Consumer medicine information

Timentin Powder for infusion

Ticarcillin; Potassium clavulanate

BRAND INFORMATION

Brand name

Timentin Powder for infusion

Active ingredient

Ticarcillin; Potassium clavulanate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Timentin Powder for infusion.

What is in this leaflet?

Please read this leaflet carefully before you use TIMENTIN.

This leaflet answers some common questions about TIMENTIN. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the expected benefits of you taking TIMENTIN against the risks this medicine could have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What is TIMENTIN used for?

TIMENTIN contains two active ingredients. One of these is a penicillin called ticarcillin and the other is clavulanate. TIMENTIN belongs to a group of medicines called Penicillins.

TIMENTIN is used to treat a wide range of infections caused by bacteria. These infections may affect the blood, the chest, bones and joints, skin and the genito-urinary tract.

TIMENTIN works by killing the bacteria that cause these infections.

Your doctor may have prescribed TIMENTIN for another reason.

TIMENTIN is not addictive.

Before you are given TIMENTIN

When you must not have it:

You must not be given TIMENTIN if:

  • you have ever had an allergic reaction to ticarcillin sodium and/or potassium clavulanate.
  • you have a history of allergy to penicillins or similar types of antibiotics (eg. cephalosporins).
  • the expiry date (EXP) printed on the pack has passed, or if the packaging is torn or shows signs of tampering

Tell your doctor if:

You must tell your doctor if:

  • you are allergic to foods, dyes, preservatives or any other medicines.
  • you have had an allergic reaction to antibiotics in the past.
  • you are taking any other medicines, including medicines you buy without a prescription.
  • you are taking the oral contraceptive pill. As with other antibiotics, you may need to take additional contraceptive precautions.
  • you have a history of cardiac disease.
  • you are on a restricted sodium intake.
  • you have a history of kidney disease.
  • you have a history of liver disease.
  • you are breastfeeding, pregnant, trying to become pregnant or trying to father a child.

How TIMENTIN is given?

How much to give

TIMENTIN will be administered as directed under the supervision of a doctor or nurse. You will not be expected to give yourself this medication.

How it is given

TIMENTIN should be administered by intravenous infusion over 30 minutes.

How long it is given for

TIMENTIN should be administered for as long as recommended by your doctor.

Use in children

The efficacy and safety of TIMENTIN have not been established in infants and children under the age of 14. Consult your doctor before use in children.

What do I do if I am given too much? (Overdose)

Immediately telephone your nearest hospital emergency department or Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have been given too much TIMENTIN, even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you are not sure what to do, contact your doctor or pharmacist.

While you are being given TIMENTIN

Things you must do

Tell your doctor if you are allergic to penicillin or other antibiotics.

Tell your doctor if you have kidney or liver problems.

Tell your doctor that you are being given TIMENTIN before taking any other prescribed medicine or performing any urine or blood tests. Some medicines may affect the way other medicines work.

Probenecid (used to treat gout) can affect how TIMENTIN works, or make it more likely that you will have side effects. Tell your doctor or pharmacist if you are taking this medicine.

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Things to be careful of

Be careful driving or operating machinery until you know how TIMENTIN affects you.

What are the side-effects?

Check with your doctor as soon as possible if you think you are experiencing any side effects or allergic reactions due to taking TIMENTIN, even if the problem is not listed below.

Like other medicines, TIMENTIN can cause some side-effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Reported side-effects include:

  • itchiness, redness, painful joints, muscle aches and pains, fever, chills,
  • headache, dizziness, imagined sensations,
  • disturbance of taste or smell, sore mouth, flatulence, nausea, vomiting, diarrhoea, abdominal pain,
  • pain or swelling at the site of injection,
  • abnormal blood results;
  • blood in your urine.

Tell your doctor IMMEDIATELY if you notice any of the following:

  • narrowing of the airways, wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be symptoms of an allergic reaction,
  • severe skin rash,
  • convulsive seizures, or
  • unusual bruising or bleeding
  • prolonged diarrhoea or inflammation of the large bowel.

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

Do not be alarmed by this list of possible side-effects. You may not experience any of them.

How do I store TIMENTIN?

Keep this medicine where children cannot reach it, such as in a locked cupboard.

TIMENTIN vials should be stored at or below 25°C.

Product description

What TIMENTIN looks like

TIMENTIN looks like a fine white to pale yellow powder. The powder is reconstituted with sterile water prior to injection.

