Last Updated on eMC 14-12-2017 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text
  • Improved presentation of SPC

Date of revision of text on the SPC:08-12-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text

Text strikethrough = deleted text

 

 

 

4.1       Therapeutic indications

 

Co-Trimoxazole Forte tablets are indicated in children (>12 to <18 years old) and adults (>18 years old) for the treatment of the following infections when owing to sensitive organisms (see section 5.1).

 

•           Treatment and prevention of Pneumocystis jirovecii pneumonitis or “PJP”. (previously known as Pneumocystis carinii pneumonia or “PCP”).

 

 

4.2       Posology and method of administration

 

 

 

Posology:

 

Standard dosage recommendations for acute infections

 

Children aged 12 years and under (infants (>6 weeks to <2 years old) and children (>2 to <12 years old)

Paediatric patients aged 12 years and under:

 

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 schedules for children are according to the child’s age and provided in the table below:

 

This dosage approximates to 6 mg trimethoprim and 30 mg sulfamethoxazole per kilogram body weight per 24 hours.

 

Special dosage recommendations

 

(Standard dosage applies unless otherwise specified)

 

Impaired hepatic function:

No data are available relating to dosage in patients with impaired hepatic function.

 

Impaired renal function:

Dosage recommendation:

Adults (>18 years old) and children over 12 years old (>12 to <18 years old):

 

Creatinine Clearance (ml/min)  Recommended Dosage

>30      10 ml every 12 hours

15 to 30            5 ml every 12 hours

<15      Not recommended

 

No information available for children aged 12 years and under with renal failure. See section 5.2 for the pharmacokinetics in the paediatric population with normal renal function of both components of Co-Trimoxazole TMP and SMZ.

 

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.

 

 

Pneumocystis jirovecii pneumonitis:

 

Treatment - Children aged 12 years and under (infants (>6 weeks to <2 years old) and children (>2 to <12 years old):

A higher dosage is recommended, using 20 mg trimethoprim and 100 mg sulfamethoxazole per kg of body weight per day (see table below) 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 Co-Trimoxazole) (see section 4.8).

 

Prevention - Children aged 12 years and under (infants (>6 weeks to <2 years old) and children (>2 to <12 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 schedules according to the child’s age that may be used for the duration of the period at risk are provided in the table below:

 

 

Age      Paediatric Suspension

6 to 12 years     10 ml every 12 hours, seven days per week

6 to 12 years     10 ml every 12 hours, three times per week on alternative days

6 to 12 years     10 ml every 12 hours, three times per week on consecutive days

6 to 12 years     20 ml once a day, three times per week on consecutive days

           

6 months to 5 years      5 ml every 12 hours, seven days per week

6 months to 5 years      5 ml every 12 hours, three times per week on alternative days

6 months to 5 years      5 ml every 12 hours, three times per week on consecutive days

6 months to 5 years      10 ml once a day, three times per week on consecutive days

           

6 weeks to 5 months     2.5 ml every 12 hours, seven days per week

6 weeks to 5 months     2.5 ml every 12 hours, three times per week on alternative days

6 weeks to 5 months     2.5 ml every 12 hours, three times per week on consecutive days

6 weeks to 5 months     5 ml once a day, three times per week on consecutive days

 

The following dose schedules may be used for the duration of the period at risk (see Standard dosage recommendations for acute infections subsection of section 4.2):

 

-           Standard dosage taken in two divided doses, seven days per week.

 

-           Standard dosage taken in two divided doses, three times per week on alternate days.

 

-           Standard dosage taken in two divided doses, three times per week on consecutive days.

 

-           Standard dosage taken as a single dose, three times per week on consecutive days.

 

Paediatric patients aged 12 years and under with renal impairment:

 

No data are available relating to dosage in paediatric patients aged 12 years and under with impaired renal function.

 

Paediatric patients aged 12 years and under with hepatic impairment:

 

No data are available relating to dosage in paediatric patients aged 12 years and under with impaired hepatic function.

 

4.3       Contraindications

 

 

•           Co-Trimoxazole should not be given to patients with a history of  Hypersensitivity to the active substance(s) sulphonamides, trimethoprim, co-trimoxazole, or to any of the excipients listed in section 6.1of Co-Trimoxazole.

•           Severe hepatic parenchymal damage. Patients with severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed.

•           Co-Trimoxazole should not be given to patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides.

•           Co-Trimoxazole should not be given to patients with acute porphyria.

•           Co-Trimoxazole should not be given to infantspremature babies nor to full-term infants during the first 6 weeks of life except for the treatment /prophylaxis of PJP in infants 4 weeks of age or greater.

