Amitiza

Lubiprostone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

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

Some side effects can be serious. If you experience any of the following symptoms, stop taking lubiprostone and call your doctor immediately:

• severe diarrhea
• 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

Lubiprostone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Amitiza is a prescription medication used to treat irritable bowel syndrome (IBS) in women 18 years of age and older and chronic idiopathic constipation (long-term constipation with no obvious cause) in men and women. It is also used to treat opioid-induced constipation (OIC), a condition when opioid medications are the cause of constipation.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Amitiza is part of the drug class:

• Other drugs for constipation

Serious side effects have been reported with Amitiza including:

• Shortness of breath: This side effect generally does not last beyond 3 hours, but may happen again with repeat dosing.

Do not take Amitiza if you:

• have or suspect you have a bowel blockage.
• have severe diarrhea.
• are pregnant, unless, after discussion with your healthcare provider, the potential benefit justifies the potential risk to the fetus.

Do not take Amitiza if you are allergic to any ingredient in it.

Before receiving Amitiza, tell your doctor about all of your medical conditions, especially if you:

• know or suspect you have a bowel blockage. If you are unsure, your healthcare provider should evaluate your condition before starting Amitiza.
• have severe diarrhea.
• have kidney or liver disease.
• cannot swallow a capsule.

Tell your doctor if you are pregnant or breastfeeding.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Store Amitiza at room temperature in a childproof container that is tightly closed and out of the reach of children.

Do not use Amitiza past the expiration date shown on the package.

You should not use this medication if you have a blockage in your digestive tract, or if you have severe diarrhea.

To make sure lubiprostone is safe for you, tell your doctor if you have any other cause for obstruction in your gastrointestinal (digestive) system, such as:

• gallstones;

• Crohn's disease;

• Hirschsprung's disease;

• impacted bowel movement;

• diverticulitis, polyps; or

• a history of hernia.

Also tell your doctor if you have liver disease.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether lubiprostone passes into breast milk or if it could harm a nursing baby. However, a nursing baby could develop diarrhea if the mother takes lubiprostone while breast-feeding. Tell your doctor if you are breast-feeding a baby, and talk with your doctor if the baby develops diarrhea.

Lubiprostone should not be given to a child.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe or ongoing nausea or diarrhea; or

• a light-headed feeling, like you might pass out.

Common side effects may include:

• mild nausea, stomach pain;

• mild diarrhea, gas, bloating; or

• headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor if you take methadone.

Other drugs may interact with lubiprostone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Bicyclic fatty acid; selectively activates intestinal ClC-2 chloride channels and increases intestinal fluid secretion.1 2 3 4 5 6

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Amitiza or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Amitiza. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Administration Instructions

• Take Amitiza orally with food and water.
• Swallow capsules whole and do not break apart or chew.
• Physicians and patients should periodically assess the need for continued therapy.

Chronic Idiopathic Constipation and Opioid-Induced Constipation

The recommended dose is 24 mcg twice daily.

Dosage in patients with hepatic impairment

For patients with moderately impaired hepatic function (Child-Pugh Class B), the recommended starting dose is 16 mcg twice daily. For patients with severely impaired hepatic function (Child-Pugh Class C), the recommended starting dose is 8 mcg twice daily. If this dose is tolerated and an adequate response has not been obtained after an appropriate interval, doses can then be escalated to full dosing with appropriate monitoring of patient response [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Irritable Bowel Syndrome with Constipation

The recommended dose is 8 mcg twice daily.

Dosage in patients with hepatic impairment

For patients with severely impaired hepatic function (Child-Pugh Class C), the recommended starting dose is 8 mcg once daily. If this dose is tolerated and an adequate response has not been obtained after an appropriate interval, doses can then be escalated to full dosing with appropriate monitoring of patient response. Dosage adjustment is not required for patients with moderately impaired hepatic function (Child-Pugh Class B) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Amitiza is available as an oval, gelatin capsule containing 8 mcg or 24 mcg of lubiprostone.

• 8 mcg capsules are pink and are printed with "SPI" on one side
• 24 mcg capsules are orange and are printed with "SPI" on one side

Pregnancy

Pregnancy Category C.

Risk Summary

There are no adequate and well-controlled studies with Amitiza 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. Amitiza should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Current available data suggest that miscarriage occurs in 15-18% of clinically recognized pregnancies, regardless of any drug exposure. Consider the risks and benefits of available therapies when treating a pregnant woman for chronic idiopathic constipation, opioid-induced constipation or irritable bowel syndrome with constipation.

