Amiprostone

Uses

Amiprostone is used for Chronic Idiopathic Constipation, Opioid-induced Constipation (OIC) in adults with chronic non-cancer pain, Irritable Bowel Syndrome with Constipation (IBS-C).

Amiprostone is also used to associated treatment for these conditions: Constipation, Opioid Induced Constipation (OIC), Chronic idiopathic constipation (CIC)

How Amiprostone works

Amiprostone acts by specifically activating ClC-2 chloride channels, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A action independent fashion. Activation of ClC-2 chloride channels causes an efflux of chloride ions into the lumen, which in turn leads to an efflux of sodium ions through a paracellular pathway to maintain isoelectric neutrality. As a result, water follows sodium into the lumen in order to maintain isotonic equilibrium, thereby increasing intestinal fluid secretion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Activation of ClC-2 chloride channels may also stimulate the recovery of muscosal barrier function by restoring tight junction protein complexes in the intestine. 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.

Dosage

Amiprostone dosage

Irritable Bowel Syndrome with Constipation:The recommended dose is 8 mcg twice daily orally with food and water.

Dosage in patients with hepatic impairment: Dosage adjustment is not required for patients with moderately impaired hepatic function. For patients with severely impaired hepatic function, the recommended starting dose is 8 mcg once daily. If tolerated then dose can be increased to 8 mcg twice

Chronic Idiopathic Constipation and Opioid-induced Constipation:The recommended dose is 24 mcg twice daily orally with food and water.

Dosage in patients with hepatic impairment: For patients with moderately impaired hepatic function, the recommended starting dose is 16 mcg twice daily. For patients with severely impaired hepatic function, the recommended starting dose is 8 mcg twice daily.

Side Effects

Diarrhea, full or bloated feeling or pressure in the stomach, nausea, stomach pain, swelling of abdominal or stomach area, Dyspnea

Toxicity

In a definitive Phase 1 cardiac repolarization study, 51 patients were administered a single oral dose of 144 mcg of lubiprostone, which is 6 times the normal single administration dose. Thirty-nine (39) of the 51 patients experienced an adverse event. The adverse events reported in >1% of this group included the following: nausea (45.1%), vomiting (27.5%), diarrhea (25.5%), dizziness (17.6%), loose or watery stools (13.7%), headache (11.8%), retching (7.8%), abdominal pain (5.9%), flushing or hot flush (5.9%), dyspnea (3.9%), pallor (3.9%), stomach discomfort (3.9%), syncope (3.9%), upper abdominal pain (2.0%), anorexia (2.0%), asthenia (2.0%), chest discomfort (2.0%), dry mouth (2.0%), hyperhidrosis (2.0%), skin irritation (2.0%) and vasovagal episode (2.0%).

Precaution

Nausea: Patients taking Amiprostone may experience nausea. Concomitant administration of food with Amiprostone may reduce symptoms of nausea.

Diarrhea: Lubistone should not be prescribed to patients that have severe diarrhea.

Bowel Obstruction: In patients with symptoms suggestive of mechanical gastrointestinal obstruction, perform a thorough evaluation to confirm the absence of an obstruction prior to initiating therapy with Amiprostone.

Interaction

There is a possibility of a dose-dependent decrease in the efficacy of Amiprostone in patients using diphenylheptane opioids.

Food Interaction

• Take with a full glass of water.
• Take with food. Taking lubiprostone with food may reduce nausea.

Amiprostone Disease Interaction

Major: GI obstructionModerate: diarrhea, dyspnea, hepatic impairment

Elimination Route

Amiprostone has low systemic availability following oral administration and concentrations of lubiprostone in plasma are below the level of quantitation (10 pg/mL).

Half Life

0.9 to 1.4 hours

Elimination Route

Peak plasma concentration was shown to be around 1.14 hours, with a majority of the drug excreted in the urine within 48 hours. Amiprostone and M3 are only detected in trace amounts in human feces.

Pregnancy & Breastfeeding use

Pregnancy category C. It is not known whether lubiprostone is excreted in human milk. Because lubiprostone increases fluid secretion in the intestine and intestinal motility, human milk-fed infants should be monitored for diarrhea. Caution should be exercised when Amiprostone is administered to a nursing woman.

Contraindication

Amiprostone is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Acute Overdose

Adverse reactions due to overdose may include: nausea, diarrhea, vomiting, dizziness, headache, abdominal pain, flushing/hot flash, retching, dyspnea, pallor, stomach discomfort, anorexia, asthenia , chest discomfort, dry mouth, hyperhidrosis , and syncope.

Storage Condition

Store between 15-30° C.

Innovators Monograph

You find simplified version here Amiprostone