Ingredients

TIMENTIN contains the active ingredients ticarcillin sodium and potassium clavulanate.

Supplier

Your TIMENTIN is supplied by:

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia.

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition.

This leaflet was revised in October 2013.

The information provided applies only to: TIMENTIN

TIMENTIN® is a registered trademark of Aspen Global Incorporated.

TIMENTIN: AUST R 11165

BRAND INFORMATION

Brand name

Timentin Powder for infusion

Active ingredient

Ticarcillin; Potassium clavulanate

Schedule

S4

 

Name of the medicine

Ticarcillin sodium 3 g, potassium clavulanate 0.1 g.

Description

Ticarcillin sodium.

Chemical name: 6-[(carboxy-3-thienylacetyl) amino]- 3,3-dimethyl-7-oxo-4-thia-1- azabicyclo(3.2.0)heptane-2-carboxylic acid disodium salt. CAS: 4697-14-7. Derived from the basic penicillin nucleus, 6-amino-penicillanic acid.

Clavulanic acid.

Chemical name: potassium Z-(3R,5R)-2-(β-hydroxyethylidene) clavam-3-carboxylate. CAS: 61177-45-5. Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins but has only weak antibacterial activity. It possesses the ability to inactivate a wide variety of β-lactamases excluding the type 1 Richmond but including the plasmid mediated β-lactamases by blocking the active site of these enzymes.
Timentin is an injectable antibacterial combination consisting of the semisynthetic antibiotic, ticarcillin sodium and the β-lactamase inhibitor, potassium clavulanate (the potassium salt of clavulanic acid).
Timentin is supplied as a white to pale yellow powder for reconstitution. Timentin is very soluble in water; its solubility being greater than 600 mg/mL. The reconstituted solution is clear, colourless or pale yellow, having a pH of 6.0 to 8.0. For the Timentin 3.1 g vials, the sodium content is approximately 15.6 mmol (360 mg). The potassium content is approximately 0.5 mmol (20 mg).

Pharmacology

Ticarcillin, like other penicillins, has a bactericidal effect on susceptible bacteria during active multiplication.
Ticarcillin is, however, susceptible to degradation by β-lactamases. The addition of clavulanic acid, a β-lactamase inhibitor, extends the antibacterial spectrum of ticarcillin so as to include organisms which are normally resistant to it by virtue of their ability to produce β-lactamases. Many of the following organisms, whose resistance is often due to β-lactamase production, are therefore susceptible to Timentin.
The 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.

In vitro susceptibility of microorganisms to ticarcillin/ clavulanate.

Where clinical efficacy of ticarcillin/ clavulanic acid has been demonstrated in clinical trials this is indicated with an asterisk (*).
Organisms that do not produce beta-lactamase are identified (with #). If an isolate is susceptible to ticarcillin, it can be considered susceptible to ticarcillin/ clavulanate.

Commonly susceptible species.

Gram positive aerobes.

Staphylococcus aureus (methicillin susceptible isolates only)*; Staphylococcus epidermidis (methicillin susceptible isolates only)*; beta-hemolytic streptococci#; Enterococcus faecalis#.

Gram positive anaerobes.

Clostridium spp.; Eubacterium spp.; Peptostreptococcus spp.#.

Gram negative anaerobes.

Bacteroides spp. including B. fragilis; Prevotella spp.; Fusobacterium spp.

Species 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 organisms.

Stenotrophomonas maltophilia; Burkholderia cepacia.

Pharmacokinetics.

Absorption.

After an intravenous infusion (30 minutes) of Timentin 3.1 g, peak serum concentrations of both ticarcillin and clavulanic acid are attained immediately after completion of infusion. Ticarcillin serum levels are similar to those produced by the administration of equivalent amounts of ticarcillin alone, with a mean peak serum level of 324 microgram/mL. The corresponding mean peak serum levels for clavulanic acid was 8 microgram/mL. See Table 1.
The mean area under the serum concentration curve for ticarcillin was 485 microgram/mL.hour. The corresponding area under the serum concentration curve for clavulanic acid was 8.2 microgram/mL.hour.
Somewhat higher and more prolonged serum levels of ticarcillin can be achieved with the concurrent administration of probenecid; however, probenecid does not enhance the serum levels of clavulanic acid.

Distribution.

