Consumer medicine information

Meropenem IV APOTEX

Meropenem

BRAND INFORMATION

Brand name

Meropenem APOTEX

Active ingredient

Meropenem

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Meropenem IV APOTEX.

What is in this leaflet

This leaflet answers some common questions about meropenem. It does not contain all 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 risks of you using this medicine against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may want to read it again.

What this medicine is used for

Meropenem is used to treat many different types of infection, such as:

  • infections of the lungs
  • infections of the kidney or bladder (urinary tract infection)
  • febrile neutropenia
  • infections around the stomach or bowel
  • infections of the vagina and womb
  • serious skin infections
  • infections in the lining of the brain (meningitis)
  • infections in the blood stream (septicaemia)

Meropenem is given by injection and is usually only used in hospitals.

How it works

Meropenem belongs to a group of medicines called carbapenem antibiotics. These medicines work by killing the bacteria that are causing your infection.

Meropenem will not work against fungal or viral infections (such as colds or flu).

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

This medicine is not addictive.

This medicine is not recommended for use in children under the age of 3 months.

Before you are given this medicine

When you must not be given it

Do not use this medicine if you have an allergy to:

  • meropenem
  • any other antibiotics such as other carbapenems, penicillins, cephalosporins, or beta lactam antibiotics
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin

Do not use this medicine after the expiry date printed on the pack has passed or if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • gastrointestinal or stomach problems, particularly colitis
  • liver or kidney problems, including dialysis

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Do not take this medicine until you and your doctor have discussed the risks and benefits involved.

Tell your doctor if you are on a low salt (sodium) diet.

If you have not told your doctor about any of the above, tell them before you are given this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you may get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and meropenem. may interfere with each other. These include:

  • probenecid, used to treat gout
  • sodium valproate, valproic acid or valpromide, medicines used to treat epilepsy or mania
  • oral anticoagulants (such as warfarin), used to thin the blood

These medicines may be affected by meropenem or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while receiving this medicine.

Other medicines not listed above may also interact with meropenem.

How this medicine is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ to the information contained in this leaflet.

How much will you be given

Your doctor will decide what dose of meropenem you will need, depending on certain factors such as your type of infection and your age.

The usual dose is 500 mg to 1 g injected every 8 hours. If you have meningitis you may require more, while a lower dose may be used for children or if you have kidney problems.

How it is given

Meropenem is injected into your vein. It must always be given by a doctor or nurse.

Many people who get meropenem in hospital will have a drip (intravenous line). Meropenem can be given directly into the vein or the drip without any need for an injection through the skin. It is given either as a slow injection over approximately 5 minutes or as a slow drip over 15 to 30 minutes. Your doctor will decide which method is best for you.

How long you will need to be given this medicine

Your doctor will decide how many days you will receive meropenem.

If you take too much (overdose)

Immediately tell your doctor or nurse if you think that you or anyone else may have been given too much of this medicine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using this medicine

Things you must do

If you are about to be started on any new medicine, tell your doctor or pharmacist that you are receiving this medicine.

Tell any other doctors, dentists and pharmacists who are treating you that you are receiving this medicine.

If you find out that you are pregnant after being given this medicine, tell your doctor immediately.

Tell your doctor if you develop severe diarrhoea, even if it occurs several weeks after you have been given meropenem. It may mean that you have a serious bowel condition and you may need urgent medical attention. Do not take any medicine for your diarrhoea without checking with your doctor first.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do occasionally do tests to monitor your liver function if you have pre-existing liver disorders.

If you are about to have blood tests, tell your doctor that you are being treated with this medicine. It may interfere with the results of some tests.

Things to be careful of

Meropenem has been associated with headache, tingling or prickling skin and convulsions (fits).

If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are receiving meropenem.

This medicine helps most people with infections, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following:

  • pain, swelling or redness around the injection site
  • nausea and/or vomiting
  • diarrhoea
  • abdominal pain
  • skin rash, itchiness
  • tingling, 'pins and needles' sensation

The above list includes the more common side effects of your medicine.

