Lubiprostone

Chronic idiopathic constipation; Opioid-induced constipation:
Moderate (Child-Pugh class B): Initially, 16 mcg bid; may increase to 24 mcg bid if tolerated and acceptable clinical response has not been achieved after an appropriate interval using a lower dose. Severe (Child-Pugh class C): Initially, 8 mcg bid; may increase to 16-24 mcg bid if tolerated and acceptable clinical response has not been achieved after an appropriate interval using a lower dose.

Constipation-predominant irritable bowel syndrome:
Severe (Child-Pugh class C): Initially, 8 mcg once daily; may increase to 8 mcg bid if tolerated and acceptable clinical response has not been achieved after an appropriate interval using a lower dose.

Lubiprostone Should be taken with food.

Known or suspected mechanical gastrointestinal obstruction.

Not established for use in the treatment of opioid-induced constipation in patients taking diphenylheptane opioids (e.g. methadone). Not indicated for the treatment of irritable bowel syndrome with constipation in men. Avoid use in patients with severe diarrhoea. Moderate to severe hepatic impairment (Child-Pugh class B or C). Pregnancy and lactation.

Significant: Dyspnoea, nausea, diarrhoea, syncope, hypotension.
Cardiac disorders: Chest pain or discomfort.
Gastrointestinal disorders: Vomiting, abdominal pain or discomfort, abdominal distension, flatulence, dyspepsia, dry mouth.
General disorders and administration site conditions: Oedema, fatigue.
Nervous system disorders: Headache, dizziness.

PO: C

Perform an extensive evaluation to confirm the absence of an obstruction before treatment initiation, particularly in patients with symptoms suggestive of mechanical gastrointestinal obstruction. Periodically assess the need for continued treatment. Monitor blood pressure and for signs of hypotension or severe diarrhoea.

Therapeutic effect may be diminished with diphenylheptane opioids (e.g. methadone, levomethadone).

Description:
Mechanism of Action: Lubiprostone, a bicyclic fatty acid prostaglandin E₁ derivative, is a locally-acting chloride channel activator. It specifically activates CIC-2 chloride channels in the apical membrane of the gastrointestinal tract, thereby causing increased intestinal fluid secretion and improved faecal transit. This activity avoids the antisecretory effects of opiates that results from the suppression of secretomotor neuron excitability. Lubiprostone enhances the chloride-rich intestinal fluid secretion without altering the Na and K concentrations in the serum.
Pharmacokinetics:
Absorption: Poorly absorbed. Time to peak plasma concentration: Approx 1 hour (active metabolite).
Distribution: Minimal distribution beyond the gastrointestinal tissue. Plasma protein binding: Approx 94%.
Metabolism: Rapidly and extensively metabolised in the stomach and jejenum by carbonyl reductase to form M3 (active metabolite) and other metabolites.
Excretion: Via faeces (in trace amounts as unchanged drug and active metabolite). Elimination half-life: 0.9-1.4 hours (active metabolite).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 157920, Lubiprostone. https://pubchem.ncbi.nlm.nih.gov/compound/Lubiprostone. Accessed Nov. 27, 2024.

Store between 15-30°C. Protect from light and extreme temperatures.

Other Gastrointestinal Drugs

A06AX03 - lubiprostone ; Belongs to the class of other laxatives.

Amitiza Capsules (Sucampo Pharmaceuticals, Inc.). U.S. FDA. https://www.fda.gov. Accessed 19/11/2024.

Anon. Lubiprostone. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 07/11/2024.

Brayfield A, Cadart C (eds). Lubiprostone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/11/2024.

Lubiprostone Capsule, Gelatin Coated (Sun Pharmaceutical Industries, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/11/2024.

Lubiprostone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 19/11/2024.

Lubiprostone. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 07/11/2024.