Trimethoprim/Sulfamethoxazole

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA).

Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase.

Thus, sulfamethoxazole and trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.

[edit] INDICATIONS

  • Urinary Tract Infections caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
  • Acute Otitis Media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
  • Acute Exacerbations of Chronic Bronchitis in Adults due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
  • Shigellosis caused by susceptible strains of Shigella flexneri and S sonnei
  • Pneumocystis Carinii Pneumonia (Treatment),and prophylaxis in individuals who are immunosuppressed
  • Traveler’s Diarrhea in Adults to susceptible strains of Escherichia coli

[edit] DOSAGE

Adults:

  • Traveler's Diarrhea: the usual dosage is 1 DS (double strength: 160mg/800 mg) tablet every 12 hours for 5 days.
  • Urinary Tract Infections: 1 DS (double strength : 160mg/800 mg) tablet every 12 hours for 10 to 14 days.
  • Chronic Bronchitis: 1 DS (double strength: 160mg/800 mg) tablet every 12 hours for 14 days.
  • Shigellosis: 1 DS (double strength : 160mg/800 mg) tablet every 12 hours for 5 days.
  • Pneumocystis Carinii Pneumonia:
    • Treatment: The recommended dosage is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days. (the dosage for a 70 kilogram person is 2 DS (double strength : 160mg/800 mg) tablets every 6 hours for 14 to 21 days).
    • Prophylaxis: The recommended dosage for prophylaxis in adults is 1 DS (double strength : 160mg/800 mg) tablet daily.
  • Acne Vulgaris (Off-label): 1 DS (double strength : 160mg/800 mg) tablet every 12-24 hours for up to 18 weeks


Pediatric patients

  • Urinary Tract Infections: 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days.
  • Shigellosis: 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 5 days.
  • Pneumocystis Carinii Pneumonia:
    • Treatment: The recommended dosage is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days.
    • Prophylaxis: the recommended dose is 750 mg/m2/day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.

[edit] DOSAGE FORMS AND STRENGTHS

  • DS (double strength) TABLETS containing 160 mg trimethoprim and 800 mg sulfamethoxazole

[edit] CONTRAINDICATIONS

  • Trimethoprim/Sulfamethoxazole is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides
  • Patients with documented megaloblastic anemia due to folate deficiency.
  • Pregnant patients and nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus.
  • Trimethoprim/Sulfamethoxazole is contraindicated in pediatric patients less than 2 months of age.
  • Trimethoprim/Sulfamethoxazole is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.

[edit] WARNINGS AND PRECAUTIONS

  • Severe allergic reactions may occur rarely
  • Severe cases of thrombocytopenia that are fatal or life threatening have been reported. Thrombocytopenia usually resolves within a week upon discontinuation of sulfamethoxazole/trimethoprim.
  • Clostridium difficile associated diarrhea (CDAD) may occur.
  • Trimethoprim/Sulfamethoxazole 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 .

[edit] INTERACTIONS

(See leaflet)

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, its use during pregnancy is contraindicated.
  • Nursing mothers: Trimethoprim/Sulfamethoxazole is excreted in breast-milk and hence nursing during treatment with Trimethoprim/Sulfamethoxazole is generally contraindicated.

[edit] SIDE EFFECTS

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).

Diarrhea, glossitis, and stomatitis are uncommon.

Exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) are rare

Hematological reactions are also rare and include various types of anemia, granulocytopenia, purpura and agranulocytosis.

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[edit] BIBLIOGRAPHY

[edit] REFERENCES