Sulfatrim

In the U.S.

• Bactrim
• Bactrim DS
• Septra
• Septra DS
• SMZ-TMP Pediatric
• Sulfatrim
• Sulfatrim Pediatric

In Canada

• Apo-Sulfatrim
• Novo-Trimel
• Nu-Cotrimox
• Septa Pediatric
• Septra Pediatric Suspension

Available Dosage Forms:

• Tablet
• Suspension

Therapeutic Class: Sulfonamide Combination

Pharmacologic Class: Folic Acid Antagonist

Chemical Class: Sulfonamide

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach pain
• black, tarry stools
• blistering, peeling, or loosening of the skin
• changes in skin color
• chest pain
• chills
• cough or hoarseness
• dark urine
• diarrhea
• dizziness
• fever with or without chills
• general feeling of tiredness or weakness
• headache
• itching
• joint or muscle pain
• light-colored stools
• loss of appetite
• lower back or side pain
• nausea
• pain, tenderness, or swelling of the foot or leg
• painful or difficult urination
• pale skin
• rash
• red skin lesions, often with a purple center
• red, irritated eyes
• shortness of breath
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• swollen or painful glands
• tightness in the chest
• unpleasant breath odor
• unusual bleeding or bruising
• vomiting of blood
• wheezing
• yellow eyes or skin

• Abdominal or stomach tenderness
• back, leg, or stomach pains
• bleeding gums
• blindness or vision changes
• blisters, hives, or itching
• bloating
• blood in the urine or stools
• bluish-colored lips, fingernails, or palms
• burning, crawling, itching, numbness, painful, prickling, "pins and needles", or tingling feelings
• burning of the face or mouth
• chest pain
• cloudy urine
• confusion
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• convulsions
• cracks in the skin
• decreased frequency or amount of urine
• diarrhea, watery and severe, which may also be bloody
• difficulty with breathing
• difficulty with swallowing
• fainting spells
• general body swelling
• general feeling of discomfort or illness
• hair loss
• hearing loss
• hives
• increased thirst
• indigestion
• irregular heartbeat
• large, flat, blue, or purplish patches in the skin
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of heat from the body
• muscle or joint pain
• nosebleeds
• not able to pass urine
• numbness or tingling in the hands, feet, or lips
• pain or burning while urinating
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• raised red swellings on the skin, the buttocks, legs, or ankles
• redness of the white part of the eyes
• redness, swelling, or soreness of the tongue
• sores, ulcers, or white spots on the lips or in the mouth
• soreness of the muscles
• stiff neck or back
• swelling of the face, hands, legs, and feet
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual weight loss
• weakness in the hands or feet
• weakness or heaviness of the legs
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Passing of gas

• Discouragement
• feeling of constant movement of self or surroundings
• feeling sad or empty
• increased sensitivity of the skin to sunlight
• irritability
• lack of feeling or emotion
• loss of interest or pleasure
• nervousness
• redness or other discoloration of the skin
• seeing, hearing, or feeling things that are not there
• sensation of spinning
• severe sunburn
• trouble concentrating
• trouble sleeping
• uncaring
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim oral suspension and other antibacterial drugs, sulfamethoxazole and trimethoprim oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of therapy.

Urinary Tract Infections

For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris. It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination.

Acute Otitis Media

For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents. To date, there are limited data on the safety of repeated use of sulfamethoxazole and trimethoprim in pediatric patients under two years of age. Sulfamethoxazole and trimethoprim is not indicated for prophylactic or prolonged administration in otitis media at any age.

Acute Exacerbations of Chronic Bronchitis in Adults

For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of a single antimicrobial agent.

Shigellosis

For the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei when antibacterial therapy is indicated.

Pneumocystis Carinii Pneumonia

For the treatment of documented Pneumocystis carinii pneumonia and for prophylaxis against Pneumocystis carinii pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing Pneumocystis carinii pneumonia.

