Dificid Side Effects: What You Need to Know

If your doctor has prescribed Dificid (Fidaxomicin) for a Clostridioides difficile (C. diff) infection, you may be wondering what side effects to expect. The good news is that Dificid is generally well tolerated — it works primarily in your gut and is minimally absorbed into your bloodstream. But like any medication, it can cause side effects.

This guide covers the common and serious side effects of Dificid based on FDA labeling, who may be at higher risk, and when you should call your doctor.

What Is Dificid?

Dificid is a brand-name macrolide antibiotic containing the active ingredient Fidaxomicin. It's FDA-approved to treat C. diff-associated diarrhea (CDAD) in adults and children ages 6 months and older. The standard dose is 200 mg taken twice daily for 10 days.

Unlike broad-spectrum antibiotics such as Vancomycin, Dificid has a narrow spectrum of activity — it specifically targets C. diff while largely sparing the beneficial bacteria in your gut. This is one reason it's associated with lower recurrence rates. For more details, see our guide on what Dificid is and how it's used.

Common Side Effects

The following side effects were reported in clinical trials and are listed in the FDA-approved prescribing information. Most are mild to moderate and often resolve on their own:

• Nausea — One of the most commonly reported side effects. Taking Dificid with food may help reduce nausea.
• Vomiting — Some patients experience vomiting during treatment. If vomiting occurs shortly after taking a dose, contact your doctor about whether to take another dose.
• Abdominal pain or discomfort — Stomach pain, bloating, and tenderness are common, though it can be hard to distinguish these from C. diff symptoms themselves.
• Gastrointestinal bleeding — Bloody or black, tarry stools have been reported. While this can occur with severe C. diff disease, report any signs of GI bleeding to your doctor immediately.
• Anemia — Some patients develop low red blood cell counts during treatment. Symptoms can include unusual tiredness, weakness, pale skin, and shortness of breath.
• Constipation — As the C. diff infection resolves, some patients may swing from diarrhea to constipation.
• Flatulence and bloating — Excess gas and a feeling of fullness are common as your digestive system recovers.
• Headache — Mild headaches have been reported during treatment.
• Acid reflux or heartburn — Some patients experience sour stomach, belching, or indigestion.

Most of these side effects are temporary. Your body is fighting a serious gut infection, and some GI symptoms are to be expected during recovery.

Serious Side Effects

Serious side effects from Dificid are rare, but they require immediate medical attention:

Allergic Reactions (Hypersensitivity)

Dificid can cause serious allergic reactions, including:

• Angioedema — Swelling of the face, lips, tongue, throat, hands, or feet. This can be life-threatening if it affects breathing.
• Dyspnea — Difficulty breathing or shortness of breath.
• Rash or hives — Itching, skin rash, or large hive-like welts.
• Pruritus — Intense itching without an obvious rash.

If you experience any signs of a severe allergic reaction — especially swelling of the face or throat, difficulty breathing, or widespread hives — call 911 or go to the nearest emergency room immediately.

Cross-Sensitivity with Macrolide Antibiotics

If you have a history of allergic reactions to macrolide antibiotics like Azithromycin (Zithromax), Clarithromycin (Biaxin), or Erythromycin, tell your doctor before starting Dificid. You may be at higher risk for an allergic reaction.

Specific Populations

Certain groups of people may need extra monitoring or caution when taking Dificid:

Older Adults

C. diff infections are more common in older adults, especially those over 65 or living in long-term care facilities. Clinical studies have not shown age-specific problems with Dificid in elderly patients, but older adults may be more susceptible to dehydration from diarrhea and should be monitored closely.

Children

Dificid is approved for children 6 months and older. Children who weigh at least 12.5 kg (about 27.5 pounds) and can swallow tablets may take the tablet form. Younger children or those who cannot swallow tablets can use the oral suspension. Dosing is weight-based and determined by the child's doctor.

Pregnant or Breastfeeding Women

There is limited data on the use of Dificid during pregnancy. Because Fidaxomicin is minimally absorbed into the bloodstream, systemic exposure is expected to be low. However, you should discuss the risks and benefits with your doctor if you are pregnant or planning to become pregnant.

It is not known whether Fidaxomicin passes into breast milk. Talk to your doctor before breastfeeding while taking Dificid.

People with Liver or Kidney Problems

Because Dificid is minimally absorbed systemically and works primarily in the gut, dose adjustments are generally not needed for patients with liver or kidney impairment. However, always inform your doctor about any pre-existing conditions.

How to Manage Side Effects

Here are practical tips for managing the most common Dificid side effects:

• For nausea: Take Dificid with food. Eat smaller, more frequent meals. Avoid greasy or spicy foods during treatment.
• For vomiting: If you vomit within an hour of taking a dose, contact your doctor about whether to retake it. Stay hydrated with clear fluids.
• For abdominal pain and bloating: Gentle heat (a warm compress) can help. Avoid carbonated drinks and gas-producing foods like beans and broccoli.
• For constipation: As diarrhea resolves, increase your water intake and eat fiber-rich foods gradually. Do not take over-the-counter anti-diarrheal medications (like Loperamide/Imodium) without your doctor's approval — these can worsen C. diff.
• For headache: Over-the-counter Acetaminophen (Tylenol) is generally safe. Avoid NSAIDs like Ibuprofen if you have active GI issues.
• Stay hydrated: C. diff-related diarrhea can cause significant fluid loss. Drink plenty of water, broth, or electrolyte solutions throughout your treatment.

Important: Do not stop taking Dificid early, even if you start feeling better. Completing the full 10-day course is essential to clear the infection and reduce the risk of recurrence. If side effects become intolerable, talk to your doctor before making any changes.

When to Call Your Doctor

Contact your healthcare provider right away if you experience:

• Signs of an allergic reaction (swelling, hives, difficulty breathing)
• Bloody or black, tarry stools
• Severe abdominal pain
• High fever (above 101°F / 38.3°C)
• Diarrhea that worsens or doesn't improve after 2-3 days of treatment
• Signs of severe dehydration (dizziness, dark urine, rapid heartbeat)
• Any symptom that concerns you

Final Thoughts

Dificid is one of the most effective treatments available for C. diff infections, and most people tolerate it well. The most common side effects — nausea, abdominal discomfort, and bloating — are usually mild and temporary. Serious allergic reactions are rare but require immediate attention.

If you're worried about side effects, talk to your doctor. The benefits of treating a C. diff infection with Dificid almost always outweigh the risks of leaving the infection untreated.

Need help finding Dificid at a pharmacy near you? Use Medfinder to check stock and compare prices. You can also learn about ways to save money on Dificid and explore how Dificid works to understand why your doctor chose it for your treatment.