TIMENTIN 0.8G 1.6G 3.2G

Active substance: TICARCILLIN

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
TIMENTIN* 0.8 G, 1.6 G, 3.2 G

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Timentin 0.8 g. Contains 50 mg clavulanic acid with 750 mg ticarcillin.
Timentin 1.6g: Contains 100 mg clavulanic acid with 1.5 g ticarcillin.
Timentin 3.2 g. Contains 200 mg clavulanic acid with 3.0 g ticarcillin.
The clavulanic acid is present as Potassium Clavulanate BP and the ticarcillin
as ticarcillin sodium.

3.

PHARMACEUTICAL FORM
Powder for solution for infusion.
Vials containing sterile powder for reconstitution.

4.

CLINICAL PARTICULARS

4.1

Therapeutic Indications
Timentin is an injectable antibiotic agent with a broad spectrum of bactericidal
activity against a wide range of Gram-positive and Gram-negative aerobic and
anaerobic bacteria. The presence of clavulanate in the formulation extends the
spectrum of activity of ticarcillin to include many β -lactamase-producing
bacteria normally resistant to ticarcillin and other
β -lactam antibiotics.
Timentin is indicated for the treatment of infections in which susceptible
organisms have been detected or are suspected.
Typical indications include:
Severe infections in hospitalised patients and proven or suspected infections in
patients with impaired or suppressed host defences including: septicaemia,
bacteraemia, peritonitis, intra-abdominal sepsis, post-surgical infections, bone
and joint infections, skin and soft tissue infections, respiratory tract infections,
serious or complicated renal infections (e.g. pyelonephritis), ear, nose and
throat infections.

A comprehensive list of sensitive and resistant organisms is provided in
Section 5.1. Consideration should be given to official guidance regarding
bacterial resistance and the appropriate use of antibacterial agents.

4.2

Posology and Method of Administration
Adult dosage (including elderly patients):
The usual dosage is 3.2 g Timentin given six to eight hourly. The maximum
recommended dosage is 3.2 g four hourly.
Children's dosage (including infants, neonates and premature infants >2 kg in
weight):
The usual dosage for children is 80 mg Timentin/kg body weight given every
eight hours. The maximum dosage for children is 80 mg Timentin/kg body
weight given every six hours. This should not exceed the maximum
recommended adult dosage.
For premature infants <2 kg in weight, the dosage is 80 mg Timentin/kg body
weight every 12 hours.
Dosage in renal impairment:
Mild impairment
(Creatinine Clearance
>30 ml/min)
3.2 g 8 hourly

Moderate impairment
(Creatinine Clearance
10-30 ml/min)
1.6 g 8 hourly

Severe impairment
(Creatinine Clearance
<10 ml/min)
1.6 g 12 hourly

Similar reductions in dosage should be made for children.
Administration:
Intravenous infusion
4.3

Contra-Indications
Timentin contains ticarcillin which is a penicillin, and should not be given to
patients with a history of hypersensitivity to beta-lactam antibiotics (e.g.
penicillins and cephalosporins).

4.4

Special warnings and precautions for use
Before initiating therapy with Timentin, careful inquiry should be made concerning
previous hypersensitivity reactions to beta-lactams (e.g. penicillins and
cephalosporins). Serious and occasionally fatal hypersensitivity reactions
(anaphylaxis) have been reported in patients receiving beta-lactam antibiotics. These

