Trimethoprim/ Sulfamethoxazole

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Upper and lower respiratory tract infections e.g. acute and chronic bronchitis, bronchiectasis, tonsillitis, sinusitis and pharyngitis, otitis media, pneumonia and pneumocystis carinii pneumonitis (Pneumocystis jirovecii pneumonitis)
• Renal and urinary tract infections e.g. pyelitis, pyelonephritis, urethritis, acute and chronic cystitis and cystopyelitis, including prostatitis
• Gastrointestinal tract infections e.g. enteritis, typhoid and paratyphoid fever, typhoid carriage, bacillary dysentery and cholera. (as an adjunct to fluid and electrolyte replacement)
• Genital tract infections: both male and female including gonococcal infections
• Skin infections e.g. pyoderma, boils, furuncles, abscesses
• Other bacterial infections: acute brucellosis, mycetoma except those caused by true fungi, nocardiosis, acute and chronic osteomyelitis

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to sulfonamides
• Allergy to sulphonylurea anti-diabetics and saluretic sulphonamide derivatives should also be considered (inj)
• Porphyria
• Liver parenchymal damage
• Megaloblastic anaemia due to folic acid deficiency
• Serious haematological disorders (inj)
• Severe renal insufficiency
• Pregnancy, in women prior to delivery
• Nursing mothers
• Infants during the first 6 weeks of life
• Blood dyscrasias(inj)
• Coadministration with dofetilide (inj)

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to sulphonamides
• Severe impairment of liver function
• Severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed
• Infants during the first 6 weeks of life
• History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides
• Acute porphyria

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment (CrCl 15-25ml/min) (sus, tab) (South African recommendations)
• Renal impairment (CrCl 15-30ml/min) (inj) (South African recommendations)
• Renal impairment (CrCl ≤30ml/min) (where repeated measurements of the plasma concentration can be performed) (Recommendations in other jurisdictions)
• Renal impairment (children ≤12 years) (Recommendations in other jurisdictions)
• Hepatic impairment (South African recommendations) 
• Mild to moderate hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Malnutrition
• Prolonged treatment
• Folate deficiency
• Severe atopy
• Bronchial asthma
• Treatment of streptococcal pharyngitis due to Group A beta haemolytic streptococci
• Risk factors for hyperkalaemia
• Risk factors for hyponatraemia
• Serious haematological disorders
• Combination treatment with other antibiotics
• Patient at risk of alcohol-related side-effects (IV, sus):
  - Alcoholism
  - Pregnancy
  - Breastfeeding
  - Children
  - Hepatic disease
  - Epilepsy  
• Glucose-6-phosphate deficiency
• Patients on sodium restricted diet (IV formulations)
• Fructose intolerance (sus)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj, tab

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

Infections caused by: Haemophilus influenzae, Streptococcus pneumoniae, Pneumocystis jiroveci, Salmonella typhi, Salmonella paratyphi, S. flexneri, S. Sonnei, Vibrio cholerae, E. coli, Citrobacter freundii, other Citrobacter spp., Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Proteus mirabilis; Proteus vulgaris, Morganella morganii, Alcaligenes faecalis, Burkholderia cepacia, Providencia rettgeri, other Providencia spp., Stenotrophomonas maltophilia, Acinetobacter anitratus, Acinetobacter baumanii, Haemophilus ducreyi, Brucella, Nocardia asteroides

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Prophylaxis of recurrent urinary tract infection

• Oral (tab): 80mg TMP/400mg SMZ, at night; Treatment duration: 6 months for patients with >3 infections/year
  (STG, Adult 2019)

Prophylaxis of opportunistic infections in HIV/AIDS

• Oral (tab): 160mg TMP/800mg SMZ, dly; Treatment duration: Until CD4>200cells/mm³ at routine count 1 year on ART, or for 6 months if  CD4 was >200cells/mm³ when prophylaxis commenced 
  (STG, Adult 2019; PHC 2020)

- HIV-infected pregnant women with CD4≤200 cells/mm³ or WHO clinical stage 2, 3 or 4 

• Oral (tab): 160mg TMP/800mg SMZ, dly; Treatment duration: Until CD4>200cells/mm³ 
  (STG, PHC 2020) 

Cystoisosporiasis

• Oral (tab): 320mg TMP/1600mg SMZ, 12hrly; Treatment duration: 10 days
  (STG, Adult 2019; PHC 2020)