Penetration of ticarcillin into cerebrospinal fluid is poor in the absence of meningeal inflammation.
An inverse relationship exists between the serum half-life of ticarcillin and creatinine clearance. The dosage of Timentin need only be adjusted in cases of severe renal impairment (see Dosage and Administration).
Neither component of Timentin is highly protein bound; ticarcillin has been found to be approximately 45% bound to human serum protein and clavulanic acid has been variously reported to be bound to human serum in the range of 9 to 30%.

Elimination.

The mean serum half-lives of ticarcillin and clavulanic acid in healthy volunteers are 68 minutes and 64 minutes respectively.
Approximately 60-70% of ticarcillin and approximately 35-45% of clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single dose of Timentin to normal volunteers with normal renal function. During the first two hours after an intravenous injection of Timentin 3.1 g, concentrations of ticarcillin in urine generally exceed 1500 microgram/mL. The corresponding concentrations of clavulanic acid in urine generally exceed 40 microgram/mL following administration of the 3.1 g dose. By 4-6 hours after injection, the urine concentrations of ticarcillin and clavulanic acid usually decline to approximately 190 microgram/mL and 2 microgram/mL.

Special patient populations.

Ticarcillin may be removed from patients undergoing dialysis; the actual amount removed depends on the duration and type of dialysis.

Indications

Timentin is indicated in the treatment of serious infections caused by susceptible strains of β-lactamase producing organisms in the conditions listed below.
Septicaemia (and bacteraemia) cases caused by β-lactamase producing organisms, including strains of K. pneumoniae, E. coli, Staph. aureus and Ps. aeruginosa.
Lower respiratory infections cases caused by β-lactamase producing susceptible organisms, including strains of Staph. aureus, H. influenzae and K. pneumoniae.
Bone and joint infections cases caused by β-lactamase producing susceptible organisms, including strains of Staph. aureus.
Skin and skin structure infections cases caused by β-lactamase producing susceptible organisms, including strains of Staph. aureus, K. pneumoniae and E. coli.
Urinary tract infections cases caused by β-lactamase producing susceptible organisms, including strains of E. coli, K. pneumoniae, Ps. aeruginosa and Staph. aureus.
Gynaecological infections including cases caused by β-lactamase producing susceptible organisms, including strains of K. pneumoniae, Staph. aureus and Staph. epidermidis.
While Timentin is indicated only for the conditions listed above, it may be used as a single agent in the treatment of mixed infections caused by ticarcillin susceptible and β-lactamase producing ticarcillin resistant organisms.
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to Timentin. Susceptibility to ticarcillin-clavulanate will vary with geography and time and local susceptibility data should be consulted where available (see Pharmacology).
Based on the in vitro synergism between ticarcillin and gentamicin sulfate/ tobramycin sulfate/ amikacin sulfate against certain strains of Ps. aeruginosa, combined therapy has been successful. Timentin may be used as combination therapy concurrently with the aminoglycosides, but both drugs should be used in full therapeutic doses. As soon as results of culture and susceptibility tests become available, antimicrobial therapy should be adjusted as indicated. Results of susceptibility tests showing synergy between ticarcillin and one aminoglycoside should not be extrapolated to combination with another aminoglycoside.

Prophylactic use.

Timentin may be administered perioperatively (preoperatively, intraoperatively and postoperatively) to patients undergoing abdominal hysterectomy or elective colorectal surgery when there is a significant risk of surgery related postoperative infection.
If signs of postsurgical infection should appear, these should be treated with appropriate therapy.

Contraindications

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

Precautions

Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving β-lactam antibiotics. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with Timentin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs. If an allergic reaction occurs, Timentin should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids, and airway management, including intubation, should also be provided as indicated.
Bleeding manifestations have occurred in some patients receiving Timentin or high doses of ticarcillin. 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.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including ticarcillin. A toxin produced with Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibiotic agent effective against Cl. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.

General.

While Timentin possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Timentin has been reported to cause hypokalaemia, and the possibility of this occurring should be kept in mind particularly when treating patients with fluid and electrolyte imbalance. Periodic monitoring of serum potassium is advisable in patients receiving prolonged therapy.
The sodium content is approximately 15.6 mmol (360 mg) per vial of Timentin 3.1 g. This should be considered when treating patients requiring restricted salt intake.
Timentin should be administered with caution to patients with cardiac disease, as cardiac failure may be exacerbated.
As with any penicillin, an allergic reaction, including anaphylaxis, may occur during Timentin administration, particularly in a hypersensitive individual.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind, particularly during prolonged treatment. If superinfections occur, appropriate measures should be taken.

