What is 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:

Serious side effects of Bactrim include:

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

What are the important side effects of Bactrim (sulfamethoxazole and trimethoprim)?

Common side effects of sulfamethoxazole/trimethoprim are:

Other side effects include:

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

Bactrim (sulfamethoxazole and trimethoprim) side effects list for healthcare professionals

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

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

Body System Adverse Reactions
Hematologic
  • Agranulocytosis
  • Aplastic anemia
  • Thrombocytopenia
  • Leukopenia
  • Neutropenia
  • Hemolytic anemia
  • Megaloblastic anemia
  • Hypoprothrombinemia
  • Methemoglobinemia
  • Eosinophilia
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
  • Conjunctival and scleral injection
  • Photosensitivity
  • Pruritus
  • Urticaria
  • Rash
  • Periarteriitis nodosa
  • Systemic lupus erythematosus
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
  • Toxic nephrosis with oliguria and anuria
  • Crystalluria
Metabolic and Nutritional
  • Hyperkalemia
  • Hyponatremia
Neurologic
  • Aseptic meningitis
  • Convulsions
  • Peripheral neuritis
  • Ataxia
  • Vertigo
  • Tinnitus
  • Headache
Psychiatric
  • Hallucinations
  • Depression
  • Apathy
  • Nervousness
Endocrine
  • 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 in patients receiving sulfonamides)
Musculoskeletal
  • Arthralgia
  • Myalgia
  • Rhabdomyolysis
Respiratory
  • Cough
  • Shortness of breath
  • Pulmonary infiltrates
Miscellaneous
  • Weakness
  • Fatigue
  • Insomnia
Eye Disorders
  • Uveitis5

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:

What drugs interact with Bactrim (sulfamethoxazole and trimethoprim)?

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

Drug(s) Recommendation Comments
Diuretics Avoid concurrent use In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported.
Warfarin Monitor prothrombin time and INR It has been reported that Bactrim may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin (a CYP2C9 substrate). This interaction should be kept in mind when Bactrim is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.
Phenytoin Monitor serum phenytoin levels Bactrim may inhibit the hepatic metabolism of phenytoin (a CYP2C9 substrate). Bactrim, given at a common clinical dosage, increased the phenytoin half-life by 39% and decreased the phenytoin metabolic clearance rate by 27%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect.
Methotrexate Avoid concurrent use Sulfonamides can also displace methotrexate from plasma protein binding sites and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations.
Cyclosporine Avoid concurrent use There have been reports of marked but reversible nephrotoxicity with coadministration of Bactrim and cyclosporine in renal transplant recipients.
Digoxin Monitor serum digoxin levels Increased digoxin blood levels can occur with concomitant Bactrim therapy, especially in elderly patients
Indomethacin Avoid concurrent use Increased sulfamethoxazole blood levels may occur in patients who are also receiving indomethacin.
Pyrimethamine Avoid concurrent use Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses exceeding 25 mg weekly may develop megaloblastic anemia if Bactrim is prescribed.
Tricyclic Antidepressants (TCAs) Monitor therapeutic response and adjust dose of TCA accordingly The efficacy of tricyclic antidepressants can decrease when coadministered with Bactrim.
Oral hypoglycemics Monitor blood glucose more frequently Like other sulfonamide-containing drugs, Bactrim potentiates the effect of oral hypoglycemic that are metabolized by CYP2C8 (e.g., pioglitazone, repaglinide, and rosiglitazone) or CYP2C9 (e.g., glipizide and glyburide) or eliminated renally via OCT2 (e.g., metformin). Additional monitoring of blood glucose may be warranted.
Amantadine Avoid concurrent use In the literature, a single case of toxic delirium has been reported after concomitant intake of Bactrim and amantadine (an OCT2 substrate). Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported.
Angiotensin Converting Enzyme Inhibitors Avoid concurrent use In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of Bactrim and an angiotensin converting enzyme inhibitor.6,7
Zidovudine Monitor for hematologic toxicity Zidovudine and Bactrim are known to induce hematological abnormalities. Hence, there is potential for an additive myelotoxicity when coadministered.8
Dofetilide Concurrent administration is contraindicated Elevated plasma concentrations of dofetilide have been reported following concurrent administration of trimethoprim and dofetilide. Increased plasma concentrations of dofetilide may cause serious ventricular arrhythmias associated with QT interval prolongation, including torsade de pointes.2,3
Procainamide Closely monitor for clinical and ECG signs of procainamide toxicity and/or procainamide plasma concentration if available Trimethoprim increases the plasma concentrations of procainamide and its active N-acetyl metabolite (NAPA) when trimethoprim and procainamide are coadministered. The increased procainamide and NAPA plasma concentrations that resulted from the pharmacokinetic interaction with trimethoprim are associated with further prolongation of the QTc interval.9

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.

Summary

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. 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. 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.

Treatment & Diagnosis

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Medically Reviewed on 5/8/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.

2. Al-Khatib SM, LaPointe N, Kramer JM, Califf RM. What Clinicians Should Know About the QT Interval. JAMA. 2003;289(16):2120-2127.

3. Boyer EW, Stork C, Wang RY. Review: The Pharmacology and Toxicology of Dofetilide. Int J Med Toxicol. 2001;4(2):16.

5. London NJ, Garg SJ, Moorthy RS, Cunningham ET. Drug-induced uveitis. J Ophthalmic Inflamm Infect. 2013;3:43.

6. Marinella MA. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol. 1999;45:209–212.

7. Margassery S, Bastani B. Life threatening hyperkalemia and acidosis secondary to trimethoprimsulfamethoxazole treatment. J. Nephrol. 2001;14(5):410-414.

8. Moh R, et al. Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d’Ivoire. Antivir Ther. 2005;10(5):615-24.

9. Kosoglou T, Rocci ML Jr, Vlasses PH. Trimethoprim alters the disposition of procainamide and Nacetylprocainamide. Clin Pharmacol Ther. Oct 1988;44(4):467-77.
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