Lubiprostone

Lubiprostoneis a Chloride Channel Activatorbelonging toGastrointestinal agent/ Drug for Constipation.

Lubiprostone is a prostaglandin derivative used to treat constipation caused by irritable bowel syndrome and opioid-use.

Absorption of the parent drug is below the quantitation level (10 pg/mL). Time to peak plasma concentration is approximately 1.1 hours.Lubiprostone is approximately 94% bound to human plasma proteins.Lubiprostone rapidly and extensively metabolised, possibly within the stomach and jejunum, via reduction and oxidation by carbonyl reductase into active M3 metabolite and other metabolites. Excretion via is approximately 60%, faeces approximately 30%.

Lubiprostoneshows side effects like Nausea, stomach pain or bloating, gas, vomiting, heartburn, headache, dizziness, swelling of the hands, feet, ankles, or lower legs, chest discomfort, tiredness.

Lubiprostoneis available in the form of Oral Capsule.

Lubiprostoneis available in India, US, Russia, China, France, Italy, Japan, Malaysia, Singapore, and Australia.

Lubiprostonebelongs to the Gastrointestinal agent acts as anChloride Channel Activator/ Drug for Constipation.

Lubiprostone is chloride channel activator that acts locally on the apical membrane of the gastrointestinal tract to increase intestinal fluid secretion and improve fecal transit. This action bypasses the antisecretory effects of opiates, which suppress secretomotor neuron excitability.

The Onset and duration of action of Lubiprostoneis not clinically established.

The Tmax ofLubiprostone is approximately 1.1 hour.

Lubiprostone is available in the form of Oral capsule.

LubiprostoneCapsule is taken orally, usually once daily.

Lubiprostone is used in the treatment of constipation associated with irritable bowel syndrome (a group of symptoms that affect your digestive system), long-term treatment with opioids (a class of medicines used to treat severe pain). It is also used in the treatment of chronic idiopathic constipation (constipation of unknown cause). This medicine works by increasing intestinal secretions, improving bowel movements, and facilitating the easy passage of stools.

Lubiprostoneis a Chloride Channel Activatorbelonging toGastrointestinal agent/ Drug for Constipation.

Lubiprostone is chloride channel activator that acts locally on the apical membrane of the gastrointestinal tract to increase intestinal fluid secretion and improve fecal transit. This action bypasses the antisecretory effects of opiates, which suppress secretomotor neuron excitability.

Lubiprostone is approved for use in the following clinical indications

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation
• Opioid-induced constipation

• Chronic idiopathic constipation

Oral: 24 mcg twice daily.

• Irritable bowel syndrome with constipation

Oral: 8 mcg twice daily; may require ≥2 months for symptom improvement.

• Opioid-induced constipation

Oral: 24 mcg twice daily.

Lubiprostone is available in various strengths as 8 mcg and 24 mcg.

Lubiprostone is available in the form of Oral capsule.

• Dosage Adjustment in Hepatic impairment Patient

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate hepatic impairment (Child-Pugh class B):

Chronic idiopathic constipation or opioid-induced constipation: Initial: 16 mcg twice daily; may increase to 24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.

Irritable bowel syndrome with constipation: No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C):

Chronic idiopathic constipation or opioid-induced constipation: Initial: 8 mcg twice daily; may increase to 16 to 24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.

Irritable bowel syndrome with constipation: Initial: 8 mcg once daily; may increase to 8 mcg twice daily if tolerated and an adequate response has not been obtained at lower dosage.

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

• Nausea

Patients taking Lubiprostone may experience nausea. If this occurs, concomitant administration of food with Lubiprostone may reduce symptoms of nausea.

• Diarrhea

Lubiprostone should not be prescribed to patients that have severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Patients should be instructed to inform their physician if severe diarrhea occurs.

• Dyspnea

In clinical trials conducted to study Lubiprostone in treatment of chronic idiopathic constipation and IBS-C there were reports of dyspnea. This was reported at 2.5% of the treated chronic idiopathic constipation population and at 0.4% in the treated IBS-C population. Although not classified as serious adverse events, some patients discontinued treatment on study because of this event. There have been postmarketing reports of dyspnea when using Lubiprostone 24 mcg. Most have not been characterized as serious adverse events, but some patients have discontinued therapy because of dyspnea. These events have usually been described as a sensation of chest tightness and difficulty taking in a breath, and generally have an acute onset within 30–60 minutes after taking the first dose. They generally resolve within a few hours after taking the dose, but recurrence has been frequently reported with subsequent doses.

