ADMINISTRATION ROUTES:
PO, IV
ALTERNATIVE NAMES:
Trisul, Deprim
ICU INDICATIONS:
- Treatment and prophylaxis of pneumocystis pneumonia (PJP)
- Stenotrophomonas and other multidrug resistant infections
- Nocardiosis
- Toxoplasmosis
- Treatment of infections caused by other susceptible organisms
PRESENTATION AND ADMINISTRATION:
PO:
Trisul tablets - Sulfamethoxazole 400 mg / Trimethoprim 80 mg (white)
Deprim and Trisul suspension – Sulfamethoxazole 200 mg / Trimethoprim 40 mg per 5 mL
IV:
Each 5 mL vial contains 480 mg (80 mg trimethoprim and 400 mg sulfamethoxazole)
Normal dilution:
1 vial (5 mL) diluted with 125 mL of compatible IV fluid
2 vials (10 mL) diluted with 250 mL of compatible IV fluid
3 vials (15 mL) diluted with 500 mL 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 (5 mL) diluted with 75 mL of 5% dextrose
6 vials (30 mL) diluted with 500 mL of 5% dextrose
More than 6 vials diluted with 1000 mL of 5% dextrose
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% dextrose, 10% dextrose, Hartmanns
If fluid restriction or high dose infusion is used, dilute ONLY with 5% dextrose
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 administer any solution that is cloudy or which has a visible precipitate.
DOSAGE:
IV:
960-1440 mg per day in divided doses
Pneumocystis (PJP): 120 mg/kg in divided doses administered QID for 14 days
PO:
Pneumocystis (PJP) prophylaxis: 960-1920 mg on alternate days
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment
| GFR (ml/min) | DOSE |
|---|---|
| <15 | 30 mg/kg BD (PJP), or 50% of dose |
| 15-30 | 60 mg/kg for 3 days then 30 mg/kg BD (PJP), or 50% of dose |
| >30-50 | dose as in normal renal function |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | 30 mg/kg BD (PJP), or 50% of dose |
| HD | 30 mg/kg BD (PJP), or 50% of dose |
| CVVHDF | 60 mg/kg for 3 days then 30 mg/kg BD (PJP), or 50% of dose |
DOSAGE IN PAEDIATRICS:
IV / PO:
6 mg/kg trimethoprim and 30 mg/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. Together, sulfamethoxazole & trimethoprim block two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.
The following organisms are usually susceptible:
- Escherichia coli
- Klebsiella spp.
- Enterobacter spp.
- Morganella morganii
- Proteus mirabilis
- Indole-positive Proteus species including Proteus vulgaris
- Haemophilus influenzae (including ampicillin- resistant strains)
- Streptococcus pneumoniae
- Shigella flexneri and Shigella sonnei
Note: 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
WARNINGS:
Fatalities associated with the administration of sulfonamides, although rare, have occurred from severe reactions. These include Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias. Sulfamethoxazole/trimethoprim should be discontinued at the first appearance of any 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 non-asthmatic 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, haemolysis 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 IN 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. Sulfamethoxazol/trimethoprim may inhibit the hepatic metabolism of phenytoin.
ADVERSE REACTIONS:
Haematologic:
Agranulocytosis, aplastic anaemia, thrombocytopaenia, leukopaenia, neutropaenia, haemolytic anaemia, megaloblastic anaemia, hypoprothrombinaemia, methaemoglobinaemia, eosinophilia
Allergic Reactions:
Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills. Henoch–Schönlein purpura, serum sickness-like syndrome, generalised allergic reactions, generalised 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
Endocrine:
The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycaemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycaemia have occurred rarely in patients receiving sulfonamides
Musculoskeletal:
Arthralgia and myalgia
Respiratory:
Pulmonary infiltrates
Miscellaneous:
Weakness, fatigue, insomnia