AMITIZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMITIZA (AMITIZA).
Amitiza (lubiprostone) is a bicyclic fatty acid metabolite that activates type 2 chloride channels (ClC-2) on the apical surface of gastrointestinal epithelial cells, increasing chloride secretion into the lumen. This promotes passive sodium and water secretion, enhancing intestinal fluid accumulation and accelerating gastrointestinal transit without affecting serum electrolyte levels. It also has a potential effect on activating chloride channels in other tissues, such as the uterus and bladder.
| Metabolism | Primarily metabolized via carbonyl reductase (cytosolic enzyme) in the gastrointestinal tract and liver to a less active metabolite (M3). Further metabolism occurs via beta-oxidation to inactive metabolites. CYP450 enzymes are not significantly involved. The drug has minimal systemic bioavailability (<10%) due to extensive first-pass metabolism. |
| Excretion | Primarily fecal (60-70%) as unchanged drug following biliary excretion; renal excretion accounts for <10%. |
| Half-life | Terminal elimination half-life is approximately 0.9-1.4 hours; clinical context: short half-life supports once-daily dosing in chronic constipation. |
| Protein binding | Approximately 96-97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 1.8 L/kg; indicates extensive tissue distribution consistent with its large apparent Vd. |
| Bioavailability | Oral bioavailability is approximately 10-15% due to first-pass metabolism; food increases bioavailability by 20-30%. |
| Onset of Action | Oral: 1 hour for first bowel movement; maximum effect within 24 hours. |
| Duration of Action | Duration of action: 6-12 hours with clinical note: may continue to improve bowel movement frequency over several days. |
24 mcg orally twice daily with food
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for renal impairment, including end-stage renal disease on dialysis. |
| Liver impairment | No dose adjustment for mild to moderate hepatic impairment (Child-Pugh A or B). For severe hepatic impairment (Child-Pugh C), contraindicated per manufacturer labeling. |
| Pediatric use | Not approved for pediatric use (<18 years). Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required. Use age-appropriate dosing (24 mcg twice daily with food) and monitor for adverse effects such as diarrhea and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMITIZA (AMITIZA).
| Breastfeeding | Lubiprostone is excreted in rat milk at concentrations similar to plasma; human data are unavailable. The M/P ratio is unknown. Caution should be exercised when administered to a nursing woman; consider developmental benefits of breastfeeding versus potential adverse effects on the infant (e.g., diarrhea). |
| Teratogenic Risk | Amitiza (lubiprostone) is classified as Pregnancy Category C. Animal studies have shown fetal toxicity at doses ≥25 times the human AUC. No adequate and well-controlled studies in pregnant women. First trimester: Potential risk based on animal data, but human data limited. Second and third trimesters: Risk of preterm labor associated with diarrhea and electrolyte imbalances. Use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known or suspected mechanical gastrointestinal obstruction","History of chronic diarrhea or severe diarrhea","Hypersensitivity to lubiprostone or any component of the formulation"]
| Precautions | ["Nausea may occur, especially with food; taking with food and water reduces risk.","Diarrhea may occur, requiring dose reduction or discontinuation.","Not recommended for use in severe diarrhea or suspected mechanical gastrointestinal obstruction.","Dyspnea (reported in up to 6% of patients) may be severe and require discontinuation.","Use in pregnancy: Category C; insufficient data in humans; animal studies show fetal abnormalities at high doses.","Should not be used in patients with known or suspected bowel obstruction (e.g., mechanical, paralytic ileus).","May cause syncope or hypotension, especially with severe diarrhea or vomiting.","Not recommended in patients with severe hepatic impairment (Child-Pugh C).","Breastfeeding: Not recommended; excreted in animal milk; unknown in humans."] |
| Food/Dietary | No specific food interactions. Taking with food may reduce gastrointestinal adverse effects like nausea. Avoid excessive alcohol, which may worsen diarrhea or dehydration. Maintain adequate fluid intake to prevent fluid imbalance. |
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| Fetal Monitoring | Monitor for signs of dehydration, electrolyte imbalances, and premature labor in pregnant patients. Assess fetal growth and well-being via ultrasound if prolonged use. Maternal monitoring: serum electrolytes, renal function, and hydration status. |
| Fertility Effects | Lubiprostone at oral doses up to 1000 mcg/kg/day (approximately 332 times the human AUC) had no effects on fertility or reproductive performance in male and female rats. Human data on fertility effects are lacking. |
| Clinical Pearls | Amitiza (lubiprostone) activates chloride channels, increasing intestinal fluid secretion. Use with caution in severe diarrhea or bowel obstruction. Contraindicated in patients with mechanical GI obstruction. May cause nausea, especially at higher doses; take with food to mitigate. Not recommended in pregnancy (Category C) unless benefit outweighs risk. Monitor for electrolyte imbalances in long-term use. Dose adjustment required in severe hepatic impairment (Child-Pugh Class C). |
| Patient Advice | Take with food to reduce nausea. · Do not take if you have a bowel blockage or severe diarrhea. · Store at room temperature; protect from moisture. · May cause headache, nausea, or vomiting; report persistent symptoms. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not crush or chew capsules; swallow whole. · If you miss a dose, skip it and take the next dose at the regular time; do not double doses. |