Cystoisosporiasis - secondary prophylaxis

• Oral (tab): 160mg TMP/800mg SMZ, dly; Treatment duration: At least 6 months and until CD4 count increases to >200cells/mm³ on ART
  (STG, Adult 2019; PHC 2020)

Pneumocystis pneumonia

• Oral (tab): <60kg: 240mg TMP/1200mg SMZ, 6hrly: Treatment duration: 21 days
• Oral (tab): ≥60kg: 360mg TMP/1600mg SMZ, 6hrly: Treatment duration: 21 days
  (STG, Adult 2019)

- If vomiting

• IV: <60kg: 240mg TMP/1200mg SMZ, 6hrly: Treatment duration: 21 days
• IV: ≥60kg: 360mg TMP/1600mg SMZ, 6hrly: Treatment duration: 21 days
  (STG, Adult 2019)

OR 
Pneumocystis pneumonia

• Oral (tab): Dose TMP/SMZ as per body weight, 6hrly; Treatment duration: 21 days

Approximate weight	Single strength  tab 80/400mg	Double strength  tab 160/800mg
<40kg	2 tabs	1 tab
>40-56kg	3 tabs	1 and 1/2 tabs
>56kg	4 tabs	2 tabs

(STG, PHC 2020) 

Pneumocystis pneumonia - secondary prophylaxis

• Oral (tab): 160mg TMP/800mg SMZ, dly; Treatment duration: Until CD4 count increases on ART to >200 cells/mm³ for at least 6 months
  (STG, Adult 2019; PHC 2020)

Cerebral toxoplasmosis

• Oral (tab): 320mg TMP/1600mg SMZ, 12hrly; Treatment duration: 28 days, Then; 160mg/800mg, 12hrly; Treatment duration: 3 months
  (STG, Adult 2019; PHC 2020) 

- Secondary prophylaxis

• Oral (tab): 320mg TMP/1600mg SMZ, dly; Treatment duration: 6 months and until CD4 count increases to >200cells/mm³ on ART
  (STG, Adult 2019; PHC 2020)  

Toxoplasmosis

• Oral (tab): 320mg TMP/1600mg SMZ, 12hrly; Treatment duration: 4 weeks; Then; 160mg TMP/800mg SMZ, 12hrly; Treatment duration: 12 weeks 
  (STG, PHC 2020) 

- Secondary prophylaxis

• Oral (tab): 160mg TMP/800mg SMZ, dly; Treatment duration: Until CD4 count increases to >200cells/mm³ on ART
  (STG, PHC 2020)  

HIV-associated diarrhoea
- If stool shows Isospora belli

• Oral (tab): 320mg TMP/1600mg SMZ, 12hrly; Treatment duration: 10 days; Then: 160mg TMP/800mg SMZ, dly; Treatment duration: Until CD4 >200 cells/mm³ on ART
  (STG, PHC 2020) 

Acute meningitis 
- Severe penicillin allergy

• Oral (tab): 80 TMP/400mg SMZ, immediately as a single dose before referral; Repeat dose if referral delayed by 12 hours
  (STG, PHC 2020)

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South African registered indications and dosages

80mg TMP/ 400mg SMZ and 160mg TMP/ 800mg SMZ tablets

Upper and lower respiratory tract infections
- Acute and chronic bronchitis, bronchiectasis, tonsillitis, sinusitis and pharyngitis, otitis media, pneumonia and pneumocystis carinii pneumonitis (Pneumocystis jirovecii pneumonitis)
Renal and urinary tract infections
- Pyelitis, pyelonephritis, urethritis, acute and chronic cystitis and cystopyelitis, including prostatitis
Gastrointestinal tract infections
- Enteritis, typhoid and paratyphoid fever, typhoid carriage, bacillary dysentery and cholera as an adjunct to fluid and electrolyte replacement
Genital tract infections
- Both male and female including gonococcal infections
Skin infections
- Pyoderma, boils, furuncles, abscesses
Other bacterial infections
- Acute brucellosis, mycetoma except those caused by true fungi, nocardiosis, acute and chronic osteomyelitis

• Oral (tab): Usual dose: 160mg TMP/ 800mg SMZ, 12hrly after meals; Max dose (for particularly severe cases): 240mg TMP/ 1200mg SMZ, 12hrly; Min. dosage for long term treatment of >14 days: 80mg TMP/ 400mg SMZ, 12hrly

