Lubiprostone

Lubiprostone is a chloride channel activator indicated for the treatment of: chronic idiopathic constipation (CIC) in adults. 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 OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established. irritable bowel syndrome with constipation (IBS-C) in women ≥ 18 years old.

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.

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.

Lubiprostone is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with known or suspected mechanical gastrointestinal obstruction.

Nausea: Patients may experience nausea, concomitant administration of food may reduce this symptom. Diarrhea: Avoid use in patients with severe diarrhea. Instruct patients to discontinue lubiprostone and contact their healthcare provider if severe diarrhea occurs during treatment. 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. 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. Bowel Obstruction: Evaluate patients with symptoms suggestive of mechanical gastrointestinal obstruction prior to initiating treatment with lubiprostone.

The following adverse reactions are described below and elsewhere in labeling: Nausea Diarrhea Syncope and Hypotension Dyspnea Most common adverse reactions (> 4%) are: CIC: nausea, diarrhea, headache, abdominal pain, abdominal distension, and flatulence. OIC: nausea and diarrhea. IBS-C: nausea, diarrhea, and abdominal pain.

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.

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