Effects on laboratory tests.

High urine concentrations of ticarcillin may produce false positive protein reactions (pseudoproteinuria) with the following methods: sulfosalicylic acid and boiling test, acetic acid test, biuret reaction, and nitric acid test. The bromphenol blue (Multistix) reagent strip test has been reported to be reliable.
The presence of clavulanic acid in Timentin may cause a nonspecific binding of IgG and albumin by red cell membranes leading to a false positive Coombs' test.

Carcinogenesis, mutagenesis, impairment of fertility

Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.

Use in pregnancy.

Reproduction studies have been performed in rats given doses up to 1050 mg/kg/day and have revealed no evidence of impaired fertility or harm to the foetus due to Timentin. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Use in lactation.

Trace quantities of Timentin are excreted in breast milk. The possibility of hypersensitivity reactions must be considered in breastfeeding infants. Therefore, Timentin should only be administered to a breastfeeding woman when the potential benefits outweigh the potential risks associated with treatment.

Paediatric use

The efficacy and safety of Timentin have not been established in infants and children under the age of 14.

Patients with renal impairment.

In patients with renal impairment, dosage should be adjusted according to the degree of impairment (see Dosage and Administration).

Patients with hepatic impairment.

There is insufficient evidence on which to base a dosage recommendation in patients with hepatic impairment.

Drug abuse and dependence.

Neither Timentin abuse nor Timentin dependence has been reported.

Interactions

As with other penicillins, the mixing of Timentin with an aminoglycoside in solutions for parenteral administration can result in substantial inactivation of the aminoglycoside (see Dosage and Administration).
Coadministration 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 nonspecific binding of IgG and albumin by red cell membranes leading to a false positive Coombs' test..
In common with other antibiotics, ticarcillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Adverse Effects

The following adverse reactions may occur.

Hypersensitivity reactions.

Skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, bronchospasm, wheezing, and anaphylactic reactions. Erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported rarely.

Central nervous system.

Headache, giddiness, hallucinations, neuromuscular hyperirritability or convulsive seizures. Convulsions may occur rarely, particularly in patients with impaired renal function or in those receiving high doses.

Gastrointestinal.

Disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhoea, epigastric pain. Pseudomembranous colitis has been reported rarely.

Haemic and lymphatic systems.

Thrombocytopenia, leucopenia, neutropenia, eosinophilia, immune haemolytic anaemia and reduction of haemoglobin or haematocrit. Thrombocytosis was noted in about 2% of patients treated with Timentin. Prolongation of prothrombin time and bleeding time, positive Coombs' test. Bleeding manifestations have occurred.

Renal and urinary effects.

Elevation of serum creatinine and/or BUN, hypernatraemia. Reduction in serum potassium and uric acid. Hypokalaemia has been reported rarely. Haemorrhagic cystitis has been reported very rarely.

Abnormalities of hepatic function tests.

Elevation of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum alkaline phosphatase, serum LDH, serum bilirubin. Transient hepatitis and cholestatic jaundice have been reported rarely.

Local reactions.

Pain, burning, erythema, infiltration, swelling and induration at the injection site, and thrombophlebitis with intravenous administration.

Dosage and Administration

Timentin should be administered by intravenous infusion (30 minutes).
Use Timentin in one patient on one occasion only. Timentin contains no antimicrobial preservative.
The maximum daily adult dose of Timentin 3.1 g is 18 g, based on the ticarcillin component.
The usual recommended dosage for average (60 kg) adults is 3.1 g (3.1 g vial containing ticarcillin 3 g and clavulanic acid 100 mg) every four to six hours, except for urinary tract infections where the drug is administered every eight hours. For patients weighing less than 60 kg, the recommended dosage is 200-300 mg/kg/day, based on ticarcillin content, given in divided doses every 4 or 6 hours.
Clinical data are insufficient at present to recommend an appropriate dosage regimen for Timentin in patients with renal failure. However, on the basis of theoretical considerations (namely absence of any change in the pharmacokinetics of ticarcillin due to clavulanic acid and the apparent greater tissue clearance of clavulanic acid as compared to ticarcillin), it is suggested that for infections complicated by renal insufficiency, the dosage regimen as used currently for ticarcillin alone may generally be adopted (see below). Note that this dosage schedule has not been tested in patients with impaired renal function.