Prophylaxis of Pneumocystis jirovecii pneumonia

• Oral (tab): 160mg TMP/800mg SMZ, dly

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In the treatment of acute infections trimethoprim/sulfamethoxazole should be administered for at least 5 days or for at least 2 days after the symptoms have disappeared. If clinical improvement is not evident after 7 days therapy, the patient should be reassessed

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The tablets must be taken by mouth, after food and must be swallowed with a drink of water

---

80mg TMP/ 400mg SMZ (per 5ml) intravenous infusion

Used when oral admin. is impossible or not indicated. Ampoule for IV infusion can only be used following dilution with appropriate infusion solutions

Respiratory tract and ear infections
- Acute exacerbation of chronic bronchitis
Urogenital tract infections 
- Caused by E.coli, Citrobacter freundii, other Citrobacter spp., Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Alcaligenes faecalis, Burkholderia cepacia, Providencia rettgeri, other Providencia spp., Stenotrophomonas maltophilia, Acinetobacter anitratus, Acinetobacter baumanii and chancroid caused by Haemophilus ducreyi
Gastrointestinal tract infections
- Typhoid and paratyphoid fever caused by Salmonella typhi and Salmonella paratyphi, shigellosis caused by susceptible strains of S. flexneri and S. sonnei (when antibacterial therapy is indicated) and cholera caused by Vibrio cholerae (as an adjunct to fluid and electrolyte therapy)
Other susceptible bacterial infections
- Brucellosis caused by Brucella and nocardiosis caused by Nocardia asteroides

Standard dosage

• IV: 10ml (2 x 5ml ampoules), twice daily (morning and evening) after appropriate dilution; Parenteral formulation should only be given during the period that oral treatment is not possible; Treatment duration: Not longer than 5 consecutive days

High dosage (for particularly severe cases)

• IV: 15ml (3 x 5ml ampoules), twice daily (morning and evening) after appropriate dilution; Parenteral formulation should only be given during the period that oral treatment is not possible; Treatment duration: Not longer than 3 consecutive days

Pneumocystis jirovecii pneumonia

• IV: Up to 20mg TMP/kg and up to 100mg SMZ/kg per 24hrs, given in equal divided doses every 6hrs; Treatment duration: 14 days

Nocardiosis

• IV: 480-640mg TMP and 2400-3200mg SMZ, dly; Treatment duration: At least 3 months

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This dose requires adjustment to the patient's age, weight and renal function and to the severity of the disease. A duration of therapy of 18 months has been reported (for nocardiosis)

---

Trimethoprim/sulfamethoxazole IV must be diluted before use. IV infusion to be used following dilution with the appropriate infusion solutions (See additional prescribing points)

Paed. forms avail. in SA and covered in this monograph: inj, sus, tab

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

Infections caused by: Haemophilus influenzae, Streptococcus pneumoniae, Pneumocystis jiroveci, Salmonella typhi, Salmonella paratyphi, S. flexneri, S. Sonnei, Vibrio cholerae, E. coli, Citrobacter freundii, other Citrobacter spp., Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Proteus mirabilis; Proteus vulgaris, Morganella morganii, Alcaligenes faecalis, Burkholderia cepacia, Providencia rettgeri, other Providencia spp., Stenotrophomonas maltophilia, Acinetobacter anitratus, Acinetobacter baumanii, Haemophilus ducreyi, Brucella, Nocardia asteroides

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Persistent diarrhoea
- Cystoisospora belli present

• Oral (syr, tab): 5mg/kg (TMP)/dose, 12hrly; Treatment duration: 10 day
  (STG, Paed. 2023)

- Cyclospora cayetanensis

• Oral (syr, tab): 5mg/kg (TMP)/dose, 6hrly; Treatment duration: 5 days
  (STG, Paed. 2023)

Persistent diarrhoea in HIV infected children
- Cystoisospora belli
- Cyclospora cayetanensis

• Oral (syr, tab): 5mg/kg (TMP)/dose, 12hrly; Treatment duration: 10 days
  (STG, Paed. 2023)

Prophylaxis in HIV infected infants and children
- Younger than 10 years 

• Oral (tab, sus): Dose once daily (every day); Dosages as per below table

Recommended daily dosage by weight band	Dose SMZ/ TMP	Suspension 200/40mg per 5ml	Single strength  tab 400/80mg	Double strength  tab 800mg/160mg
3-5.9kg	100/20mg	2.5ml	1/4 tab	-
6-13.9kg	200/40mg	5ml	1/2 tab	-
14-24.9kg	400/80mg	10ml	1 tab	1/2 tab
>25kg	800/160mg	-	2 tabs	1 tab

