patients. Adverse Reactions Leading to Discontinuation In the 6 clinical trials described above, 5% of patients treated with 2 mg of prucalopride tablets once daily discontinued due to adverse reactions, compared to 3% of patients in the placebo group. The most common adverse reactions leading to discontinuation were nausea (2% prucalopride tablets, 1% placebo), headache (1% prucalopride tablets, 1% placebo), diarrhea (1% prucalopride tablets, <1% placebo), or abdominal pain (1% prucalopride tablets, 1% placebo). Adverse Reactions of Special Interest Adverse reactions of special interest were evaluated in a pool of 28 completed clinical trials (19 double- blind and 9 open-label) for prucalopride tablets at doses including 0.5 mg, 1 mg, 2 mg, or 4 mg per day in adult patients with CIC (the recommended dosage of prucalopride tablets for CIC is 2 mg once daily). The total exposure in the double-blind trials was 565 patient-years in the prucalopride tablets group, 384...
Contraindications
4 CONTRAINDICATIONS Prucalopride tablets are contraindicated in patients with: A history of hypersensitivity to prucalopride tablets. 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. Hypersensitivity to prucalopride tablets (4) 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. (4)
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from case reports with prucalopride use in pregnant women are insufficient to identify any drug-associated risks of miscarriage, major birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with prucalopride administration during the period of organogenesis to pregnant rats and rabbits at doses up to approximately 390 times and 780 times, respectively, the recommended human dose of 2 mg/day (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In oral embryofetal development studies in rats and rabbits, prucalopride was administered to pregnant animals at doses of 5, 20, and 80 mg/kg/day throughout the period of organogenesis. No adverse embryofetal developmental effects were observed in either rats or rabbits up to the highest oral dose of 80 mg/kg/day (about 390 times and 780 times the recommended human dose of 2 mg/day, respectively, based on body surface area). In an oral pre- and post-natal development study in rats, prucalopride was administered at doses of 5, 20, and 80 mg/kg/day. At the 80-mg/kg dose(about 390 times the recommended human dose of 2 mg/day, based on body surface area), a slight decrease in overall survival rate of pups after 7 days was observed, which could be due to maternal toxicity observed at this dose.
Overdosage
10 OVERDOSAGE 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 tablets 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Prucalopride tablets containing 1 mg prucalopride are white to off-white, round biconvex, film-coated tablets debossed with "P1" on one side and no debossing on the other side. They are supplied as: NDC 70069-821-01: HDPE bottle of 30 tablets, with child-resistant closure. Prucalopride tablets containing 2 mg prucalopride are pink, round biconvex, film-coated tablets debossed with "P2" on one side and no debossing on the other side. They are supplied as: NDC 70069-822-01: HDPE bottle of 30 tablets, with child-resistant closure. Store prucalopride tablets at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (between 59°F to 86°F) [see USP Controlled Room Temperature]. Store prucalopride tablets in the original container to protect from moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.