DIFICLIR (Fidaxomicin)
Macrocyclic antibiotic for Clostridioides difficile infection (CDI)
DIFICLIR (fidaxomicin) is a macrocyclic antibiotic prescribed to treat Clostridioides difficile infection (CDI), a serious bacterial infection of the colon. Available as 200 mg film-coated tablets, fidaxomicin works by selectively killing C. difficile bacteria while preserving the normal intestinal microbiota. This narrow-spectrum activity distinguishes it from older CDI treatments and helps reduce the risk of recurrent infection. DIFICLIR is approved for adults, adolescents, and children weighing at least 12.5 kg.
Quick Facts
Key Takeaways
- DIFICLIR (fidaxomicin) is a targeted antibiotic specifically designed to treat Clostridioides difficile infection (CDI), available as 200 mg film-coated tablets taken twice daily for 10 days.
- Unlike broader-spectrum antibiotics, fidaxomicin selectively kills C. difficile while preserving the normal gut microbiota, which significantly reduces the risk of recurrent infection.
- Clinical trials show fidaxomicin reduces CDI recurrence rates to approximately 13% compared to 27% with vancomycin, making it a preferred option for patients at risk of recurrence.
- An extended-pulsed dosing regimen (days 1-5 twice daily, then every other day for days 7-25) may further reduce recurrence and is recommended in current guidelines.
- Common side effects are mild and include nausea, vomiting, and constipation. Patients allergic to macrolide antibiotics should consult their prescriber before use.
What Is DIFICLIR and What Is It Used For?
DIFICLIR contains the active substance fidaxomicin, a macrocyclic antibiotic that belongs to a distinct class of antibacterial agents. Unlike many other antibiotics, fidaxomicin has an exceptionally narrow spectrum of activity, meaning it primarily targets Clostridioides difficile and has minimal impact on the rest of the intestinal microbiome. This selectivity is crucial because disruption of the normal gut flora is a major risk factor for both the initial development and recurrence of CDI.
Clostridioides difficile infection is a serious condition that affects the lining of the large intestine (colon), causing symptoms ranging from mild diarrhea to severe, potentially life-threatening complications including pseudomembranous colitis, toxic megacolon, and colonic perforation. CDI is most commonly associated with prior antibiotic use, which disrupts the normal protective bacteria in the gut, allowing C. difficile to proliferate and produce toxins (toxin A and toxin B) that damage the intestinal mucosa.
DIFICLIR film-coated tablets are approved for use in adults, adolescents, and children weighing at least 12.5 kg. For patients weighing less than 12.5 kg, an oral suspension formulation is available, providing appropriate dosing for younger or smaller patients. The European Medicines Agency (EMA) granted marketing authorization for DIFICLIR across the European Union, and the drug is also available under the brand name Dificid in the United States.
How Does Fidaxomicin Work?
Fidaxomicin exerts its antibacterial effect by inhibiting bacterial RNA polymerase, the enzyme responsible for transcribing DNA into RNA. By blocking this critical step in bacterial protein synthesis, fidaxomicin prevents C. difficile from growing and reproducing. The drug is bactericidal, meaning it directly kills the bacteria rather than merely inhibiting their growth.
A key pharmacological advantage of fidaxomicin is its minimal systemic absorption. After oral administration, the drug remains largely within the gastrointestinal tract, achieving high local concentrations in the colon where C. difficile resides. Plasma concentrations of fidaxomicin are very low, which contributes to a favorable safety profile with few systemic side effects. Additionally, fidaxomicin inhibits C. difficile spore formation, which may contribute to its ability to reduce recurrence rates compared to other CDI treatments.
The narrow-spectrum activity of fidaxomicin has been extensively studied. Research published in the New England Journal of Medicine and other leading journals has demonstrated that fidaxomicin preserves key components of the gut microbiota, including Bacteroides species, while effectively eliminating C. difficile. This microbiome-sparing property is a fundamental advantage in CDI treatment, as a healthy microbiome provides colonization resistance against C. difficile reinfection.
What Should You Know Before Taking DIFICLIR?
Contraindications
DIFICLIR should not be used if you are allergic (hypersensitive) to fidaxomicin or to any of the other ingredients in the tablets. The excipients include microcrystalline cellulose, pregelatinized starch, hydroxypropyl cellulose, butylhydroxytoluene, sodium starch glycolate, and magnesium stearate. The film coating contains polyvinyl alcohol, titanium dioxide (E171), talc, polyethylene glycol, and lecithin (soy). Patients with a known allergy to soy should be aware of the soy lecithin content in the tablet coating.
