Side Effects of Bactrim (sulfamethoxazole and trimethoprim)

Bactrim (sulfamethoxazole and trimethoprim) is a combination of antibiotics used to treat infections due to susceptible bacteria. Examples include urinary tract infections, flares of chronic bronchitis due to bacteria, middle ear infections, for prevention of infections due to pneumococcus in organ transplant recipients, for the treatment or prevention of Pneumocystis carinii pneumonia, chancroid, and prevention of toxoplasma encephalitis in patients with AIDS. 

Sulfamethoxazole is an anti-bacterial sulfonamide (a “sulfa” drug) that disrupts the production of dihydrofolic acid, while trimethoprim disrupts the production of tetrahydrofolic acid. Dihydrofolic acid and tetrahydrofolic acid are forms of folic acid that bacteria and human cells use for producing proteins. Trimethoprim inhibits production of tetrahydrofolic acid by inhibiting the enzyme responsible for making tetrahydrofolic acid from dihydrofolic acid. 

By combining both drugs, two important steps required in the production of bacterial proteins are interrupted, and the combination is more effective than either drug alone. 

Common side effects of Bactrim include:

• dizziness,
• headache,
• lethargy,
• diarrhea,
• loss of appetite,
• nausea,
• vomiting, and
• rash.

Serious side effects of Bactrim include:

• liver damage,
• low white blood cell count,
• low platelet count (thrombocytopenia), and
• anemia.

Drug interactions of Bactrim include warfarin, because Bactrim enhances its blood-thinning effects, possibly leading to bleeding. 

Sulfonamides such as sulfamethoxazole can add to the kidney damage caused by cyclosporines. All sulfonamides can crystallize in urine when the urine is acidic. Since methenamine causes an acidic urine, it should not be used with sulfonamides. 

Blood levels of phenytoin may be increased by treatment with Bactrim and can lead to dizziness and reduced attention. Bactrim also may increase blood levels of digoxin and possibly lead to serious toxic effects. 

Anemia can occur in persons receiving Bactrim in combination with divalproex, valproic acid, methotrexate, pyrimethamine, triamterene, or trimetrexate. 

Increased blood levels of potassium may occur when Bactrim is combined with ACE inhibitors. 

Use of sulfonamides may cause bilirubin to be displaced from proteins in the infant’s blood. Displacement of bilirubin can lead to jaundice and a dangerous condition called kernicterus in the infant. For this reason, Bactrim should not be used near term (late in pregnancy) among women. 

Bactrim should not be used by breastfeeding mothers because sulfamethoxazole is excreted in milk and can cause kernicterus. 

Common side effects of sulfamethoxazole/trimethoprim are:

• dizziness,
• headache,
• lethargy,
• diarrhea,
• anorexia,
• nausea,
• vomiting, and
• rash.

Other side effects include:

• liver damage,
• low white blood cell count,
• low platelet count (thrombocytopenia), and
• anemia.

The following serious adverse reactions are described elsewhere in the labeling:

• Embryo-fetal Toxicity
• Hypersensitivity and Other Fatal Reactions
• Thrombocytopenia
• Clostridium difficile-Associated Diarrhea
• Sulfite Sensitivity
• Risk Associated with Concurrent Use of Leucovorin for Pneumocystis jirovecii Pneumonia
• Infusion Reactions
• Hypoglycemia
• Electrolyte Abnormalities

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions are gastrointestinal disturbances (nausea, vomiting, and anorexia) and allergic skin reactions (such as rash and urticaria).

Local reaction, pain and slight irritation on intravenous (IV) administration are infrequent. Thrombophlebitis has been observed.

Table 3: Adverse Reactions Reported with Bactrim

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Bactrim. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• Thrombotic thrombocytopenia purpura
• Idiopathic thrombocytopenic purpura
• QT prolongation resulting in ventricular tachycardia and torsade de pointes

Potential For Bactrim To Affect Other Drugs

Trimethoprim is an inhibitor of CYP2C8 as well as OCT2 transporter. Sulfamethoxazole is an inhibitor of CYP2C9. Avoid coadministration of Bactrim with drugs that are substrates of CYP2C8 and 2C9 or OCT2.

Table 4: Drug Interactions with Bactrim

Interactions With Laboratory Or Diagnostic Testing

Bactrim, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive binding protein technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA).

The presence of Bactrim may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values.