Lubiprostone Side Effects: What to Expect and When to Call Your Doctor

Like all medications, Lubiprostone (Amitiza) can cause side effects. Most people who take it experience mild to moderate symptoms that get better over time, especially with the right strategies. But some side effects — like shortness of breath or fainting — need immediate attention. This guide walks you through the full picture, so you know what's normal, what to manage at home, and when to call your doctor.

The Most Common Lubiprostone Side Effects

In clinical trials, the most frequently reported side effects in patients taking Lubiprostone 24 mcg twice daily for chronic idiopathic constipation (CIC) were:

• Nausea (up to 29%): The most common side effect. Usually mild to moderate and often improves with continued use. Taking Lubiprostone with food and water significantly reduces nausea.
• Diarrhea (7–12%): Loose stools are a common effect — expected given how the drug works by increasing intestinal fluid. Usually manageable; see below for when it becomes serious.
• Headache (2–11%): Reported by some patients, particularly early in treatment. Usually mild and resolves on its own.
• Abdominal pain or discomfort: Cramping and abdominal pain are common, especially early in treatment.
• Abdominal distension and flatulence: Bloating and gas are reported by a meaningful number of patients.

How to Manage the Common Side Effects

For nausea: Always take Lubiprostone with food and water. The FDA label specifically recommends this to reduce nausea. Don't take it on an empty stomach. If nausea persists or is severe, talk to your doctor — they may adjust your dose.

For diarrhea: Mild to moderate diarrhea is expected as the drug increases fluid in the intestine. Stay hydrated, especially if diarrhea is frequent. Diarrhea often improves after the first few weeks as your body adjusts.

For headache: OTC analgesics like acetaminophen may help. If headaches are frequent or severe, contact your doctor.

Serious Side Effects: Call Your Doctor Right Away

While uncommon, some Lubiprostone side effects can be serious. Contact your healthcare provider immediately if you experience any of the following:

Dyspnea (Shortness of Breath / Chest Tightness)

One of the most important warnings in the Lubiprostone labeling is the potential for acute dyspnea — a sensation of chest tightness and difficulty breathing — typically occurring within 30–60 minutes after the first dose. This usually resolves within a few hours but can recur with subsequent doses. If you experience this, contact your doctor before taking another dose. This side effect has been reported more with the 24 mcg dose.

Syncope (Fainting) and Hypotension (Low Blood Pressure)

Post-marketing reports have documented cases of syncope (fainting) and hypotension with Lubiprostone, some requiring hospitalization. Most cases occurred in patients taking 24 mcg twice daily and some happened within an hour of taking the first dose. If you feel faint or dizzy, lie down and call your doctor. Be aware that vomiting or diarrhea can increase this risk by causing dehydration.

Severe Diarrhea

While mild diarrhea is common and often expected, severe diarrhea is a reason to stop Lubiprostone and call your doctor. The FDA label states the drug should not be used in patients with severe diarrhea. Stopping Lubiprostone is appropriate if diarrhea is frequent, severe, or accompanied by dehydration.

Allergic Reactions

Although uncommon, allergic reactions to Lubiprostone have been reported, including rash, swelling, and throat tightness. Get emergency help immediately if you have hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Special Considerations: Pregnancy and Breastfeeding

Lubiprostone is Pregnancy Category C. Animal studies showed dose-dependent fetal loss in guinea pigs at doses comparable to human doses. For this reason, women of childbearing potential must have a negative pregnancy test before starting Lubiprostone and should use contraception during treatment. If you become pregnant while taking Lubiprostone, call your doctor immediately.

It is not known whether Lubiprostone passes into breast milk. If you are breastfeeding and your baby develops diarrhea, tell your doctor, as Lubiprostone could potentially cause diarrhea in breastfed infants.

The Bottom Line

Most people tolerate Lubiprostone well, especially when they take it with food to minimize nausea. Being aware of the serious side effects — particularly dyspnea in the first hour and syncope — means you'll know immediately when to seek care. For a complete picture, also review our guide on Lubiprostone drug interactions. And if you're having trouble finding your medication, medfinder can help you locate a pharmacy that has it in stock.