What are the side effects of Co-trimoxazole (Trimethoprim-Sulfamethoxazole)?

From the Guidelines

Co-trimoxazole can cause several side effects, including common and mild effects like nausea, vomiting, and skin rashes, as well as rare but serious effects like severe skin reactions, kidney problems, and liver inflammation, as reported in various studies 1.

Common Side Effects

• Nausea and vomiting
• Loss of appetite
• Skin rashes
• Headaches
• Dizziness or lethargy
• Gastrointestinal disturbances like diarrhea

Serious Side Effects

• Photosensitivity (increased sensitivity to sunlight)
• Allergic skin reactions
• Blood disorders such as reduced white blood cell or platelet counts
• Severe skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis
• Kidney problems, particularly in patients with pre-existing kidney disease or dehydration
• Liver inflammation

Special Considerations

• Elderly patients and those with HIV/AIDS may experience side effects more frequently 1.
• Patients should seek immediate medical attention if they develop fever, sore throat, mouth sores, unusual bleeding or bruising, yellowing of the skin or eyes, or severe skin reactions 1.
• Co-trimoxazole can interact with other medications, such as methotrexate, and increase the risk of adverse effects 1.
• The medication can also contribute to the development of antibiotic resistance, which is a significant public health concern 1.

From the FDA Drug Label

The most common adverse reactions are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria) Fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura Allergic/Immune Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, rash, periarteritis nodosa, hemophagocytic lymphohistiocytosis (HLH), systemic lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized erythematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND) Gastrointestinal: Hepatitis, (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, renal insufficiency, oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine. Metabolic and Nutritional: Hyperkalemia, hyponatremia, metabolic acidosis Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache. Psychiatric: Hallucinations, depression, apathy, nervousness. Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Musculoskeletal: Arthralgia, myalgia, rhabdomyolysis. Respiratory: Cough, shortness of breath and pulmonary infiltrates, acute eosinophilic pneumonia, acute and delayed lung injury, interstitial lung disease, acute respiratory failure Cardiovascular System: QT prolongation resulting in ventricular tachycardia and torsades de pointes, circulatory shock Miscellaneous: Weakness, fatigue, insomnia.

The side effects of co-trimoxazole include:

• Gastrointestinal disturbances: nausea, vomiting, anorexia
• Allergic skin reactions: rash, urticaria
• Severe cutaneous adverse reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP, AFND
• Hematologic reactions: agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia
• Allergic/Immune Reactions: anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema
• Gastrointestinal reactions: hepatitis, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis
• Genitourinary reactions: renal failure, interstitial nephritis, BUN and serum creatinine elevation
• Metabolic and Nutritional reactions: hyperkalemia, hyponatremia, metabolic acidosis
• Neurologic reactions: aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache
• Psychiatric reactions: hallucinations, depression, apathy, nervousness
• Musculoskeletal reactions: arthralgia, myalgia, rhabdomyolysis
• Respiratory reactions: cough, shortness of breath, pulmonary infiltrates, acute eosinophilic pneumonia
• Cardiovascular System reactions: QT prolongation, ventricular tachycardia, torsades de pointes, circulatory shock
• Miscellaneous reactions: weakness, fatigue, insomnia 2

From the Research

Side Effects of Co-Trimoxazole

The side effects of co-trimoxazole are a combination of the adverse event profiles of sulphonamide and trimethoprim 3. Some of the common side effects include:

• Skin rashes characteristic of sulfonamide sensitivity
• Hematologic adverse reactions, such as those related to the action of trimethoprim on human folate metabolism 4
• Exfoliative skin rashes, although rare 4

Comparison with Trimethoprim

Studies have shown that using trimethoprim alone can reduce the incidence and potential severity of adverse events compared to co-trimoxazole 3. Additionally, patient compliance is greater with trimethoprim due to its simpler dosage regimen 5.

• Trimethoprim has been found to have equivalent effectiveness to co-trimoxazole in controlling symptoms of acute lower urinary tract infections 5
• Side-effects are more frequent with co-trimoxazole, although the difference is not significant 5

Long-term Therapy

Long-term administration of co-trimoxazole does not seem to represent an additional hazard, provided the dose is correct and hematologic monitoring is performed regularly 4.

• The suggestion that co-trimoxazole has a toxic effect on the kidney has not been substantiated 4