Lubiprostone

What is Lubiprostone?

• Lubiprostone (Amitiza) is a chloride channel activator, used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation.

Lubiprostone

Lubiprostone Structure

What are the uses of this medicine?

Lubiprostone (Amitiza) is used for the treatment of:

• chronic idiopathic constipation (CIC) in adults.
• opioid-induced constipation (OIC) in adult patients with chronic, non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
• irritable bowel syndrome with constipation (IBS-C) in women ≥ 18 years old.

Limitations of Use: Effectiveness of lubiprostone in the treatment of OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established.

How does this medicine work?

• 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.
• 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.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with known or suspected mechanical gastrointestinal obstruction.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• medications for high blood pressure and methadone (Dolophine, Methadose).

Is this medicine FDA approved?

• Lubiprostone was approved for use in the United States in 2006 for short term therapy of chronic constipation and indications were expanded in 2008 to management of patients with irritable bowel syndrome and constipation.

How should this medicine be used?

Recommended dosage: In chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC):

• 24 mcg twice daily.

In irritable bowel syndrome with constipation (IBS-C):

• 8 mcg twice daily.

Administration:

• Lubiprostone comes as a capsule to take by mouth.
• It is usually taken with food and water twice a day in the morning and evening.
• Take lubiprostone at around the same times every day.
• Swallow capsules whole and do not break apart or chew.
• Take capsules with food and water.
• Assess periodically the need for continuous therapy.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 8 mcg and 24 mcg

This medicine is available in fallowing brand namesː

• Amitiza

What side effects can this medication cause?

The most common side effects in Adults with CIC:

• Nausea
• Diarrhea
• Headache
• Abdominal pain
• Abdominal distension
• Flatulence
• Vomiting
• Loose stools
• Edema<1
• Abdominal discomfort
• Dizziness
• Chest discomfort/pain
• Dyspnea
• Dyspepsia
• Fatigue
• Dry mouth

The most common side effects in Adults with OIC:

• Nausea
• Diarrhea
• Abdominal pain
• Flatulence
• Abdominal distension
• Vomiting
• Headache
• Peripheral edema
• Abdominal discomfort

The most common side effects in Adults with IBS-C:

• Nausea
• Diarrhea
• Abdominal pain
• Abdominal distension

What special precautions should I follow?

• Patients taking lubiprostone may experience nausea. Concomitant administration of food with lubiprostone may reduce symptoms of nausea.
• Avoid use of lubiprostone in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue lubiprostone and contact their healthcare provider if severe diarrhea occurs.
• Syncope and hypotension have been reported. Several cases reported concomitant use of medications known to lower blood pressure, which may increase the risk for the development of syncope or hypotension. Patients should be aware of the risk of syncope and hypotension during treatment and that other adverse reactions may increase this risk, such as diarrhea or vomiting.
• Inform patients that they may experience dyspnea within an hour of the first dose. Dyspnea generally resolves within 3 hours, but may recur with repeat dosing. Instruct patients to inform their healthcare provider if dyspnea occurs.
• Advise lactating women to monitor their human milk-fed infants for diarrhea while taking lubiprostone.
• Evaluate patients with symptoms suggestive of mechanical gastrointestinal obstruction prior to initiating treatment with lubiprostone.
• Lubiprostone has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.

What to do in case of emergency/overdose?

Symptoms of 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.

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Limited available data with lubiprostone use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes.
• You will need to have a negative pregnancy test before you begin to take lubiprostone.
• You must use birth control while taking this medication. Talk to your doctor about the method of birth control that is best for you.
• If you become pregnant while taking lubiprostone, call your doctor right away.

Can this medicine be used in children?

• Safety and effectiveness have not been established in pediatric patients with IBS-C, pediatric functional constipation (PFC), and OIC.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• lubiprostone

Inactive ingredients:

• medium-chain triglycerides
• gelatin, unspecified
• sorbitol
• ferric oxide red
• titanium dioxide
• water

Who manufactures and distributes this medicine?

Manufactured for:

• Par Pharmaceutical
• Chestnut Ridge, NY U.S.A.

Amitiza: Marketed by:

• Sucampo Pharma Americas, Inc.
• Bethesda, MD

and

• Takeda Pharmaceuticals America, Inc.
• Deerfield, IL

• Amitiza® is a registered trademark of Sucampo Pharmaceuticals, Inc.

What should I know about storage and disposal of this medication?

• Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Protect from light and extreme temperatures.

• Dailymed label info on Lubiprostone
• FDA Lubiprostone

Lubiprostone Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

• Cholestyramine
• Colesevelam
• Colestipol
• Crofelemer
• Difenoxin
• Diphenoxylate
• Kaolin
• Loperamide
• Methylcellulose
• Octreotide
• Pectin
• Rifamycin
• Rifaximin
• Somatostatin
• Telotristat

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

• Hyoscyamine, Methscopolamine, Scopolamine

Antihistamines

• Cyclizine, Dimenhydrinate, Hydroxyzine, Meclizine, and Promethazine

Cannabinoid Receptor Agonists

• Dronabinol, Nabilone, Tetrahydrocannabinol
• Phenothiazines [See Antipsychotic Agents]
• Chlorpromazine, Prochlorperazine

Serotonin 5-HT3 Receptor Antagonists

• Alosetron, Dolasetron, Granisetron, Ondansetron, Palonosetron

Substance P/Neurokinin 1 Receptor Antagonists

• Aprepitant, Fosaprepitant, Rolapitant

Miscellaneous

• Dexamethasone, Metoclopramide, Trimethobenzamide

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

• Dexlansoprazole, Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

• Bisacodyl
• Cascara Sagrada
• Castor Oil
• Docusate
• Fiber, Bran
• Lactulose
• Magnesium Sulfate
• Methylcellulose
• Naldemedine (Opioid Antagonist)
• Naloxegol (Opioid Antagonist)
• Plecanatide (for Chronic Idiopathic Constipation)
• Prucalopride (for Chronic Idiopathic Constipation)
• Senna

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

• Balsalazide, Mesalamine, Olsalazine, Sulfasalazine

Immunosuppressive Agents

• Azathioprine, Mercaptopurine, Methotrexate

Tumor Necrosis Factor Antagonists

• Adalimumab, Certolizumab, Golimumab, Infliximab

Miscellaneous

• Metronidazole, Natalizumab, Vedolizumab

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

• Dicyclomine, Glycopyrrolate, Hyoscyamine, Methscopolamine

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

• Eluxadoline