Amitiza lubiprostone 24 ug Capsule, Gelatin Coated, 60-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Chloride Channel Activator class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Lubiprostone is used to treat three types of constipation-related problems in adults: chronic idiopathic constipation (ongoing constipation with no clear cause), opioid-induced con...
- Always take lubiprostone with food and water. Nausea is the most common complaint with this medicine, and taking it with a meal makes a real difference for most people. Swallow the...
- Should I take this with food or on an empty stomach?
- Nausea is the most frequently reported side effect, but for many people it improves over time or stays manageable when the capsule is taken with food. If nausea is really bothering...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with lubiprostone — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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UNII WZB9127XOA
A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII C9H2L21V7U
A fat derived from coconut or palm oil containing shorter fatty acid chains. It serves as a solvent and carrier to help dissolve or suspend active ingredients, improving absorption and stability in liquid formulations.
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UNII 506T60A25R
Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $5.950 | $356.99 / 60 capsules |
| Medicaid paysCMS SDUD · 12 mo | $6.17 | $370.11 / 60 capsules |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lubiprostone 24 ug 00254-3029-02 | Par | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone 24 ug 00480-4138-06 | Teva | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone .024 mg 31722-0404-60 | Camber | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone 24 ug 43598-0168-60 | Dr. | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone 24 ug 60687-0827-32 | American | 1 capsule | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone 24 ug 63304-0352-60 | Sun | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone 24 ug 69339-0163-17 | Natco | 40 capsules | $0.624 | AB | Availability likely | save 90% |
| Lubiprostone .024 mg 72603-0289-01 | Northstar | 60 capsules | $0.624 | AB | Availability likely | save 90% |
| Amitiza 24 ugthis 64764-0240-60 | Takeda | 60 capsules | $5.950 | AB | FDA listed | — |
| Amitiza 24 ug 23635-0524-60 | SpecGx | 60 capsules | $6.449 | AB | Availability likely | +8% |
| Lubiprostone 24 ug 00406-6424-60 | SpecGx | 60 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 51407-0745-60 | Golden | 60 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 70710-1642-01 | Zydus | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 70771-1764-01 | Zydus | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 71205-0832-00 | Proficient | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 71205-0834-00 | Proficient | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 72189-0607-60 | Direct | 60 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 76420-0778-01 | Asclemed | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 76420-0907-01 | Asclemed | 100 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 80425-0355-02 | Advanced | 60 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 82804-0001-30 | Proficient | 30 capsules | — | AB | FDA listed | — |
| Lubiprostone 24 ug 83008-0001-60 | Quality | 60 capsules | — | AB | Discontinued | — |
| Lubiprostone 24 ug 82804-0304-60 | Proficient | 60 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8779187 ↗ | Drug product | — | Jan 23, 2027 |
| US 8779187 ↗ | Drug product | — | Jan 23, 2027 |
| US 8026393 ↗ | Drug product | — | Oct 25, 2027 |
| US 8026393 ↗ | Drug product | — | Oct 25, 2027 |
| US 8338639 ↗ | Drug product | — | Jan 23, 2027 |
| US 8338639 ↗ | Drug product | — | Jan 23, 2027 |
Is there a generic version of AMITIZA 24 MCG CAPSULE?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 64764-0240-40 | 4 CARTON in 1 CARTON (64764-240-40) / 1 BLISTER PACK in 1 CARTON / 4 CAPSULE, GELATIN COATED in 1 BLISTER PACK | — | — | 2006-01-31 | Discontinued by firm |
| 64764-0240-60 You're viewing this | 60 CAPSULE, GELATIN COATED in 1 BOTTLE (64764-240-60) | $5.95 / ea | $356.99 | 2006-01-31 | Active |
Pack size FAQ
What quantity is in NDC 64764-0240-60?
What NDC number is used to bill for this package of Amitiza lubiprostone 24 ug Capsule, Gelatin Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Amitiza is a chloride channel activator indicated for the treatment of: chronic idiopathic constipation (CIC) in adults. ( 1.1 ) 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. ( 1.2 ) Limitations of Use: Effectiveness of Amitiza in the treatment of OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established.
