- Approval Id
- bd2f26b27eaeba59
- Drug Approval Emc Name
- Co-Trimoxazole 16mg/80mg per ml Solution for Infusion
- Drug Name
- Co-Trimoxazole 16mg/80mg per ml Solution for Infusion
- Company Name
- Wockhardt UK Ltd
- Company Address
- Ash Road North, Wrexham Industrial Estate, Wrexham, LL13 9UF
- Company Website
- www.wockhardt.co.uk
- Company Telephone
- +44 (0)1978 661 261
- Company Fax
- +44 (0)1978 661 702
- Company Medical Info Email
- [email protected]
- Atc Code
- J01EE01
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK
- Authorisation Number
- 8. Marketing authorisation number(s) PL 29831/0792
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 16/12/2025
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 29831/0792
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 16/12/2025
- Instruction Composition
- 2. Qualitative and quantitative composition Each 5 ml of Co-trimoxazole 16mg/80mg per ml Solution for Infusion contains 80mg trimethoprim and 400mg sulfamethoxazole. Excipient(s) with known effect: This product contains 1.7 mmoles of sodium, 11.14 vol % ethanol (alcohol) per 5 ml, 2.34 g propylene glycol per 5ml and sodium metabisulphite. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Solution for Infusion A colourless or slightly yellow solution.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Co-trimoxazole Solution for Infusion is indicated in children (≥6 weeks) and adults for the treatment of the following infections when owing to sensitive organisms (see section
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antibacterials for systemic use - Sulphonamides and trimethoprim, ATC code: J01EE01. 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. Resistance In vitro studies have shown that bacterial resistance can develop more slowly with both sulfamethoxazole and trimethoprim in combination that with either sulfamethoxazole or trimethoprim alone. Resistance to sulfamethoxazole may occur by different mechanisms. Bacterial mutations cause an increase the concentration of PABA and thereby out-compete with sulfamethoxazole resulting in a reduction of the inhibitory effect on dihydropteroate synthetase enzyme. Another resistance mechanism is plasmid-mediated and results from production of an altered dihydropteroate synthetase enzyme, with reduced affinity for sulfamethoxazole compared to the wild-type enzyme. Resistance to trimethoprim occurs through a plasmid-mediated mutation which results in production of an altered dihydrofolate reductase enzyme having a reduced affinity for trimethoprim compared to the wild-type enzyme. Many common pathogenic bacteria are susceptible in vitro to trimethoprim and sulfamethoxazole at concentrations well below those reached in blood, tissue fluids and urine after the administration of recommended doses. In common with other antibiotics, however, in vitro activity does not necessarily imply that clinical efficacy has been demonstrated and it must be noted that satisfactory susceptibility testing is achieved only with recommended media free from inhibitory substances, especially thymidine and thymine. Susceptibility testing breakpoints EUCAST (European Committee on Antimicrobial Susceptibility Testing) limits Enterobacteriaceae: S≤ 2 R> 4 S. maltophilia: S≤ 4 R> 4 Acinetobacter: S≤ 2 R> 4 Staphylococcus: S≤ 2 R> 4 Enterococcus: S≤ 0.032 R> 1 Streptococcus ABCG: S≤ 1 R> 2 Streptococcus pneumoniae: S≤ 1 R> 2 Hemophilus influenza: S≤ 0.5 R> 1 Moraxella catarrhalis: S≤0.5 R >1 Psuedomonas aeruginosa and other non-enterobacteriaceae: S≤ 2* R> 4* S = susceptible, R = resistant. *These are CLSI breakpoints since no EUCAST breakpoints are currently available for these organisms. Trimethoprim: sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as trimethoprim concentration. Antibacterial Spectrum The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. This information gives only an approximate guidance on probabilities whether microorganisms will be susceptible to trimethoprim/sulfamethoxazole or not. Trimethoprim/sulfamethoxazole susceptibility against a number of bacteria are shown in the table below: Commonly susceptible species: Gram-positive aerobes: Staphylococcus aureus Staphylococcus saprophyticus Streptococcus pyogenes Gram-negative aerobes: Enterobacter cloacae Haemophilus influenzae Klebsiella oxytoca Moraxella catarrhalis Salmonella spp. Stenotrophomonas maltophilia Yersinia spp. Species for which acquired resistance may be a problem: Gram-positive aerobes: Enterococcus faecalis Enterococcus faecium Nocardia spp. Staphylococcus epidermidis Streptococcus pneumoniae Gram-negative aerobes: Citrobacter spp. Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella pneumonia Proteus mirabilis Proteus vulgaris Providencia spp. Serratia marcesans Inherently resistant organisms: Gram-negative aerobes: Pseudomonas aeruginosa Shigella spp. Vibrio cholera Many strains of Bacteroides fragilis are sensitive. Some strains of Campylobacter fetus subsp. jejuni and Chlamydia are sensitive without evidence of synergy. Some varieties of non-tuberculous mycobacteria are sensitive to sulfamethoxazole but not trimethoprim. Mycoplasmas, Ureaplasma urealyticum, Mycobacterium tuberculosis and Treponema pallidum are insensitive. Satisfactory sensitivity testing is achieved only with recommended media free from inhibitory substances especially thymidine and thymine. 