Travelers' Diarrhea in Adults

For the treatment of travelers' diarrhea due to susceptible strains of enterotoxigenic E. coli.

Sulfamethoxazole and trimethoprim is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides, in patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides, and in patients with documented megaloblastic anemia due to folate deficiency. Sulfamethoxazole and trimethoprim is also contraindicated in pregnant patients and nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus. Sulfamethoxazole and trimethoprim oral suspension is contraindicated in pediatric patients less than 2 months of age. Sulfamethoxazole and trimethoprim is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.

General

Prescribing sulfamethoxazole and trimethoprim in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Sulfamethoxazole and trimethoprim oral suspension should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states) and to those with severe allergies or bronchial asthma. In glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. This reaction is frequently dose-related (see CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION).

Use in the Elderly

Cases of hypoglycemia in non-diabetic patients treated with sulfamethoxazole and trimethoprim are seen rarely, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of sulfamethoxazole and trimethoprim are particularly at risk.

Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid therapy.

Trimethoprim has been noted to impair phenylalanine metabolism, but this is of no significance in phenylketonuric patients on appropriate dietary restriction.

As with all drugs containing sulfonamides, caution is advisable in patients with porphyria or thyroid dysfunction.

Use in the Treatment of and Prophylaxis for Pneumocystis Carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS)

AIDS patients may not tolerate or respond to sulfamethoxazole and trimethoprim in the same manner as non-AIDS patients. The incidence of side effects, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with sulfamethoxazole and trimethoprim therapy in AIDS patients who are being treated for Pneumocystis carinii pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of sulfamethoxazole and trimethoprim in non-AIDS patients. The incidence of hyperkalemia appears to be increased in AIDS patients receiving sulfamethoxazole and trimethoprim. Adverse effects are generally less severe in patients receiving sulfamethoxazole and trimethoprim for prophylaxis. A history of mild intolerance to sulfamethoxazole and trimethoprim oral suspension in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis.6 However, if a patient develops skin rash or any sign of adverse reaction, therapy with sulfamethoxazole and trimethoprim should be reevaluated (see WARNINGS).

High dosage of trimethoprim, as used in patients with Pneumocystis carinii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.

During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.

Information for patients

Patients should be counseled that antibacterial drugs including sulfamethoxazole and trimethoprim oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When sulfamethoxazole and trimethoprim oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by sulfamethoxazole and trimethoprim oral suspension or other antibaceterial drugs in the future.

Patients should be instructed to maintain an adequate fluid intake in order to prevent crystalluria and stone formation.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with and without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Laboratory tests

Complete blood counts should be done frequently in patients receiving sulfamethoxazole and trimethoprim; if a significant reduction in the count of any formed blood element is noted, sulfamethoxazole and trimethoprim should be discontinued. Urinalyses with careful microscopic examination and renal function tests should be performed during therapy, particularly for those patients with impaired renal function.

Drug Interactions

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

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

Sulfamethoxazole and trimethoprim may inhibit the hepatic metabolism of phenytoin. Sulfamethoxazole and 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 and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations.

There have been reports of marked but reversible nephrotoxicity with coadministration of sulfamethoxazole and trimethoprim and cyclosporine in renal transplant recipients.

Increased digoxin blood levels can occur with concomitant sulfamethoxazole and trimethoprim therapy, especially in elderly patients. Serum digoxin levels should be monitored. Increased sulfamethoxazole blood levels may occur in patients who are also receiving indomethacin.

Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses exceeding 25 mg weekly may develop megaloblastic anemia if sulfamethoxazole and trimethoprim is prescribed.

The efficacy of tricyclic antidepressants can decrease when coadministered with sulfamethoxazole and trimethoprim.

Like other sulfonamide-containing drugs, sulfamethoxazole and trimethoprim potentiates the effect of oral hypoglycemics.

In the literature, a single case of toxic delirium has been reported after concomitant intake of sulfamethoxazole/trimethoprim and amantadine.

