Lubiprostone
Capsule, Gelatin Coated · Oral
Uses
Lubiprostone 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 lubiprostone 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 ) 1.1 Chronic Idiopathic Constipation in Adults Lubiprostone is indicated for the treatment of chronic idiopathic constipation (CIC) in adults. 1.2 Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain Lubiprostone 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 Lubiprostone in the treatment of opioid-induced constipation in patients taking diphenylheptane opioids (e.g., methadone) has not been established. [see Clinical Studies (14.2) ] 1.3 Irritable Bowel Syndrome with Constipation Lubiprostone is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) in women at least 18 years old.
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. 2.1 Recommended Dosage The recommended oral dosage of Lubiprostone 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 2.2 Administration Instructions Take lubiprostone 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
Lubiprostone 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
Lubiprostone 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 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 lubiprostone 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 lubiprostone 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 lubiprostone. ( 4 , 5.5 ) 5.1 Nausea Patients taking lubiprostone may experience nausea. Concomitant administration of food with lubiprostone may reduce symptoms of nausea [ see Adverse Reactions (6.1) ] . 5.2 Diarrhea 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 [ see Adverse Reactions (6.1) ] . 5.3 Syncope and Hypotension Syncope and hypotension have been reported with lubiprostone 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 lubiprostone. Some patients had concomitant diarrhea or vomiting prior to developing the adverse reaction. Syncope and hypotension generally resolved following lubiprostone 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. 5.4 Dyspnea In clinical trials, dyspnea was reported by 3%, 1%, and < 1% of the treated CIC, OIC, and IBS-C populations receiving lubiprostone, respectively, compared to 0%, 1%, and < 1% of placebo-treated patients. There have been postmarketing reports of dyspnea when using lubiprostone 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. 5.5 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 lubiprostone [see Contraindication (4) ] .
Side effects
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 Sun Pharmaceutical Industries, Inc. at 1-800-406-7984 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 lubiprostone for CIC, OIC, and IBS-C, 1648 patients were treated with lubiprostone 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 Lubiprostone 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 lubiprostone 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 Lubiprostone than placebo. Table 2. Adverse Reactions Reported in at least 1% of patients treated with Lubiprostone and greater than placebo in Clinical Trials of Adults with CIC System/Adverse Reaction Placebo Lubiprostone 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 lubiprostone 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 lubiprostone 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 lubiprostone. 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 lubiprostone 24 mcg twice daily in 860 patients with OIC for up to 12 months and from 632 patients receiving placebo twice daily for up to 12 weeks. The total population (N = 1492) had a mean age of 50 (range 20–89) years; was 63% female; 83% Caucasian, 14% African American, 1% American Indian/Alaska Native, 1% Asian; 5% were of Hispanic ethnicity, and 9% were elderly (≥65 years of age). The most common adverse reactions (>4%) in OIC were nausea and diarrhea. Table 3 presents data for the adverse reactions that occurred in at least 1% of patients and that occurred more frequently with study drug than placebo. Table 3. Adverse Reactions Reported in at least 1% of patients treated with Lubiprostone and greater than placebo in Clinical Trials of Adults with OIC System/Adverse Reaction Placebo Lubiprostone 24 mcg Twice Daily N = 632 % N = 860 % Nausea 5 11 Diarrhea 2 8 Abdominal pain 1 4 Flatulence 3 4 Abdominal distension 2 3 Vomiting 2 3 Headache 1 2 Peripheral edema <1 1 Abdominal discomfort This term combines "abdominal tenderness," "abdominal rigidity," "gastrointestinal discomfort," "stomach discomfort", and "abdominal discomfort." 1 1 Nausea: Approximately 11% of patients who received lubiprostone experienced nausea; 1% of patients had severe nausea and 2% of patients discontinued treatment due to nausea. Diarrhea: Approximately 8% of patients who received lubiprostone experienced diarrhea; 2% of patients had severe diarrhea and 1% of patients discontinued treatment due to diarrhea. Less common adverse reactions (<1%): fecal incontinence, blood potassium decreased. Irritable Bowel Syndrome with Constipation Adverse reactions in adult dose-finding, efficacy, and long-term clinical studies: The data described below reflect exposure to lubiprostone 8 mcg twice daily in 1011 patients with IBS-C for up to 12 months and from 435 patients receiving placebo twice daily for up to 16 weeks.
