Lubiprostone (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- AMITIZA
- LUBIPROSTONE
Contraindications
Lubiprostone is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction [see Warnings and Precautions (5.5)] .
Adverse Reactions
The following adverse reactions are described below and elsewhere in labeling: Nausea [see Warnings and Precautions (5.1)] Diarrhea [see Warnings and Precautions (5.2)] Syncope and Hypotension [see Warnings and Precautions (5.3)] Dyspnea [see Warnings and Precautions (5.4)]
Mechanism of Action
Lubiprostone is a locally acting chloride channel activator that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentrations in the serum. Lubiprostone acts by specifically activating ClC-2, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A–independent fashion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby facilitating the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. Lubiprostone, via activation of apical ClC-2 channels in intestinal epithelial cells, bypasses the antisecretory action of opiates that results from suppression of secretomotor neuron excitability. Activation of ClC-2 by lubiprostone has also been shown to stimulate recovery of mucosal barrier function and reduce intestinal permeability via the restoration of tight junction protein complexes in ex vivostudies of ischemic porcine intestine.
Overdosage
There have been six reports of overdosage with lubiprostone during clinical development. Of these six cases, only two subjects reported adverse events: one reported vomiting, diarrhea and stomach ache after taking 168 to 192 mcg of lubiprostone, and another reported diarrhea and a joint injury on the day of overdose after taking 36 mcg of lubiprostone. Adverse reactions that occurred in at least 1% of healthy subjects given a single oral dose of 144 mcg of lubiprostone (6 times the highest recommended dose) in a cardiac repolarization study included nausea (45%), diarrhea (35%), vomiting (27%), dizziness (14%), headache (12%), abdominal pain (8%), flushing/hot flash (8%), retching (8%), dyspnea (4%), pallor (4%), stomach discomfort (4%), anorexia (2%), asthenia (2%), chest discomfort (2%), dry mouth (2%), hyperhidrosis (2%), and syncope (2%).