Yes

Antibiotic, Sulfonamide Derivative

Oral treatment of urinary tract infections due to E. coli, Klebsiella and Enterobacter sp, M. morganii, P. mirabilis and P. vulgaris; acute otitis media in children and acute exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or S. pneumoniae; prophylaxis of Pneumocystis carinii pneumonitis (PCP), traveler's diarrhea due to enterotoxigenic E. coli or Cyclospora

I.V. treatment or severe or complicated infections when oral therapy is not feasible, for documented PCP, empiric treatment of PCP in immune compromised patients; treatment of documented or suspected shigellosis, typhoid fever, Nocardia asteroides infection, or other infections caused by susceptible bacteria

Unlabeled use: Cholera and salmonella-type infections and nocardiosis; chronic prostatitis; as prophylaxis in neutropenic patients with P. carinii infections, in leukemics, and in patients following renal transplantation, to decrease incidence of gram-negative rod infections

C; D (if used near term, per expert analysis)

Do not use at term to avoid kernicterus in the newborn and use during pregnancy only if risks outweigh the benefits since folic acid metabolism may be affected

Hypersensitivity to any sulfa drug or any component; porphyria; megaloblastic anemia due to folate deficiency; infants <2 months of age; marked hepatic damage

Use with caution in patients with G-6-PD deficiency, impaired renal or hepatic function; maintain adequate hydration to prevent crystalluria; adjust dosage in patients with renal impairment. Injection vehicle contains benzyl alcohol and sodium metabisulfite. Fatalities associated with severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias; discontinue use at first sign of rash. Elderly patients appear at greater risk for more severe adverse reactions. May cause hypoglycemia, particularly in malnourished, or patients with renal or hepatic impairment. Use with caution in patients with porphyria or thyroid dysfunction. Slow acetylators may be more prone to adverse reactions.

>10%:

Dermatologic: Allergic skin reactions including rashes and urticaria, photosensitivity

Gastrointestinal: Nausea, vomiting, anorexia

1% to 10%:

Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)

Hematologic: Blood dyscrasias

Hepatic: Hepatitis

<1%: Confusion, depression, hallucinations, seizures, fever, ataxia, kernicterus in neonates, erythema multiforme, stomatitis, diarrhea, pseudomembranous colitis, pancytopenia, pancreatitis, rhabdomyolysis, thrombocytopenia, megaloblastic anemia, granulocytopenia, aplastic anemia, hemolysis (with G-6-PD deficiency), cholestatic jaundice, interstitial nephritis, serum sickness

Symptoms of acute overdose include nausea, vomiting, GI distress, hematuria, crystalluria

Following GI decontamination, treatment is supportive; adequate fluid intake is essential; peritoneal dialysis is not effective and hemodialysis only moderately effective in removing co-trimoxazole

CYP2C9 enzyme inhibitor

Increased effect/toxicity: Phenytoin, cyclosporines (nephrotoxicity), methotrexate (displaced from binding sites), dapsone, sulfonylureas, and oral anticoagulants; may compete for renal secretion of methotrexate; digoxin concentrations increased

Do not refrigerate injection; is less soluble in more alkaline pH; protect from light; do not use NS as a diluent; injection vehicle contains benzyl alcohol and sodium metabisulfite

5 mL/125 mL D₅W = 6 hours

5 mL/100 mL D₅W = 4 hours

5 mL/75 mL D₅W = 2 hours

Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid; trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway

Absorption: Oral: 90% to 100%

Distribution: Crosses the placenta; distributes widely into body tissues, breast milk, and fluids including middle ear fluid, prostatic fluid, bile, aqueous humor, and CSF

Protein binding: SMX: 68%; TMP: 68%

Metabolism: SMX is N-acetylated and glucuronidated; TMP is metabolized to oxide and hydroxylated metabolites

Half-life: SMX: 9 hours; TMP: 6-17 hours, both are prolonged in renal failure

Time to peak serum concentration: Within 1-4 hours

Elimination: In urine as metabolites and unchanged drug

Dosage recommendations are based on the trimethoprim component

Mild to moderate infections: Oral, I.V.: 8 mg TMP/kg/day in divided doses every 12 hours

Serious infection/ Pneumocystis: I.V.: 20 mg TMP/kg/day in divided doses every 6 hours

Urinary tract infection prophylaxis: Oral: 2 mg TMP/kg/dose daily

Prophylaxis of Pneumocystis: Oral, I.V.: 10 mg TMP/kg/day or 150 mg TMP/m²/day in divided doses every 12 hours for 3 days/week; dose should not exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole 3 days/week

Adults:

Urinary tract infection/chronic bronchitis: Oral: 1 double strength tablet every 12 hours for 10-14 days

Sepsis: I.V.: 20 TMP/kg/day divided every 6 hours

Pneumocystis carinii:

Prophylaxis: Oral: 1 double strength tablet daily or 3 times/week

Treatment: Oral, I.V.: 15-20 mg TMP/kg/day in 3-4 divided doses

Dosing adjustment in renal impairment: Adults:

I.V.:

Cl_cr 15-30 mL/minute: Administer 2.5-5 mg/kg every 12 hours

Cl_cr <15 mL/minute: Administer 2.5-5 mg/kg every 24 hours

Oral:

Cl_cr 15-30 mL/minute: Administer 1 double strength tablet every 24 hours or 1 single strength tablet every 12 hours

Cl_cr <15 mL/minute: Not recommended

Should be administered with a glass of water on empty stomach

creatinine (Jaffé alkaline picrate reaction); increased serum methotrexate by dihydrofolate reductase method