5.2 Pharmacokinetic properties Absorption Peak plasma levels of trimethoprim and sulfamethoxazole are higher and achieved more rapidly after one hour of intravenous infusion of Co-trimoxazole 16mg/80mg per ml Solution for Infusion than after oral administration of an equivalent dose of a Co-trimoxazole oral presentation. Plasma concentrations, elimination half-life and urinary excretion rates show no significant differences following either the oral or intravenous route of administration. Distribution Approximately 50% of trimethoprim in the plasma is protein bound. Tissue levels of trimethoprim are generally higher than corresponding plasma levels, the lungs and kidneys showing especially high concentrations. Trimethoprim concentrations exceed those in plasma in the case of bile, prostatic fluid and tissue, sputum, and vaginal secretions. Levels in the aqueous humour, breast milk, cerebrospinal fluid, middle ear fluid, synovial fluid and tissue (interstitial) fluid are adequate for antibacterial activity. Trimethoprim passes into amniotic fluid and foetal tissues reaching concentrations approximating those of maternal serum. Approximately 66% of sulfamethoxazole in the plasma is protein bound. The concentration of active sulfamethoxazole in amniotic fluid, aqueous humour, bile, cerebrospinal fluid, middle ear fluid, sputum, synovial fluid and tissue (interstitial) fluid is of the order of 20 to 50% of the plasma concentration. Biotransformation Trimethoprim does not induce its own metabolism and therefore no dose modification is required on this account during long-term treatment. 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 sulfamethoxazol 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. The principal route of excretion of sulfamethoxazole is renal; between 15% and 30% of the dose recovered in the urine is in the active form. In older patients there is a reduced renal clearance of sulfamethoxazole. Special patient population Renal impairment The elimination half-life of trimethoprim is increased by a factor of 1.5-3.0 when the creatinine clearance is less than 10 mL/minute. When the creatinine clearance falls below 30 mL/min the dosage of Co-trimoxazole should be reduced (see section 4.2). Elderly patients In elderly patients, a slight reduction in renal clearance of sulfamethoxazole but not trimethoprim has been observed. Paediatric population 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). 5.3 Preclinical safety data At doses in excess of the recommended human therapeutic dose, trimethoprim and sulfamethoxazole have been reported to cause cleft palate and other foetal abnormalities in rats, findings typical of a folate antagonist. Effects with trimethoprim were preventable by administration of dietary folate. In rabbits, foetal loss was seen at doses of trimethoprim in excess of human therapeutic doses.
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Propylene glycol (E1520) Trometamol Sodium hydroxide (E524) Sodium metabisulphite (E223) Ethanol Hydrochloric acid Water for injections 6.2 Incompatibilities None known. 6.3 Shelf life 2 years. 6.4 Special precautions for storage This medicinal product does not require any special temperature storage conditions. Keep the ampoules in the outer carton in order to protect from light. 6.5 Nature and contents of container Neutral glass ampoules (5ml nominal fill volume) Pack size: 10 x 5ml ampoules 6.6 Special precautions for disposal and other handling Co-trimoxazole Solution for Infusion must be diluted before administration. DILUTION SHOULD BE CARRIED OUT IMMEDIATELY BEFORE USE. After adding Co-trimoxazole 16mg/80mg per ml Solution for Infusion to the infusion solution shakes thoroughly to ensure complete mixing. If visible turbidity or crystallisation appears at any time before or during an infusion, the mixture should be discarded. It is recommended that Co-trimoxazole 16mg/80mg per ml Solution for Infusion is diluted according to the following schedules: One ampoule (5ml) added to 125 ml infusion solution. Two ampoules (10ml) added to 250 ml infusion solution. Three ampoules (15ml) added to 500 ml infusion solution. Co-trimoxazole 16mg/80mg per ml Solution for Infusion is known to be compatible, when diluted as recommended above, with the following fluids: Glucose Intravenous Infusion BP (5% w/v and 10% w/v); Sodium Chloride Intravenous Infusion BP (0.9% w/v); Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP; Ringer's Solution for Injection BPC 1959. The pH of the solution is in the range 9.5 to 11.0. No other substance should be mixed with the infusion. The duration of the infusion should be approximately one to one and a half hour, but this should be balanced against the fluid requirements of the patient. When fluid restriction is necessary, Co-trimoxazole 16mg/80mg per ml Solution for Infusion may be administered at a higher concentration, 5 ml diluted with 75 ml of glucose 5% w/v in water. The resultant solution, whilst being clear to the naked eye, may on occasion exceed the BP limits set for particulate matter in large volume parenterals. The solution should be infused over a period not exceeding one hour. Discard any unused solution.