Co-trimoxazole IV, PO

• Treatment and prophylaxis of pneumocystis pneumonia

• Stenotrophomonas and other multidrug resistant infections

• Nocardiosis

• Toxoplasmosis

• Treatment of infections caused by other susceptible organism

PO:
Trisul tablets - Sulfamethoxazole 400mg / Trimethoprim 80mg (white)
Deprim and Trisul suspension – Sulfamethoxazole 200mg / Trimethoprim 40mg per 5ml

IV:
Each 5ml vial contains 480mg (80mg trimethoprim and 400mg sulfamethoxazole)
Normal dilution:
1 vial (5ml) diluted with 125ml of compatible IV fluid
2 vials (10ml) diluted with 250ml of compatible IV fluid
3 vials (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 vial (5ml) diluted with 75ml of 5% glucose
6 vials (30ml) diluted with 500ml of 5% glucose
More than 6 vials 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 Hartmann's
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 Hartmann's, 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.

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:

• Known hypersensitivity to trimethoprim or sulfonamides

• Megaloblastic anaemia due to folate deficiency

IMPORTANT DRUG INTERACTIONS FOR THE ICU
In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopaenia 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.

Haematologic:
Agranulocytosis, aplastic anaemia, thrombocytopaenia, leukopaenia, neutropaenia, haemolytic anaemia, megaloblastic anaemia, hypoprothrombinemia, methaemoglobinaemia, 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, diarrhoea, 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.