Rarely may cause depression, hallucination, or confusion; sulfonamides may cause euphoria, restlessness, irritability, disorientation, panic, and delusions

May rarely cause granulocytopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take oral medication with 8 oz of water on an empty stomach (1 hour before or 2 hours after meals) for best absorption. Finish all medication; do not skip doses. You may experience increased sensitivity to sunlight; use sunblock, wear protective clothing and dark glasses, or avoid direct exposure to sunlight. Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or vomiting. Report skin rash, sore throat, blackened stool, or unusual bruising or bleeding immediately. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Maintain adequate fluid intake to prevent crystalluria; infuse I.V. co-trimoxazole over 60-90 minutes; must be further diluted 1:25 (5 mL drug to 125 mL diluent, ie, D₅W); in patients who require fluid restriction, a 1:15 dilution (5 mL drug to 75 mL diluent, ie, D₅W) or a 1:10 dilution (5 mL drug to 50 mL diluent, ie, D₅W) can be administered

Monitor CBC, renal function test, liver function test, urinalysis

The 5:1 ratio (SMX to TMP) remains constant in all dosage forms:

Suspension, oral: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (20 mL, 100 mL, 150 mL, 200 mL, 480 mL)

Tablet: Sulfamethoxazole 400 mg and trimethoprim 80 mg

Tablet, double strength: Sulfamethoxazole 800 mg and trimethoprim 160 mg

"1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus. USPHS/IDSA Prevention of Opportunistic Working Group," MMWR Morb Mortal Wkly Rep, 1997, 46(RR-12):1-46.

Bissuel F, Cotte L, Crapanne JB, et al, "Trimethoprim-Sulphamethoxazole Rechallenge in 20 Previously Allergic HIV-Infected Patients After Homeopathic," AIDS, 1995, 9(4):407-8.

Cockerill FR and Edson RS, "Trimethoprim-Sulfamethoxazole," Mayo Clin Proc, 1991, 66(12):1260-9.

Cook DE and Ponte CD, "Suspected Trimethoprim/Sulfamethoxazole-Induced Hypoprothrombinemia," J Fam Pract, 1994, 39(6):589-91.

Dawkins B, Albury D, and Olsen TE, "Trimethoprim/Sulfamethoxazole-Induced Thrombocytopenia - A Case Report Supported by the Laboratory Diagnosis," Aust N Z J Med, 1995, 25:83.

Domingo P, Ferrer S, Cruz J, et al, "Trimethoprim-Sulfamethoxazole-Induced Renal Tubular Acidosis in a Patient With AIDS," Clin Infect Dis, 1995, 20(5):143, 45-7.

Fischl MA, Dickinson GM, and La Voie L, "Safety and Efficacy of Sulfamethoxazole and Trimethoprim Chemoprophylaxis for Pneumocystis carinii Pneumonia in AIDS," JAMA, 1988, 259(8):1185-9.

Hennessy S, Strom BL, Berlin JA, et al, "Predicting Cutaneous Hypersensitivity Reactions to Co-Trimoxazole in HIV-Infected Individuals Receiving Primary Pneumocystis carinii Pneumonia Prophylaxis," J Gen Intern Med, 1995, 10(7):380-6.

Hughes W, Leoung G, Kramer F, et al, "Comparison of Atovaquone (566C80) With Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients With AIDS," N Engl J Med, 1993, 328(21):1521-7.

Hughes WT, " Pneumocystis carinii Pneumonia: New Approaches to Diagnosis, Treatment, and Prevention," Pediatr Infect Dis J, 1991, 10(5):391-9.

Jick H and Derby LE, "A Large Population-Based Follow-Up Study of Trimethoprim-Sulfamethoxazole, Trimethoprim, and Cephalexin for Uncommon Serious Drug Toxicity," Pharmacotherapy, 1995, 15(4):428-32.

Jick H and Derby LE, "Is Co-Trimoxazole Safe?" Lancet, 1995, 345(8957):1118-9.

Lundstrom TS and Sobel JD, "Vancomycin, Trimethoprim-Sulfamethoxazole, and Rifampin," Infect Dis Clin North Am, 1995, 9(3):747-67.

Masur H, "Prevention and Treatment of Pneumocystis Pneumonia," N Engl J Med, 1992, 327(26):1853-60.

Naber K, Vergin H, and Weigand W, "Pharmacokinetics of Co-trimoxazole and Co-tetroxazine in Geriatric Patients," Infection, 1981, 9(5):239-43.

Noto H, Kaneko Y, Takano T, et al, "Severe Hyponatremia and Hyperkalemia Induced by Trimethoprim-Sulfamethoxazole in Patients With Pneumocystis carinii Pneumonia," Intern Med, 1995, 34(2):96-9.

Sattler FR, Cowan R, Nielsen DM, et al, " Trimethoprim-Sulfamethoxazole Compared With Pentamidine for Treatment of Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome," Ann Intern Med, 1988, 109(4):280-7.

Singh N, Gayowski T, Yu VL, et al, "Trimethoprim-Sulfamethoxazole for the Prevention of Spontaneous Bacterial Peritonitis in Cirrhosis: A Randomized Trial," Ann Intern Med, 1995, 122(8):595-8.

Torre D, Casari S, Speranza F, et al, "Randomized Trial of Trimethoprim-Sulfamethoxazole Versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients With AIDS. Italian Collaborative Study Group," Antimicrob Agents Chemother, 1998, 42(6):1346-9.

Varoquaux O, Lajoie D, Gobert C, et al, "Pharmacokinetics of the Trimethoprim-Sulfamethoxazole Combination in the Elderly," Br J Clin Pharmacol, 1985, 20:575-81.