 

5.2       Pharmacokinetic properties

 

The pharmacokinetics in the paediatric population with normal renal function of both components of Co-Trimoxazole, TMP and SMZ are age dependent. Elimination of TMP-SMZ is reduced in neonates, during the first two months of life, thereafter both TMP and SMZ show a higher elimination with a higher body clearance and a shorter elimination half-life. The differences are most prominent in young infants (> 1.7 months up to 24 months) and decrease with increasing age, as compared to young children (1 year up to 3.6 years), children (7.5 years and < 10 years) and adults (see section 4.2).

 

 

 

 

10        DATE OF REVISION OF THE TEXT

 

 

 

November 2017 08/12/2017 03/01/2017

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:03-01-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text

Text strikethrough = deleted text

 

2          QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 5 ml contains 40 mg Trimethoprim and 200 mg Sulfamethoxazole and 40 mg Trimethoprim

 

 

4.2       Posology and method of administration

 

Method of administration:  oral.

It may be preferable to take Septrin with some food or drink to minimise the possibility of gastrointestinal disturbances.

Posology:

 

 

Children Paediatric patients aged 12 years and under:

 

 

Method of administration:

 

Oral

 

It may be preferable to take Co-Trimoxazole Septrin with some food or drink to minimise the possibility of gastrointestinal disturbances.

 

 

4.3       Contraindications

 

•           Co-Trimoxazole Septrin should not be given to patients with a history of hypersensitivity to sulphonamides, trimethoprim, co-trimoxazole or any excipients of Co-TrimoxazoleSeptrin.

•           Severe hepatic parenchymal damage. Contra-indicated in patients showing marked liver parenchymal damage.

•           Contra-indicated in Patients with severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed.

•           Co-Trimoxazole should not be given to patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides.

•           Co-Trimoxazole  should not be given to patients with acute porphyria.

•           Co-Trimoxazole  should not be given to premature babies nor to full-term infants during the first 6 weeks of life except for the treatment /prophylaxis of PJCP in infants 4 weeks of age or greater.

 

4.4       Special warnings and precautions for use

 

Fatalities, although very rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract.

 

 

For patients with known renal impairment special measures should be adopted (see section 4.2).

 

Supplementation with folinic acid may be considered during treatment but this should be initiated with caution due to possible interference with antimicrobial efficacy (see section 4.5).

 

Septrin has been associated with metabolic acidosis when other possible underlying causes have been excluded. Close monitoring is always advisable when metabolic acidosis is suspected.

 

 

Hyperkalaemia: caution should be exercised in patients taking any other drugs that can cause hyperkalaemia.

 

Repaglinide: trimethoprim may increase the exposure of repaglinide which may result in hypoglycaemia.

 

Folinic acid: folinic acid supplementation has been shown to interfere with the antimicrobial efficacy of trimethoprim-sulfamethoxazole. This has been observed in Pneumocystis jiroveci pneumonia prophylaxis and treatment.

 

Contraceptives: oral contraceptive failures have been reported with antibiotics. The mechanism of this effect has not been elucidated. Women on treatment with antibiotics should temporarily use a barrier method in addition to the oral contraceptive, or choose another method of contraception.

 

Pregnancy

 

Trimethoprim and sulfamethoxazole cross the placenta and their safety in pregnant women has not been established.

 

4.8       Undesirable effects

 

* see description of selected adverse reactions

1 Cholestatic jaundice and hepatic necrosis may be fatal.

 

Description of selected adverse reactions

 

Reporting of suspected adverse reactions

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at

 

5.1       Pharmacodynamic properties

 

Mechanism of actionMode of Action

 

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.

Trimethoprim binds to plasmodial DHFR but less tightly than to the bacterial enzyme. Its affinity for mammalian DHFR is some 50,000 times less than for the corresponding bacterial enzyme.

 

Septrin is an antibacterial drug composed of two active principles, sulfamethoxazole and trimethoprim. Sulfamethoxazole is a competitive inhibitor of dihydropteroate synthetase enzyme. Sulfamethoxazole competitively inhibits the utilisation of para-aminobenzoic acid (PABA) in the synthesis of dihydrofolate by the bacterial cell resulting in bacteriostasis. Trimethoprim binds to and reversibly inhibits bacterial dihydrofolate reductase (DHFR) and blocks the production of 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.

 

 

5.2       Pharmacokinetic properties

           

Renal excretion of intact sulfamethoxazole accounts for 15-30% of the dose. This drug is more extensively metabolised than trimethoprim, via acetylation, oxidation or glucuronidation. Over a 72 hour period, approximately 85% of the dose can be accounted for in the urine as unchanged drug plus the major (N4-acetylated) metabolite.

 

 

10        DATE OF REVISION OF THE TEXT

 

29/10/2014March 2015 03/01/2017

 

 

Reasons for adding or updating:

  • New SPC for new product

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO