Side Effects of Amitiza (lubiprostone)

Amitiza (lubiprostone) is a chloride channel activator used to treat idiopathic (due to an unknown cause) chronic constipation.

Chronic constipation most commonly occurs because of slow transit of stool through the colon that allows too much fluid to be removed from the stool, leading to hard or lumpy stools, abdominal pain or discomfort, and straining during bowel movements, as well as difficulty passing stools.

Signs and symptoms of chronic constipation can be reduced by increasing fluid in the stool. Amitiza causes an increase in the secretion of fluid into the intestines. The added fluid softens the stool and also may speed up transit of stool in the colon.

Common side effects of Amitiza include

• nausea,
• diarrhea,
• headache,
• frequent bowel movements,
• fecal incontinence,
• gas (flatulence),
• decreased appetite, and
• rash.

Serious side effects of Amitiza include

• trouble breathing or shortness of breath,
• severe or ongoing nausea or diarrhea, and
• lightheaded feeling.

Amitiza has no known drug interactions.

Use of Amitiza in pregnant women has not been adequately evaluated during pregnancy.

It is unknown if Amitiza is excreted in breast milk. Consult your doctor before breastfeeding.

The most common side effects of lubiprostone are:

• nausea,
• diarrhea,
• headache,
• frequent bowel movements,
• fecal incontinence,
• flatulence,
• decreased appetite, and
• rash.

Nausea was reduced when lubiprostone was administered with food. Some patients may experience shortness of breath.

The following adverse reactions are described below and elsewhere in labeling:

• Nausea
• Diarrhea
• Syncope and Hypotension
• Dyspnea

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 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 Reactions¹ in Clinical Trials of Adults with CIC

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 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 Reactions¹ in Clinical Trials of Adults with OIC

Nausea: Approximately 11% of patients who received Amitiza experienced nausea; 1% of patients had severe nausea and 2% of patients discontinued treatment due to nausea.

Diarrhea: Approximately 8% of patients who received Amitiza 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 Amitiza 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. The total population (N = 1267) had a mean age of 47 (range 18-85) years; was 92% female; 78% Caucasian, 13% African American, 9% Hispanic, 0.4% Asian, and 8% elderly (≥65 years of age).

The most common adverse reactions (>4%) in IBS-C were nausea, diarrhea, and abdominal pain.

Table 5 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 5: Adverse Reactions¹ in Clinical Trials of Adults with IBS-C

Nausea: Approximately 8% of patients who received Amitiza 8 mcg twice daily experienced nausea; 1% of patients had severe nausea and 1% of patients discontinued treatment due to nausea.

Diarrhea: Approximately 7% of patients who received Amitiza 8 mcg twice daily experienced diarrhea; <1% of patients had severe diarrhea and <1% of patients discontinued treatment due to diarrhea.

Less common adverse reactions (<1%): dyspepsia, loose stools, vomiting, fatigue, dry mouth, edema, increased alanine aminotransferase, increased aspartate aminotransferase, constipation, eructation, gastroesophageal reflux disease, dyspnea, erythema, gastritis, increased weight, palpitations, urinary tract infection, anorexia, anxiety, depression, fecal incontinence, fibromyalgia, hard feces, lethargy, rectal hemorrhage, pollakiuria.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Amitiza. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular: syncope and/or hypotension, tachycardia

Gastrointestinal: ischemic colitis

General: asthenia

Immune System: hypersensitivity reactions including rash, swelling, and throat tightness malaise

Muscoskeletal: muscle cramps or muscle spasms.

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 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.