If you have a known allergy to macrolide antibiotics (a class that includes erythromycin, clarithromycin, and azithromycin), inform your prescribing physician before starting DIFICLIR. Although fidaxomicin is structurally distinct from conventional macrolides, cross-sensitivity is a theoretical consideration, and your doctor will assess whether the medication is appropriate for you.
Warnings and Precautions
Discuss the following with your healthcare provider before starting DIFICLIR:
- Severe allergic reactions: In rare cases, serious allergic reactions have been reported, including difficulty breathing (dyspnea), swelling of the face or throat (angioedema), severe skin rash, severe itching (pruritus), and severe hives (urticaria). If you experience any of these symptoms, stop taking DIFICLIR immediately and seek emergency medical attention.
- Kidney or liver problems: If you have significant renal or hepatic impairment, your doctor will evaluate whether DIFICLIR is appropriate. There is limited clinical data on the use of fidaxomicin in patients with severe organ dysfunction, so careful monitoring may be necessary.
- Severe CDI (pseudomembranous colitis): Clinical trial data for fidaxomicin in the most severe forms of CDI, including fulminant colitis and toxic megacolon, are limited. Your physician will determine whether DIFICLIR is the most appropriate treatment based on the severity of your condition.
- Children under 12.5 kg: The film-coated tablet formulation should not be given to children weighing less than 12.5 kg. An oral suspension formulation of DIFICLIR is available for these patients, providing weight-appropriate dosing.
If you develop signs of a severe allergic reaction (difficulty breathing, facial or throat swelling, severe rash, or widespread hives), stop taking DIFICLIR immediately and contact emergency medical services or go to the nearest emergency department.
Pregnancy and Breastfeeding
DIFICLIR should not be taken during pregnancy unless your doctor determines that the benefit outweighs the potential risk to the unborn child. There is insufficient clinical data on the use of fidaxomicin in pregnant women, and animal reproductive toxicity studies have not demonstrated direct harmful effects but are not considered conclusive for human safety. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your healthcare provider before taking this medication.
It is not known whether fidaxomicin passes into human breast milk. However, given the drug's minimal systemic absorption after oral administration, significant transfer to breast milk is considered unlikely. Nevertheless, breastfeeding women should consult their physician before taking DIFICLIR, and a decision should be made whether to discontinue breastfeeding or to discontinue the medication, considering the importance of the treatment to the mother.
Driving and Operating Machinery
DIFICLIR is not expected to affect your ability to drive or operate machinery. No studies on the effects of fidaxomicin on driving performance have been conducted, but based on the pharmacological profile and known side effect profile, no impairment is anticipated.
DIFICLIR contains less than 1 mmol (23 mg) sodium per tablet, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
How Does DIFICLIR Interact with Other Drugs?
Fidaxomicin is a substrate and inhibitor of P-glycoprotein (P-gp), a membrane transport protein involved in the absorption, distribution, and excretion of many drugs. Blood levels of fidaxomicin may be increased when co-administered with potent P-gp inhibitors, and fidaxomicin itself may increase the blood levels of other P-gp substrates. Although fidaxomicin has minimal systemic absorption, the potential for clinically significant interactions exists, particularly in the gastrointestinal tract where drug concentrations are high.
The following table summarizes the known drug interactions with DIFICLIR. You should not take DIFICLIR in combination with any of these medications unless specifically directed by your physician:
| Drug | Drug Class | Interaction Type | Clinical Significance |
|---|---|---|---|
| Ciclosporin | Immunosuppressant | P-gp inhibitor; increases fidaxomicin levels | Avoid co-administration; may significantly increase fidaxomicin exposure |
| Ketoconazole | Antifungal | P-gp inhibitor; increases fidaxomicin levels | Avoid co-administration; monitor if no alternative |
| Erythromycin | Macrolide antibiotic | P-gp inhibitor; may alter fidaxomicin levels | Avoid co-administration; consult physician |
| Clarithromycin | Macrolide antibiotic | P-gp inhibitor; may alter fidaxomicin levels | Avoid co-administration; consult physician |
| Verapamil | Calcium channel blocker | P-gp inhibitor; may increase fidaxomicin levels | Avoid co-administration; monitor blood pressure |
| Dronedarone | Antiarrhythmic | P-gp inhibitor; may alter fidaxomicin levels | Avoid co-administration; cardiology review |
| Amiodarone | Antiarrhythmic | P-gp inhibitor; may alter fidaxomicin levels | Avoid co-administration; cardiology review |
| Dabigatran etexilate | Direct oral anticoagulant | P-gp substrate; fidaxomicin may increase dabigatran levels | Avoid co-administration; increased bleeding risk |
Always inform your healthcare provider and pharmacist about all prescription medications, over-the-counter drugs, herbal supplements, and vitamins you are currently taking or have recently taken. This information is essential for identifying potential interactions and ensuring the safe use of DIFICLIR.