( 1.2 , 7.1 ) irritable bowel syndrome with constipation (IBS-C) in women ≥ 18 years old. ( 1.3 )
1.1Chronic Idiopathic Constipation in Adults Amitiza ® is indicated for the treatment of chronic idiopathic constipation (CIC) in adults.
1.2Opioid-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) ]
1.3Irritable Bowel Syndrome with Constipation Amitiza is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in women at least 18 years old.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended Dosage ( 2.1 ) CIC and OIC: 24 mcg twice daily. IBS-C: 8 mcg twice daily. See full prescribing information for dosage adjustment by indication and degree of hepatic impairment. Administration Instructions ( 2.2 ) Swallow capsules whole and do not break apart or chew, Take capsules with food and water, Assess periodically the need for continuous therapy.
2.1Recommended Dosage The recommended oral dosage of Amitiza by indication and adjustments for patients with moderate (Child Pugh Class B) and severe (Child Pugh Class C) hepatic impairment are shown in Table 1. Table 1. Recommended Dosage Regimen CIC and OIC IBS-C Recommended Adult Dosage Regimen 24 mcg twice daily 8 mcg twice daily Dosage Adjustment for Hepatic Impairment [see Use in Specific Populations (8.6) ] Moderate Impairment (Child-Pugh Class B) : 16 mcg twice daily If the 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.
Moderate Impairment (Child-Pugh Class B) : No adjustment necessary Severe Impairment (Child-Pugh Class C) : 8 mcg twice daily Severe Impairment (Child-Pugh Class C) : 8 mcg once daily
2.2Administration 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.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 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 Capsules: 8 mcg and 24 mcg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Amitiza is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction [see Warnings and Precautions (5.5) ] . Patients with known or suspected mechanical gastrointestinal obstruction. ( 4 , 5.5 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Nausea : Patients may experience nausea; concomitant administration of food may reduce this symptom. ( 2.2 , 5.1 ) Diarrhea : Avoid use in patients with severe diarrhea. Instruct patients to discontinue Amitiza and contact their healthcare provider if severe diarrhea occurs during treatment.
( 5.2 ) Syncope and Hypotension : May occur after taking the first dose or with subsequent doses. Generally resolves prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue Amitiza and contact their healthcare provider if symptoms occur.
( 5.3 ) Dyspnea : May occur within an hour of first dose. Generally resolves within 3 hours, but may recur with repeat dosing. Instruct patients to contact their healthcare provider if symptoms occur.
( 5.4 ) Bowel Obstruction : Evaluate patients with symptoms suggestive of mechanical gastrointestinal obstruction prior to initiating treatment with Amitiza. ( 4 , 5.5 )
5.1Nausea Patients taking Amitiza may experience nausea. Concomitant administration of food with Amitiza may reduce symptoms of nausea [ see Adverse Reactions (6.1) ] .
5.2Diarrhea 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) ] .
5.3Syncope 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.
5.4Dyspnea 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 to 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.
5.5Bowel 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 [see Contraindication (4) ] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in labeling: Nausea [see Warnings and Precautions (5.1) ] Diarrhea [see Warnings and Precautions (5.2) ] Syncope and Hypotension [see Warnings and Precautions (5.3) ] Dyspnea [see Warnings and Precautions (5.4) ] Most common adverse reactions (> 4%) are: CIC: nausea, diarrhea, headache, abdominal pain, abdominal distension, and flatulence. ( 6.1 ) OIC: nausea and diarrhea. ( 6.1 ) IBS-C: nausea, diarrhea, and abdominal pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-825-3327 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. During clinical development of Amitiza for CIC, OIC, and IBS-C, 1648 patients were treated with Amitiza for 6 months and 710 patients were treated for 1 year (not mutually exclusive). Chronic Idiopathic Constipation Adverse reactions in adult dose-finding, efficacy, and long-term clinical studies: The data described below reflect exposure to Amitiza 24 mcg twice daily in 1113 patients with CIC over 3- or 4-week, 6-month, and 12-month treatment periods; and from 316 patients receiving placebo over short-term exposure (≤4 weeks).