Drug interactions
7.1 Methadone 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 lubiprostone in patients using diphenylheptane opioids. No in vivo interaction studies have been conducted. The effectiveness of lubiprostone 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
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 ) 8.1 Pregnancy 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. 8.2 Lactation 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 lubiprostone and any potential adverse effects on the breastfed infant from lubiprostone or from the underlying maternal condition. Clinical Considerations Infants of nursing mothers being treated with lubiprostone should be monitored for diarrhea. 8.4 Pediatric 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 lubiprostone 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 lubiprostone were similar to those reported in adults. In a 36-week, long-term safety extension trial after approximately 9 months of treatment with lubiprostone, 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 ). 8.5 Geriatric Use Chronic Idiopathic Constipation The efficacy of lubiprostone 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 lubiprostone, 16% were at least 65 years of age, and 4% were at least 75 years of age. Elderly patients taking lubiprostone experienced a lower rate of associated nausea compared to the overall study population taking lubiprostone (19% vs. 29%, respectively).
Pregnancy
8.1 Pregnancy 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
8.4 Pediatric 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 lubiprostone 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 lubiprostone were similar to those reported in adults. In a 36-week, long-term safety extension trial after approximately 9 months of treatment with lubiprostone, 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
8.5 Geriatric Use Chronic Idiopathic Constipation The efficacy of lubiprostone 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 lubiprostone, 16% were at least 65 years of age, and 4% were at least 75 years of age. Elderly patients taking lubiprostone experienced a lower rate of associated nausea compared to the overall study population taking lubiprostone (19% vs. 29%, respectively). Opioid-Induced Constipation The safety profile of lubiprostone 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 lubiprostone 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 lubiprostone 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 lubiprostone did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.
Overdosage
There have been six reports of overdosage with lubiprostone 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 lubiprostone, and another reported diarrhea and a joint injury on the day of overdose after taking 36 mcg of lubiprostone. Adverse reactions that occurred in at least 1% of healthy subjects given a single oral dose of 144 mcg of lubiprostone (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%).
Description
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. Lubiprostone 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
Mechanism of action
12.1 Mechanism 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
Lubiprostone is available as an oval, soft gelatin capsule containing 8 mcg or 24 mcg of lubiprostone with "SPI" printed on one side. Lubiprostone is available as follows: 8 mcg pink capsule Bottles of 60 (NDC 63304-351-60) 24 mcg orange capsule Bottles of 60 (NDC 63304-352-60) Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light and extreme temperatures.
Storage
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light and extreme temperatures.
Patient information
Administration Instructions Instruct patients to take lubiprostone 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 lubiprostone. Instruct patients to discontinue lubiprostone 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 lubiprostone. Syncope and hypotension generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue Lubiprostone 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 lubiprostone [ see Use in Specific Populations (8.2) ] .
