Prucalopride

Prucalopride is a Serotonin 5-HT₄ Receptor Agonist belonging to Gastrointestinal agent.

Prucalopride is a 5-HT4 receptor agonist indicated to treat adults with chronic idiopathic constipation.

Prucalopride is Rapidly absorbed from the GI tract. Its Absolute bioavailability is >90%. Time taken to reach peak plasma concentration is 2-3 hr. Prucalopride has a steady-state volume of distribution (Vss) of 567 liters after intravenous administration. The plasma protein binding of prucalopride is approximately 30%. Prucalopride is a substrate of CYP3A4, in vitro. In an oral dose study with radiolabeled prucalopride in healthy subjects, prucalopride made up 92 to 94% of the total radioactivity in plasma. There are 7 different known minor metabolites, the most abundant metabolite (O-desmethyl prucalopride acid) represents 0 to 1.7% of the total plasma exposure. Renal excretion is the main route of elimination of prucalopride. Non-renal elimination contributes up to about 35% of the total.

Prucalopride shows side effects like Headache, stomach pain, nausea, diarrhea, dizziness.

Prucalopride is available in the form of Oral Tablet.

Prucalopride is available in India, US, Malaysia, Canada, France, Italy, Spain, UK, Singapore, and Australia.

Prucalopride belongs to the Gastrointestinal agent acts as a Serotonin 5-HT₄ Receptor Agonist.

Prucalopride is a selective, high affinity 5-HT₄ receptor agonist whose action at the receptor site promotes cholinergic and nonadrenergic, noncholinergic neurotransmission by enteric neurons leading to stimulation of the peristaltic reflex, intestinal secretions, and gastrointestinal motility.

The Data of Onset and duration of action of Prucalopride is not clinically established.

The Tmax of Prucalopride is approximately 2-3 hour.

Prucalopride is available in the form of Oral tablet.

Prucalopride tablet is taken orally, usually once daily.

Prucalopride is a medicine used to treat chronic constipation when other medicines (such as laxatives) cannot provide adequate relief. It works by increasing the concentration of a chemical substance that stimulates bowel movements. Prucalopride makes it easier to pass stool from the body.

Prucalopride is a Serotonin 5-HT₄ Receptor Agonist belonging to Gastrointestinal agent.

Prucalopride is a selective, high affinity 5-HT₄ receptor agonist whose action at the receptor site promotes cholinergic and nonadrenergic, noncholinergic neurotransmission by enteric neurons leading to stimulation of the peristaltic reflex, intestinal secretions, and gastrointestinal motility.

Prucalopride is approved for use in the following clinical indications

• Chronic idiopathic constipation

Prucalopride is a 5-HT4 receptor agonist indicated to treat adults with chronic idiopathic constipation.

• Chronic idiopathic constipation

Oral: 2 mg once daily; consider adjunctive laxative therapy if no bowel movement within ≥3 consecutive days.

Prucalopride is available in various strengths as 1 mg; 2 mg.

Prucalopride is available in the form of Oral tablet.

• Dosage Adjustment in Kidney Patient

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: 1 mg once daily.

Prucalopride is contraindicated in patients with

• A history of hypersensitivity to prucalopride. Reactions including dyspnea, rash, pruritus, urticaria, and facial edema have been observed.
• 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.

• Suicidal Ideation and Behavior

In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. 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 persistent 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 is present in breast milk. There are no data on the effects of prucalopride on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for prucalopride and any potential adverse effects on the breastfed child from prucalopride or from the underlying maternal condition.

Prucalopride is not recommended for use in pregnancy unless necessary.

Common

• Abdominal pain, nausea, diarrhea, Headache, Abdominal distension, abnormal bowel sounds, decreased appetite, flatulence, vomiting, Pollakiuria, Dizziness, fatigue, migraine.

Rare

• Facial edema, palpitations, Pruritus, skin rash, urticaria, Amnesia, anxiety, depression, insomnia, loss of balance, nightmares, suicidal ideation, suicidal tendencies, visual hallucination, Dyspnea.

• Anticholinergic Agents

May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Fosfomycin

Gastrointestinal Agents (Prokinetic) may decrease the serum concentration of Fosfomycin.

• Levosulpiride

Benzamide Derivatives may enhance the adverse/toxic effect of Levosulpiride.

• Opioid Agonists

May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Sirolimus (Conventional)

Gastrointestinal Agents (Prokinetic) may increase the serum concentration of Sirolimus (Conventional).

The common side effects of Prucalopride include the following

Common side effects

• Headache, stomach pain, nausea, diarrhea, dizziness.

Rare side effects

• Difficulty breathing or shortness of breath, rash, itching, hives, swelling of face, lips, tongue, or throat.

• Pregnancy

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. 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.

• Nursing Mothers

Prucalopride is present in breast milk. There are no data on the effects of prucalopride on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for prucalopride and any potential adverse effects on the breastfed child from prucalopride or from the underlying maternal condition.

• Pediatric Use

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

• Geriatric Use

Of the 2484 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. No overall differences in safety and effectiveness were observed between elderly and younger patients.

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.

Pharmacodynamic

Prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon. As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit.

Pharmacokinetics

• Absorption

Prucalopride is Rapidly absorbed from the GI tract. Its Absolute bioavailability is >90%. Time taken to reach peak plasma concentration is 2-3 hr.

• Distribution

Prucalopride has a steady-state volume of distribution (Vss) of 567 liters after intravenous administration. The plasma protein binding of prucalopride is approximately 30%.

• Metabolism and Excretion

Prucalopride is a substrate of CYP3A4, in vitro. In an oral dose study with radiolabeled prucalopride in healthy subjects, prucalopride made up 92 to 94% of the total radioactivity in plasma. There are 7 different known minor metabolites, the most abundant metabolite (O-desmethyl prucalopride acid) represents 0 to 1.7% of the total plasma exposure. Renal excretion is the main route of elimination of prucalopride. Non-renal elimination contributes up to about 35% of the total.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210166s000lbl.pdf
• https://www.mims.com/philippines/drug/info/prucalopride?mtype=generic
• https://www.uptodate.com/contents/prucalopride-drug-information#F50990398
• https://go.drugbank.com/drugs/DB06480
• https://www.practo.com/medicine-info/prucalopride-2178-api