The placebo population (N = 316) had a mean age of 48 (range 21 to 81) years; was 87% female; 81% Caucasian, 10% African American, 7% Hispanic, 1% Asian, and 12% elderly (≥65 years of age). Of those patients treated with Amitiza 24 mcg twice daily (N=1113), the mean age was 50 (range 19-86) years; 87% were female; 86% Caucasian, 8% African American, 5% Hispanic, 1% Asian, and 17% elderly (≥65 years of age). The most common adverse reactions (>4%) in CIC were nausea, diarrhea, headache, abdominal pain, abdominal distension, and flatulence.
Table 2 presents data for the adverse reactions that occurred in at least 1% of patients and that occurred more frequently with Amitiza than placebo. Table 2. Adverse Reactions Reported in at least 1% of patients treated with Amitiza and greater than placebo in Clinical Trials of Adults with CIC System/Adverse Reaction Placebo Amitiza 24 mcg Twice Daily N = 316 % N = 1113 % Nausea 3 29 Diarrhea 1 12 Headache 5 11 Abdominal pain 3 8 Abdominal distension 2 6 Flatulence 2 6 Vomiting 0 3 Loose stools 0 3 Edema <1 3 Abdominal discomfort This term combines "abdominal tenderness," "abdominal rigidity," "gastrointestinal discomfort," "stomach discomfort", and "abdominal discomfort." 1 3 Dizziness 1 3 Chest discomfort/pain 0 2 Dyspnea 0 2 Dyspepsia <1 2 Fatigue 1 2 Dry mouth <1 1 Nausea: Approximately 29% of patients who received Amitiza experienced nausea; 4% of patients had severe nausea and 9% of patients discontinued treatment due to nausea.
The rate of nausea was lower among male (8%) and elderly (19%) patients. No patients in the clinical studies were hospitalized due to nausea. Diarrhea: Approximately 12% of patients who received Amitiza experienced diarrhea; 2% of patients had severe diarrhea and 2% of patients discontinued treatment due to diarrhea.
Electrolytes: No serious adverse reactions of electrolyte imbalance were reported in clinical studies, and no clinically significant changes were seen in serum electrolyte levels in patients receiving Amitiza. Less common adverse reactions (<1%): fecal incontinence, muscle cramp, defecation urgency, frequent bowel movements, hyperhidrosis, pharyngolaryngeal pain, intestinal functional disorder, anxiety, cold sweat, constipation, cough, dysgeusia, eructation, influenza, joint swelling, myalgia, pain, syncope, tremor, decreased appetite.
Opioid-Induced Constipation Adverse reactions in adult efficacy and long-term clinical studies: The data described below reflect exposure to Amitiza 2…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Methadone Diphenylheptane opioids (e.g., methadone) have been shown in nonclinical studies 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. No in vivo interaction studies have been conducted.
The effectiveness of Amitiza in the treatment of OIC in patients taking diphenylhepatane opioids (e.g., methadone) has not been established [see Indications and Usage (1.2) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy : Based on animal data, may cause fetal harm. ( 8.1 ) Pediatrics : Safety and effectiveness have not been established in pediatric patients with IBS-C, pediatric functional constipation (PFC), and OIC. ( 8.4 )
8.1Pregnancy Risk Summary Following oral administration, concentrations of lubiprostone in plasma are below the level of quantitation; however, one of the metabolites, M3, has measurable systemic concentrations [see Clinical Pharmacology (12.3) ] . Limited available data with lubiprostone use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Animal reproduction studies did not show an increase in structural malformations .
Although 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/m 2 )), these effects were probably secondary to maternal toxicity and occurred after the period of organogenesis (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data 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/m 2 ). 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/m 2 )); however, these effects were probably secondary to maternal toxicity.
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/m 2 )). 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.
8.2Lactation Risk Summary There are no data available on the presence of lubiprostone in human milk or the effect of lubiprostone on milk production. There are limited data available on the effect of lubiprostone on the breastfed infant. Neither lubiprostone nor its active metabolite (M3) were present in the milk of lactating rats.
When a drug is not present in animal milk, it is likely that the drug will not be present in human milk. If present, lubiprostone may cause diarrhea in the breastfed infant (see Clinical Considerations ) . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Amitiza and any potential adverse effects on the breastfed infant from Amitiza or from the underlying maternal condition.
