Last Updated on eMC 27-11-2017 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 1 - Name of the medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • 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 10 - Date of revision of the text
  • Improved presentation of SPC

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

 

 

1.         NAME OF THE MEDICINAL PRODUCT

 

Co-Trimoxazole  80 mg/400 mg per 5 ml Adult Suspension

 

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 5 ml contains 400 mg Sulfamethoxazole and 80 mg Trimethoprim. 80 mg trimethoprim and 400 mg sulfamethoxazole

 

 

Excipient(s) with known effect:

 

This product contains less than 1 mmol of sodium (23 mg) per dose, and therefore is essentially sodium free.

Also contains 2.5 g sucrose per 5 ml and less than 100 mg of ethanol per 5 ml and methyl hydroxybenzoate.. 

 

3.         PHARMACEUTICAL FORM

 

Oral suspension

 

4.1       Therapeutic indications

 

Co-Trimoxazole Adult Suspension is indicated for the treatment of the following infections when owing to sensitive organisms (see section 5.1):

 

Treatment and prevention of Pneumocystis jiroveci .(P. carinii) pneumonitis

Treatment and prophylaxis of toxoplasmosis

Treatment of nocardiosis

 

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

 

Acute uncomplicated urinary tract infections

Acute otitis media

Acute exacerbation of chronic bronchitis

 

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

 

4.3       Contraindications

 

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

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

 

 

4.4       Special warnings and precautions for use

 

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

 

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

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Co-trimoxazole may increase the free plasma levels of methotrexate. If Co-Trimoxazole  is considered appropriate therapy in patients receiving other anti-folate drugs such as methotrexate, a folate supplement should be considered (see section 4.4).

 

 

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.

 

If trimethoprim-sulfamethoxazole is considered appropriate therapy in patients receiving other anti-folate drugs such as methotrexate, a folate supplement should be considered (see section 4.4).

 

4.8       Undesirable effects

 

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 www.mhra.gov.uk/yellowcard.

 

 

5.1       Pharmacodynamic properties

 

 

Mode of Action Mechanism 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

 

            Approximately 50% of trimethoprim in the plasma is protein bound.  The half-life in man is in the range 8.6 to 17 hours in the presence of normal renal function.  It is increased by a factor of 1.5 to 3.0 when the creatinine clearance is less than 10 ml/minute.  There appears to be no significant difference in the elderly compared with young patients.

            The principal route of excretion of trimethoprim is renal and approximately 50% of the dose is excreted in the urine within 24 hours as unchanged drug.  Several metabolites have been identified in the urine.  Urinary concentrations of trimethoprim vary widely.

 

            Biotransformation

           

            Renal excretion of intact sullfamethoxazole 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.

           

            Elimination

           

            The half-life of trimethoprim in man is in the range 8.6 to 17 hours in the presence of normal renal function.  It is increased by a factor of 1.5 to 3.0 when the creatinine clearance is less than 10 ml/minute. There appears to be no significant difference in older patients compared with young patients.

           

            The principal route of excretion of trimethoprim is renal and approximately 50% of the dose is excreted in the urine within 24 hours as unchanged drug. Several metabolites have been identified in the urine. Urinary concentrations of trimethoprim vary widely.

           

            The half-life of sulfamethoxazole in man is approximately 9 to 11 hours in the presence of normal renal function.There is no change in the half-life of active sulfamethoxazole with a reduction in renal function but there is prolongation of the half-life of the major, acetylated metabolite when the creatinine clearance is below 25 ml/minute.

 

 

 

10.       DATE OF REVISION OF THE TEXT

23/09/2014

           

March 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