Fosfomycin is an antibiotic used to treat uncomplicated urinary tract infections (UTIs), primarily available as an oral powder and sometimes administered intravenously for more serious infections. A single oral dose is generally effective and has a favorable safety profile, but all medications carry a risk of adverse reactions. An adverse reaction is an unintended, harmful response to a medication, and fosfomycin's effects can range from mild and common side effects to severe, rare complications. This article provides a detailed overview of the potential adverse reactions to fosfomycin, distinguishing between different formulations and severities.
Common Adverse Reactions
Most adverse reactions to oral fosfomycin are mild and typically affect the gastrointestinal system. These symptoms are often temporary and resolve on their own, especially with a single-dose treatment regimen.
- Gastrointestinal Issues: Diarrhea and nausea are the most frequently reported side effects. Patients may also experience abdominal pain, indigestion, or heartburn. Mild diarrhea is common and may be caused by the antibiotic's effect on gut bacteria.
- Headache and Dizziness: Headaches are a very common complaint, affecting a significant portion of patients. Dizziness is another possible side effect that can affect balance and coordination.
- Vaginal Discomfort: Vaginitis, vaginal itching, and unusual discharge are reported, likely due to the disruption of normal vaginal flora by the antibiotic.
- Other Mild Reactions: Other less common, mild adverse effects can include fatigue, weakness, rash, or a runny nose.
Severe Adverse Reactions
While less frequent, severe adverse reactions can occur and require immediate medical attention. These may be more common or pronounced with high-dose or intravenous fosfomycin.
- Hypersensitivity (Allergic) Reactions: Severe allergic reactions, including anaphylaxis, are possible with any antibiotic. Signs include hives, rash, severe itching, difficulty breathing, or swelling of the face, lips, tongue, or throat.
- Clostridioides difficile-Associated Diarrhea (CDAD): As with many antibiotics, fosfomycin can cause an overgrowth of harmful bacteria like C. difficile, leading to severe, watery, or bloody diarrhea. This can occur weeks or months after completing the course of medication and may require specific treatment.
- Hepatotoxicity (Liver Problems): Although rare, fosfomycin use can lead to liver injury, including hepatitis and elevated liver enzymes. Symptoms include yellowing of the skin or eyes (jaundice), dark urine, fatigue, and abdominal pain. These effects are generally reversible upon discontinuation of the drug.
- Hematologic Effects: Rare but serious hematologic adverse reactions can include aplastic anemia, a condition where the body stops producing enough new blood cells, or agranulocytosis, a severe drop in white blood cells.
- Electrolyte Imbalances (Intravenous Fosfomycin): The intravenous (IV) formulation of fosfomycin contains a high sodium load, which can lead to hypernatremia (high sodium levels) and hypokalemia (low potassium levels), particularly with prolonged use or in intensive care settings.
Comparison of Common vs. Severe Adverse Reactions
| Feature | Common Adverse Reactions | Severe Adverse Reactions |
|---|---|---|
| Incidence | High (e.g., diarrhea up to 10.4%) | Low (rare to very rare) |
| Symptom examples | Nausea, headache, dizziness, mild diarrhea, vaginal itching | Severe allergic reactions (anaphylaxis), C. difficile colitis, liver toxicity, blood count abnormalities |
| Timing | Typically occur during or shortly after treatment | Can appear during treatment or up to two months after stopping |
| Management | Often resolves on its own; symptomatic relief possible | Requires immediate medical attention; may involve drug discontinuation |
| Prognosis | Generally self-limiting and not dangerous | Potentially life-threatening, but reversible with prompt treatment |
Risk Factors and Considerations
While anyone taking fosfomycin can experience an adverse reaction, certain individuals may be at a higher risk.
- Kidney Disease: Since fosfomycin is primarily excreted by the kidneys, patients with significant renal impairment or on dialysis are at a higher risk of prolonged side effects due to the drug remaining in their system longer.
- Allergies: A history of allergic reactions to other antibiotics or medications increases the risk of a hypersensitivity reaction to fosfomycin.
- Infants and Children: The safety and effectiveness of fosfomycin have not been established in children under 12 years of age.
- Prolonged Use: While oral fosfomycin is a single-dose treatment, prolonged use for other types of infections (often with IV formulations) can increase the incidence of adverse events, including electrolyte disturbances and superinfections.
- Medication Interactions: Certain drugs, like metoclopramide, can affect how the body absorbs fosfomycin, potentially altering its effectiveness.
Conclusion
For most patients, oral fosfomycin is a safe and effective treatment for uncomplicated UTIs, with a low incidence of adverse effects. However, it is essential for patients to be aware of the potential for both common and severe reactions. Mild gastrointestinal upset, headaches, and vaginal discomfort are the most common issues and often pass quickly. Conversely, serious events like allergic reactions, severe diarrhea caused by C. difficile, and liver or blood disorders are rare but require immediate medical intervention. Communicating openly with a healthcare provider about any persistent or concerning symptoms is the best way to ensure safety and proper management while taking fosfomycin.
Further information on fosfomycin's mechanism of action and resistance can be found on the National Institutes of Health website.