Clinical Considerations Infants of nursing mothers being treated with Amitiza should be monitored for diarrhea.
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients with IBS-C, pediatric functional constipation (PFC), and OIC. Efficacy was not demonstrated for the treatment of PFC in patients 6 years of a…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Following oral administration, concentrations of lubiprostone in plasma are below the level of quantitation; however, one of the metabolites, M3, has measurable systemic concentrations [see Clinical Pharmacology (12.3) ] . Limited available data with lubiprostone use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Animal reproduction studies did not show an increase in structural malformations .
Although 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/m 2 )), these effects were probably secondary to maternal toxicity and occurred after the period of organogenesis (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data 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/m 2 ). 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/m 2 )); however, these effects were probably secondary to maternal toxicity.
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/m 2 )). 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.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients with IBS-C, pediatric functional constipation (PFC), and OIC. Efficacy was not demonstrated for the treatment of PFC in patients 6 years of age and older in a 12 week, randomized, double-blind, placebo-controlled trial conducted in 606 patients 6 to 17 years with PFC comparing Amitiza to placebo. The primary efficacy endpoint was an overall response based on spontaneous bowel movement frequency over the duration of the trial; the treatment difference from placebo was not statistically significant.
In this age group, adverse reactions to Amitiza were similar to those reported in adults. In a 36-week, long-term safety extension trial after approximately 9 months of treatment with Amitiza, a single case of reversible elevation of ALT (17-times upper limit of normal [ULN]), AST (13-times ULN), and GGT (9-times [ULN]) was observed in a child with baseline elevated values (less than or equal to 2.5-times ULN). Juvenile Animal Toxicity Data In a 13-week oral toxicity study in juvenile rats, a significant decrease in total bone mineral density was observed in female pups at 0.5 mg/kg/day; in male pups, a significantly lower cortical thickness at the tibial diaphysis was observed at 0.5 mg/kg.
The 0.5 mg/kg/day dose is approximately 101 times the maximum recommended adult dose of 48 mcg/day, based on body surface area (mg/m 2 ).
🧓 Geriatric Use ▾
8.5Geriatric Use Chronic Idiopathic Constipation The efficacy of Amitiza 24 mcg twice daily in the elderly (at least 65 years of age) subpopulation with CIC was consistent with the efficacy in the overall study population. Of the total number of patients treated in the dose-finding, efficacy, and long-term studies of Amitiza, 16% were at least 65 years of age, and 4% were at least 75 years of age. Elderly patients taking Amitiza 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 (at least 65 years of age) subpopulation with OIC (9% were at least 65 years of age and 2% were at least 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 (at least 65 years of age) subpopulation with IBS-C (8% were at least 65 years of age and 2% were at least 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.
🆘 Overdosage ▾
10 OVERDOSAGE There have been six reports of overdosage with Amitiza during clinical development. Of these six cases, only two subjects reported adverse events: one reported vomiting, diarrhea and stomach ache after taking 168 to 192 mcg of Amitiza, and another reported diarrhea and a joint injury on the day of overdose after taking 36 mcg of Amitiza. Adverse reactions that occurred in at least 1% of healthy subjects given a single oral dose of 144 mcg of Amitiza (6 times the highest recommended dose) in a cardiac repolarization study included 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%).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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.
Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. 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. Activation of ClC-2 by lubiprostone has also been shown to stimulate recovery of mucosal barrier function and reduce intestinal permeability via the restoration of tight junction protein complexes in ex vivo studies of ischemic porcine intestine.
12.2Pharmacodynamics Although the pharmacologic effects of lubiprostone in humans have not been fully evaluated, 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.
12.3Pharmacokinetics Following oral administration, concentrations of lubiprostone in plasma are below the level of quantitation (10 pg/mL). Therefore, standard pharmacokinetic parameters such as area under the curve (AUC), maximum concentration (C max ), and half-life (t ½ ) cannot be reliably calculated. However, the pharmacokinetic parameters of M3 (only measurable active metabolite of lubiprostone) have been characterized.
