Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: EUMEDICA S.A., Winston Churchill Avenue 67, BE-1180, Brussels, Belgium
Pharmacotherapeutic group: β-lactam antibacterials – penicillins
ATC code: J01CA17
The product is an injectable antibiotic active in vitro against many aerobic gram-negative bacteria, with the notable exception of Pseudomonas aeruginosa and Acinetobacter spp.
β-lactam antibiotics act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. β-lactam antibiotics irreversibly bind to the active site of specific transpeptidases and carboxypeptidases known as Penicillin Binding Proteins (PBP), preventing peptidoglycan production.
Temocillin is stable to most types of β-lactamases, including most AmpC and Extended Spectrum β-Lactamases. The only suspected mechanisms of resistance to temocillin are outer membrane impermeabilisation or active efflux.
β-lactamase-producing Enterobacteriaceae resistant to 2nd or 3rd generation cephalosporins may be sensitive to Negaban.
Following the BSAC (British Society for Antimicrobial Chemotherapy) method for Enterobacteriaceae:
Commonly susceptible organisms:
Escherichia coli
Klebsiella pneumoniae
Citrobacter spp.
Proteus mirabilis
Proteus spp (indole +)
Morganella morganii
Pasteurella multocida
Providencia stuartii
Salmonella typhimurium
Yersinia enterocolitica
Moraxella catarrhalis
Haemophilus influenzae
Neisseria meningitides
Species for which acquired resistance may be a problem:
Serratia marcescens
Enterobacter spp.
Inherently resistant organisms:
Acinetobacter spp.
Pseudomonas aeruginosa
Gram positive organisms
Anaerobic bacteria
Mean pharmacokinetic parameters of temocillin following administration of a single dose:
| MEAN PARAMETER | HEALTHY SUBJECTS | ELDERLY PATIENTS | RENALLY IMPAIRED PATIENTS* | |||
|---|---|---|---|---|---|---|
| I.V. BOLUS | I.M. | I.V. | I.V. | |||
| Dose | 1 g | 2 g | 4 g | 1 g | 1 g | 7.5 mg/kg |
| No. of subjects | 6 | 6 | 8 | 6 | 10 | 5 |
| Cmax (mg/L) | 173.1 | 281.2 | 482.9 | 72.7 | 93.2+ | 49.5 |
| T½β (h) | 4.2 | 4.2 | 4.2 | 5.4 | 11.7 | 28.2 |
| CLtot (ml/min) | 33.2 | 38.3 | 48.5 | - | 11.2 | 8.8 |
| VDss (L) | 11.1 | 12.1 | 14.7 | - | 10.9 | 18.3 (VD AREA) |
- = Not determined
* = CLCR <10 ml/min/1.73m²
+ = Approx. 1 h post-dose
The protein serum binding rate is 85% in healthy volunteers.
Concentrations of temocillin in gall bladder bile at a mean of 2.4 hours after I.V. injection of 1 g were variable. Temocillin was not detected in the bile of 2 out of 10 patients but in some cases concentrations were considerably higher than those in serum. The mean concentration in gall bladder bile was 205 μg/ml. Concentrations of temocillin in prostate homogenate between 1 and 3 hours after I.M. injection of 1 g of temocillin ranged from 2.3-16 μg/ml (mean 8.25) compared with a mean serum concentration of 12.5 μg/ml.
In a series of studies, the penetration of temocillin into tissues was investigated by assaying either tissue fluid or homogenate for temocillin. Following I.V. injection of 1 g of temocillin, concentrations in the fluid of cantharidine-induced skin blisters reached a mean peak of 44.3 μg/ml at 3 hours. The mean half-life of temocillin in blister fluid was 4.0 hours.
Temocillin concentrations in peripheral lymph after a 1 g I.V. injection were of a similar order to those in blister fluid, reaching a mean peak of 30.6 μg/ml between 1.5 and 2 hours. The mean half-life of elimination from lymph was 4.4 hours. As was found in skin blisters, concentrations of temocillin in lymph were above the MIC of susceptible bacteria at 12 hours after administration.
Only a small proportion of temocillin passes into the cerebrospinal fluid.
Temocillin is excreted unchanged mainly in the kidney. Excretion may be delayed in cases of kidney failure so the dosage must be reduced, depending on the degree of kidney failure shown by the creatinine clearance values.
|<>_.Creatinine clearance (ml/min)
No. of subjects |<>_.Dose (g) |<>_.Cmax (mg/L) |<>_.T½β (h) |<>_.CLtot (ml/min) |<>_.VDss (L) |<>_.Urine excretion (% in 24h) |
| 30-60 | 5 | 0.5 | 69.8 | 13.6 | 16.3 | 16.3 | 51.6 |
| 5 | 1 | 122.0 | 20.0 | 15.5 | 16.0 | 40.2 | |
| 10-30 | 5 | 0.5 | 49.4 | 18.9 | 13.3 | 22.1 | 23.1 |
| 2 | 1 | 118.0 | 17.0 | 9.9 | 13.8 | 17.0 | |
| <10 | 5 | 0.5 | 49.5 | 28.2 | 8.8 | 19.9 | 8.3 |
| 5 | 1 | - | 26.6 | - | 7.3 | - |
- = Not determined
The non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity, mutagenic toxicity and toxicity to reproduction and development. Fertility studies performed in rats administered temocillin subcutaneously showed no adverse effects on male and female fertility at 0.18 times the exposure levels achieved for the maximum recommended human intravenous daily dose.
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