This word document deals with summarized drug profile of cotrimoxazole. Important pharmacological headings, along with important counselling tips and drug catchpoints have also been elucidated.

1. CO-TRIMOXAZOLE DRUG PROFILE
BASIC FEATURES:
Class: Antimetabolite, sulfonamide antibiotics.
Mechanism of action:
1. Cotrimoxazole  consists of (sulfamethoxazole+ trimethoprim).
2. Sulfamethoxazole  competes with PABA (para-amino benzoic acid)
 inhibits bacterial synthesis of dihydrofolic acid.
3. Trimethoprim  reversibly blocks dihydrofolate reductase enzyme 
blocks production of tetrahydrofolic acid from dihydrofolic acid 
inhibits production of DNA bases.
4. Combined action of sulfamethoxazole and trimethoprim  results in
death of susceptible organism (bactericidal effect).
Mechanisms of resistance:
1. Plasmid mediated alterations in dihydrofolate reductase
2. Changes in cell permeability
3. Overproduction of PABA
4. Structural change in dihydropteroate synthesis.
Metabolic route: Both trimethoprim & sulfamethoxazole  excreted in urine.
FDA-APPROVED INDICATIONS:
1. UTI
2. Acute otitis media
3. Acute exacerbations of chronic bronchitis in adults
4. Shigellosis
5. Pneumocystis jirovecii pneumonia (especially in HIV patients): Both
treatment and prophylaxis

2. 6. Traveler’s diarrhea in adults
7. Alternative therapy for toxoplasmosis
8. Community-acquired MRSA skin infections
9. Infections due to Listeria, Nocardia, Salmonella, Brucella,
Paracoccidioides, meliodosis, Burkholderia, Stenotrophomonas,
cyclospora, isospora, Whipple’s disease.
SIDE-EFFECTS/TOXICITY:
1. SJS
2. Toxic epidermal necrolysis (TEN)
3. Fulminant hepatic necrosis
4. Stomatitis
5. Glossitis
6. Nausea
7. Abdominal pain
8. Pancreatitis
9. Diarrhea
10. CDAD
11. Hepatitis
12.Renal failure
13.Interstitial nephritis
14.Convulsions
15.Peripheral neuritis
16.Ataxia
17.Vertigo
18.Hallucinations
19.Depression
20.Fatigue
21.Insomnia
22.Lung hypersensitivity reactions
23.Lupus
24.Arthralgia
25.Myalgias
26.Hypoglycemia
27.Hypoprothrombinemia
28.Methemoglobinemia
29.Hyperkalemia

3. 30.Crystalluria
31.Megaloblastic anemia
32.Thrombocytopenia
33.Agranulocytosis
34.Aplastic anemia
35.Miscellaneous blood dyscrasias.
CONTRAINDICATIONS:
1. Known hypersensitivity to trimethoprim or sulfamethoxazole
2. History of drug-induced immune thrombocytopenia due to co-
trimoxazole or any other sulfonamide
3. Documented megaloblastic anemia due to folate deficiency
4. Pregnancy
5. Nursing mothers
6. Children less than 2 months of age
7. Marked hepatic or severe renal insufficiency.
SIGNIFICANT DRUG INTERACTIONS/FOOD
INTERACTIONS:
1. Cotrimoxazole  can be given without regard to meals
2. Cotrimoxazole + thiazides  increased risk of thrombocytopenia
3. Cotrimoxazole + phenytoin, methotrexate, digoxin, OHA, warfarin
 increased effects of latter.
4. Cotrimoxazole + indomethacin  increased levels of
sulfamethoxazole
5. Cotrimoxazole + TCAs  reduced efficacy of latter
6. Cotrimoxazole + ACE-Inhibitors  high risk of hyperkalemia.
DOSAGE FORMS:
1. Trimethoprim/sulfamethoxazole in a fixed dose ratio of 1:5
2. Bactrim and Septra  contain 400 mg sulfamethoxazole and 80 mg
trimethoprim
3. Bactrim DS & Septra DS  contain 800 mg sulfamethoxazole and
160 mg trimethoprim

4. 4. Oral suspension  contains 200 mg sulfamethoxazole and 40 mg
trimethoprim per teaspoon
5. Intravenous formulation  contains (400 mg sulfamethoxazole and 80
mg trimethoprim)/ 5 ml.
DOSING:
INFECTION DOSE
UTI/ Shigellosis/ Acute
exacerbations of chronic
bronchitis
1 DS tablet OR 2 tablets OR 4 teaspoonfuls
(20 ml) OR 10 ml IV, every 12 hours for 10-
14 days.
Pneumocystis
jirovecii
pneumonia
Treatment 75-100 mg/kg sulfamethoxazole and 15-20
mg/kg trimethoprim per 24 hours, given in
equally divided doses, every 6 hours, for 14-
21 days.
Thus  a patient weighing 64 kg  should
take 4 tablets OR 2 DS tablets OR 20 ml IV
every 6 hours.
Prophylaxis 1 DS or single strength tablet daily
OR
1 DS tablet every Monday, Wednesday and
Friday.
Traveler’s diarrhea 1 DS tablet OR 2 tablets OR 4 teaspoonfuls
(20 ml), every 12 hours for 5 days.
DOSING IN SPECIAL POPULATIONS:
In renal impairment:
CREATININE CLEARANCE
(ml/min)
DOSE TO BE ADJUSTED
15-30 Use half the normal dose

5. <15, hemodialysis, CAPD, CRRT Avoid use.
In hepatic dysfunction: No dose adjustment necessary
Pediatrics:
1. Not recommended for children below 2 months of age
2. For selected infections:
INFECTION DOSE
UTI/ Acute otitis media (40 mg/kg sulfamethoxazole + 8
mg/kg) per 24 hours, given in 2
divided doses, every 12 hours for
10 days.
Shigellosis Daily dosage for 5 days.
Pneumocystis
jirovecii
pneumonia
Treatment 750 mg/m2
sulfamethoxazole +
150 mg/m2
trimethoprim per 24
hours, given in equally divided
doses, every 6 hours, for 14-21
days.
Prophylaxis 750 mg/m2
/day
sulfamethoxazole + 150
mg/m2
/day trimethoprim, given
in equally divided doses twice a
day, on 3 consecutive days per
week.
The total daily dose  should
not exceed 1600 mg
sulfomethoxazole and 320 mg
trimethoprim.
IMPORTANT DRUG CATCHPOINTS:
1. Can be taken without regard to meals
2. Since cotrimoxazole may interfere with folic acid metabolism  it
SHOULD BE USED DURING PREGNANCY ONLY IF
POTENTIAL BENEFITS JUSTIFIES POTENTIAL RISK TO
THE FETUS!

6. 3. Avoid drug usage in treatment of Group A β-hemolytic streptococcal
infections.
4. Although not FDA-approved  the usual dose of cotrimoxazole for
systemic infections due to typical bacteria is 10 mg/kg/day of
trimethoprim and 50 mg/kg/day of sulfamethoxazole.
5. If the following symptoms occur  consult physician or pharmacist
immediately, since they may be early indications of serious
reactions:
 Rash
 Sore throat
 Fever
 Arthralgia
 Pallor
 Purpura
 Jaundice
6. In patients taking cotrimoxazole  DRINK ADEQUATE
AMOUNTS OF WATER to avoid risk of CRYSTALLURIA and
STONE FORMATION.
WORK WELL AND SMART!
DR. VISHNU R. NAIR