(STG, Paed. 2023) 

Pneumonia in HIV exposed or infected children (Additional agent required)
- Between 2-6 months

• IV/Oral (inj, sus, tab): 5mg (TMP)/25mg SMZ/kg/dose, 6hrly; Treatment duration: 21 days; Prophylaxis at the end of this treatment period should be continued until CD4 count recovers to normal
  (STG, Paed. 2023)

HIV infected children
- All HIV-infected infants <1 year, starting from 6 weeks of age
- Any child 1–5 years of age with CD4% <25%
- Any child >5 years of age with CD4 count <200 cells/mm³
Acute meningitis 
- Severe penicillin allergy

• Oral (tab): Dose as per body weight SMZ/ TMP immediately as a single dose before referral; Repeat dose if referral delayed by 12hrs

Recommended daily by weight band	Dose SMZ/ TMP	Suspension 200/40mg per 5ml	Single strength  tab 400/80mg	Double strength  tab 800mg/160mg
3-4.9kg	100/20mg	2.5ml	1/4 tab	-
5-13.9kg	200/40mg	5ml	1/2 tab	-
14-29.9kg	400/80mg	10ml	1 tab	1/2 tab
>30kg	800/160mg	-	2 tabs	1 tab

(STG, PHC 2020)

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South African registered indications and dosages

40mg TMP/ 200mg SMZ (per 5ml) suspension; 80mg TMP/ 400mg SMZ and 160mg TMP/ 800mg SMZ tablets

Upper and lower respiratory tract infections
- Acute and chronic bronchitis, bronchiectasis, tonsillitis, sinusitis and pharyngitis, otitis media, pneumonia and pneumocystis carinii pneumonitis (Pneumocystis jirovecii pneumonitis)
Renal and urinary tract infections
- Pyelitis, pyelonephritis, urethritis, acute and chronic cystitis and cystopyelitis, including prostatitis
Gastrointestinal tract infections
- Enteritis, typhoid and paratyphoid fever, typhoid carriage, bacillary dysentery and cholera as an adjunct to fluid and electrolyte replacement
Genital tract infections
- Both male and female including gonococcal infections
Skin infections
- Pyoderma, boils, furuncles, abscesses
Other bacterial infections
- Acute brucellosis, mycetoma except those caused by true fungi, nocardiosis, acute and chronic osteomyelitis

Oral (sus)

• Younger than 6 weeks: Contraindicated
• Between 6 weeks to 5 months: 2.5ml, twice daily
• Between 6 months to 5 years: 5ml, twice daily
• Between 6-12 years: 10ml, twice daily

Oral (tab)

• Older than 12 years: See adult dosage

Pneumocystis jirovecii pneumonia
- Prophylaxis

• Oral (tab, sus): 150mg/m²/day TMP & 750mg/m²/day SMZ, in equally divided doses, 12hrly, on 3 consecutive days per week; Max: 320mg TMP/1600mg SMZ/24hrs

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In the treatment of acute infections trimethoprim/sulfamethoxazole should be administered for at least 5 days or for at least 2 days after the symptoms have disappeared. If clinical improvement is not evident after 7 days therapy, the patient should be reassessed

---

The tablets and suspension must be taken by mouth, after food. The tablets must be swallowed with a drink of water

---

80mg TMP/ 400mg SMZ (per 5ml) intravenous infusion

Used when oral admin. is impossible or not indicated. Ampoule for IV infusion can only be used following dilution with appropriate infusion solutions

Respiratory tract and ear infections
- Acute exacerbation of chronic bronchitis or otitis media in children caused by Haemophilus influenzae and Streptococcus pneumoniae
Urogenital tract infections 
- Caused by E.coli, Citrobacter freundii, other Citrobacter spp., Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Alcaligenes faecalis, Burkholderia cepacia, Providencia rettgeri, other Providencia spp., Stenotrophomonas maltophilia, Acinetobacter anitratus, Acinetobacter baumanii and chancroid caused by Haemophilus ducreyi
Gastrointestinal tract infections
- Typhoid and paratyphoid fever caused by Salmonella typhi and Salmonella paratyphi, shigellosis caused by susceptible strains of S.flexneri and S.sonnei (when antibacterial therapy is indicated) and cholera caused by Vibrio cholerae (as an adjunct to fluid and electrolyte therapy)
Other susceptible bacterial infections
- Brucellosis caused by Brucella and nocardiosis caused by Nocardia asteroides
Pneumocystis jirovecii pneumonia

