Zotrim

Side Effects
Interactions

SIDE EFFECTS

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

FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, OTHER BLOOD DYSCRASIAS AND HYPERSENSITIVITY OF THE RESPIRATORY TRACT (see WARNINGS section).

Phenazopyridine Hydrochloride: Headache, rash and occasional gastrointestinal disturbance. An anaphylactoid-like reaction has been described.

Methemoglobinemia, hemolytic anemia, renal and hepatic toxicity have been described, usually at overdosage levels (see OVERDOSAGE section).

Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.

Allergic: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schonlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa, and systemic lupus erythematosus have been reported.

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, and crystalluria.

Metabolic: Hyperkalemia, hyponatremia.

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 rarely in patients receiving sulfonamides.

Musculoskeletal: Arthralgia and myalgia.

Respiratory System: Cough, shortness of breath, and pulmonary infiltrates (see WARNINGS section).

Miscellaneous: Weakness, fatigue, insomnia.

Read the Zotrim (sulfamethoxazole, trimethoprim, phenazopyridine) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

In elderly patients concurrently receiving trimethoprim/sulfamethoxazole and certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. It has been reported that trimethoprim/sulfamethoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when trimethoprim/sulfamethoxazole is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

Trimethoprim/sulfamethoxazole may inhibit the hepatic metabolism of phenytoin.

Sulfamethoxazole/trimethoprim, 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.

Sulfonamides can also displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations.

Interaction between Trimethoprim/sulfamethoxazole and Phenazopyridine Hydrochloride

In a prospective two-way crossover drug interaction study between trimethoprim/ sulfamethoxazole double strength and phenazopyridine hydrochloride (200 mg) administered first singly, then in combination to 12 healthy female subjects for three days, it was determined that plasma concentrations of trimethoprim, sulfamethoxazole, and phenazopyridine hydrochloride were significantly increased compared to when either drug product was administered alone (see CLINICAL PHARMACOLOGY section). Some laboratory values were altered when phenazopyridine hydrochloride was administered concomitantly with trimethoprim/sulfamethoxazole. No values fell outside the normal range. The clinical significance of these changes is unknown.

CHANGES* IN HEMATOLOGY AND CLINICAL CHEMISTRY PARAMETERS BETWEEN SINGLE TREATMENT TRIMETHOPRIM/SULFAMETHOXAZOLE OR PHENAZOPYRIDINE (TMP/SMX OR PZP) AND COMBINATION TREATMENT TMP/SMX AND PZP (N=12)

Parameter

Baseline= (SD)

PZP given alone= (SD)

TMP/SMX alone= (SD)

TMP/SMX and PZP In combination= (SD)

Normal Values

HEMATOLOGY

 

Hemoglobin (gm/dL)

13.8 (1.0)

13.0 (0.8)

13.1 (0.9)

12.7 (0.9)

11.0-15.0

WBC (x103/mL)

7.0 (1.8)

8.1 (2.6)

7.7 (2.1)

7.2 (2.0)

4.0-10.0

CLINICAL CHEMISTRY

Creatinine (mg/dL)

0.9 (0.2)

0.9 (0.1)

1.0 (0.1)

1.1 (0.2)

0.5-1.4

Total Bilirubin mg/dL)

0.7 (0.2)

0.6 (0.2)

0.5 (0.1)

0.6 (0.2)

0.2-1.2

Direct Bilirubin (mg/dL)

0.3 (0.1)

0.1 (0.1)

0.3 (0.0)

0.3 (0.2)

0.0-0.3

Indirect Bilirubin (mg/dL)

0.4 (0.2)

0.7 (0.3)

0.17 (0.1)

0.8 (0.3)

0.0-1.1

SGOT (U/L)

24.2 (4.2)

25.3 (7.0)

24.8 (4.2)

27.2 (8.6)

14-36

SGPT (U/L)

31.3 (6.7)

31.3 (11.7)

32.8 (9.6)

34.1 (14.1)

11-56

Alkaline Phosphatase (U/L)

80.7 (19.1)

86.2 (15.4)

83.2 (15.9)

86.8 (16.4)

38-126

*Changes from baseline are statistically significant (p<0.05) unless otherwise noted = Mean values

Changes from baselines are not statistically significant

Drug/Laboratory Test Interactions

Due to its properties as an azo dye, phenazopyridine hydrochloride may interfere with urinalysis based on spectrometry or color reactions.

Sulfamethoxazole/Trimethoprim, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive binding protein technique (CBPA) when bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by radioimmunoassay (RIA). The presence of trimethoprim and sulfamethoxazole may also interfere with the Jaffe alkaline picrate reaction assay for creatinine, resulting in overestimation of about 10% in the range of normal values.

Last reviewed on RxList: 1/28/2005
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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