Amitiza

Name: Amitiza

What other information should I know?

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Amitiza Side Effects

Common side effects of Amitiza include:

  • Nausea
  • Diarrhea (that is not severe)
  • Heartburn
  • Bloating
  • Vomiting
  • Dry mouth
  • Runny nose
  • Cough
  • Gas
  • Dizziness
  • Headache
  • Joint pain
  • Back pain
  • Trouble sleeping

Let your doctor know if any of these side effects persist or get worse.

Serious side effects of Amitiza:

  • Severe diarrhea
  • Swelling of arms and/or legs
  • Changes in mental health
  • Mood changes

A very serious allergic reaction is rare, but seek immediate medical attention if you develop any of the following:

  • Rash
  • Itching
  • Swelling (especially in the face, tongue, or throat)
  • Severe dizziness
  • Trouble breathing

Seek immediate medical attention if you develop trouble breathing, chest tightness, discomfort, or pain.

Amitiza may infrequently cause an episode of dyspnea (difficulty breathing). While this reaction is usually not serious and goes away within three hours, you may not be able to tell the difference between dyspnea and the severe reactions listed above.

Description

Amitiza (lubiprostone) is a chloride channel activator for oral use.

The chemical name for lubiprostone is (–)-7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanoic acid. The molecular formula of lubiprostone is C20H32F2O5 with a molecular weight of 390.46 and a chemical structure as follows:

Lubiprostone drug substance occurs as white, odorless crystals or crystalline powder, is very soluble in ether and ethanol, and is practically insoluble in hexane and water. Amitiza is available as an imprinted, oval, soft gelatin capsule in two strengths. Pink capsules contain 8 mcg of lubiprostone and the following inactive ingredients: medium-chain triglycerides, gelatin, sorbitol, ferric oxide, titanium dioxide, and purified water. Orange capsules contain 24 mcg of lubiprostone and the following inactive ingredients: medium-chain triglycerides, gelatin, sorbitol, FD&C Red #40, D&C Yellow #10, and purified water.

Overdose

There have been two confirmed reports of overdosage with Amitiza. The first report involved a 3-year-old child who accidentally ingested 7 or 8 capsules of 24 mcg of Amitiza and fully recovered. The second report was a study patient who self-administered a total of 96 mcg of Amitiza per day for 8 days. The patient experienced no adverse reactions during this time. Additionally, in a Phase 1 cardiac repolarization study, 38 of 51 healthy volunteers given a single oral dose of 144 mcg of Amitiza (6 times the highest recommended dose) experienced an adverse event that was at least possibly related to the study drug. Adverse reactions that occurred in at least 1% of these volunteers included the following: nausea (45%), diarrhea (35%), vomiting (27%), dizziness (14%), headache (12%), abdominal pain (8%), flushing/hot flash (8%), retching (8%), dyspnea (4%), pallor (4%), stomach discomfort (4%), anorexia (2%), asthenia (2%), chest discomfort (2%), dry mouth (2%), hyperhidrosis (2%), and syncope (2%).

Amitiza Overview

Amitiza is a prescription medication used to treat irritable bowel syndrome (IBS) in women and chronic idiopathic constipation in men and women. It is also used to treat opioid-induced constipation (OIC). Amitiza belongs to a group of drugs called CIC-2 chloride channel activators, which increase fluid secretions in the bowel to stimulate the movement of stool. Amitiza comes in capsule form and is usually taken twice daily with food and water. The capsule should be swallowed whole, not chewed or broken.

Common side effects include nausea, diarrhea, and headache.

Amitiza Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Amitiza there are no specific foods that you must exclude from your diet when receiving Amitiza.

What is the most important information I should know about lubiprostone?

Do not take lubiprostone if you have severe diarrhea. Call your doctor for instructions.

Call your doctor at once if you have severe or ongoing nausea or diarrhea.