reactions are more likely to occur in individuals with a history of beta-lactam
hypersensitivity.
Changes in liver function tests have been observed in some patients receiving
Timentin. The clinical significance of these changes is uncertain but Timentin should
be used with care in patients with evidence of severe hepatic dysfunction.
In patients with renal impairment, dosage should be adjusted according to the degree
of impairment (see Section 4.2).
It should be noted that each gram of ticarcillin contains 5.3 mmol of sodium
(approx.). This should be included in the daily allowance of patients on sodiumrestricted diets.
Timentin has only rarely been reported to cause hypokalemia; however, the
possibility of this occurring should be kept in mind particularly when treating patients
with fluid and electrolyte imbalance. Periodic monitoring of serum potassium may be
advisable in patients receiving prolonged therapy.
Bleeding manifestations have occurred in some patients receiving beta-lactam
antibiotics. These reactions have been associated with abnormalities of coagulation
tests such as clotting time, platelet aggregation and prothrombin time and are more
likely to occur in patients with renal impairment. If bleeding manifestations appear,
Timentin treatment should be discontinued and appropriate therapy instituted.
The presence of clavulanic acid in Timentin may cause a non-specific binding of IgG
and albumin by red cell membranes leading to a false positive Coombs test.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

4.5

Interaction with other medicinal products and other forms of interaction
Timentin acts synergistically with aminoglycosides against a number of
organisms including Pseudomonas. Timentin prescribed concurrently with an
aminoglycoside, may therefore be preferred in the treatment of life-threatening
infections, particularly in patients with impaired host defences. In such
instances the two products should be administered separately, at the
recommended dosages.
Co-administration of probenecid cannot be recommended. Probenecid
decreases the renal tubular secretion of ticarcillin. Concurrent administration
of probenecid delays ticarcillin renal excretion but does not delay the excretion
of clavulanic acid.

The presence of clavulanic acid in Timentin may cause a non-specific binding
of IgG and albumin by red cell membranes leading to a false positive Coombs
test.
In common with other antibiotics, Timentin may affect the gut flora, leading to
lower oestrogen reabsorption and reduced efficacy of combined oral
contraceptives. Therefore, alternative non-hormonal methods of contraception
are recommended.
Penicillins reduce the excretion of methotrexate (potential increase in
toxicity).
4.6

Pregnancy and Lactation
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 sensitisation, there are no detrimental effects for the
breast-fed infant.

4.7

Effects on Ability to Drive and Use Machines
Adverse effects on the ability to drive or operate machinery have not been
observed.

4.8

Undesirable Effects
Hypersensitivity reactions:
Hypersensitivity effects, including skin rashes:
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.

Hepatic effects:
A moderate rise in AST and/or ALT has been noted in patients receiving
ampicillin class antibiotics. 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, leukopenia, eosinophilia and reduction of haemoglobin
have been reported rarely. 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.
4.9

Overdose
Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident
and should be treated symptomatically.
Disturbances of the fluid and electrolyte balances may be evident and may be
treated symptomatically.
Ticarcillin and clavulanic acid may be removed from circulation by
haemodialysis.
As with other penicillins, Timentin overdosage has the potential to cause
neuromuscular hyperirritability or convulsive seizures.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic Properties
Timentin is an injectable antibiotic, active against a wide range of both Grampositive and Gram-negative bacteria, including β-lactamase-producing strains.

Resistance 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 defense 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.
Gram-Positive
Aerobes: Staphylococcus species including Staphylococcus aureus and
Staphylococcus epidermidis, Streptococcus species including Enterococcus
faecalis.
Anaerobes: Peptococcus species, Peptostreptococcus species, Clostridium
species, Eubacterium species.
Gram-Negative
Aerobes: Escherichia coli, Haemophilus species including Haemophilus
influenzae, Moraxella catarrhalis, Klebsiella species including Klebsiella
pneumoniae, Enterobacter species, Proteus species including indole-positive
strains, Providentia stuartii, Pseudomonas species including Pseudomonas
aeruginosa, Serratia species including Serratia marcescens, Citrobacter
species, Acinetobacter species, Yersinia enterocolitica
Anaerobes: Bacteroides species including Bacteroides fragilis, Fusobacterium
species, Veillonella species.
Breakpoints
The breakpoints listed below have been obtained from the National Committee
for Clinical Laboratory Standards (NCCLS) (Performance Standards for
Antimicrobial Disk Susceptibility Tests; Approved Standard - Seventh
Edition).
Enterobacteriaceae:
Pseudomonas aeruginos:
Other non-Enterobacteriaceae:
Staphylococcus spp.:

S≤16/2 μg/mL
S≤64/2 μg/mL
S≤16/2 μg/mL
S≤8/2 μg/mL

R ≥ 128/2 μg/mL
R ≥ 128/2 μg/mL
R ≥ 128/2 μg/mL
R ≥ 16/2 μg/mL

S = susceptible, R = resistant
There are no NCCLS breakpoints for other organisms listed in this document.

