Co-trimoxazole (trimethoprim and sulfamethoxazole) oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing co-trimoxazole (trimethoprim and sulfamethoxazole).
Drugs List
Therapeutic Indications
Uses
Co-trimoxazole sensitive infections
Pneumocystis jirovecii: prophylaxis
Pneumocystis jirovecii: treatment
Treatment of nocardial infections
Treatment and prophylaxis of Pneumocystis jirovecii pneumonitis. Treatment and prophylaxis of toxoplasmosis. Treatment of nocardiosis.
Treatment of co-trimoxazole sensitive infections, including acute exacerbation of chronic bronchitis, acute uncomplicated urinary tract infections and acute otitis media.
Unlicensed Uses
Treatment of Stenotrophomonas maltophilia, Burkholderia cepacia in cystic fibrosis and hospital acquired pneumonia in adults.
Dosage
Treatment should be continued until patients are symptom free for 2 days. The majority of patients will require at least 5 days of treatment. If clinical improvement is not evident after 7 days of therapy, the patient should be reassessed. For acute uncomplicated lower urinary tract infections, short-term therapy of 1 to 3 days duration has been shown to be effective.
Adults
Acute infections
Co-trimoxazole 160mg + 800mg every 12 hours. This dosage approximates to 6mg trimethoprim and 30mg sulfamethoxazole per kilogram body weight per 24 hours.
Treatment of Pneumocystis jiroveci pneumonitis
Co-trimoxazole 20mg + 100mg/kg daily in two or more divided doses for two weeks.
The aim is to obtain peak plasma or serum levels of trimethoprim of equal to or greater than 5 microgram/ml (verified in patients receiving 1 hour infusions of intravenous co-trimoxazole).
Prophylaxis of Pneumocystis jiroveci pneumonitis
Co-trimoxazole 160mg + 800mg once daily.
OR
Co-trimoxazole 160mg + 800mg three times per week on alternate days.
OR
Co-trimoxazole 320mg + 1600mg daily in two divided doses three times per week on alternate days.
This dosage approximates to co-trimoxazole 150mg + 750mg per square metre daily. The total daily dose should not exceed co-trimoxazole 320mg + 1600mg.
Treatment of nocardiosis
6 to 8 tablets of co-trimoxazole 80mg + 400mg daily for up to three months have been used.
Treatment and prophylaxis of toxoplasmosis
There is no consensus on the most appropriate dosage for the prophylaxis of this condition. The decision should be based on clinical experience.
However for prophylaxis the dosages suggested for prophylaxis of Pneumocystis jiroveci pneumonitis may be appropriate.
Children
Acute infections
Children aged 12 to 18 years
Co-trimoxazole 160mg + 800mg every 12 hours. This dosage approximates to 6mg trimethoprim and 30mg sulfamethoxazole per kilogram body weight per 24 hours, given in two equally divided doses.
Children aged 6 to 12 years
Co-trimoxazole 80mg + 400mg every 12 hours.
Children aged 6 months to 6 years
Co-trimoxazole 40mg + 200mg every 12 hours.
Children aged 6 weeks to 6 months
Co-trimoxazole 20mg + 100mg every 12 hours.
Treatment of Pneumocystis jiroveci pneumonitis
Children aged 6 weeks to 12 years
Co-trimoxazole 20mg + 100mg/kg daily in two to four divided doses for fourteen to twenty one days.
The aim is to obtain peak plasma or serum levels of trimethoprim of equal to or greater than 5 microgram/ml (verified in patients receiving 1 hour infusions of intravenous co-trimoxazole).
Prophylaxis of Pneumocystis jiroveci pneumonitis
Children aged 6 to 12 years
Co-trimoxazole 80mg + 400mg according to one of the schedules below.
Children aged 6 months to 5 years
Co-trimoxazole 40mg + 200mg according to one of the schedules below.
Children aged 6 weeks to 5 months
Co-trimoxazole 20mg + 100mg according to one of the schedules below.
