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Pronunciation |
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(koe
trye MOKS a
zole) |
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U.S. Brand
Names |
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Bactrim™; Bactrim™ DS;
Cotrim®; Cotrim® DS; Septra®; Septra® DS;
Sulfatrim® |
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Generic
Available |
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Yes |
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Canadian Brand
Names |
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Apo®-Sulfatrim; Novo-Trimel; Nu-Cotrimox;
Pro-Trin®; Roubac®; Trisulfa®;
Trisulfa-S® |
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Synonyms |
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SMZ-TMP; Sulfamethoxazole and Trimethoprim; TMP-SMZ; Trimethoprim and
Sulfamethoxazole |
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Pharmacological Index |
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Antibiotic, Sulfonamide Derivative |
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Use |
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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
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Pregnancy Risk
Factor |
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C; D (if used near term, per expert analysis) |
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Pregnancy/Breast-Feeding
Implications |
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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 |
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Contraindications |
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Hypersensitivity to any sulfa drug or any component; porphyria; megaloblastic
anemia due to folate deficiency; infants <2 months of age; marked hepatic
damage |
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Warnings/Precautions |
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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. |
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Adverse
Reactions |
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>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 |
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Overdosage/Toxicology |
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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 |
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Drug
Interactions |
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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 |
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Stability |
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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 |
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Mechanism of
Action |
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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 |
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Pharmacodynamics/Kinetics |
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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 |
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Usual Dosage |
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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.:
Clcr 15-30 mL/minute: Administer 2.5-5 mg/kg every 12 hours
Clcr <15 mL/minute: Administer 2.5-5 mg/kg every 24 hours
Oral:
Clcr 15-30 mL/minute: Administer 1 double strength tablet every 24
hours or 1 single strength tablet every 12 hours
Clcr <15 mL/minute: Not recommended |
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Dietary
Considerations |
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Should be administered with a glass of water on empty
stomach |
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Test
Interactions |
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creatinine
(Jaffé alkaline
picrate reaction); increased serum methotrexate by dihydrofolate reductase
method |
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Mental Health: Effects
on Mental Status |
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Rarely may cause depression, hallucination, or confusion; sulfonamides may
cause euphoria, restlessness, irritability, disorientation, panic, and
delusions |
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Mental Health:
Effects on Psychiatric
Treatment |
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May rarely cause granulocytopenia; use caution with clozapine and
carbamazepine |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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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. |
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Nursing
Implications |
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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
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Dosage Forms |
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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
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References |
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"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,"
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Hughes W, Leoung G, Kramer F, et al,
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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,
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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. |
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