Trimethoprim with sulfamethoxazole

Sulfamethoxazole is a sulfonamide

See also Trimethoprim with sulfamethoxazole (table)

For drug interactions see Trimethoprim, Trimethoprim with sulfamethoxazole

Also known as co-trimoxazole.

Mode of action

Sulfamethoxazole and trimethoprim are bacteriostatic; they competitively inhibit bacterial folate production essential for bacterial growth.

Indications

Treatment and primary and secondary prevention of PJP

Infections caused by L. monocytogenes (alternative to ampicillin or benzylpenicillin), Nocardia spp., Stenotrophomonas maltophilia

Melioidosis (with other agents)

Shigellosis

Primary prevention of cerebral toxoplasmosis in HIV patients

Prevention and treatment of pertussis (if a macrolide unsuitable)

Community-acquired MRSA infections, eg skin and soft tissue infections

Precautions

Serious allergic reaction to sulfonamides—contraindicated.

Previous drug-induced immune thrombocytopenia from trimethoprim or sulfonamides—contraindicated.

HIV infection—increases frequency of allergic reactions to drugs; these are often intolerable and may require use of an alternative. Desensitisation may allow reintroduction of trimethoprim with sulfamethoxazole (see Practice points).

Systemic lupus erythematosus—may worsen due to sulfonamide.

Slow acetylator phenotype—greater risk of adverse effects with sulfonamides.

Treatment with oral typhoid vaccine—trimethoprim with sulfamethoxazole is active against S. typhi and may inactivate the vaccine.

Drugs that cause potassium retention, eg ACE inhibitors—increase risk of hyperkalaemia; monitor potassium concentration.

Blood

Contraindicated in megaloblastic anaemia due to folate deficiency.

Folate deficiency may worsen, increasing risk of blood dyscrasias; consider using calcium folinate supplement. Blood dyscrasias may worsen.

Sulfonamides increase the risk of haemolysis in G6PD deficiency.

Renal

Contraindicated by the manufacturer if CrCl <15 mL/minute.

Impairment increases risk of hyperkalaemia or hypoglycaemia occurring. Reduce dose to avoid sulfamethoxazole accumulation.

Low urine pH increases risk of crystalluria (sulfamethoxazole poorly soluble at low pH).

Hepatic

Contraindicated in severe impairment. Hepatic impairment may increase risk of adverse effects.

Elderly

Avoid use; increased risk of severe adverse effects (particularly blood dyscrasias and skin disorders).

Children

Manufacturer contraindicates use in preterm babies and in babies <6 weeks old due to theoretical increased risk of kernicterus (sulfonamides displace bilirubin from plasma albumin). However, there is no evidence that this occurs with sulfamethoxazole and the WHO recommends trimethoprim with sulfamethoxazole for serious neonatal infections in developing countries.

Pregnancy

Avoid trimethoprim in the first trimester as its use (alone or in combination with sulfamethoxazole) has been associated with congenital anomalies (eg oral clefts, cardiovascular and neural tube defects) and an increased risk of miscarriage.

Sulfamethoxazole is contraindicated in late pregnancy due to the risk of haemolytic anaemia, jaundice and, theoretically, kernicterus in the neonate.

Breastfeeding

Safe if neonate is healthy and full-term; avoid if ill, stressed or preterm infant, and in those with hyperbilirubinaemia or G6PD deficiency.

Adverse effects

See also Sulfadiazine, Trimethoprim

Some adverse effects may be hypersensitivity reactions; the most common adverse effects are GI and skin sensitivity reactions.

Incidence of some adverse effects (rash, fever, nausea, neutropenia, thrombocytopenia, raised hepatic aminotransferases) is substantially higher in patients with AIDS.

Common (>1%)

fever, nausea, vomiting, diarrhoea, anorexia, rash, itch, sore mouth, hyperkalaemia, thrombocytopenia (rarely significant)

Infrequent (0.1–1%)

headache, drowsiness, photosensitivity, blood dyscrasias, eg neutropenia

Rare (<0.1%)

megaloblastic anaemia, methaemoglobinaemia, erythema, hypoglycaemia (may affect consciousness and cause seizures), hyponatraemia, hepatitis, crystalluria, urinary obstruction with anuria/oliguria, lowered mental acuity, depression, tremor, ataxia (after IV use in HIV patients), Clostridioides difficile-associated disease, aseptic meningitis, circulatory shock (mainly in immunocompromised patients)

Hypersensitivity

May present with fever, dyspnoea, cough, rash, eosinophilia; the most serious effects include anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness-like syndrome, lupus-like syndrome, multi-organ hypersensitivity syndrome, pneumonitis, hepatitis, interstitial nephritis, systemic vasculitis and pancytopenia.

Dosage – Trimethoprim with sulfamethoxazole

Ratio of trimethoprim to sulfamethoxazole is 1:5.