Amitiza Dosage and Administration

Administration

Oral Administration

Administer orally with food and water.1 2 9

Dosage

Adults

Periodically assess need for continued therapy.1 4

Chronic Idiopathic Constipation Oral

24 mcg twice daily.1 2 4

May reduce dosage to 24 mcg daily in patients experiencing severe nausea.1

Irritable Bowel Syndrome with Constipation in Women Oral

8 mcg twice daily.1

Special Populations

No special population recommendations at this time.1

Interactions for Amitiza

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 in vitro.1 Does not induce CYP1A2, CYP2B6, CYP2C9, or CYP3A4 in vitro.1 Pharmacokinetic interactions unlikely with drugs metabolized by these CYP isoenzymes.1

Not metabolized by isoenzymes.1

Highly Protein-bound Drugs

Pharmacokinetic interaction unlikely.1

Advice to Patients

  • Advise patients to take the drug twice daily (morning and evening) with food and water.1

  • Importance of advising patients to swallow capsules whole without chewing or breaking apart.1

  • Importance of advising patients that nausea may occur; administer with food and water to reduce nausea.1 Advise patients to contact a clinician if nausea becomes severe.1

  • Clinicians and patients periodically should assess the need for continued treatment.1

  • Importance of advising patients that diarrhea may occur.1 Advise patients to notify a clinician9 and not to take lubiprostone if they experience severe diarrhea.1

  • Importance of advising patients that dyspnea may occur; advise patients to notify clinician if dyspnea becomes severe.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise pregnant women of risk to the fetus.1 Importance of using effective method of contraception.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Lubiprostone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

8 mcg

Amitiza

Sucampo

24 mcg

Amitiza

Sucampo

Before Using Amitiza

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of lubiprostone in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of lubiprostone in the elderly.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bowel or stomach blockage or
  • Diarrhea, severe—Should not be used in patients with these conditions.
  • Liver disease, moderate to severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Uses of Amitiza

  • It is used to treat hard stools (constipation).
  • It is used to treat irritable bowel syndrome.
  • It may be given to you for other reasons. Talk with the doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Chest pain or pressure.
  • Very loose stools (diarrhea).
  • Shortness of breath.
  • Low blood pressure has happened with Amitiza. Rarely, low blood pressure has led to the need to go to the hospital. Diarrhea and throwing up may raise the chance of low blood pressure. Call your doctor right away if you feel very dizzy or feel like passing out.

Indications and Usage for Amitiza

Chronic Idiopathic Constipation

Amitiza® is indicated for the treatment of chronic idiopathic constipation in adults.

1.2 Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

Amitiza is indicated for the treatment of 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.

Limitations of Use:

  • Effectiveness of Amitiza in the treatment of opioid-induced constipation in patients taking diphenylheptane opioids (e.g., methadone) has not been established. [see Clinical Studies (14.2)]

Irritable Bowel Syndrome with Constipation

Amitiza is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in women ≥ 18 years old.

Warnings and Precautions

Nausea

Patients taking Amitiza may experience nausea. Concomitant administration of food with Amitiza may reduce symptoms of nausea [see Adverse Reactions (6.1)].

Diarrhea

Avoid use of Amitiza in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue Amitiza and contact their healthcare provider if severe diarrhea occurs [see Adverse Reactions (6.1)].

5.3 Syncope and Hypotension

Syncope and hypotension have been reported with Amitiza in the postmarketing setting and a few of these adverse reactions resulted in hospitalization. Most cases occurred in patients taking 24 mcg twice daily and some occurred within an hour after taking the first dose or subsequent doses of Amitiza. Some patients had concomitant diarrhea or vomiting prior to developing the adverse reaction. Syncope and hypotension generally resolved following Amitiza discontinuation or prior to next dose, but recurrence has been reported with subsequent doses. 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.

Dyspnea

In clinical trials, dyspnea was reported by 3%, 1%, and < 1% of the treated CIC, OIC, and IBS-C populations receiving Amitiza, respectively, compared to 0%, 1%, and < 1% of placebo-treated patients. There have been postmarketing reports of dyspnea when using Amitiza 24 mcg twice daily. Some patients have discontinued treatment 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. Instruct patients to contact their healthcare provider if dyspnea occurs.

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 Amitiza.

Drug Interactions

No in vivo drug–drug interaction studies have been performed with Amitiza.