• Younger than 6 weeks: Contraindicated
• Between 6 weeks to 12 years: IV: Average dosage: 2ml/5kg (6mg TMP/ 30mg SMZ) body weight, dly divided into 2 equal doses given in the morning and evening
• Older than 12 years: See adult dosage

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This dose requires adjustment to the patient's age, weight and renal function and to the severity of the disease. A duration of therapy of 18 months has been reported (for nocardiosis)

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Trimethoprim/sulfamethoxazole IV must be diluted before use. IV infusion to be used following dilution with the appropriate infusion solutions (See additional prescribing points)

Pregnancy

South African recommendations

• Contraindicated
• Trimethoprim and sulfamethoxazole cross the placenta and their safety in pregnant women has not been established and should not be used during pregnancy

Recommendations in other jurisdictions

• Caution; not recommended
• Trimethoprim and sulfamethoxazole cross the placenta and their safety in pregnant women has not been established. Case-control studies have shown that there may be an association between exposure to folate antagonists and birth defects in humans
• Trimethoprim is a folate antagonist and, in animal studies, both agents have been shown to cause foetal abnormalities
• Trimethoprim/ sulfamethoxazole should not be used in pregnancy, particularly in the first trimester, unless clearly necessary. Folate supplementation should be considered if trimethoprim/ sulfamethoxazole is used in pregnancy
• Sulfamethoxazole competes with bilirubin for binding to plasma albumin. As significantly maternally derived drug levels persist for several days in the newborn, there may be a risk of precipitating or exacerbating neonatal hyperbilirubinaemia, with an associated theoretical risk of kernicterus, when trimethoprim/ sulfamethoxazole is administered to the mother near the time of delivery. This theoretical risk is particularly relevant in infants at increased risk of hyperbilirubinaemia, such as those who are preterm and those with glucose-6-phosphate dehydrogenase deficiency

Breastfeeding

South African recommendations

• Contraindicated
• The components of trimethoprim and sulfamethoxazole are excreted in breast milk
• Administration of trimethoprim and sulfamethoxazole should be avoided in lactating mothers where the mother or infant has, or is at particular risk of developing, hyperbilirubinemia and should not be given to the newborn infant during the first weeks of life

Recommendations in other jurisdictions

• Caution; not recommended 
• Trimethoprim and sulfamethoxazole are excreted in breast milk. Administration of trimethoprim/ sulfamethoxazole should be avoided in breastfeeding mothers where the mother or infant has or is at particular risk of developing hyperbilirubinaemia
• Additionally, administration of trimethoprim/ sulfamethoxazole should be avoided in infants younger than eight weeks in view of the predisposition of young infants to hyperbilirubinaemia

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

South African recommendations

Suspension and tablets

• CrCl >25ml/min: No dose adjustment recommended
• CrCl 15-25ml/min: Caution; dose adjustment recommended
  Standard dosage for a maximum of 3 days followed by half the standard daily dosage
• CrCl <15ml/min: Contraindicated
  Not to be administered unless haemodialysis facilities are available when half the standard daily dosage may be given
  Measurements of plasma concentrations of sulfamethoxazole at intervals of 2 days are recommended in samples obtained 12 hours after administration of trimethoprim/sulfamethoxazole
  If the concentration of total sulfamethoxazole exceeds 150μg/ml then treatment should be interrupted until the value falls below 120μg/ml
  No Information is available for children with renal failure

Injection

Adults and children >12 years

• CrCl >30ml/min: No dose adjustment recommended
• CrCl 15-30ml/min: Caution; dose adjustment recommended
• CrCl ≤15ml/min: Contraindicated

Creatinine Clearance (ml/min)	Recommended Dosage
>30	100% of standard dose
15-30	50% of standard dose
<15	Not recommended

Recommendations in other jurisdictions

Adults and children >12 years

• CrCl >30ml/min: No dose adjustment recommended
• CrCl ≤30ml/min: Caution; dose adjustment recommended
  The elimination half-life of trimethoprim is increased by a factor of 1.5-3.0 when the creatinine clearance is less than 10ml/minute. When the creatinine clearance falls below 30ml/min the dosage of co-trimoxazole should be reduced
• CrCl ≤30ml/min: Contraindicated (where repeated measurements of the plasma concentration cannot be performed)

