Prucalopride (prucalopride succinate)
GI Stimulants Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Prucalopride succinate, a selective type 4 serotonin (5-HT4) receptor agonist, is a GI prokinetic agent.
Prucalopride, a selective type 4 serotonin (5-HT4) receptor agonist, is a GI prokinetic agent. The drug increases bowel motility by binding with high affinity to 5-HT4 receptors, facilitating release of acetylcholine to enhance the amplitude of contractions and stimulate colonic peristalsis. In animal studies, prucalopride has been shown to induce contractions starting from the proximal colon to the anal sphincter.
Following oral administration of a single 2-mg dose of prucalopride in patients with chronic idiopathic constipation, the number of high-amplitude propagating contractions was increased during the first 12 hours; with once-daily administration, mean colonic transit time was reduced by 12 hours from a baseline of 65 hours.
Prucalopride is devoid of effects mediated via type 2A, 2B, or 3 serotonin (5-HT2A, 5-HT2B, or 5-HT3), motilin, or cholecystokinin A receptors in vitro at concentrations exceeding the 5-HT4 receptor affinity by 150-fold or greater. In animal pharmacology studies, prucalopride had no clinically relevant effects on cardiovascular and cardiac electrophysiologic parameters at concentrations of at least 50 times the therapeutic peak plasma concentration in humans. Certain nonselective 5-HT4 receptor agonists (i.e., cisapride, tegaserod) have been associated with adverse cardiovascular events; while cardiac arrhythmias associated with cisapride use have been attributed to the drug's lack of selectivity for the 5-HT4 receptor (i.e., affinity for the human ether-a-go-go gene (hERG)-encoded cardiac potassium channel), the precise mechanism by which tegaserod use may be associated with ischemic cardiovascular events has not been fully established. (See Cardiovascular Safety under Cautions: Warnings/Precautions.)
Following oral administration, bioavailability of prucalopride exceeds 90% and peak plasma concentrations are achieved within 2-3 hours. Administration with a high-fat meal does not alter oral bioavailability. Pharmacokinetics of prucalopride are dose proportional and time independent during continued use.
The elimination half-life is approximately 1 day. The parent drug accounts for 92-94% of plasma exposure. Prucalopride is eliminated mainly by the kidneys by passive filtration and active secretion and to a lesser extent (up to 35%) by nonrenal mechanisms.
Approximately 84.2% of an orally administered dose is excreted in urine, with 60-65% of the dose excreted in urine as unchanged drug; 13.3% of an administered dose is excreted in feces, with 5% of the dose excreted in feces as unchanged drug. Prucalopride is a substrate of cytochrome P-450 (CYP) isoenzyme 3A4 in vitro. Seven minor metabolites have been identified; the most common metabolite (O-desmethylprucalopride acid) accounts for only 3.2 or 3.1% of the dose recovered in urine or feces, respectively.
Age, sex, race, and body weight (after adjustment for renal function) do not appear to affect the pharmacokinetics of prucalopride.
USES: This medication is used to treat chronic constipation. It is used when other medications used to treat constipation (such as laxatives) have not provided relief. Prucalopride works by improving how well your stomach and intestines move food through the bowels during digestion.
Generic name: prucalopride succinate
Pronunciation: (proo-KAL-oh-pride)
Drug class: GI Stimulants
Therapeutic class: Gastrointestinal Therapy Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Prucalopride
Indications
The following indications are listed for Prucalopride:
- Chronic Idiopathic Constipation
Dosing
Dosage of prucalopride succinate is expressed in terms of prucalopride.
For the symptomatic treatment of chronic idiopathic constipation, the recommended adult dosage of prucalopride is 2 mg once daily. In clinical trials, a dosage of 4 mg daily was not found to provide any additional benefit over the 2-mg dosage. In addition, most patients (81%) who received an initial dosage of 1 mg daily required an increase in dosage to 2 mg daily. (See Uses: Chronic Idiopathic Constipation.)