The interaction between DIFICLIR and P-gp inhibitors is primarily of concern because it may lead to increased systemic exposure to fidaxomicin. While fidaxomicin has a favorable safety profile, significantly elevated blood levels could theoretically increase the risk of adverse effects. Your doctor will weigh the risks and benefits before prescribing DIFICLIR alongside any of the drugs listed above.
What Is the Correct Dosage of DIFICLIR?
Always take DIFICLIR exactly as prescribed by your doctor or pharmacist. Do not change the dose or duration of treatment without medical advice. The tablets should be swallowed whole with a glass of water. DIFICLIR can be taken before, during, or after meals, as food does not significantly affect its efficacy.
Adults, Adolescents, and Children (≥ 12.5 kg)
Standard Regimen (10 Days)
One 200 mg tablet taken twice daily (morning and evening, approximately every 12 hours) for a total of 10 days.
| Time | Day 1-10 |
|---|---|
| Morning | 200 mg (1 tablet) |
| Evening | 200 mg (1 tablet) |
Extended-Pulsed Regimen (25 Days)
Your doctor may prescribe an alternative extended-pulsed regimen, which has been shown to further reduce CDI recurrence rates. This regimen involves a higher-intensity initial phase followed by intermittent dosing:
| Phase | Days | Dosage |
|---|---|---|
| Initial phase | Days 1-5 | 200 mg twice daily (morning and evening) |
| Rest day | Day 6 | No tablet |
| Pulsed phase | Days 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 | 200 mg once daily (every other day) |
The extended-pulsed regimen was evaluated in the EXTEND study, which demonstrated a sustained clinical cure rate of approximately 70% compared to 59% with the standard 10-day regimen. This approach allows the normal gut microbiota to recover between doses, further strengthening colonization resistance against C. difficile.
Children Weighing Less Than 12.5 kg
Children weighing less than 12.5 kg should not take the film-coated tablet formulation, as these patients require a lower dose. DIFICLIR granules for oral suspension are available for this patient population and should be used according to the weight-based dosing instructions provided by the prescribing physician. The oral suspension may also be more appropriate for older children or patients who have difficulty swallowing tablets.
Elderly Patients
No dose adjustment is required for elderly patients. Clinical trials included a significant proportion of patients aged 65 years and older, and no clinically meaningful differences in safety or efficacy were observed in this population compared to younger adults. However, elderly patients may be at higher risk for CDI recurrence due to comorbidities and concurrent medications, and the extended-pulsed regimen may be particularly beneficial in this group.
Missed Dose
If you miss a dose of DIFICLIR, take it as soon as you remember. However, if it is nearly time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten one. Maintaining consistent dosing intervals is important for optimal treatment outcomes.
Overdose
If you have taken more tablets than prescribed, contact your doctor immediately or go to a hospital emergency department. Take the medicine packaging with you so the medical team can identify what you have taken. While no specific antidote exists for fidaxomicin overdose, the drug's minimal systemic absorption means that serious toxicity from oral overdose is considered unlikely. Treatment would be supportive and symptomatic.
Do not stop taking DIFICLIR before completing the full prescribed course, even if your symptoms improve. Stopping treatment early may allow the infection to return or worsen. If you are experiencing side effects that make it difficult to continue treatment, contact your healthcare provider for advice.
What Are the Side Effects of DIFICLIR?
Like all medicines, DIFICLIR can cause side effects, although not everyone experiences them. Most side effects associated with fidaxomicin are mild to moderate in severity and tend to resolve during or shortly after treatment. The side effects are categorized below by frequency, based on data from clinical trials and post-marketing surveillance.
