- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- Administrative data
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- 11. Legal status
Renal impairment Adults and children over 40 kgAn initial loading dose of 3 g should be followed by doses based on creatinine clearance rate and type of dialysis as indicated below:- Creatinine clearance greater than 60 ml/minute: 3 g every 4 hours OR 5g every 6 hours- Creatinine clearance 30 to 60 ml/minute: 2 g every 4 hours OR 3g every 8 hours- Creatinine clearance 10 to 30 ml/minute: 2 g every 8 hours OR 3 g every 12 hours - Creatinine clearance less than 10 ml/minute: 1 g i.m. every 6 hours OR 2 g every 12 hours OR 3 g every 24 hours- Creatinine clearance less than 10 ml/minute (with hepatic dysfunction): 1 g i.m. every 12 hours OR 2 g every 24 hours- Patients on peritoneal dialysis: as for creatinine clearance less than 10 ml/minute- Patients on haemodialysis: as for creatinine clearance less than 10 ml/minute supplemented with 3 g after each dialysis.
Renal impairment Children under 40 kgSimilar dosage adjustment as for adults, e.g. an initial loading dose of 75 mg/kg should be followed by doses based on creatinine clearance and type of dialysis as indicated below:
|- Greater than 30 ml/minute:||75 mg/kg every 8 hours|
|- 10 to 30 ml/minute:||37.5 mg/kg every 8 hours|
|- Less than 10 ml/minute:||37.5 mg/kg every 12 hours|
Pregnancy:Animal studies with Timentin have shown no teratogenic effects. Penicillins are generally considered safe for use in pregnancy. Limited information is available concerning the results of the use of Timentin in human pregnancy. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore Timentin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
Lactation:Trace quantities of Timentin are excreted in breast milk. Timentin may be administered during the period of lactation. With the exception of the risk of sensitization, there are no detrimental effects for the breast-fed infant.
Hypersensitivity reactions:Hypersensitivity effects including:Skin rashes, pruritus, urticaria, and anaphylactic reactions.Bullous reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported very rarely.
Gastrointestinal effects:Nausea, vomiting and diarrhea have been reported. Pseudomembranous colitis has been reported rarely (see Warnings and Precautions).
Hepatic effects:A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics but the significance of these findings is unknown. Hepatitis and cholestatic jaundice have been reported very rarely. These events have been noted with other penicillins and cephalosporins.
Renal and urinary effects:Hypokalaemia has been reported rarely. Haemorrhagic cystitis has been reported very rarely.
Central Nervous System effects:Convulsions may occur rarely, particularly in patients with impaired renal function or in those receiving high doses.
Haematological effects:Thrombocytopenia, leucopenia and eosinophilia have been reported rarely and reduction of haemoglobin. Haemolytic anaemia has been reported very rarely. Prolongation of prothrombin time and bleeding time. Bleeding manifestations have occurred.
Local effects:Pain, burning, swelling and induration at the injection site and thrombophlebitis with intravenous administration.
Reporting of suspected adverse reactionsReporting 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
Mechanism of ActionTicarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria. Ticarcillin is derived from the basic penicillin nucleus, 6-amino-penicillanic acid.Ticarcillin is, however, susceptible to degradation by beta-lactamases and therefore the spectrum of activity does not normally include organisms which produce these enzymes.Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in micro-organisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated beta-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins.The formulation of ticarcillin with clavulanic acid in ticarcillin-clavulanate protects ticarcillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of ticarcillin to include many bacteria normally resistant to ticarcillin and other beta-lactam antibiotics. Thus ticarcillin-clavulanate possesses the distinctive properties of a broad spectrum antibiotic and a beta-lactamase inhibitor.
Mechanism of ResistanceResistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in Timentin anticipates this defence mechanism by blocking the β-lactamase enzymes, thus rendering the organisms sensitive to ticarcillin's rapid bactericidal effect at concentrations readily attainable in the body.Clavulanate, by itself, has little antibacterial effect; however, in association with ticarcillin, as Timentin it produces an antibiotic agent with a breadth of spectrum suitable for empiric use in a wide range of infections treated parenterally in hospital.
Timentin BreakpointsMinimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
|S (≤)||R (>)|
|Viridans group streptococci||IE3||IE3|
|1 For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L. 2With the exception of S. saprophyticus, most staphylococci are penicillinase producers. The benzylpenicillin breakpoint will mostly, but not unequivocally, separate beta-lactamase producers from non-producers. If the MIC is >0.12 mg/L, report resistant. If the MIC is ≤0.12mg/L, test susceptibility with the benzylpenicillin disk. Isolates positive for beta-lactamase are resistant to benzylpenicillin, phenoxymethylpenicillin, amino-, carboxy- and ureidopenicillins. Isolates negative for beta-lactamase and susceptible to cefoxitin (cefoxitin is used to screen for methicillin resistance) can be reported susceptible to these drugs. Isolates positive for beta-lactamase and susceptible to cefoxitin are susceptible to penicillin-beta-lactamase inhibitor combinations and penicillinase-resistant penicillins (oxacillin, cloxacillin, dicloxacillin and flucloxacillin). Isolates resistant to cefoxitin are methicillin resistant and resistant to beta-lactam agents, except those with approved anti-MRSA activity and clinical breakpoints. 3Insufficient evidence that the species in question is a good target for therapy with the drug. An MIC with a comment but without an accompanying S or R-categorization may be reported.|
Microbiological SusceptibilityThe prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when treating severe infections.Timentin is usually active against the following microorganisms in vitro.
|Commonly susceptible species|
|Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible)* Staphylococcus epidermidis (methicillin-susceptible)* Staphylococcus saprophyticus Beta-hemolytic streptococci Streptococcus bovis Enterococcus faecalis |
|Gram-negative aerobes: Moraxella catarrhalis Pasteurella multocida|
|Gram-positive anaerobes: Clostridium spp. Eubacterium spp. Peptostreptococcus spp.|
|Gram-negative anaerobes: Bacteroides spp. including B. fragilis Prevotella spp. Fusobacterium spp.|
|Microorganisms for which acquired resistance may be a problem|
|Gram-positive aerobes: Streptococcus pneumoniae Viridans group streptococci|
|Gram-negative aerobes: Acinetobacter spp. Citrobacter spp. Enterobacter spp. Escherichia coli Haemophilus influenzae Klebsiella spp. Morganella morganii Neisseria gonorrhoeae Proteus spp. Providencia spp. Pseudomonas spp . including Pseudomonas aeruginosa Serratia spp. Salmonella spp.|
|Gram-negative anaerobes: Veillonella spp.|
|Inherently resistant microorganisms|
|Stenotrophomonas maltophilia Burkholderia cepacia|
|Water for Injections BP||Glucose Intravenous Infusion BP (5% w/v)|
|3.2 g||100 ml||100-150 ml|
|1.6 g||50 ml||100 ml|
Trading as:GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT
Stockley Park West, Uxbridge, Middlesex, UB11 1BT
+44 (0)208 990 4328
0800 221 441
0800 221 441