Animal Data

In developmental toxicity studies, pregnant rats and rabbits received oral lubiprostone during organogenesis at doses up to approximately 338 times (rats) and approximately 34 times (rabbits) the maximum recommended human dose (MRHD) based on body surface area (mg/m2). Maximal animal doses were 2000 mcg/kg/day (rats) and 100 mcg/kg/day (rabbits). In rats, there were increased incidences of early resorptions and soft tissue malformations (situs inversus, cleft palate) at the 2000 mcg/kg/day dose; however, these effects were probably secondary to maternal toxicity. A dose-dependent increase in fetal loss occurred when guinea pigs received lubiprostone after the period of organogenesis, on days 40 to 53 of gestation, at daily oral doses of 1, 10, and 25 mcg/kg/day (approximately 0.2, 2 and 6 times the MRHD based on body surface area (mg/m2)). The potential of lubiprostone to cause fetal loss was also examined in pregnant Rhesus monkeys. Monkeys received lubiprostone post-organogenesis on gestation days 110 through 130 at daily oral doses of 10 and 30 mcg/kg/day (approximately 3 and 10 times the MRHD based on body surface area (mg/m2)). Fetal loss was noted in one monkey from the 10-mcg/kg dose group, which is within normal historical rates for this species. There was no drug-related adverse effect seen in monkeys.

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 Amitiza is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Chronic Idiopathic Constipation

The efficacy of Amitiza 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 Amitiza, 15.5% were ≥ 65 years of age, and 4.2% were ≥ 75 years of age. Elderly patients taking Amitiza 24 mcg twice daily experienced a lower rate of associated nausea compared to the overall study population taking Amitiza (19% vs. 29%, respectively).

Opioid-Induced Constipation

The safety profile of Amitiza in the elderly (≥ 65 years of age) subpopulation (8.8% were ≥ 65 years of age and 1.6% were ≥ 75 years of age) was consistent with the safety profile in the overall study population. Clinical studies of Amitiza did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.

Irritable Bowel Syndrome with Constipation

The safety profile of Amitiza 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 Amitiza did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.

Renal Impairment

No dosage adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3)].

Hepatic Impairment

Patients with moderate hepatic impairment (Child-Pugh Class B) and severe hepatic impairment (Child-Pugh Class C) experienced markedly higher systemic exposure of lubiprostone active metabolite M3, when compared to normal subjects [see Clinical Pharmacology (12.3)]. Clinical safety results demonstrated an increased incidence and severity of adverse events in subjects with greater severity of hepatic impairment.

In case of chronic idiopathic constipation or opioid-induced constipation indications, the starting dosage of Amitiza should be reduced in patients with moderate hepatic impairment. The starting dose of Amitiza should be reduced in all patients with severe hepatic impairment, regardless of the indication [see Dosage and Administration (2.1, 2.2)]. No dosing adjustment is required in patients with mild hepatic impairment (Child-Pugh Class A).

NDC 64764-080-60

60 Capsules

Amitiza®

(lubiprostone) capsules

8 mcg

Swallow Whole – Do NOT Break Apart or Chew.

Each soft gel capsule contains 8 mcg of lubiprostone.

Dispense in a tightly closed, light-resistant container.

Sucampo logo

Takeda logo

Rx Only

See package insert for complete prescribing information.

Keep out of reach of children.

Marketed by: Sucampo Pharma Americas, LLC, Rockville, MD 20850 and Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

Active ingredient made in Japan; encapsulated in the United States.

© 2016 Sucampo Pharma Americas, LLC

Lot:

Exp.:

Store at 25°C (77°F); excursions 15°-30°C (59°-86°F).

PROTECT FROM EXTREME TEMPERATURES.

Keep container tightly closed.

Amitiza (lubiprostone) increases the secretion of fluid in your intestines to help make it easier to pass stools (bowel movements).

Amitiza is used to treat chronic constipation, or constipation caused by opioid (narcotic) pain medicine. It may also be used to treat irritable bowel syndrome in women with constipation as the main symptom.

Amitiza is for use only in adults.

You should not use Amitiza if you have a blockage in your digestive tract, or if you have severe diarrhea.

To make sure Amitiza is safe for you, tell your doctor if you have any other cause for obstruction in your gastrointestinal (digestive) system, such as:

• gallstones;

• Crohn's disease;

• Hirschsprung's disease;

• impacted bowel movement;

• diverticulitis, polyps; or

• a history of hernia.

Also tell your doctor if you have liver disease.

