Side Effects of Gantanol (sulfamethoxazole)

Gantanol (sulfamethoxazole) is an anti-bacterial sulfonamide used to treat bacterial infections such as urinary tract infections (UTIs), meningitis, ear infections, and eye infections. It prevents the formation of dihydrofolic acid, a compound that bacteria must be able to make in order to survive. 

Although it was once a very useful antibiotic, it is almost obsolete as a single agent today due to the development of bacterial resistance to its effects. Sulfamethoxazole is now used primarily in combination with trimethoprim (Bactrim or Septra). According to the FDA database, all brand and generic formulations of sulfamethoxazole have been discontinued. 

Common side effects of Gantanol include:

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

Serious side effects of Gantanol include:

• severe skin rash [including Stevens-Johnson syndrome (aching joints and muscles; redness, blistering, and peeling of the skin)];
• toxic epidermal necrolysis (difficulty in swallowing; peeling, redness, loosening, and blistering of the skin),
• liver damage,
• low white blood cell count,
• low platelet count (thrombocytopenia),
• anemia, and
• crystals in the urine which may damage the kidney and cause bleeding into the urine. 

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

Sulfonamides such as sulfamethoxazole can increase the metabolism of cyclosporine, causing loss of effectiveness of cyclosporine, and can add to the kidney damage caused by cyclosporine. All sulfonamides can crystallize in urine when the urine is acidic. 

Since methenamine causes an acidic urine, it should not be used with sulfonamides. The effects of the sulfonamide class of antibiotics on the fetus have not been adequately studied. Physicians may use them if the benefits are deemed to outweigh potential risks. 

Use of sulfonamides near term may cause bilirubin to be displaced from proteins in the infant's blood. Displacement of bilirubin can lead to a dangerous condition called kernicterus in which the bilirubin damages the brain. For this reason, sulfonamides should not be used near term birth. 

Gantanol is excreted in breast milk and should not be used in women who are breastfeeding. Sulfonamides can cause kernicterus in nursing newborns.

Common side effects of sulfamethoxazole are:

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

Sulfamethoxazole should be stopped at the first appearance of a skin rash since the rash may become severe.

Serious rashes include:

• Stevens-Johnson syndrome (aching joints and muscles; redness, blistering, and peeling of the skin);
• toxic epidermal necrolysis (difficulty in swallowing; peeling, redness, loosening, and blistering of the skin).

Sulfamethoxazole therapy also can cause extensive sunburn, following exposure to sunlight. Patients receiving sulfamethoxazole should avoid excessive exposure to sunlight and should wear sunscreen.

Other important rare side effects include:

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

Sulfamethoxazole may form crystals in the urine which may damage the kidney and cause bleeding into the urine. It is important to drink additional liquids during sulfonamide therapy to prevent these side effects.

Included in the listing that follows are adverse reactions that have not been reported with this specific drug; however, the pharmacologic similarities among the sulfonamides require that each of the reactions be considered with Gantanol (sulfamethoxazole) administration.

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

Allergic Reactions: Anaphylaxis, allergic myocarditis, serum sickness, conjunctival and scleral injection, generalized allergic reactions. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported.

Dermatologic: Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis, photosensitivity, pruritus, urticaria, rash, generalized skin eruptions.

Gastrointestinal: Hepatitis, hepatocellular necrosis, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.

Genitourinary: Creatinine elevation, toxic nephrosis with oliguria and anuria. The frequency of renal complications is considerably lower in patients receiving the more soluble sulfonamides.

Neurologic: Convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.

Psychiatric: Hallucinations, depression, apathy.

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, myalgia.

Respiratory: Pulmonary infiltrates.

Miscellaneous: Edema (including periorbital), pyrexia, chills, weakness, fatigue, insomnia.

In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombopenia with purpura has been reported.

It has been reported that sulfamethoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when Gantanol (sulfamethoxazole) is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

Sulfamethoxazole may inhibit the hepatic metabolism of phenytoin. At a 1.6-g dose, sulfamethoxazole produced a slight but significant increase in the half-life of phenytoin but did not produce a corresponding decrease in the metabolic clearance rate. 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.

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