Absorption Peak plasma concentrations of M3, after a single oral dose of 24 mcg of lubiprostone, occurred at approximately 1.1 hours. The C max was 41.5 pg/mL and the mean AUC 0–t was 57.1 pg∙hr/mL. The AUC 0–t of M3 increases dose proportionally after single 24-mcg and 144-mcg doses of lubiprostone (6-times the maximum recommended 24 mcg dose).
Food Effect A study was conducted with a single 72-mcg dose of 3 H-labeled lubiprostone (3-times the maximum recommended 24 mcg dose) to evaluate the potential of a food effect on lubiprostone absorption, metabolism, and excretion. Pharmacokinetic parameters of total radioactivity demonstrated that C max decreased by 55% while AUC 0–∞ was unchanged when lubiprostone was administered with a high-fat meal. The clinical relevance of the effect of food on the pharmacokinetics of lubiprostone is not clear.
However, lubiprostone was administered with food and water in a majority of clinical trials. Distribution In vitro protein binding studies indicate lubiprostone is approximately 94% bound to human plasma proteins. Elimination Metabolism Lubiprostone is rapidly and extensively metabolized by 15-position reduction, α-chain β-oxidation, and ω-chain ω-oxidation.
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 that M3, a metabolite of lubiprostone, is formed by the reduction of the 15-carbonyl moiety to a hydroxy moiety by microsomal carbonyl reductase. M3 makes up less than 10% of the dose of radiolabeled lubiprostone.
Animal studies have shown that metabolism of lubiprostone rapidly occurs within the stomach and jejunum, most likely in the absence of any systemic absorption. Excretion Lubiprostone could not be detected in plasma; however, M3 has a t ½ ranging from 0.9 to 1.4 hours. After a single oral dose of 72 mcg of 3 H-labeled lubiprostone, 60% of total administered…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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.
Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. 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. Activation of ClC-2 by lubiprostone has also been shown to stimulate recovery of mucosal barrier function and reduce intestinal permeability via the restoration of tight junction protein complexes in ex vivo studies of ischemic porcine intestine.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Amitiza is available as an oval, soft gelatin capsule containing 8 mcg or 24 mcg of lubiprostone with "SPI" printed on one side. Amitiza is available as follows: 8 mcg pink capsule Bottles of 60 (NDC 64764-080-60) 24 mcg orange capsule Bottles of 60 (NDC 64764-240-60) Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light and extreme temperatures.
📦 Storage and Handling ▾
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light and extreme temperatures.
📋 Description ▾
11 DESCRIPTION Amitiza (lubiprostone) is a chloride channel activator for oral use. The chemical name for lubiprostone is (–)-7-[(2 R ,4a R ,5 R ,7a R )-2-(1,1-difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[ b ]pyran-5-yl]heptanoic acid. The molecular formula of lubiprostone is C 20 H 32 F 2 O 5 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: ferric oxide, gelatin, medium-chain triglycerides, purified water, sorbitol, and titanium dioxide. Orange capsules contain 24 mcg of lubiprostone and the following inactive ingredients: D&C Yellow #10, FD&C Red #40, gelatin, medium-chain triglycerides, purified water, and sorbitol.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Administration Instructions Instruct patients to take Amitiza orally with food and water to reduce the occurrence of nausea [see Warnings and Precautions (5.1) ] . Swallow capsules whole and do not break apart or chew. Physicians and patients should periodically assess the need for continued therapy.
Diarrhea Inform patients that they may experience diarrhea during treatment with Amitiza. Instruct patients to discontinue Amitiza and contact their healthcare provider if severe diarrhea occurs [see Warnings and Precautions (5.2) ]. Syncope and Hypotension Inform patients that they may experience syncope and hypotension after taking the first dose or subsequent doses of Amitiza.
Syncope and hypotension generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue Amitiza and to contact their healthcare provider if these reactions occur [see Warnings and Precautions (5.3) ] . Inform patients that other adverse reactions may increase the risk of syncope and hypotension, such as diarrhea or vomiting.
Dyspnea 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 [see Warnings and Precautions (5.4) ] .
Lactation Advise lactating women to monitor their human milk-fed infants for diarrhea while taking Amitiza [ see Use in Specific Populations (8.2) ] .