In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole/trimethoprim and an angiotensin converting enzyme inhibitor.7,8

Drug/Laboratory Test Interactions

Sulfamethoxazole and trimethoprim, 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 sulfamethoxazole and trimethoprim may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values.

Carcinogenesis, mutagenesis, impairment of fertility

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with sulfamethoxazole and trimethoprim.

Bacterial mutagenic studies have not been performed with sulfamethoxazole and trimethoprim in combination. Trimethoprim was demonstrated to be nonmutagenic in the Ames assay. No chromosomal damage was observed in human leukocytes cultured in vitro with sulfamethoxazole and trimethoprim alone or in combination; the concentrations used exceeded blood levels of these compounds following therapy with sulfamethoxazole and trimethoprim. Observations of leukocytes obtained from patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.

No adverse effects on fertility or general reproductive performance were observed in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim.

Pregnancy

Pregnancy Category C. In rats, oral doses of 533 mg/kg or 200 mg/kg produced teratologic effects manifested mainly as cleft palates.

The highest dose which did not cause cleft palates in rats was 512 mg/kg sulfamethoxazole or 192 mg/kg trimethoprim when administered separately. In two studies in rats, no teratology was observed when 512 mg/kg of sulfamethoxazole was used in combination with 128 mg/kg of trimethoprim. In one study, however, cleft palates were observed in one litter out of 9 when 355 mg/kg of sulfamethoxazole was used in combination with 88 mg/kg of trimethoprim.

In some rabbit studies, an overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with doses of trimethoprim 6 times the human therapeutic dose.

While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell,9 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or sulfamethoxazole and trimethoprim. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving sulfamethoxazole and trimethoprim. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter.

Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, sulfamethoxazole and trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

See CONTRAINDICATIONS section.

Nursing mothers

See CONTRAINDICATIONS section.

Pediatric use

Sulfamethoxazole and trimethoprim is not recommended for infants younger than 2 months of age (see INDICATIONS AND USAGE and CONTRAINDICATIONS section).

Geriatric use

Clinical studies of sulfamethoxazole and trimethoprim did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

There may be an increased risk of severe adverse reactions in elderly patients, particularly when complicating conditions exist, e.g., impaired kidney and/or liver function, possible folate deficiency, or concomitant use of other drugs. Severe skin reactions, generalized bone marrow suppression (see WARNINGSand ADVERSE REACTIONS sections), a specific decrease in platelets (with or without purpura), and hyperkalemia are the most frequently reported severe adverse reactions in elderly patients. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Increased digoxin blood levels can occur with concomitant sulfamethoxazole and trimethoprim therapy, especially in elderly patients. Serum digoxin levels should be monitored. Hematological changes indicative of folic acid deficiency may occur in elderly patients. These effects are reversible by folinic acid therapy. Appropriate dosage adjustments should be made for patients with impaired kidney function and duration of use should be as short as possible to minimize risks of undesired reactions (see DOSAGE AND ADMINISTRATION sections). The trimethoprim component of sulfamethoxazole and trimethoprim may cause hyperkalemia when administered to patients with underlying disorders of potassium metabolism, with renal insufficiency or when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors. Close monitoring of serum potassium is warranted in these patients. Discontinuation of sulfamethoxazole and trimethoprim treatment is recommended to help lower potassium serum levels.

Pharmacokinetics parameters for sulfamethoxazole were similar for geriatric subjects and younger adult subjects. The mean maximum serum trimethoprim concentration was higher and mean renal clearance of trimethoprim was lower in geriatric subjects compared with younger subjects  (see CLINICAL PHARMACOLOGY: Geriatric Pharmacokinetics).