Creatinine Clearance (ml/min)	Recommended Dosage
>30	Oral (tab):160mg TMP/800mg SMZ, 12hrly Oral (sus): 80mg TMP/400mg SMZ, 12hrly IV: 2 amp (10ml), every 12hrs
15-30	Oral (tab): 80mg TMP/400mg SMZ, 12hrly Oral (sus): 40mg TMP/200mg SMZ, 12hrly IV: 1 amp (5ml), every 12hrs
<15	Not recommended

Measurements of plasma concentration of sulfamethoxazole at intervals of 2 to 3 days are recommended in samples obtained 12 hours after administration of co-trimoxazole. If the concentration of total sulfamethoxazole exceeds 150 microgram/ml then treatment should be interrupted until the value falls below 120 microgram/ml

Children ≤12 years

• Caution; no information available
• No information available for children aged 12 years and under with renal failure

South African recommendations

• Caution: no information available
  Use is contraindicated in patients with liver parenchymal damage

Recommendations in other jurisdictions

• Mild to moderate: Caution; no information available
  No data are available relating to dosage in patients with impaired hepatic function
  Caution should be exercised when treating patients with severe hepatic parenchymal damage as there may be changes in the absorption and biotransformation of trimethoprim and sulfamethoxazole
• Severe: Contraindicated

South African recommendations

• Caution; no dose adjustment recommended
  In elderly patients, a slight reduction in renal clearance of sulfamethoxazole but not trimethoprim has been observed (sus, tab)
  Elderly patients with normal renal function should receive the usual adult dosage (inj)

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Particular care is always advisable when treating elderly patients because, as a group, they are more susceptible to adverse reactions and more likely to suffer serious effects as a result particularly when complicating conditions exist, such as impaired renal and/or hepatic function and/or concomitant use of other drugs
  In elderly patients, a slight reduction in renal clearance of sulfamethoxazole but not trimethoprim has been observed

Central Nervous System Disorders

• Depression
• Hallucination
• Psychotic disorder
• Headache
• Aseptic meningitis
• Seizures
• Peripheral neuropathy
• Ataxia
• Dizziness

Respiratory Disorders

• Cough
• Dyspnoea
• Lung infiltration
• Respiratory hypersensitivity

Gastrointestinal Disorders

• Pseudomembranous colitis
• Nausea and vomiting
• Diarrhoea
• Glossitis
• Stomatitis
• Pancreatitis

Hepatobiliary Disorders

• Increased hepatic enzymes
• Cholestatic jaundice
• Hepatic necrosis
• Increased transaminases
• Increased blood bilirubin

Genitourinary Disorders

• Renal impairment (sometimes reported as renal failure)
• Tubulointerstitial nephritis
• Renal tubular acidosis

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hypoglycaemia
• Hyponatraemia
• Decreased appetite
• Metabolic acidosis

Musculoskeletal Disorders

• Rhabdomyolysis
• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Purpura
• Rash
• Photosensitivity
• Exfoliative dermatitis
• Angioedema
• Fixed drug eruption
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Acute generalised exanthematous pustulosis
• Acute febrile neutrophilic dermatosis (Sweet's syndrome)

Immune, Blood and Lymphatic System Disorders

• Fungal overgrowth
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Agranulocytosis
• Megaloblastic anaemia
• Aplastic anaemia
• Haemolytic anaemia
• Methaemoglobinaemia
• Eosinophilia
• Haemolysis (in certain susceptible G6PD deficient patients)
• Serum sickness
• Anaphylactic reaction
• Allergic myocarditis
• Hypersensitivity vasculitis resembling Henoch-Schoenlein purpura
• Periarteritis nodosa
• Systemic lupus erythematosus
• Severe hypersensitivity reactions associated with pneumocystis jirovecii pneumonitis
• Fever