Based upon the results of in vitro human microsome studies, there is low likelihood of pharmacokinetic drug–drug interactions. In vitro studies using human liver microsomes indicate that cytochrome P450 isoenzymes are not involved in the metabolism of lubiprostone. Further in vitro studies indicate microsomal carbonyl reductase may be involved in the extensive biotransformation of lubiprostone to the metabolite M3 [see Clinical Pharmacology (12.3)]. Additionally, in vitro studies in human liver microsomes demonstrate that lubiprostone does not inhibit cytochrome P450 isoforms 3A4, 2D6, 1A2, 2A6, 2B6, 2C9, 2C19, or 2E1, and in vitro studies of primary cultures of human hepatocytes show no induction of cytochrome P450 isoforms 1A2, 2B6, 2C9, and 3A4 by lubiprostone. Based on the available information, no protein binding–mediated drug interactions of clinical significance are anticipated.

Interaction potential with diphenylheptane opioids (e.g. methadone): Non-clinical studies have shown opioids of the diphenylheptane chemical class (e.g., methadone) to dose-dependently reduce the activation of ClC-2 by lubiprostone in the gastrointestinal tract. There is a possibility of a dose-dependent decrease in the efficacy of Amitiza in patients using diphenylheptane opioids.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Two 2-year oral (gavage) carcinogenicity studies (one in Crl:B6C3F1 mice and one in Sprague-Dawley rats) were conducted with lubiprostone. In the 2-year carcinogenicity study in mice, lubiprostone doses of 25, 75, 200, and 500 mcg/kg/day (approximately 2, 6, 17, and 42 times the highest recommended human dose, respectively, based on body surface area) were used. In the 2-year rat carcinogenicity study, lubiprostone doses of 20, 100, and 400 mcg/kg/day (approximately 3, 17, and 68 times the highest recommended human dose, respectively, based on body surface area) were used. In the mouse carcinogenicity study, there was no significant increase in any tumor incidences. There was a significant increase in the incidence of interstitial cell adenoma of the testes in male rats at the 400 mcg/kg/day dose. In female rats, treatment with lubiprostone produced hepatocellular adenoma at the 400 mcg/kg/day dose.

Mutagenesis

Lubiprostone was not genotoxic in the in vitro Ames reverse mutation assay, the in vitro mouse lymphoma (L5178Y TK+/–) forward mutation assay, the in vitro Chinese hamster lung (CHL/IU) chromosomal aberration assay, and the in vivo mouse bone marrow micronucleus assay.

Impairment of Fertility

Lubiprostone, at oral doses of up to 1000 mcg/kg/day, had no effect on the fertility and reproductive function of male and female rats. However, the number of implantation sites and live embryos were significantly reduced in rats at the 1000 mcg/kg/day dose as compared to control. The number of dead or resorbed embryos in the 1000 mcg/kg/day group was higher compared to the control group, but was not statistically significant. The 1000 mcg/kg/day dose in rats is approximately 169 times the highest recommended human dose of 48 mcg/day, based on body surface area.

How should I take Amitiza?

Amitiza is usually taken twice daily. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take Amitiza with food or milk.

Drink a full glass of water when you take this medication.

Do not crush, chew, break, or open a capsule. Swallow it whole.

You may have tightness in your chest or feel short of breath within 1 hour after taking Amitiza. This side effect should go away within 3 hours, but it may occur again when you take your next dose. Talk with your doctor if this side effect becomes bothersome.

Do not take Amitiza if you have severe diarrhea. Call your doctor for instructions.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Highlights for Amitiza

Amitiza is used to treat long-term constipation, and constipation caused by the use of opioids (drugs that relieve pain). It’s also used to treat irritable bowel syndrome with constipation in women.

This drug comes in the form of a capsule you take by mouth.

Amitiza is a brand name for the drug lubiprostone. This drug is not available as a generic drug.

The more common side effects of this drug can include nausea, diarrhea, headache, or gas. They can also include pain and swelling in the abdomen (stomach area).

In some cases, Amitiza may cause shortness of breath soon after you take it. You may have chest tightness and find it hard to take a breath. This feeling should go away within a few hours. 

IMPORTANT INFORMATION
  • Diarrhea See Details

  • Shortness of breath See Details

  • Nausea See Details

What is Amitiza?

This drug is a prescription drug. It comes in the form of a capsule you take by mouth.

Amitiza is a brand name for the drug lubiprostone. This drug is not available as a generic drug.

Why it's used

This drug is used to treat long-term constipation, and constipation caused by the use of opioids (drugs that relieve pain). It’s also used to treat irritable bowel syndrome with constipation in women.

How it works

This drug belongs to a class of drugs called chloride channel activators. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

More Details

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