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Lubiprostone


General


Pronunciation

(loo bi PROS tone)


Brand Names: U.S.

  • Amitiza

Indications


Use: Labeled Indications

Treatment of chronic idiopathic constipation; treatment of opioid-induced constipation with chronic non-cancer pain; treatment of irritable bowel syndrome with constipation in adult women


Contraindications


Known or suspected mechanical bowel obstruction


Dosing and Administration


Dosing: Adult

Chronic idiopathic constipation: Oral: 24 mcg twice daily

Irritable bowel syndrome with constipation: Females ≥18 years: Oral: 8 mcg twice daily

Opioid-induced constipation with chronic non-cancer pain: Oral: 24 mcg twice daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate hepatic impairment (Child-Pugh class B):

Chronic idiopathic constipation: Initial: 16 mcg twice daily; may increase to 24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.

Irritable bowel syndrome with constipation: No dosage adjustment necessary.

Opioid-induced constipation with chronic non-cancer pain: Initial: 16 mcg twice daily; may increase to 24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.

Severe hepatic impairment (Child-Pugh class C):

Chronic idiopathic constipation: Initial: 8 mcg twice daily; may increase to 16-24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.

Irritable bowel syndrome with constipation: Initial: 8 mcg once daily; may increase to 8 mcg twice daily if tolerated and an adequate response has not been obtained at lower dosage.

Opioid-induced constipation with chronic non-cancer pain: Initial: 8 mcg twice daily; may increase to 16-24 mcg twice daily if tolerated and an adequate response has not been obtained with lower dosage.


Administration

Administer with food and water. Swallow whole; do not break or chew.


Dietary Considerations

Take with food and water to decrease nausea.


Storage

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


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Amitiza: 8 mcg

Amitiza: 24 mcg [contains fd&c red #40, fd&c yellow #10 (quinoline yellow)]


Drug Interactions

Methadone: May diminish the therapeutic effect of Lubiprostone. Monitor therapy


Adverse Reactions


>10%:

Central nervous system: Headache (2% to 11%)

Gastrointestinal: Nausea (8% to 29%; severe: 1% to 4%; dose related; male: 8%; elderly: 19%), diarrhea (7% to 12%; severe <1% to 2%)

1% to 10%:

Cardiovascular: Edema (3%), peripheral edema (1% to 3%), chest discomfort (2%)

Central nervous system: Dizziness (3%), fatigue (2%)

Gastrointestinal: Abdominal pain (4% to 8%), flatulence (4% to 6%), abdominal distention (3% to 6%), abdominal distress (3%), loose stools (3%), vomiting (3%), dyspepsia (2%), xerostomia (1%)

Respiratory: Dyspnea (<1% to 3%)

<1% (Limited to important or life-threatening): Anorexia, bowel urgency, cough, decreased appetite, depression, dysgeusia, eructation, erythema, fecal incontinence, fibromyalgia syndrome, frequent bowel movements, gastritis, gastroesophageal reflux disease, gastrointestinal disease, hyperhidrosis, hypersensitivity reaction, hypokalemia, increased liver enzymes, influenza, ischemic colitis, joint swelling, muscle spasm, myalgia, pain, palpitations, pharyngolaryngeal pain, pollakiuria, rectal hemorrhage, syncope, tachycardia, urinary tract infection, weight gain


Warnings/Precautions


Special Populations: Hepatic Function Impairment

Cmax and AUC are increased in patients with moderate-to-severe hepatic impairment.


Warnings/Precautions

Concerns related to adverse effects:

- Dyspnea: Often described as chest tightness, dyspnea has been observed with use; generally occurs following the first dose with an acute onset (within 30-60 minutes following the first dose) and resolves within a few hours; however, has been frequently reported with subsequent dosing.

- Nausea: Nausea may occur; administer with food to reduce symptoms.

Disease-related concerns:

- Diarrhea: Avoid use in patients with severe diarrhea.

- Gastrointestinal obstruction: Symptoms of mechanical gastrointestinal obstruction should be evaluated before prescribing this medicine; use is contraindicated in patients with bowel obstruction.

- Hepatic impairment: Patients with moderate-to-severe hepatic impairment (Child-Pugh class B or C) have higher systemic drug exposure; dosage adjustment may be recommended, depending on the indication and severity of hepatic impairment.

Concurrent drug therapy issues:

- Agents which may lower efficacy: Diphenylheptane opioids (eg, methadone) may potentially decrease the efficacy of lubiprostone in a dose-dependent manner (by decreasing the activation of ClC-2 by lubiprostone in the GI tract); efficacy of lubiprostone in the treatment of opioid-induced constipation in patients taking diphenylheptane opioids has not been established.

Special populations:

- Males: Not approved for use in males with irritable bowel syndrome with constipation.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.


Actions


Pharmacology

Bicyclic fatty acid that acts locally at the apical portion of the intestine as a chloride channel activator, specifically ClC-2, thereby increasing intestinal fluid secretion and intestinal motility. When used for opioid induced constipation, activation of apical ClC-2 channels bypasses the antisecretory action of opiates resulting from suppression of secretomotor neuron excitability. ClC-2 activation does not alter serum sodium or potassium concentrations.


Absorption

Systemic: Parent drug: Poor (below levels of detection); Active metabolite (M3): Low


Distribution

Gastrointestinal tissue; minimal beyond gastrointestinal tissue


Metabolism

Rapid and extensive within stomach and jejunum by carbonyl reductase to M3 (active metabolite) and others


Excretion

Parent drug and M3: Feces (trace amounts)


Time to Peak

Plasma: M3: ~1 hour


Half-Life Elimination

M3: 0.9-1.4 hours


Protein Binding

~94%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, dyspepsia, diarrhea, flatulence, or bloating. Have patient report immediately to prescriber angina, significant nausea, considerable diarrhea, or dyspnea (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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