Pharmacokinetics in children

The following mean ± SD (range) pharmacokinetic parameters have been observed after intravenous administration [Hoppu 1989; Siber 1982; Autmizguine 2017]:

* l/hour; **median, oral administration

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

The IV fluid contains propylene glycol and ethanol. In children < 5 years of age, the maximum tolerated dose of propylene glycol is already exceeded at normal doses. Sulfametrol + trimethoprim (Rokiprim) is therefore preferred .

Dosages

Renal impaiment in children > 3 months

Infection, infection in CF (normal to very high doses), treatment of pneumonia caused by Pneumocystis jirovecii:
GFR 50-80 ml/min/1.73m²: No adjustment needed
GFR 30-50 ml/min/1.73m²: No adjustment needed
GFR 10-30 ml/min/1.73m²: 100% of the normal dose each time and the interval between two doses: 24 hours
GFR < 10 ml/min/1.73m²: Contraindicated

Prophylaxis of recurrent urinary tract/respiratory tract infections:
GFR 50-80 ml/min/1.73m²: No adjustment needed
GFR 30-50 ml/min/1.73m²: No adjustment needed
GFR 10-30 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 24 hours
GFR < 10 ml/min/1.73m²: Contraindicated

Prophylaxis of pneumonia caused by Pneumocystis jirovecii:
GFR 50-80 ml/min/1.73m²: No adjustment needed
GFR 30-50 ml/min/1.73m²: No adjustment needed
GFR 10-30 ml/min/1.73m²: No adjustment needed
GFR < 10 ml/min/1.73m²: Contraindicated

Clinical consequences

In reduced renal function, the clearance of trimethoprim, sulfamethoxazole and the N-acetyl metabolite of sulfamethoxazole decreases. The risk of side effects is elevated as a result. The side effects of sulphonamides include crystalluria, kidney stones, renal colic, nephritis, haematuria, albuminuria, oliguria and anuria, due to crystals of poorly soluble sulphonamides being formed. This can be reduced by sufficient diuresis and alkalization of the urine. Abnormalities have occurred in the blood count on rare occasions. The N4-acetyl metabolites have no antimicrobial activity but do cause the same side effects as the sulphonamides. Side effects of trimethoprim include reduced haematopoiesis due to interference with the metabolization of folic acid during long-term or high-dosage use. Serum creatinine concentration may possibly increase; this is mostly reversible after the drug is discontinued. At a daily dosage of 20 mg/kg bodyweight, hyperkalaemia may develop slowly. If the level is not high enough, the antibacterial effect may possibly not be sufficient.

Patients on dialysis

Infection, infections in CF (normal to very high dose):
PD, IHD, CVVH: 100% of the normal dose each time and the interval between two doses: 24 hours

Prophylaxis of recurrent urinary tract/respiratory tract infections:
PD, IHD, CVVH: 50% of the normal dose each time and the interval between two doses: 24 hours

Treatment of pneumonia caused by Pneumocystis jirovecii:
PD, IHD: 100% of the normal dose each time and the interval between two doses: 24 hours
CVVH: No generalized recommendations are given. At low GFR values, there is a relative contraindication for co-trimoxazole. CVVH gives some clearance. The dosage should be selected and adjusted according to the indication, the residual renal function, CVVH settings and level measurements.

Prophylaxis of pneumonia caused by Pneumocystis jirovecii:
PD, IHD, CVVH: no adjustment needed

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Allergic skin reaction and rashes occur regularly in children. Further: nausea, vomiting, diarrhoea, diarrhoea, headaches, fever, kidney damage, hepatitis, hepatic function disorders, myelosuppression [Boast 2015], itching [Miller 2015]. Rarely: convulsions, abnormal blood counts (such as thrombocytopenia [Hayashi 2015] and neutropenia [Boast 2015]), pseudomembranous colitis, epidermal necrolysis, erythema multiforme and Stevens-Johnson syndrome. The risk of abnormal blood counts is exacerbated at high dosages such as for Pneumocystis jirovecii.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The co-trimoxazole infusion solution may only be administered intravenously by means of an infusion but must not be injected into the veins undiluted. It should also be noted that the concentrate for solution for intravenous infusion contains propylene glycol and ethanol. 

Although co-trimoxazole is contraindicated in severe haematological abnormalities, it may be necessary in certain cases (AIDS patients). Regular blood tests are recommended in such cases. It is also advisable to carry out regular blood tests when treatment lasts longer than 14 days. In high dosages, the plasma concentration should also be determined.

The dose should be adjusted in patients with hepatic and/or renal function disorders. If treatment in this group of patients is continued for a prolonged period, urine analysis and renal function tests should be done regularly.

High doses of trimethoprim such as those used in treating Pneumocystis jirovecii pneumonia can cause progressive but reversible increases in serum potassium. Lower trimethoprim dosages can also result in hyperkalaemia in the event of underlying abnormalities in the potassium metabolism, renal function disorders or concomitant use of drugs that can cause hyperkalaemia. Accurate checks of serum potassium are needed in these patients.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIBACTERIALS FOR SYSTEMIC USE

SULFONAMIDES AND TRIMETHOPRIM

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

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Changes

Therapeutic Drug Monitoring

Overdose