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Each 5 ml of Co-trimoxazole 16mg/80mg per ml Solution for Infusion contains 80mg trimethoprim and 400mg sulfamethoxazole. Excipient(s) with known effect: This product contains 1.7 mmoles of sodium, 11.14 vol % ethanol (alcohol) per 5 ml, 2.34 g propylene glycol per 5ml and sodium metabisulphite. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Solution for Infusion A colourless or slightly yellow solution.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Co-trimoxazole Solution for Infusion is indicated in children (≥6 weeks) and adults for the treatment of the following infections when owing to sensitive organisms (see section
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antibacterials for systemic use - Sulphonamides and trimethoprim, ATC code: J01EE01. 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. Resistance In vitro studies have shown that bacterial resistance can develop more slowly with both sulfamethoxazole and trimethoprim in combination that with either sulfamethoxazole or trimethoprim alone. Resistance to sulfamethoxazole may occur by different mechanisms. Bacterial mutations cause an increase the concentration of PABA and thereby out-compete with sulfamethoxazole resulting in a reduction of the inhibitory effect on dihydropteroate synthetase enzyme. Another resistance mechanism is plasmid-mediated and results from production of an altered dihydropteroate synthetase enzyme, with reduced affinity for sulfamethoxazole compared to the wild-type enzyme. Resistance to trimethoprim occurs through a plasmid-mediated mutation which results in production of an altered dihydrofolate reductase enzyme having a reduced affinity for trimethoprim compared to the wild-type enzyme. Many common pathogenic bacteria are susceptible in vitro to trimethoprim and sulfamethoxazole at concentrations well below those reached in blood, tissue fluids and urine after the administration of recommended doses. In common with other antibiotics, however, in vitro activity does not necessarily imply that clinical efficacy has been demonstrated and it must be noted that satisfactory susceptibility testing is achieved only with recommended media free from inhibitory substances, especially thymidine and thymine. Susceptibility testing breakpoints EUCAST (European Committee on Antimicrobial Susceptibility Testing) limits Enterobacteriaceae: S≤ 2 R> 4 S. maltophilia: S≤ 4 R> 4 Acinetobacter: S≤ 2 R> 4 Staphylococcus: S≤ 2 R> 4 Enterococcus: S≤ 0.032 R> 1 Streptococcus ABCG: S≤ 1 R> 2 Streptococcus pneumoniae: S≤ 1 R> 2 Hemophilus influenza: S≤ 0.5 R> 1 Moraxella catarrhalis: S≤0.5 R >1 Psuedomonas aeruginosa and other non-enterobacteriaceae: S≤ 2* R> 4* S = susceptible, R = resistant. *These are CLSI breakpoints since no EUCAST breakpoints are currently available for these organisms. Trimethoprim: sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as trimethoprim concentration. Antibacterial Spectrum The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. This information gives only an approximate guidance on probabilities whether microorganisms will be susceptible to trimethoprim/sulfamethoxazole or not. Trimethoprim/sulfamethoxazole susceptibility against a number of bacteria are shown in the table below: Commonly susceptible species: Gram-positive aerobes: Staphylococcus aureus Staphylococcus saprophyticus Streptococcus pyogenes Gram-negative aerobes: Enterobacter cloacae Haemophilus influenzae Klebsiella oxytoca Moraxella catarrhalis Salmonella spp. Stenotrophomonas maltophilia Yersinia spp. Species for which acquired resistance may be a problem: Gram-positive aerobes: Enterococcus faecalis Enterococcus faecium Nocardia spp. Staphylococcus epidermidis Streptococcus pneumoniae Gram-negative aerobes: Citrobacter spp. Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella pneumonia Proteus mirabilis Proteus vulgaris Providencia spp. Serratia marcesans Inherently resistant organisms: Gram-negative aerobes: Pseudomonas aeruginosa Shigella spp. Vibrio cholera Many strains of Bacteroides fragilis are sensitive. Some strains of Campylobacter fetus subsp. jejuni and Chlamydia are sensitive without evidence of synergy. Some varieties of non-tuberculous mycobacteria are sensitive to sulfamethoxazole but not trimethoprim. Mycoplasmas, Ureaplasma urealyticum, Mycobacterium tuberculosis and Treponema pallidum are insensitive. Satisfactory sensitivity testing is achieved only with recommended media free from inhibitory substances especially thymidine and thymine. 5.2 Pharmacokinetic properties Absorption Peak plasma levels of trimethoprim and sulfamethoxazole are higher and achieved more rapidly after one hour of intravenous infusion of Co-trimoxazole 16mg/80mg per ml Solution for Infusion than after oral administration of an equivalent dose of a Co-trimoxazole oral presentation. Plasma concentrations, elimination half-life and urinary excretion rates show no significant differences following either the oral or intravenous route of administration. Distribution Approximately 50% of trimethoprim in the plasma is protein bound. Tissue levels of trimethoprim are generally higher than corresponding plasma levels, the lungs and kidneys showing especially high concentrations. Trimethoprim concentrations exceed those in plasma in the case of bile, prostatic fluid and tissue, sputum, and vaginal secretions. Levels in the aqueous humour, breast milk, cerebrospinal fluid, middle ear fluid, synovial fluid and tissue (interstitial) fluid are adequate for antibacterial activity. Trimethoprim passes into amniotic fluid and foetal tissues reaching concentrations approximating those of maternal serum. Approximately 66% of sulfamethoxazole in the plasma is protein bound. The concentration of active sulfamethoxazole in amniotic fluid, aqueous humour, bile, cerebrospinal fluid, middle ear fluid, sputum, synovial fluid and tissue (interstitial) fluid is of the order of 20 to 50% of the plasma concentration. Biotransformation Trimethoprim does not induce its own metabolism and therefore no dose modification is required on this account during long-term treatment. 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 sulfamethoxazol 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. The principal route of excretion of sulfamethoxazole is renal; between 15% and 30% of the dose recovered in the urine is in the active form. In older patients there is a reduced renal clearance of sulfamethoxazole. Special patient population Renal impairment The elimination half-life of trimethoprim is increased by a factor of 1.5-3.0 when the creatinine clearance is less than 10 mL/minute. When the creatinine clearance falls below 30 mL/min the dosage of Co-trimoxazole should be reduced (see section 4.2). Elderly patients In elderly patients, a slight reduction in renal clearance of sulfamethoxazole but not trimethoprim has been observed. Paediatric population 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). 5.3 Preclinical safety data At doses in excess of the recommended human therapeutic dose, trimethoprim and sulfamethoxazole have been reported to cause cleft palate and other foetal abnormalities in rats, findings typical of a folate antagonist. Effects with trimethoprim were preventable by administration of dietary folate. In rabbits, foetal loss was seen at doses of trimethoprim in excess of human therapeutic doses.
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Propylene glycol (E1520) Trometamol Sodium hydroxide (E524) Sodium metabisulphite (E223) Ethanol Hydrochloric acid Water for injections 6.2 Incompatibilities None known. 6.3 Shelf life 2 years. 6.4 Special precautions for storage This medicinal product does not require any special temperature storage conditions. Keep the ampoules in the outer carton in order to protect from light. 6.5 Nature and contents of container Neutral glass ampoules (5ml nominal fill volume) Pack size: 10 x 5ml ampoules 6.6 Special precautions for disposal and other handling Co-trimoxazole Solution for Infusion must be diluted before administration. DILUTION SHOULD BE CARRIED OUT IMMEDIATELY BEFORE USE. After adding Co-trimoxazole 16mg/80mg per ml Solution for Infusion to the infusion solution shakes thoroughly to ensure complete mixing. If visible turbidity or crystallisation appears at any time before or during an infusion, the mixture should be discarded. It is recommended that Co-trimoxazole 16mg/80mg per ml Solution for Infusion is diluted according to the following schedules: One ampoule (5ml) added to 125 ml infusion solution. Two ampoules (10ml) added to 250 ml infusion solution. Three ampoules (15ml) added to 500 ml infusion solution. Co-trimoxazole 16mg/80mg per ml Solution for Infusion is known to be compatible, when diluted as recommended above, with the following fluids: Glucose Intravenous Infusion BP (5% w/v and 10% w/v); Sodium Chloride Intravenous Infusion BP (0.9% w/v); Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP; Ringer's Solution for Injection BPC 1959. The pH of the solution is in the range 9.5 to 11.0. No other substance should be mixed with the infusion. The duration of the infusion should be approximately one to one and a half hour, but this should be balanced against the fluid requirements of the patient. When fluid restriction is necessary, Co-trimoxazole 16mg/80mg per ml Solution for Infusion may be administered at a higher concentration, 5 ml diluted with 75 ml of glucose 5% w/v in water. The resultant solution, whilst being clear to the naked eye, may on occasion exceed the BP limits set for particulate matter in large volume parenterals. The solution should be infused over a period not exceeding one hour. Discard any unused solution.