Sensory Disorders

• Vertigo
• Uveitis
  - Uveitis syndrome
• Tinnitus

• Dofetilide
• Zidovudine
• Ciclosporin
• Rifampicin
• Agents that form cations at physiological pH and are also partly excreted by active renal secretion
• Procainamide
• Amantadine
• Thiazide diuretics
• Pyrimethamine
• Warfarin
• Phenytoin
• Digoxin
• Methotrexate
• Lamivudine
• Sulphonylurea hypoglycaemic agents
• Agents that cause hyperkalaemia
• ACE inhibitors
• Angiotensin receptor blockers
• Potassium-sparing diuretics
• Spironolactone
• Repaglinide
• Folic acid
• Oral contraceptives
• Azathioprine

Other

• Laboratory interactions (See additional prescribing points)

None routine. Specific cases may require

• Full blood count (particularly for long treatment periods)
• Serum potassium
• Renal function
• Blood urea nitrogen (BUN)

Additional observations

• Signs or symptoms of skin reactions

Instructions for use (IV)

• Trimethoprim/sulfamethoxazole must be diluted before administration
• The following infusion solutions can be used for dilution:
  - Glucose 5% and 10%
  - Xylitol 10%
  - Ringer's Solution
  - Dextran 70.6% in glucose 5%
  - Sodium chloride 0.9%
  - Sodium chloride 0.45% + glucose 2.5%
• Refer to product specific information for dilution schedules

Sulfamethoxazole competitively inhibits the utilisation of para-aminobenzoic acid in the synthesis of dihydrofolate by the bacterial cell resulting in bacteriostasis. Trimethoprim reversibly inhibits bacterial dihydrofolate reductase (DHFR), an enzyme active in the folate metabolic pathway converting dihydrofolate to tetrahydrofolate. Depending on the conditions the effect may be bactericidal. Thus trimethoprim and sulfamethoxazole block two consecutive steps in the biosynthesis of purines and therefore nucleic acids essential to many bacteria. This action produces marked potentiation of activity in vitro between the two agents.

Spectrum of activity: Haemophilus influenzae, Streptococcus pneumoniae, Pneumocystis jiroveci, Salmonella typhi, Salmonella paratyphi, S. flexneri, S. Sonnei, Vibrio cholerae, E. coli, Citrobacter freundii, other Citrobacter spp., Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Proteus mirabilis; Proteus vulgaris, Morganella morganii, Alcaligenes faecalis, Burkholderia cepacia, Providencia rettgeri, other Providencia spp., Stenotrophomonas maltophilia, Acinetobacter anitratus, Acinetobacter baumanii, Haemophilus ducreyi, Brucella, Nocardia asteroides

 

COMBINATION PREPARATIONS

Trimethoprim/ Sulfamethoxazole

Tablet 80mg/400mg

• Adco Co-Trimoxazole (Adcock)
• Bactrim Adult (Roche) originator
• Cascicot (Be-Tabs)
• Cozole (Be-Tabs)
• Doctrim Tablets ( Dezzo Trading)
• Durobac (Innovata)
• Ilvitrim (Medicine Dev)
• Lagatrim (Akacia)
• Novatrim (Svizera SA)
• Nucotrim (Gulf Drug)
• Pharma-Q Co-Trimoxazole (Pharma-Q)
• Purbac Adult (Pharmacare)
• Sandoz Co-Trimoxazole (Sandoz) 
• Trimethox (Caps Pharma)
• Trixazole (Medicine Dev)
• Ultrasept (Thebe)
• Xeroprim (Oethmaan Biosims)

Tablet 160mg/800mg

• Bactrim DS (Roche) originator
• Co-Trimoxazole Ascendis Ds (Dezzo)
• Co-Trimoxazole DS PharmC (Pharmacorp)
• Durobac DS (Innovata)
• Purbac DS (Pharmacare)
• Sandoz Co-Trimoxazole (Sandoz) 

Capsule 80mg/400mg

• Spectrim (Alliance) Discontinued: 21/12/2020

Suspension (per 5ml) 40mg/200mg

• Cascicot (Be-Tabs)
• Co-Trim (Alliance)
• Cozole (Be-Tabs)
• Doctrim (Gulf Drug)
• Dynazole (Thebe)
• Ilvitrim (Medicine Dev)
• Novatrim Suspension (Unimed Healthcare)
• Purbac Paed (Pharmacare)
• Resmed Co-Trimoxazole Oral Suspension (Resmed)
• Ultrasept (Thebe)
• Xerazole (F.D.C. SA)

Injection (per 5ml) 80mg/400mg

• Bactrim (Lebasi Pharmaceuticals) originator
• Pharma-Q Co-Trimoxazole (Pharma-Q)
• Purbac (Pharmacare)