Sulfamethoxazole Trimethoprim Risks, Warnings, and Complications

FETAL TOXICITY: Research has shown that use of sulfamethoxazole and trimethoprim during pregnancy can increase the risk of congenital malformations (birth defects), including neural tube defects, heart and blood vessel defects, urinary tract defects, cleft palate and cleft lip, and club foot. 

Before starting treatment with sulfamethoxazole and trimethoprim, tell your doctor if you are pregnant. Call your doctor immediately if you get pregnant while on this medicine. 

SERIOUS SKIN REACTIONS: Rare but potentially fatal hypersensitivity reactions have occurred in people who took sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), fulminant hepatic necrosis (rapid liver damage), agranulocytosis (low white blood cells), aplastic anemia (bone marrow suppression), and other dyscrasias (diseases of the blood, bone marrow, and lymph tissue).

Stop taking sulfamethoxazole and trimethoprim and seek emergency medical attention at the first sign of a drug reaction, including a skin rash, hives, itching, peeling, blistering, swelling, sore throat, fever, joint pain, pale skin, red or purple discoloration of the skin, yellowing of the eyes or skin (jaundice), cough, or shortness of breath, which can all be signs of serious allergic reactions.

THROMBOCYTOPENIA: There are reports of severe, even life-threatening, thrombocytopenia (low platelets) in people who took sulfamethoxazole and trimethoprim. The thrombocytopenia usually resolves within a week of stopping treatment with sulfamethoxazole and trimethoprim.

Tell your doctor immediately if you have any unusual bleeding or bruising, petechiae (tiny red spots in your skin), or purpura (red or purple skin discoloration).

STREPTOCOCCAL INFECTIONS AND RHEUMATIC FEVER: Sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections. Antibiotics such as trimethoprim-sulfamethoxazole do not kill these bacteria and cannot prevent complications such as rheumatic fever.

CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA (CDAD): All antibiotics increase the risk of diarrhea caused by a bacterium called Clostridium difficile. Clostridium difficile associated diarrhea (CDAD) can range from mild diarrhea to fatal colitis. It occurs due to changes in the gut flora after treatment with antibiotics which allows C. difficile overgrowth. 

Seek immediate medical care if you develop severe watery, or bloody diarrhea up to 2 months or more after taking sulfamethoxazole and trimethoprim. Treatment for CDAD consists of stopping antibiotics that don’t kill C. difficile, starting antibiotic treatment for C. difficile, replacing fluids and electrolytes, and supplementing protein. 

ADJUNCTIVE TREATMENT WITH LEUCOVORIN FOR PNEUMOCYSTIS CARINII PNEUMONIA: A randomized placebo-controlled trial found that the use of sulfamethoxazole-trimethoprim concurrently with leucovorin for pneumocystis carinii pneumonia (now called pneumocystis jiroveci pneumonia) resulted in treatment failure and excess mortality in HIV-positive and AIDS patients. Therefore, co-administration of these two drugs for the treatment of Pneumocystis carinii pneumonia should be avoided.

HYPERKALEMIA (HIGH POTASSIUM): Trimethoprim can cause hyperkalemia (high potassium) in patients with potassium metabolism disorders or renal insufficiency (renal impairment or reduced kidney function). This complication can also occur in those taking other drugs that can cause hyperkalemia (high serum potassium levels), such as angiotensin-converting enzyme (ACE) inhibitors. 

Give your doctor a complete medical history and a list of medications. Your healthcare provider may want to closely monitor serum potassium levels if you are at risk of hyperkalemia.

DRUG INDUCED ASEPTIC MENINGITIS: Sulfamethoxazole trimethoprim can cause noninfectious drug-induced meningitis (inflammation of the meninges or membranes that cover the brain and spinal cord). Seek immediate medical care for signs of aseptic meningitis, such as fever, chills, headache, and neck stiffness.