Common
- Nausea
- Vomiting
- Constipation
Uncommon
- Decreased appetite
- Dizziness
- Headache
- Dry mouth
- Altered taste (dysgeusia)
- Abdominal bloating
- Flatulence (gas)
- Skin rash
- Itching (pruritus)
Not Known
- Swelling of face and throat (angioedema)
- Difficulty breathing (dyspnea)
Additional in Children and Adolescents
- Hives (urticaria)
Gastrointestinal Side Effects
The most frequently reported side effects of DIFICLIR are gastrointestinal in nature. Nausea and vomiting are the most common, occurring in up to 10% of patients in clinical trials. It is important to distinguish between gastrointestinal symptoms caused by the medication and those related to the underlying CDI, which itself causes significant diarrhea and abdominal discomfort. Constipation, while paradoxical in the context of CDI treatment, has been reported and may indicate resolution of the diarrheal illness.
Less commonly, patients may experience decreased appetite, dry mouth, taste disturbances (dysgeusia), abdominal bloating, and flatulence. These symptoms are generally mild and self-limiting, resolving without the need to discontinue treatment. If gastrointestinal symptoms are severe or persistent, patients should inform their healthcare provider.
Neurological Side Effects
Dizziness and headache have been reported uncommonly (in up to 1 in 100 patients). These side effects are typically mild and transient. If dizziness is experienced, patients should avoid driving or operating heavy machinery until symptoms resolve. There is no evidence of significant central nervous system effects from fidaxomicin, consistent with its minimal systemic absorption.
Skin and Allergic Reactions
Skin rash and itching (pruritus) have been reported uncommonly. In very rare cases, severe allergic reactions have been observed, including angioedema (swelling of the face and throat) and dyspnea (difficulty breathing). These reactions require immediate discontinuation of DIFICLIR and emergency medical treatment. In pediatric clinical studies, urticaria (hives) was additionally reported.
Stop taking DIFICLIR and seek emergency medical attention if you experience any of the following: difficulty breathing, swelling of the face, lips, tongue, or throat, severe skin rash or blistering, severe itching with widespread hives. These may be signs of a serious allergic reaction (anaphylaxis) that requires immediate treatment.
Reporting Side Effects
Reporting suspected adverse reactions after a medicine has been authorized is important for ongoing safety monitoring. Healthcare professionals and patients are encouraged to report any suspected side effects to their national pharmacovigilance authority. In the EU, reports can be submitted through the national reporting systems of each member state. In the UK, reports should be made through the Yellow Card Scheme. In the US, adverse events can be reported to the FDA's MedWatch program.
How Should You Store DIFICLIR?
Keep DIFICLIR tablets out of the sight and reach of children at all times. The tablets are supplied in perforated aluminum/aluminum unit-dose blisters, which provide protection from moisture and light. No special temperature storage conditions are required for this medication.
Do not use DIFICLIR after the expiry date stated on the carton and blister after "EXP." The expiry date refers to the last day of the stated month. Once a tablet has been removed from its blister, it should be taken promptly.
Unused medications should not be disposed of via wastewater or household waste. Return any unused or expired tablets to your pharmacist for safe disposal. These measures help to protect the environment and prevent accidental exposure to others.
What Does DIFICLIR Contain?
Active Ingredient
Each film-coated tablet contains 200 mg of fidaxomicin. Fidaxomicin is a fermentation product derived from the actinomycete Dactylosporangium aurantiacum, making it a natural product antibiotic.
Inactive Ingredients (Excipients)
Tablet core: Microcrystalline cellulose, pregelatinized starch, hydroxypropyl cellulose, butylhydroxytoluene (BHT), sodium starch glycolate, and magnesium stearate.
Film coating: Polyvinyl alcohol, titanium dioxide (E171), talc, polyethylene glycol, and lecithin (soy-derived).
The film coating of DIFICLIR tablets contains soy lecithin. Patients with known soy allergy should discuss this with their doctor, although allergic reactions to soy lecithin in pharmaceutical formulations are extremely rare due to the highly purified nature of the ingredient.
Tablet Appearance and Packaging
DIFICLIR 200 mg film-coated tablets are white to off-white, capsule-shaped, and debossed with "FDX" on one side and "200" on the other. The tablets are available in the following pack sizes:
- 20 × 1 film-coated tablets in perforated aluminum/aluminum unit-dose blisters
- 100 × 1 film-coated tablets in perforated aluminum/aluminum unit-dose blisters
Not all pack sizes may be marketed in every country. DIFICLIR is also available as granules for oral suspension, which is the recommended formulation for patients who weigh less than 12.5 kg or who have difficulty swallowing tablets.