Table 1
Susceptible
Aerobic Gram-positive micro-organisms
Staphylococcus aureus
Aerobic Gram-negative micro-organisms
Acinetobacter species
Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Proteus species
Serratia species
Anaerobic micro-organisms
Bacteroides fragilis
Intermediate
Aerobic Gram-negative micro-organisms
Serratia marcescens
Insusceptible
Aerobic Gram-positive micro-organisms
Enterococcus
Aerobic Gram-negative micro-organisms:
Citrobacter species
Enterobacter species
Pseudomonas aeruginosa

The prevalence of resistance may vary geographically and with time for
selected species. Where possible, local information on resistance is
included. This information gives only an approximate guidance on
probabilities whether microorganisms will be susceptible to ticarcillin
disodium clavulanate potassium (commonly known as Timentin) or not.

5.2

Pharmacokinetic Properties
The pharmacokinetics of the two components are closely matched and both
components are well distributed in body fluids and tissues. Both clavulanate
and ticarcillin have low levels of serum binding; about 20% and 45%
respectively.
As with other penicillins the major route of elimination for ticarcillin is via the
kidney; clavulanate is also excreted by this route.

5.3

Pre-clinical Safety Data
Not applicable.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of Excipients
None.

6.2.

Incompatibilities
Timentin is not compatible with the following:
Proteinaceous fluids (e.g. protein hydrolysates); blood and plasma;
intravenous lipids.
If Timentin is prescribed concurrently with an aminoglycoside the antibiotics
should not be mixed in the syringe, intravenous fluid container or giving set
because loss of activity of the aminoglycoside can occur under these
conditions.

6.3.

Shelf-Life
24 months.

6.4.

Special Precautions for Storage
Timentin should be stored in a dry place at temperatures below 25°C.

6.5

Nature and Contents of Container
Clear Type I or Type III glass vials fitted with a chlorobutyl rubber bung and an
aluminium seal. Supplied in packs of four vials.

6.6.

Instructions for Use, Handling and Disposal
The sterile powder should be dissolved in approximately 5 ml/10 ml (1.6 g/3.2
g vial) prior to dilution into the infusion container (e.g mini-bag) or in-line
burette.
The following approximate infusion volumes are suggested:
Water for Injections BP
3.2g
1.6g

100ml
50ml

Glucose Intravenous
Infusion BP (5% w/v)
100-150ml
100ml

Detailed instructions are given in the Package Enclosure Leaflet.
Each dose of Timentin should be infused intravenously over a period of 30-40
minutes; avoid continuous infusion over longer periods as this may result in
subtherapeutic concentrations.
800 mg Timentin has a displacement value of 0.55 ml.
Heat is generated when Timentin dissolves. Reconstituted solutions are
normally a pale straw colour.
Timentin presentations are not for multi-dose use or for direct IV or IM
injection. Any residual antibiotic solution should be discarded if less than the
fully made up vial is used.

7.

MARKETING AUTHORISATION HOLDER
Beecham Group plc
Great West Road, Brentford, Middlesex TW8 9GS
Trading as:
GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT
Or
Beecham Research or Bencard or Bridge Pharmaceuticals or SmithKline and
French
Laboratories or SmithKline Beecham Pharmaceuticals all at:
Welwyn Garden City, Hertfordshire AL7 1EY

8.

MARKETING AUTHORISATION NUMBER(S)

PL 00038/0329

9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15 April 2003

10

DATE OF REVISION OF THE TEXT
03/10/2011

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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