The following dose schedules may be suitable:
In two divided doses daily 7 days per week.
In two divided doses three times per week on alternate days.
In two divided doses three times per week on consecutive days.
In a single dose three times per week on consecutive days.
This dosage approximates to co-trimoxazole 150mg + 750mg per square metre daily. The total daily dose should not exceed co-trimoxazole 320mg + 1600mg.
The following alternative dosage schedule may be suitable.
Children aged 1 month to 18 years
Co-trimoxazole 75mg + 375mg per square metre body surface area (up to a maximum of 160mg + 800mg) twice daily for three days of the week (either consecutively or on alternate days).
Patients with Renal Impairment
Adults and adolescents over 12 years of age
Creatinine clearance greater than 30ml/minute
No dosage adjustment necessary.
Creatinine clearance 15 to 30ml/minute
Administer half the standard dose.
Creatinine clearance less than 15ml/minute
Not recommended.
Measurements of plasma concentration of sulfamethoxazole at intervals of two to three days are recommended in samples obtained 12 hours after administration. If the concentration of total sulfamethoxazole exceeds 150 microgram/ml then treatment should be interrupted until the value falls below 120 microgram/ml.
Contraindications
Children under 6 weeks - if for the treatment of acute infection
Neonates under 6 weeks - if for the prophylaxis of pneumocystis pneumonia
Neonates under 6 weeks - if for the treatment of pneumocystis pneumonia
Acute porphyria
Megaloblastic anaemia secondary to folate deficiency
Renal impairment - creatinine clearance below 15ml/minute
Severe hepatic impairment
Precautions and Warnings
Allergic disposition
Elderly
Females of childbearing potential
Alcoholism
Asthma
Breastfeeding
Folate deficiency
G6PD deficiency
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
Malabsorption syndrome
Malnutrition
Mild hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below or equal to 30ml/minute
Rheumatoid arthritis
Severe haematological disorder
Consider reducing dose if creatinine clearance is < or equal to 30ml/min
Monitor for haemolysis in G6PD deficiency
Advise patient ability to drive or operate machinery may be impaired
Consult national/regional policy on the use of anti-infectives
Folate supplementation may be necessary in some patients
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain sucrose
Some formulations may contain alcohol
Ensure patient has adequate fluid intake
Maintain hydration and urinary output
Monitor for signs of bone marrow depression
Monitor plasma levels and adapt dose in patients with renal impairment
Monitor plasma potassium in patients at risk of hyperkalaemia
Monitor plasma sodium in patients at risk of hyponatraemia
Perform blood counts in patients with alcohol dependence
Perform blood counts on prolonged use of this treatment
Advise patient to seek immediate medical advice if rash occurs
Discontinue treatment if Stevens-Johnson Syndrome suspected
Superinfection may occur during therapy
May affect results of some laboratory tests
Discontinue if blood dyscrasia develops
Discontinue treatment if rash occurs
Female: Barrier or non-hormonal contraception required during treatment
Co-trimoxazole should only be used where, in the judgement of the physician, the benefits of treatment outweigh any possible risks and only when preferable to using a single agent.
Co-trimoxazole should not be administered to patients with severe haematological disorders, unless they are under close supervision.
Severe reactions and fatalities have been reported including Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract. Advise patient to report signs of rash. If signs or symptoms of progressive skin rash are present, co-trimoxazole should be permanently discontinued.
Monitor blood counts monthly in patients on long-term treatment as asymptomatic changes may occur due to the lack of available folate. Blood counts should also be taken in patients who are predisposed to folate deficiency (such as the elderly, chronic alcoholics and patients with rheumatoid arthritis), patients with malabsorption syndromes or malnutrition, and patients receiving concurrent anticonvulsant medication.
It is essential to maintain an adequate fluid intake and urinary output. Evidence of crystalluria in vivo is rare, although sulfonamide crystals have been noted in cooled urine from treated patients. Patients suffering from malnutrition may be at increased risk of crystalluria.
Pregnancy and Lactation
Pregnancy
Use co-trimoxazole with caution in pregnancy.