Frequently Asked Questions About DIFICLIR
DIFICLIR (fidaxomicin) is a macrocyclic antibiotic used specifically to treat Clostridioides difficile infection (CDI), a serious bacterial infection of the colon that causes severe diarrhea, abdominal pain, and potentially life-threatening complications such as pseudomembranous colitis and toxic megacolon. It is approved for use in adults, adolescents, and children weighing at least 12.5 kg. Fidaxomicin selectively kills C. difficile bacteria while largely preserving the normal gut microbiota, which helps reduce the risk of recurrent infection.
DIFICLIR (fidaxomicin) and vancomycin are both used to treat CDI, but they differ in important ways. Fidaxomicin has a narrow spectrum of activity that selectively targets C. difficile while preserving the normal gut microbiota. Vancomycin, while effective against C. difficile, has broader antimicrobial activity that can disrupt the protective gut flora. In the pivotal MODIFY I and II clinical trials, fidaxomicin demonstrated similar initial cure rates to vancomycin but significantly lower recurrence rates (13% vs 27%). The IDSA/SHEA 2021 guidelines recommend fidaxomicin as a preferred treatment option, particularly for patients at risk of recurrent CDI.
The most common side effects of DIFICLIR (affecting up to 1 in 10 patients) include nausea, vomiting, and constipation. Less common side effects (affecting up to 1 in 100 patients) include decreased appetite, dizziness, headache, dry mouth, altered taste (dysgeusia), abdominal bloating, flatulence, skin rash, and itching. These side effects are generally mild to moderate and resolve during or shortly after treatment. Severe allergic reactions are very rare but require immediate medical attention.
Yes, DIFICLIR can be taken with or without food. The tablets should be swallowed whole with a glass of water, and food intake does not significantly affect the efficacy of fidaxomicin. Patients can take their doses at mealtimes or between meals, whichever is more convenient and helps them maintain a consistent dosing schedule (every 12 hours for the standard regimen).
DIFICLIR should not be taken during pregnancy unless the prescribing physician specifically determines that the benefit outweighs the potential risk, as there is insufficient data on fidaxomicin use in pregnant women. Regarding breastfeeding, it is not known whether fidaxomicin passes into breast milk, although it is considered unlikely due to the drug's minimal systemic absorption. Breastfeeding women should consult their healthcare provider before taking DIFICLIR to weigh the benefits of treatment against any potential risks.
The extended-pulsed regimen is an alternative dosing schedule for DIFICLIR that spans 25 days. It consists of an initial phase (days 1-5) where 200 mg is taken twice daily, followed by a rest day (day 6) with no tablet, and then a pulsed phase (days 7-25) where 200 mg is taken once daily on alternate days. This regimen was evaluated in the EXTEND clinical trial and showed improved sustained clinical cure rates (approximately 70%) compared to the standard 10-day regimen (59%). The intermittent dosing allows the normal gut microbiota to recover between doses, strengthening the body's natural defense against C. difficile recolonization.
References
This article is based on the following peer-reviewed sources and international guidelines:
- European Medicines Agency (EMA). DIFICLIR (fidaxomicin) - Summary of Product Characteristics. EMA EPAR - DIFICLIR. Last updated 2024.
- Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422-431. doi:10.1056/NEJMoa0910812.
- Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial (MODIFY II). Lancet Infect Dis. 2012;12(4):281-289. doi:10.1016/S1473-3099(11)70374-7.
- Guery B, Menichetti F, Anttila VJ, et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018;18(3):296-307. doi:10.1016/S1473-3099(17)30751-X.
- Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549.
- van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27 Suppl 2:S1-S21. doi:10.1016/j.cmi.2021.09.038.
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List, 2023. WHO Essential Medicines.
- British National Formulary (BNF). Fidaxomicin - Drug Monograph. National Institute for Health and Care Excellence (NICE). BNF - Fidaxomicin. Accessed 2025.
Medical Editorial Team
This article has been written and reviewed by qualified medical professionals following international guidelines and the GRADE evidence framework.
iMedic Medical Writers
Specialist physicians in infectious disease and clinical pharmacology with expertise in antimicrobial therapy and CDI management.
iMedic Medical Review Board
Board-certified physicians who independently verify all medical claims against current evidence and international guidelines (IDSA, ESCMID, WHO).
All medical content on iMedic.health is based on Evidence Level 1A (systematic reviews and meta-analyses of randomized controlled trials). We follow the GRADE evidence framework and adhere to international treatment guidelines. Our content receives no pharmaceutical funding and maintains complete editorial independence. Read our full editorial standards.