Dosage regimen in renal insufficiency.

An initial loading dose of 3.1 g intravenously followed by intravenous doses based on creatinine clearance or type of dialysis as indicated in Table 2.
The half-life of Ticarcillin in patients with renal failure is approximately 13 hours.
To calculate creatinine clearance1 from a serum creatinine value use the following formula (Equation 1).
Dosage for any individual patient must take into consideration the site and severity of infection, the susceptibility of the organisms causing infection, and the status of the patient's host defence mechanisms.
The duration of therapy depends upon the severity of infection. Generally, Timentin should be continued for at least two days after the signs and symptoms of infection have disappeared. The usual duration is 10 to 14 days; however, in difficult and complicated infections, more prolonged therapy may be required.
Frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed.
In certain infections, involving abscess formation, appropriate surgical drainage should be performed in conjunction with antimicrobial therapy.

Prophylaxis.

For prophylactic use, the following dose is recommended.
For patients undergoing caesarean section, the first dose of 3.1 g is administered intravenously as soon as the umbilical cord is clamped. This is to be followed by two additional doses of 3.1 g every 4 hours after the first dose for a total of 3 doses.
For patients undergoing abdominal hysterectomy, a dose of 3.1 g administered half to one hour prior to the initial incision followed by 2 additional doses of 3.1 g every 4 hours for a total of 3 doses.
For patients undergoing elective colorectal surgery, a dose of 3.1 g administered intravenously half to one hour prior to the initial incision followed by 2 additional doses of 3.1 g every eight hours for a total of 3 doses. An alternative regimen in which a dose of 3.1 g administered intravenously 15 minutes prior to induction of anaesthesia and followed 2 hours later by a second dose of 3.1 g, has also proved effective.

Directions for intravenous infusion.

The 3.1 g vial should be reconstituted by shaking with approximately 13 mL of sterile water for injection, or sodium chloride injection; when dissolved, the concentration of ticarcillin will be approximately 200 mg/mL and the concentration of clavulanic acid 6.7 mg/mL. Each 5.0 mL of the 3.1 g dose reconstituted with approximately 13 mL of diluent will contain approximately 1 g of ticarcillin and 33 mg of clavulanic acid.
The dissolved drug should be further diluted to desired volume using a suitable solution (see Compatibility and stability). The solution of reconstituted drug may then be administered over a period of 30 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place. If this method or the ‘piggyback’ method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of Timentin.
When Timentin is given in combination with another antimicrobial, such as an aminoglycoside, each drug should be given seperately in accordance with the recommended dosage and routes of administration for each drug.
After reconstitution and prior to administration, Timentin, as with other parenteral drugs, should be inspected visually for particulate matter and discolouration, and discarded if unsuitable.

Compatibility and stability.

The stock solution at 200 mg/mL is stable for up to six hours at room temperature (25°C) or up to 72 hours under refrigeration (4°C). Timentin stability studies in the following intravenous solutions indicate that Timentin will provide sufficient activity at either room temperature or stored under refrigeration within the stated time periods and at concentrations between 10 mg/mL and 100 mg/mL with any of the diluents on the following list. See Table 3.

Note.

Timentin is incompatible with sodium bicarbonate.
It is not recommended that dextrose containing solutions be frozen.
Frozen solutions should be thawed at room temperature (25°C) and used immediately.
Unused solutions must be discarded after the time periods stated above.

Overdosage

As with other penicillins, Timentin in overdosage has the potential to cause neuromuscular hyperirritability or convulsive seizures. Ticarcillin may be removed from circulation by haemodialysis. The molecular weight, degree of protein binding and pharmacokinetic profile of clavulanic acid, together with information from a single patient with renal insufficiency, all suggest that this compound may also be removed by haemodialysis.
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.

Presentation

Powder for reconstitution (white to pale yellow, sterile), ticarcillin sodium (≡ ticarcillin 3 g), potassium clavulanate (≡ clavulanic acid 0.1 g), 3.1 g: 1's*, 10's (vials).
*Not currently marketed in Australia.

Storage

Timentin vials should be stored at or below 25°C.

References

1. Cockroft, D.W. et al. Prediction of Creatinine Clearance from Serum Creatinine. Nephron, 1976; 16:31–41.

Poison Schedule

S4.