• Bowel Obstruction

In patients with symptoms suggestive of mechanical gastrointestinal obstruction, the treating physician should perform a thorough evaluation to confirm the absence of such an obstruction prior to initiating therapy with Lubiprostone.

It is not known whether lubiprostone is excreted in human milk. In rats, neither lubiprostone nor its active metabolites were detectable in breast milk following oral administration of lubiprostone. 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 Lubiprostone is administered to a nursing woman.

Pregnancy category C:  Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Common

• Diarrhea, nausea, Headache, Chest discomfort, chest pain, edema, peripheral edema, Abdominal distention, abdominal distress, abdominal pain, dyspepsia, flatulence, loose stools, vomiting, xerostomia, Dizziness, fatigue, Dyspnea Palpitations, syncope, Diaphoresis, erythema of skin, hyperhidrosis, Decreased serum potassium, weight gain, Anorexia, bowel urgency, decreased appetite, dysgeusia, eructation, fecal incontinence, frequent bowel movements, gastritis, gastroesophageal reflux disease, Pollakiuria, urinary tract infection, Rectal hemorrhage, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Influenza, Anxiety, depression, fibromyalgia syndrome, lethargy, pain, Joint swelling, muscle cramps, myalgia, tremor, Cough, pharyngolaryngeal pain.

Rare

• Bloody diarrhea, ischemic colitis, Hypersensitivity reaction, Arthralgia, asthenia, back pain, muscle spasm, neck pain, Respiratory tract infection.

Levomethadone: May diminish the therapeutic effect of Lubiprostone.

Methadone: May diminish the therapeutic effect of Lubiprostone.

The common side effectsof Lubiprostone include the following

Common side effects

• Nausea, stomach pain or bloating, gas, vomiting, heartburn, headache, dizziness, swelling of the hands, feet, ankles, or lower legs, chest discomfort, tiredness.

Rare side effects

• Shortness of breath or difficulty taking in a breath, chest tightness, fainting, lightheadedness, rash, swelling of the face, lips, mouth, tongue or throat, throat tightness, severe diarrhea.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies with Lubiprostone in pregnant women. A dose dependent increase in fetal loss was observed in pregnant guinea pigs that received Lubiprostone doses equivalent to 0.2 to 6 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2). Animal studies did not show an increase in structural malformations. Lubiprostone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether Lubiprostone is excreted in human milk. In rats, neither Lubiprostone nor its active metabolites were detectable in breast milk following oral administration of Lubiprostone. 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 Lubiprostone is administered to a nursing woman.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been studied.

• Geriatric Use

Chronic Idiopathic Constipation

The efficacy of Lubiprostone in the elderly (≥ 65 years of age) subpopulation was consistent with the efficacy in the overall study population. Of the total number of constipated patients treated in the dose-finding, efficacy, and long-term studies of Lubiprostone, 15.5% were ≥ 65 years of age, and 4.2% were ≥ 75 years of age. Elderly patients taking Lubiprostone (any dosage) experienced a lower incidence of associated nausea compared to the overall study population taking Lubiprostone (18% vs. 29%, respectively).

Irritable Bowel Syndrome with Constipation

The safety profile of Lubiprostone in the elderly (≥ 65 years of age) subpopulation (8.0% were ≥ 65 years of age and 1.8% were ≥ 75 years of age) was consistent with the safety profile in the overall study population. Clinical studies of Lubiprostone did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.

Pharmacodynamic

Animal studies have shown that oral administration of lubiprostone increases chloride ion transport into the intestinal lumen, enhances fluid secretion into the bowels, and improves fecal transit.

Pharmacokinetics

• Absorption

Absorption of the parent drug is below the quantitation level (10 pg/mL). Time to peak plasma concentration is approximately 1.1 hours.

• Distribution

Lubiprostone is approximately 94% bound to human plasma proteins.

• Metabolism and Excretion

Lubiprostone rapidly and extensively metabolised, possibly within the stomach and jejunum, via reduction and oxidation by carbonyl reductase into active M3 metabolite and other metabolites. Excretion via is approximately 60%, faeces approximately 30%.

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