Co-trimoxazole

Co-trimoxazole

ADMINISTRATION ROUTES:

  • PO, IV

ALTERNATIVE NAMES:

  • Trisul, Deprim

ICU INDICATIONS:

  1. Treatment and prophylaxis of PCP
  2. Stenotrophomonas and other multidrug resistant infections
  3. Nocardiosis
  4. Toxoplasmosis
  5. Treatment of infections caused by other susceptible organisms

PRESENTATION AND ADMINISTRATION:

  • PO:
    Trisul tablets – Sulfamethoxazole 400mg / Trimethoprim 80mg (white)
    Deprim and Trisul suspension – Sulfamethoxazole 200mg / Trimethoprim 40mg per 5ml
  • IV:
    Each 5ml ampoule contains 480mg (80mg trimethoprim and 400mg sulfamethoxazole)
    Normal dilution:
    1 ampoule (5ml) diluted with 125ml of compatible IV fluid
    2 ampoules (10ml) diluted with 250ml of compatible IV fluid
    3 ampoules (15ml) diluted with 500ml of compatible IV fluid
    Inspect for signs of turbidity or precipitation – if present, discard. Infuse over 60 to 90 minutes
    Fluid restriction or high dose infusion:
    1 ampoule (5ml) diluted with 75ml of 5% glucose 6 ampoules (30ml) diluted with 500ml of 5% glucose
    More than 6 ampoules diluted with 1000ml of 5% glucose
    Inspect for signs of turbidity or precipitation – if present, discard. Infuse over a period not exceeding 60 minutes and flush line thoroughly after drug administration.
    Compatible with the following IV fluids:
    0.45% sodium chloride, 0.9% sodium chloride, glucose and sodium chloride, 5% glucose, 10% glucose, Hartmanns
    If fluid restriction or high dose infusion is used, dilute ONLY with 5% glucose
    Do not mix with any other drugs
    Precipitation may occur if solutions are stored at low temperatures. If necessary, infusion solutions may be stored at room temperature. Solutions not used within 24 hours of preparation must be discarded. When diluted in Hartmanns, the prepared solution is stable for 8 hours at a 1 in 25 dilution and for 24 hours at a 1 in 35 dilution. DO NOT use any solution that is cloudy or which has a visible precipitate.

DOSAGE:

  • IV:
    Usual dosage 960-1440mg per day in divided doses;
    For PCP treatment use 120mg/kg in divided doses administered every 6 hours for 14 days
  • PO:
    PCP prophylaxis: 960-1920mg on alternate days.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    <15: 30mg/kg twice daily (PCP); or 50% of dose
    15-30: 60mg/kg for 3 days then 30mg/kg twice daily (PCP); or 50% of
    dose
    >30-50: dose as in normal renal function
  • Dose in renal replacement therapy
    CAPD: 30mg/kg twice daily (PCP); or 50% of dose
    HD: 30mg/kg twice daily (PCP); or 50% of dose
    CVVHDF: 60mg/kg for 3 days then 30mg/kg twice daily (PCP); or 50% of
    dose

DOSAGE IN PAEDIATRICS:

  • IV/ PO:
    6mg/kg trimethoprim and 30mg/kg sulfamethoxazole per day in equal divided doses

CLINICAL PHARMACOLOGY:

  • 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; trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.
  • The following organisms are usually susceptible:
    Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, indole-positive Proteus species including Proteus vulgaris, Haemophilus influenzae (including ampicillin- resistant strains), Streptococcus pneumoniae, Shigella flexneri and Shigella sonnei.
  • It should be noted, however, that there are little clinical data on the use of sulfamethoxazole; trimethoprim IV infusion in serious systemic infections due to Haemophilus influenzae and Streptococcus pneumoniae.

CONTRAINDICATIONS:

  1. known hypersensitivity to trimethoprim or sulfonamides
  2. megaloblasticanemia due to folate deficiency

WARNINGS

  • FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA AND OTHER BLOOD DYSCRASIAS. SULFAMETHOXAZOLE; TRIMETHOPRIM SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH
  • Sulfamethoxazole; trimethoprim IV infusion contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

PRECAUTIONS

  • General:
    Sulfamethoxazole; trimethoprim 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.
  • Laboratory Tests:
    No tests in addition to routine ICU tests are indicated
  • Drug/Laboratory Test Interactions:
    None of note

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • 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; trimethoprim may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when sulfamethoxazole; trimethoprim is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed. Sulfamethoxazole; trimethoprim may inhibit the hepatic metabolism of phenytoin.

ADVERSE REACTIONS

  • Hematologic:
    Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.
  • Allergic Reactions:
    Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills. Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, conjunctival and scleral injection, photosensitivity, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported.
  • Gastrointestinal:
    Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.
  • Genitourinary:
    Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, and crystalluria.
  • Neurologic:
    Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.
  • Psychiatric:
    Hallucinations, depression, apathy, nervousness.
  • Endocrine:
    The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
  • Musculoskeletal:
    Arthralgia and myalgia.
  • Respiratory:
    Pulmonary infiltrates.
  • Miscellaneous:
    Weakness, fatigue, insomnia.

Critical Care Drug Manual

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