Cotrimoxazole 400/80

Rx

Indications

Cotrimoxazole 400/80 tablets are indicated in children (12 – 18 years old) and adults (above 18 years old) for the treatment of the following infections when owing to sensitive organisms:

• Treatment and prevention of Pneumocystis jirovecii pneumonitis or “PJP”.
• Treatment and prophylaxis of toxoplasmosis.
• Treatment of nocardiosis.

The following infections may be treated with Cotrimoxazole where there is bacterial evidence of sensitivity to Cotrimoxazole and good reason to prefer the combination of antibiotics in Cotrimoxazole to a single antibiotic:

• Acute uncomplicated urinary tract infection.
• Acute otitis media.
• Acute exacerbation of chronic bronchitis.

Dosage:

Standard dosage recommendations for acute infections:

• Adults (above 18 years old):
  2 tablets every 12 hours.
• Children (12 – 18 years old):
  The standard dosage for children is equivalent to approximately 6 mg trimethoprim and 30 mg sulfamethoxazole per kg body weight per day, given in two equally divided doses. Two tablets every 12 hours.
  Treatment should be continued until the patient has been symptom free for two days; the majority will require treatment for at least 5 days. If clinical improvement is not evident after 7 days therapy, the patient should be reassessed.
  As an alternative to standard dosage for acute uncomplicated lower urinary tract infections, short-term therapy of 1 to 3 days duration has been shown to be effective.
• Elderly patients:
  See Special warnings and precautions for use. Unless otherwise specified standard dosage applies.
• Impaired hepatic function:
  No data are available relating to dosage in patients with impaired hepatic function.
• Impaired renal function in children (12 – 18 years old) and adults (> 18 years old):
  Creatinine clearance > 30 ml/min: Recommended dose is 2 tablets every 12 hours.
  Creatinine clearance 15 – 30 ml/min: Recommended dose is 1 tablet every 12 hours.
  Creatinine clearance < 15 ml/min: 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 Cotrimoxazole. If the concentration of total sulfamethoxazole exceeds 150 microgram/ml then treatment should be interrupted until the value falls below 120 microgram/ml.

Pneumocystis jirovecii pneumonitis:

• Treatment – children (12 – 18 years old) and adults (> 18 years old):
  A higher dosage is recommended, using 20 mg trimethoprim and 100 mg sulfamethoxazole per kg of body weight per day in two or more divided doses for two weeks. The aim is to obtain peak plasma or serum levels of trimethoprim of greater than or equal to 5 microgram/ml (verified in patients receiving 1-hour infusions of intravenous Cotrimoxazole).
• Prevention – Adults (> 18 years old):
  The following dose schedules may be used:
  2 tablets daily 7 days per week.
  2 tablets three times per week on alternative days.
  4 tablets per day in two divided doses three times per week on alternative days.
• Prevention – Children (12 – 18 years old):
  The standard dosage for children is equivalent to approximately 6 mg trimethoprim and 30 mg sulfamethoxazole per kg body weight per day, given in two equally divided doses.
  The following dose schedules may be used for the duration of the period at risk:
  2 tablets every 12 hours, seven days per week.
  2 tablets every 12 hours, three times per week on alternative days.
  2 tablets every 12 hours, three times per week on consecutive days.
  4 tablets once a day, three times per week on consecutive days.
  The daily dose given on a treatment day approximates to 150 mg trimethoprim/m²/day and 750 mg sulfamethoxazole/m²/day. The total daily dose should not exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole.

Nocardiosis – Adults (> 18 years old):
There is no consensus on the most appropriate dosage. Adult doses of 6 to 8 tablets daily for up to 3 months have been used.

Toxoplasmosis:

There is no consensus on the most appropriate dosage for the treatment or prophylaxis of this condition. The decision should be based on clinical experience. For prophylaxis, however, the dosages suggested for prevention of Pneumocystis jirovecii pneumonitis may be appropriate.

Usage

Cotrimoxazole 400/80 is administered orally with some food or drink.

• Hypersensitivity to the active substance(s) sulfonamides, trimethoprim or to any of the excipients.
• Patients with 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.
• Patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides.
• Patients with acute porphyria.

Very common

• Hyperkalaemia.

Common

• Overgrowth fungal.
• Headache.
• Nausea, diarrhoea.
• Rash.

• Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of Cotrimoxazole. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment. If symptoms or signs of SJS, TEN (e.g. progressive skin rash often with blisters or mucosal lesions) or DRESS (e.g. fever, eosinophilia) are present, Cotrimoxazole treatment should be discontinued.
• At the start of treatment, the occurrence of a generalised febrile erythema associated with pustules, should raise the suspicion of acute generalised exanthematous pustulosis (AGEP); it requires cessation of treatment and contraindicates any new administration of Cotrimoxazole alone or in combination with other drugs.
• 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, e.g. impaired kidney and/or liver function and/or concomitant use of other drugs.
• For patients with known renal impairment special measures should be adopted.
• An adequate urinary output should be maintained at all times. Evidence of crystalluria in vivo is rare, although sulfonamides crystals have been noted in cooled urine from treated patients. In patients suffering from malnutrition the risk may be increased.
• Regular monthly blood counts are advisable when Cotrimoxazole is given for long periods, or to folate deficient patients or to the elderly; since there exists a possibility of asymptomatic changes in haematological laboratory indices due to lack of available folate. Supplementation with folinic acid may be considered during treatment but this should be initiated with caution due to possible interference with antimicrobial efficacy.
• In glucose-6-phosphate dehydrogenase (G-6-PD) deficient patients haemolysis may occur.
• Cotrimoxazole should be given with caution to patients with severe atopy or bronchial asthma.
• Cotrimoxazole should not be used in the treatment of streptococcal pharyngitis due to Group A beta-haemolytic streptococci; eradication of these organisms from the oropharynx is less effective than with penicillin.
• Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
• The administration of Cotrimoxazole to patients known or suspected to be at risk of porphyria should be avoided. Both trimethoprim and sulphonamides (although not specifically sulfamethoxazole) have been associated with clinical exacerbation of porphyria.
• Close monitoring of serum potassium is warranted in patients at risk of hyperkalaemia and hyponatraemia.
  Cotrimoxazole has been associated with metabolic acidosis when other possible underlying causes have been excluded. Close monitoring is always advisable when metabolic acidosis is suspected.
• Except under careful supervision Cotrimoxazole should not be given to patients with serious haematological disorders. Cotrimoxazole has been given to patients receiving cytotoxic therapy with little or no additional effect on the bone marrow or peripheral blood.
• The combination of antibiotics in Cotrimoxazole should only be used where, in the judgement of the physician, the benefits of treatment outweigh any possible risks; consideration should be given to the use of a single effective antibacterial agent.
• Cotrimoxazole should not be used in pregnancy, particularly in the first trimester, unless clearly necessary. Folate supplementation should be considered if Cotrimoxazole is used in pregnancy.
• Administration of Cotrimoxazole should be avoided in lactating mothers where the mother or infant has, or is at particular risk of developing, hyperbilirubinaemia. Additionally, administration of Cotrimoxazole should be avoided in infants younger than eight weeks in view of the predisposition of young infants to hyperbilirubinaemia.
• Patients should be aware of how they react to drug before driving or operating machinery.