What are the side effects of Bactrim (Trimethoprim/Sulfamethoxazole)?

From the Guidelines

Bactrim can cause several side effects, including gastrointestinal adverse effects, hypersensitivity skin reactions, and rarely, severe conditions like Stevens-Johnson syndrome and hepatic necrosis, as reported in a 2005 CDC guideline 1. The side effects of Bactrim (sulfamethoxazole-trimethoprim) can range from common to severe. Common side effects include:

• Nausea
• Vomiting
• Loss of appetite
• Skin rash Some people may experience:
• Headaches
• Dizziness
• Lethargy Bactrim may also cause photosensitivity, making the skin more sensitive to sunlight, so using sunscreen and protective clothing is recommended during treatment. More serious but less common side effects include:
• Severe skin reactions like Stevens-Johnson syndrome
• Blood disorders such as decreased white blood cell or platelet counts
• Liver or kidney problems
• Severe allergic reactions Bactrim can also cause electrolyte imbalances, particularly affecting potassium levels. It is essential to note that Bactrim is contraindicated in patients with known hypersensitivity to trimethoprim or sulfonamides, and should be prescribed with caution to patients with impaired hepatic and renal functions, folate deficiency, blood dyscrasias, and in older adults, as stated in the 2005 CDC guideline 1. If you experience severe skin rash, difficulty breathing, unusual bleeding or bruising, yellowing of the skin or eyes, or severe diarrhea while taking Bactrim, seek medical attention immediately. People with kidney or liver disease, folate deficiency, G6PD deficiency, or allergies to sulfa drugs should use Bactrim with caution or avoid it altogether, as the 2005 CDC guideline 1 and other studies, such as the 2020 guideline for antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation 1, suggest.

From the FDA Drug Label

Adverse Reactions The following adverse reactions associated with the use of sulfamethoxazole and trimethoprim were identified in clinical trials, post-marketing or published reports. 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 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, 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. Cross-sensitivity may exist with these agents Diuresis and hypoglycemia have occurred. 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 Bactrim include:

• Gastrointestinal disturbances such as nausea, vomiting, anorexia
• Allergic skin reactions such as rash and urticaria
• Severe cutaneous adverse reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis
• Hematologic reactions such as agranulocytosis, aplastic anemia, and thrombocytopenia
• Allergic reactions such as anaphylaxis and serum sickness-like syndrome
• Gastrointestinal reactions such as hepatitis, pseudomembranous enterocolitis, and pancreatitis
• Genitourinary reactions such as renal failure and interstitial nephritis
• Metabolic and nutritional reactions such as hyperkalemia and metabolic acidosis
• Neurologic reactions such as aseptic meningitis and convulsions
• Psychiatric reactions such as hallucinations and depression
• Endocrine reactions such as diuresis and hypoglycemia
• Musculoskeletal reactions such as arthralgia and myalgia
• Respiratory reactions such as cough and shortness of breath
• Cardiovascular reactions such as QT prolongation and circulatory shock
• Miscellaneous reactions such as weakness, fatigue, and insomnia 2

From the Research

Side Effects of Bactrim

Bactrim, also known as trimethoprim-sulfamethoxazole, is a commonly prescribed antibiotic. However, it can cause several side effects, including:

• Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis 3, 4, 5, 6
• Rash, with a nearly 3-fold higher risk compared to other antibiotics 4
• Drug reaction with eosinophilia and systemic symptoms, with a 10-fold increase in reports compared to azithromycin 4
• Pancytopenia, neutropenia, thrombocytopenia, and aplastic anaemia, with a 10-fold, 6-fold, 4-fold, and 4-fold increase in reports, respectively 4
• Hyperkalaemia and hyponatraemia, with a 56-fold and 10-fold increase in reports, respectively 4
• Ocular complications, including labial adhesions and persistent skin dyspigmentation 6, 7

Specific Studies

Several studies have investigated the side effects of Bactrim:

• A case report published in the Journal of the American Podiatric Medical Association described a 61-year-old man who developed Stevens-Johnson syndrome and toxic epidermal necrolysis after taking trimethoprim-sulfamethoxazole for a peripherally inserted central catheter infection 3
• A systematic review and meta-analysis published in the British Journal of Clinical Pharmacology found that sulfamethoxazole-trimethoprim had a higher risk of adverse drug events, including rash and Stevens-Johnson syndrome, compared to other antibiotics 4
• A pharmacovigilance study published in the International Journal of Antimicrobial Agents found that sulfamethoxazole-trimethoprim was associated with a higher risk of Stevens-Johnson syndrome and toxic epidermal necrolysis compared to other antibiotics 5
• A retrospective review published in Pediatric Dermatology found that sulfamethoxazole-trimethoprim was a common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in children 6
• A study published in The Ocular Surface found that patients with lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis had worse chronic ocular complications compared to those with trimethoprim-sulfamethoxazole-induced Stevens-Johnson syndrome/toxic epidermal necrolysis 7