1. Kremers P, Duvivier J, Heusghem C. Pharmacokinetic Studies of Co-Trimoxazole in Man after Single and Repeated Doses. J Clin Pharmacol. Feb-Mar 1974; 14:112–117.
2. Kaplan SA, et al. Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man. J Infect Dis. Nov 1973; 128 (Suppl): S547–S555.
3. Varoquaux O, et al. Pharmacokinetics of the trimethoprim-sulfamethoxazole combination in the elderly. Br J Clin Pharmacol. 1985;20:575–581.
4. Rudoy RC, Nelson JD, Haltalin KC. Antimicrobial Agents Chemother. May 1974;5:439–443.
5. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Fourth Edition. NCCLS Document M7–A4, Vol.17, No. 2, NCCLS, Wayne, PA, January, 1997.
6. Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327: 1842–1848.
7. Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol. 45:209–212.
8. Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment. J. Nephrol. 14:410–414.
9. Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis. Nov 1973; 128 (Suppl):S657–S663.
10. Masur H. Prevention and treatment of Pneumocystis pneumonia. N Engl J Med. 1992; 327: 1853–1880.
11. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR. 1992; 41(RR-4):1–11.
12. CDC Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR. 1991; 40(RR-2):1–13.

Manufactured for:

STI PHARMA LLC

Langhorne, PA 19047

Rev. 02/13

Applies to sulfamethoxazole / trimethoprim: oral suspension, oral tablet

Other dosage forms:

• intravenous solution

Along with its needed effects, sulfamethoxazole / trimethoprim may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking sulfamethoxazole / trimethoprim:

• Abdominal or stomach pain
• black, tarry stools
• blistering, peeling, or loosening of the skin
• changes in skin color
• chest pain
• chills
• cough or hoarseness
• dark urine
• diarrhea
• dizziness
• fever with or without chills
• general feeling of tiredness or weakness
• headache
• itching
• joint or muscle pain
• light-colored stools
• loss of appetite
• lower back or side pain
• nausea
• pain, tenderness, or swelling of the foot or leg
• painful or difficult urination
• pale skin
• rash
• red skin lesions, often with a purple center
• red, irritated eyes
• shortness of breath
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• swollen or painful glands
• tightness in the chest
• unpleasant breath odor
• unusual bleeding or bruising
• vomiting of blood
• wheezing
• yellow eyes or skin

• Abdominal or stomach tenderness
• back, leg, or stomach pains
• bleeding gums
• blindness or vision changes
• blisters, hives, or itching
• bloating
• blood in the urine or stools
• bluish-colored lips, fingernails, or palms
• burning, crawling, itching, numbness, painful, prickling, "pins and needles", or tingling feelings
• burning of the face or mouth
• chest pain
• cloudy urine
• confusion
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• convulsions
• cracks in the skin
• decreased frequency or amount of urine
• diarrhea, watery and severe, which may also be bloody
• difficulty with breathing
• difficulty with swallowing
• fainting spells
• general body swelling
• general feeling of discomfort or illness
• hair loss
• hearing loss
• hives
• increased thirst
• indigestion
• irregular heartbeat
• large, flat, blue, or purplish patches in the skin
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of heat from the body
• muscle or joint pain
• nosebleeds
• not able to pass urine
• numbness or tingling in the hands, feet, or lips
• pain or burning while urinating
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• raised red swellings on the skin, the buttocks, legs, or ankles
• redness of the white part of the eyes
• redness, swelling, or soreness of the tongue
• sores, ulcers, or white spots on the lips or in the mouth
• soreness of the muscles
• stiff neck or back
• swelling of the face, hands, legs, and feet
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual weight loss
• weakness in the hands or feet
• weakness or heaviness of the legs
• weight gain

Some side effects of sulfamethoxazole / trimethoprim may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Passing of gas

• Discouragement
• feeling of constant movement of self or surroundings
• feeling sad or empty
• increased sensitivity of the skin to sunlight
• irritability
• lack of feeling or emotion
• loss of interest or pleasure
• nervousness
• redness or other discoloration of the skin
• seeing, hearing, or feeling things that are not there
• sensation of spinning
• severe sunburn
• trouble concentrating
• trouble sleeping
• uncaring
• weight loss