Prucalopride succinate is administered orally once daily without regard to food.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Prucalopride 1 Mg Tablet | Maintenance | Take 2 tablets (2 mg) by oral route once daily. |
| Prucalopride 2 Mg Tablet | Maintenance | Take 1 tablet (2 mg) by oral route once daily. |
| Drug label | Dosing type | Instructions |
|---|---|---|
| Prucalopride 1 Mg Tablet | Maintenance | Take 2 tablets (2 mg) by oral route once daily. |
| Prucalopride 2 Mg Tablet | Maintenance | Take 1 tablet (2 mg) by oral route once daily. |
Drug interactions
There is no enhanced messaging for this drug.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Gastric Stimulants/Pramlintide
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Pramlintide slows gastric emptying. Gastric stimulants may result in decreased effects.(1)
CLINICAL EFFECTS: Concurrent use of pramlintide and use of gastric stimulants may result in decreased effects of both agents.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that stimulate gastrointestinal motility.(1)
DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1)
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Prucalopride is contraindicated in patients with intestinal perforation or obstruction due to a structural or functional disorder of the gut wall, obstructive ileus, or severe inflammatory conditions of the intestinal tract including Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum. Prucalopride also is contraindicated in patients with known hypersensitivity to the drug.
- Crohn's disease
- Gastrointestinal obstruction
- Gastrointestinal perforation
- Ileus
- Toxic megacolon
- Ulcerative colitis
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
- Depression
- Kidney disease with likely reduction in glomerular filtration rate (GFr)
- Suicidal ideation
Adverse reactions
Adverse effects reported in clinical trials in 2% or more of patients with chronic idiopathic constipation receiving prucalopride and at an incidence greater than that reported with placebo include headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue.
Rare or Very Rare
- Self-injurious ideation
- Suicidal
- Suicidal ideation
More Frequent
- Abdominal distension
- Acute abdominal pain
- Diarrhea
- Dizziness
- Fatigue
- Flatulence
- Headache disorder
- Nausea
- Vomiting
Rare or Very Rare
- Anorexia
- Bowel sounds hyperactive
- Depression
- Dyspnea
- Facial edema
- Hallucinations
- Increased urinary frequency
- Insomnia
- Migraine
- Nightmares
- Pruritus of skin
- Skin rash
- Symptoms of anxiety
- Urticaria
Precautions
No enhanced messaging available.
Safety and efficacy of prucalopride have not been established in pediatric patients.
Available data from case reports of prucalopride use in pregnant women are insufficient to identify any drug-associated risks of spontaneous abortion, major birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies in rats and rabbits, no adverse embryofetal developmental effects were observed at dosages up to approximately 390 and 780 times, respectively, the recommended human dosage. The highest dosage in rats was maternally toxic; a slight decrease in pup survival was observed at this dosage.
Prucalopride is distributed into human milk. It is not known whether prucalopride affects the breast-fed child or affects milk production. The benefits of breast-feeding should be considered along with the importance of the drug to the woman and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.
During weaning, prucalopride was distributed into human breast milk with a milk-to-plasma ratio of 2.65:1 (based on area under the concentration-time curve (AUC)); mean infant exposure was estimated to be 1.74 mcg/kg daily (about 6% of the maternal dose) adjusted for body weight. However, the manufacturer states that the prucalopride concentration in breast milk during weaning may not reflect the concentration attained during full milk production.
In controlled trials of at least 12-weeks' duration in patients with chronic idiopathic constipation, 15% of patients receiving prucalopride 1 or 2 mg daily were 65 years of age or older, while 5% were 75 years of age or older. No overall differences in safety and efficacy were observed in these studies between geriatric patients and younger adults, and no unanticipated safety concerns were identified in an additional 4-week double-blind, placebo-controlled, dose-escalation study in 89 geriatric nursing home patients with chronic idiopathic constipation. Geriatric patients had higher prucalopride exposure (26-28% higher AUC and peak plasma concentrations) compared with younger adults; however, the effect of age on the pharmacokinetics of prucalopride appears to be related to decreased renal function. Therefore, dosage of the drug in geriatric patients should be based on renal function.
ICD codes
| Code | Type | Description |
|---|---|---|
| Chronic idiopathic constipation | ||
| K59.04 | ICD10CM | Chronic idiopathic constipation |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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