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Serotonin Receptor Agonists for Constipation

Oral Administration Oral Solid Formulations

The tablets can be administered with or without food.

Adverse Reactions

suicidal ideation / Delayed / Incidence not known


migraine / Early / 0-2.0
dyspnea / Early / Incidence not known
edema / Delayed / Incidence not known
depression / Delayed / Incidence not known
hallucinations / Early / Incidence not known


headache / Early / 19.0-19.0
abdominal pain / Early / 16.0-16.0
nausea / Early / 14.0-14.0
diarrhea / Early / 13.0-13.0
dizziness / Early / 4.0-4.0
flatulence / Early / 3.0-3.0
vomiting / Early / 3.0-3.0
anorexia / Delayed / 0-2.0
fatigue / Early / 2.0-2.0
increased urinary frequency / Early / 0-2.0
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
insomnia / Early / Incidence not known
nightmares / Early / Incidence not known
anxiety / Delayed / Incidence not known

Common Brand Names


Dea Class



An oral selective serotonin (5HT-4) receptor agonist
Used once daily for the treatment of chronic idiopathic constipation (CIC) in adults
Promotes spontaneous bowel movements; monitor for depressed mood or suicidal thoughts or behaviors

Dosage And Indications
For the treatment of chronic idiopathic constipation (CIC). Oral dosage Adults

2 mg PO once daily.

Dosing Considerations
Hepatic Impairment

No dosage adjustments are needed.

Renal Impairment

CrCl 30 mL/minute or more: No dosage adjustments are needed.
CrCl less than 30 mL/minute: Reduce dosage to 1 mg PO once daily. Avoid in patients with end-stage renal disease requiring dialysis.

Drug Interactions

Fosfomycin: (Moderate) Prucalopride may decrease the systemic absorption of fosfomycin due to the prokinetic action of prucalopride. This may result in lower fosfomycin serum concentrations and urinary excretion. Monitor for evidence of clinical effectiveness of fosfomycin. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.

How Supplied

MOTEGRITY/Prucalopride Oral Tab: 1mg, 2mg

Maximum Dosage

2 mg/day PO.


2 mg/day PO.


Safety and efficacy have not been established.


Safety and efficacy have not been established.


Safety and efficacy have not been established.

Mechanism Of Action

Serotonin (5HT4) receptors are involved in initiating peristalsis. Prucalopride, a selective serotonin type 4 (5-HT4) receptor agonist, is a gastrointestinal (GI) prokinetic agent that stimulates colonic peristalsis (high-amplitude propagating contractions [HAPCs]), which increases bowel motility. Prucalopride did not have effects mediated via 5-HT2A, 5-HT2B, 5-HT3, motilin or CCK-A receptors in vitro at concentrations exceeding 5-HT4 receptor affinity by 150-fold or greater. In isolated GI tissues from various animal species, prucalopride facilitated acetylcholine release to enhance the amplitude of contractions and stimulate peristalsis. In rats and dogs, prucalopride stimulated gastrointestinal motility with contractions starting from the proximal colon to the anal sphincter.[63829]


Prucalopride is administered orally. Prucalopride is approximately 30% protein-bound. Prucalopride exhibits dose-proportional pharmacokinetics within and beyond the therapeutic range (tested up to 20 mg, 10 times the maximum approved recommended human dose). Prucalopride has a steady-state volume of distribution (Vss) of 567 liters after intravenous administration. During prolonged administration, prucalopride displays time-independent kinetics. The plasma clearance of prucalopride averages 317 mL/minute. Prucalopride is a CYP3A4 substrate in vitro; however, prucalopride is primarily renally excreted and only 35% of the drug is removed via non-renal elimination. 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. Following oral administration of radiolabeled prucalopride in healthy subjects, 60% to 65% of the administered dose is excreted unchanged in urine and about 5% in feces. On average, 84.2% of the administered radioactive dose was recovered in urine, and 13.3% of the dose was recovered in feces. Seven metabolites were recovered in urine and feces, with the most abundant metabolite (O-desmethyl prucalopride acid) accounting for 3.2% and 3.1% of the dose in urine and feces, respectively. None of the other metabolites accounted for more than 3% of the dose. Renal elimination of prucalopride involves both passive filtration and active secretion. The terminal half-life is approximately 1 day.[63829]
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
Prucalopride is a CYP3A4 substrate in vitro; however, the drug is primarily renally excreted, and clinical drug interaction studies have not indicated a potential for strong CYP3A4 inhibitors (e.g., ketoconazole) to cause clinically relevant drug interactions. In vitro data indicate low potential for prucalopride to inhibit CYP enzymes (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) and transporters (P-glycoprotein, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, BSEP, and MRP2 transporters) or induce CYP enzymes (1A2, 2B6, and 3A4) at the clinically relevant concentrations.[63829]
Co-administration of oral erythromycin (500 mg PO 4 times daily) with prucalopride increased the erythromycin mean Cmax by 40% and mean exposure (AUC) by 28%. The mechanism for this pharmacokinetic change is not clear. The increased exposure to erythromycin is unlikely to result in a clinically significant drug interaction.[63829]

Oral Route

Following a single oral dose of prucalopride 2 mg in healthy subjects, peak plasma concentrations are observed within 2 to 3 hours after administration. The absolute oral bioavailability is greater than 90%. Concomitant intake with a high-fat meal (1000 kcal total, 500 kcal from fat) does not influence the oral bioavailability of prucalopride. Following administration of prucalopride 2 mg PO once daily, steady-state is attained within 3 to 4 days, and steady-state plasma concentrations fluctuate between trough and peak values of 2.5 and 7 ng/mL, respectively, with mean plasma AUC of 109 hour x ng/mL. The accumulation ratio after once daily oral dosing ranged from 1.9 to 2.3.

Pregnancy And Lactation

The limited data from case reports with prucalopride use in human pregnancy are insufficient to identify any drug-associated risks of miscarriage, major birth defects, or adverse maternal or fetal outcomes. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to prucalopride during pregnancy. Healthcare providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting 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.

Prucalopride is excreted in human breast milk. There are no data available regarding the the effects of prucalopride on the breast-fed infant or the effects on milk production. In an open-label study in 8 healthy lactating women in the weaning stage, plasma and milk samples were collected at pre-dose (day 1 and 4), and then 2, 4, 8, 12, and 24 hours (day 4) after a 2 mg dose of prucalopride was administered once daily for 4 days. Prucalopride is excreted in breast milk with a milk to plasma AUC ratio of 2.65:1; the average amount passed to the infant was estimated to be 1.74 mcg/kg/day, which is about 6% of the maternal dose, adjusted for body weight. The prucalopride concentration detected in breast milk during weaning may not reflect the prucalopride concentration in breast milk during full milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for prucalopride and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.