The manufacturer does not recommend the use of co-trimoxazole during pregnancy, especially in the first trimester of pregnancy unless clearly necessary. Also recommending that if co-trimoxazole is used during pregnancy, folate supplementation should be considered.
In animal studies trimethoprim and sulfamethoxazole have been shown to cause foetal abnormalities, including cardiovascular defects, neural tube defects and oral clefts.
At the time of writing, there is little published information regarding the use of co-trimoxazole during pregnancy. Trimethoprim and sulfamethoxazole have been shown to cross the placenta. Folic acid supplementation started before conception, or concurrently, may decrease the risk of congenital defects, associated with folate antagonists use during pregnancy.
Co-trimoxazole can cause neonatal haemolysis and methaemoglobinaemia when used in the third trimester. If co-trimoxazole is administered close to the delivery, hyperbilirubinaemia and associated kernicterus may occur in the neonate. This theoretical risk is more likely in infants at an increased risk of hyperbilirubinaemia, such as preterm babies and those with glucose-6-phosphate dehydrogenase deficiency (Briggs, 2015).
Lactation
Use co-trimoxazole with caution during breastfeeding.
The manufacturer recommends that co-trimoxazole should be avoided during breastfeeding, where the mother or infant has, or is at particular risk of developing, hyperbilirubinaemia. Additionally, administration of co-trimoxazole for should be avoided during breastfeeding where the breastfed infant is younger than eight weeks due to the increased risk of hyperbilirubinaemia in the infant.
Trimethoprim and sulfamethoxazole are excreted into breast milk. Briggs (2015) recommends that sulfonamides should be avoided in ill, stressed or premature infants, infants with hyperbilirubinaemia or glucose-6-phosphate dehydrogenase deficiency.
Side Effects
Agranulocytosis
Allergic myocarditis
Anaphylaxis
Angioedema
Anorexia
Antibiotic-associated colitis
Aplastic anaemia
Arthralgia
Aseptic meningitis
Ataxia
Blood dyscrasias
Bone marrow depression
Cholestatic jaundice
Convulsions
Cough
Crystalluria
Depression
Diarrhoea
Dizziness
Drug fever
Eosinophilia
Erythema multiforme
Exfoliative dermatitis
Fever
Fixed drug eruption
Glossitis
Haemolysis
Haemolytic anaemia
Hallucinations
Headache
Hepatic impairment
Hepatic necrosis
Hyperkalaemia
Hypersensitivity reactions
Hypoglycaemia
Hyponatraemia
Increase of liver transaminases
Interstitial nephritis
Jaundice
Leucopenia
Megaloblastic anaemia
Methaemoglobinaemia
Moniliasis
Myalgia
Myocarditis
Nausea
Neutropenia
Pancreatitis
Periarteritis nodosa
Peripheral neuritis
Peripheral neuropathy
Photosensitivity
Pseudomembranous colitis
Pulmonary infiltrates
Purpura
Rash
Renal impairment
Rhabdomyolysis
Serum bilirubin increased
Serum sickness
Shortness of breath
Stevens-Johnson syndrome
Stomatitis
Systemic lupus erythematosus
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Uveitis
Vasculitis (allergic)
Vertigo
Vomiting
Effects on Laboratory Tests
Trimethoprim and sulfonamides have been reported to interfere with diagnostic tests including serum-methotrexate and serum plasma creatinine levels, also urea, urinary glucose and urobilinogen tests.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2020
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Co-Trimoxazole 80/400mg Tablets. Accord UK Ltd. Revised November 2019.
Summary of Product Characteristics: Co-Trimoxazole 80/400mg Tablets. Aspen. Revised March 2018.
Summary of Product Characteristics: Co-Trimoxazole 40mg/200mg per 5ml Paediatric Suspension. Aspen. Revised March 2018.
Summary of Product Characteristics: Co-Trimoxazole 80mg/400mg per 5ml Adult Suspension. Aspen. Revised March 2018.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 February 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.