FDA pregnancy category C. It is not known whether Amitiza will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether lubiprostone passes into breast milk or if it could harm a nursing baby. However, a nursing baby could develop diarrhea if the mother takes Amitiza while breast-feeding. Tell your doctor if you are breast-feeding a baby, and talk with your doctor if the baby develops diarrhea.

This medicine should not be given to a child.

Applies to lubiprostone: oral capsule, oral capsule liquid filled

Along with its needed effects, lubiprostone (the active ingredient contained in Amitiza) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking lubiprostone:

• Diarrhea
• full or bloated feeling or pressure in the stomach
• nausea
• stomach pain
• swelling of the abdominal or stomach area

• Abdominal or stomach discomfort
• black, tarry stools
• blood in the stools
• chest discomfort or pain
• chills
• cold or flu-like symptoms
• cough
• difficult or labored breathing
• fever
• general feeling of discomfort or illness
• headache
• increased sweating
• joint pain
• loss of appetite
• loss of bowel control
• muscle aches and pains
• runny nose
• shivering
• sore throat
• sweating
• tightness in the chest
• trouble sleeping
• unusual tiredness or weakness
• vomiting

• Abdominal or stomach tenderness
• blurred vision
• confusion
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, pounding, or irregular heartbeat or pulse
• hives or skin rash
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• swelling

Get emergency help immediately if any of the following symptoms of overdose occur while taking lubiprostone:

• Dry heaves
• dry mouth
• feeling of warmth
• lack or loss of strength
• paleness of the skin
• redness of the face, neck, arms, and occasionally, upper chest
• severe, unusual tiredness or weakness
• weight loss

Some side effects of lubiprostone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Excess air or gas in the stomach or intestines
• passing gas

• Acid or sour stomach
• belching
• bladder pain
• bloody or cloudy urine
• change in taste
• cold sweats
• difficult, burning, or painful urination
• difficulty with moving
• discouragement
• dizziness
• fear or nervousness
• feeling sad or empty
• frequent urge to urinate
• heartburn
• increased weight
• indigestion
• irritability
• loss of interest or pleasure
• loss of taste
• lower back or side pain
• muscle cramps
• muscle stiffness
• sore throat
• stomach upset
• swollen joints
• tingling of the hands or feet
• unusual drowsiness, dullness, tiredness, or feeling of sluggishness

Lubiprostone can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Medications that might interact with this drug

When lubiprostone is used with certain drugs, it may not work as well to treat your condition. This is because the amount of lubiprostone in your body may be decreased. Examples of these drugs include:

• Methadone. Your doctor may stop your use of methadone. They may prescribe another medication instead.

People with bowel obstruction

Tell your doctor if you have or think you may have any sort of bowel obstruction (blockage in your intestines). Symptoms of bowel obstruction can include pain in your abdomen (stomach area), nausea, vomiting, or not being able to pass gas or have a bowel movement. You should not take this drug if you have a bowel obstruction.

Pregnant women

This drug is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus.

Women who are breast-feeding

It’s not known if this drug passes into breast milk. It may cause side effects in a child who is breastfed.

Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For children

This medication has not been studied in children. It should not be used in people younger than 18 years.

When to call the doctor

Call your doctor right away if you become pregnant while taking this drug.

Allergies

This drug can cause a severe allergic reaction. Symptoms can include:

• rash
• swelling of your throat or tongue
• trouble breathing

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 9-1-1 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

What are you taking this medication for?

Brand: Amitiza

• Typical starting dosage: 24 mcg, taken twice per day with food and water.

This medication has not been studied in children. It should not be used in people younger than 18 years.

Liver disease: If you have liver disease, your doctor may start you at a lower dosage. They may prescribe 8 mcg twice per day, or 16 mcg twice per day.

Brand: Amitiza

• Typical starting dosage: 24 mcg, taken twice per day with food and water.

This medication has not been studied in children. It should not be used in people younger than 18 years.

Liver disease: If you have liver disease, your doctor may start you at a lower dosage. They may prescribe 8 mcg twice per day, or 16 mcg twice per day.

Brand: Amitiza

• Typical starting dosage: 8 mcg, taken twice per day with food and water.

This medication has not been studied in children. It should not be used in people younger than 18 years.

Liver disease: If you have liver disease, your doctor may start you at a lower dosage. They may prescribe 8 mcg once per day.

Take this drug with food. This may help to reduce upset stomach.

Take this drug at the time(s) recommended by your doctor

Store this drug carefully

A prescription for this medication is refillable

Not every pharmacy stocks every form of this drug. When filling your prescription, be sure to call ahead.

Insurance

Are there any alternatives?