Label text from the FDA structured product label by Sun Pharmaceutical Industries, Inc. (revised Jul 14, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Lubiprostone in 38 products
Lubiprostone NDC products (38)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60687-827 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | American Health Packaging | ANDA |
| 60687-816 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | American Health Packaging | ANDA |
| 65162-842 | Lubiprostone 24 ug/1 Capsule | Amneal Pharmaceuticals LLC | ANDA |
| 65162-841 | Lubiprostone 8 ug/1 Capsule | Amneal Pharmaceuticals LLC | ANDA |
| 76420-777 | Lubiprostone 8 ug/1 Capsule | Asclemed USA, Inc. | ANDA |
| 76420-778 | Lubiprostone 24 ug/1 Capsule | Asclemed USA, Inc. | ANDA |
| 31722-403 | Lubiprostone .008 mg/1 Capsule | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-404 | Lubiprostone .024 mg/1 Capsule | Camber Pharmaceuticals, Inc. | ANDA |
| 72603-288 | Lubiprostone .008 mg/1 Capsule | Northstar Rx LLC | ANDA |
| 72603-289 | Lubiprostone .024 mg/1 Capsule | Northstar Rx LLC | ANDA |
| 82804-304 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Proficient Rx LP | ANDA |
| 0480-4138 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 0480-3479 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 70771-1763 | Lubiprostone 8 ug/1 Capsule | Zydus Lifesciences Limited | ANDA |
| 70771-1764 | Lubiprostone 24 ug/1 Capsule | Zydus Lifesciences Limited | ANDA |
| 70710-1641 | Lubiprostone 8 ug/1 Capsule | Zydus Pharmaceuticals USA Inc. | ANDA |
| 70710-1642 | Lubiprostone 24 ug/1 Capsule | Zydus Pharmaceuticals USA Inc. | ANDA |
| 80425-0354 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Advanced Rx of Tennessee, LLC | NDA AUTHORIZED GENERIC |
| 80425-0355 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Advanced Rx of Tennessee, LLC | NDA AUTHORIZED GENERIC |
| 76420-907 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Asclemed USA, Inc. | NDA AUTHORIZED GENERIC |
| 76420-906 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Asclemed USA, Inc. | NDA AUTHORIZED GENERIC |
| 72189-607 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Direct Rx | NDA AUTHORIZED GENERIC |
| 43598-168 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Dr. Reddy's Laboratories Inc. | NDA AUTHORIZED GENERIC |
| 43598-163 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Dr. Reddy's Laboratories Inc. | NDA AUTHORIZED GENERIC |
| 51407-745 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Golden State Medical Supply, Inc. | NDA AUTHORIZED GENERIC |
| 51407-744 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Golden State Medical Supply, Inc. | NDA AUTHORIZED GENERIC |
| 69339-163 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Natco Pharma USA LLC | NDA AUTHORIZED GENERIC |
| 69339-162 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Natco Pharma USA LLC | NDA AUTHORIZED GENERIC |
| 0254-3028 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Par Health USA, LLC | NDA AUTHORIZED GENERIC |
| 0254-3029 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Par Health USA, LLC | NDA AUTHORIZED GENERIC |
| 71205-834 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Proficient Rx LP | NDA AUTHORIZED GENERIC |
| 71205-832 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Proficient Rx LP | NDA AUTHORIZED GENERIC |
| 71205-831 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Proficient Rx LP | NDA AUTHORIZED GENERIC |
| 82804-001 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Proficient Rx LP | NDA AUTHORIZED GENERIC |
| 0406-6424 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | SpecGx LLC | NDA AUTHORIZED GENERIC |
| 0406-6408 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | SpecGx LLC | NDA AUTHORIZED GENERIC |
| 63304-352 | Lubiprostone 24 ug/1 Capsule, Gelatin Coated | Sun Pharmaceutical Industries, Inc. | NDA AUTHORIZED GENERIC |
| 63304-351 | Lubiprostone 8 ug/1 Capsule, Gelatin Coated | Sun Pharmaceutical Industries, Inc. | NDA AUTHORIZED GENERIC |
Frequently asked questions
What is Lubiprostone used for?
Lubiprostone 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:…
What are the side effects of Lubiprostone?
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… See the full label for the complete list.
Who makes Lubiprostone?
Lubiprostone is listed by 17 labelers in the FDA NDC directory, including American Health Packaging, Amneal Pharmaceuticals LLC, Asclemed USA, Inc., Camber Pharmaceuticals, Inc..