Doses are expressed as: 160/800 mg = trimethoprim 160 mg with sulfamethoxazole 800 mg (equivalent to 1 double strength tablet).

8/40 mg is equivalent to 1 mL of oral liquid.

Mild-to-moderate infections

Adult, oral 80/400–160/800 mg every 12 hours.

Child, oral 4/20 mg/kg every 12 hours (for 3 days for impetigo).

Severe infections

Adult, IV 160/800–320/1600 mg every 12 hours.

Child, IV 5/25 mg/kg every 12 hours.

Maximum

Oral/IV, 20/100 mg/kg daily in divided doses (in PJP).

Renal impairment

Adult, CrCl 25–50 mL/minute, oral/IV 160/800 mg every 12 hours for 14 days, then 160/800 mg every 24 hours.

Adult, CrCl 15–25 mL/minute, oral/IV 160/800 mg every 12 hours for 3 days, then 160/800 mg every 24 hours.

Adult, CrCl <15 mL/minute, seek specialist advice.

Melioidosis

See also Table – Melioidosis

Use with ceftazidime or meropenem for acute treatment and alone for maintenance.

Adult >60 kg, oral/IV 320/1600 mg every 12 hours.

Adult 40–60 kg, oral/IV 240/1200 mg every 12 hours.

Child, oral/IV 6/30 mg/kg (maximum 240/1200 mg) every 12 hours.

PJP

Treatment

Adult, oral/IV 5/25 mg/kg every 6–8 hours for 21 days.

Child, oral/IV 5/25 mg/kg (maximum 320/1600 mg) every 6–8 hours for 21 days.

Primary or secondary prevention

Seek specialist advice. Local protocols may differ from the doses below.

Adult, oral 80/400–160/800 mg once daily; or 160/800 mg once daily on 3 days a week.

Child, oral 2.5/12.5 mg/kg (maximum 160/800 mg) twice daily on 3 days a week.

Shigellosis

Adult, oral 160/800 mg every 12 hours for 5 days.

Child, oral 4/20 mg/kg (maximum 160/800 mg) every 12 hours for 5 days.

Primary prevention of toxoplasmosis

Adult, oral 80/400–160/800 mg once daily; or 160/800 mg once daily on 3 days a week.

Child, oral 5/25 mg/kg daily in 2 doses, or 5/25 mg/kg in 1 or 2 doses on 3 days a week.

Pertussis prevention and treatment

Adult, oral 160/800 mg every 12 hours for 7 days.

Child, oral 4/20 mg/kg (maximum 160/800 mg) every 12 hours for 7 days.

Administration advice

IV: dilute each 5 mL in 100–125 mL fluid (75 mL if fluid restricted), preferably glucose 5%, and infuse over 60–90 minutes.

Counselling

Take this medicine with food to reduce stomach upset. Drink a lot of fluid (at least 2–3 L daily) during prolonged or high-dose treatment.

To reduce risk of rash from the sun avoid sun exposure, wear protective clothing and use sunscreen.

Tell your doctor straight away if you get a sore throat, fever, troublesome rash, cough, difficulty in breathing, joint pain, dark urine or pale stools.

Practice points

use trimethoprim alone for common infections in adults (particularly UTI); trimethoprim with sulfamethoxazole offers no advantage and there is a higher incidence of adverse effects

to prevent crystalluria maintain adequate urine output; recommended adult fluid intake is at least 2–3 L in 24 hours

stop if rash or other symptom of hypersensitivity develops

people allergic to, or unable to tolerate, trimethoprim with sulfamethoxazole may benefit from desensitisation if use of this agent is considered necessary

Monitor

complete blood count and folate status during prolonged or high-dose treatment

renal function and obtain urinalysis each month during prolonged treatment, particularly in people with pre-existing renal impairment

serum potassium in patients taking trimethoprim for more than 3 days and at risk of hyperkalaemia; risk factors include high dose, renal impairment, older age and use of other drugs that can cause hyperkalaemia

PJP

drug of choice for most people, but HIV patients have a higher incidence of fever, dermatological and haematological reactions

in patients with HIV and significant hypoxia, begin corticosteroids at the same time as trimethoprim with sulfamethoxazole to prevent early deterioration and accelerate recovery

Products

Search for Trimethoprim with sulfamethoxazole on the PBS

tab, trimethoprim 80 mg, sulfamethoxazole 400 mg (scored), 10, Resprim

tab, trimethoprim 160 mg, sulfamethoxazole 800 mg (scored), 10, Bactrim DS, Resprim Forte, Septrin Forte, PBS/PBS-A[30]1

oral liquid, trimethoprim 8 mg/mL, sulfamethoxazole 40 mg/mL, 100 mL, Septrin, PBS

inj, trimethoprim 16 mg/mL, sulfamethoxazole 80 mg/mL, 5 mL, 10, Bactrima

1 prophylaxis of PJP

a generic brands available