Lubiprostone

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. …

• Recommended Dosage 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
• Swallow capsules whole and do not break apart or chew, Take capsules with food and water, Assess periodically the need for continuous therapy
• 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 ] 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 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

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 )

• 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. …

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. …

• Administration Instructions Instruct patients to take lubiprostone orally with food and water to reduce the occurrence of nausea [see Warnings and Precautions ]
• 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 ]. …

• Lubiprostone is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction [see Warnings and Precautions ]
• Patients with known or suspected mechanical gastrointestinal obstruction

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) ] .

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. …

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 Dr. Reddy's Laboratories Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

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. …

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. …

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

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.