Tell your doctor or nurse as soon as possible if you notice any of the following:

  • shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin (signs of an allergic reaction)
  • severe diarrhoea, even if it occurs several weeks after you have been given meropenem
  • convulsions / seizures (fits)
  • unexpected breathlessness and/or red/brown urine - this may indicate damage to your red blood cells
  • fever, red or purple skin rash that spreads, severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • severe blisters, widespread skin rash, itching, skin reaction which makes the skin look scalded (can also be accompanied by fever and chills)

The above list includes serious side effects and you may need medical attention.

Occasionally, meropenem may be associated with changes in your blood that may require your doctor to do certain blood tests.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

Storage and disposal

Storage

The hospital staff will store meropenem in a safe place at a temperature below 30 degrees C.

They will also check that the expiry date has not passed.

Disposal

The hospital staff will dispose of any unused meropenem.

Product description

What it looks like

500mg:
White to slightly yellow sterile powder in a 20 mL glass vial

AUST R 218843.

1000mg:
White to slightly yellow sterile powder in a 30 mL glass vial

AUST R 218840.

Meropenem vials come in a pack size of 10 vials.

* Not all strengths may be available.

Ingredients

Each vial contains 500 mg or 1000 mg of meropenem trihydrate as the active ingredient.

It also contains sodium carbonate as the inactive ingredient.

This medicine does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
Australia
Tel: (02) 8877 8333
Web: www1.apotex.com/au

APO and APOTEX are registered trademarks of Apotex Inc.

This leaflet was prepared in July 2020.

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Meropenem APOTEX

Active ingredient

Meropenem

Schedule

S4

 

1 Name of Medicine

Meropenem, as meropenem trihydrate.

2 Qualitative and Quantitative Composition

20 mL vial.

Contains meropenem trihydrate equivalent to meropenem 500 mg.

30 mL vial.

Contains meropenem trihydrate equivalent to meropenem 1000 mg.

Excipients with known effect.

Sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Meropenem powder for injection is presented as a sterile white powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Meropenem is indicated for treatment of the following infections, in adults and children (aged 3 months and over), when the causative organisms are known or suspected to be resistant to commonly used antibiotics:
Community acquired lower respiratory tract infection.
Hospital acquired lower respiratory tract infection.
Complicated urinary tract infection.
Febrile neutropenia.
Intra-abdominal and gynaecological (polymicrobial) infections.
Complicated skin and skin structure infections.
Meningitis.
Septicaemia.

4.2 Dose and Method of Administration

Adults.

Usual dose.

500 mg to 1 g by intravenous administration every 8 hours depending on type and severity of infection, the known or suspected susceptibility of the pathogen(s) and the condition of the patient.

Exceptions.

1. Febrile episodes in neutropenic patients: the dose should be 1 g every 8 hours.
2. Meningitis: the dose should be 2 g every 8 hours.
As with other antibiotics, caution may be required in using meropenem as monotherapy in critically ill patients with known or suspected Pseudomonas aeruginosa lower respiratory tract infection.
Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa infection.
Meropenem should be given as an intravenous bolus injection over approximately 5 minutes or by intravenous infusion over approximately 15 to 30 minutes (see Constitution and compatibility). There is limited safety data available to support the administration of a 2 g bolus dose.

Dosage schedule for adults with impaired renal function.

Dosage should be reduced in patients with creatinine clearance less than 51 mL/min, as scheduled in Table 1.
Meropenem is cleared by haemodialysis. If continued treatment with meropenem is necessary, it is recommended that the unit dose (based on the type and severity of infection) is administered at the completion of the haemodialysis procedure to restore therapeutically effective plasma concentrations.
There is no experience with peritoneal dialysis.

Use in adults with hepatic insufficiency.

No dosage adjustment is necessary in patients with impaired hepatic metabolism.

Elderly patients.

No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 mL/min.

Children.

For infants and children over 3 months and up to 12 years of age the recommended intravenous dose is 10 to 40 mg/kg every 8 hours depending on type and severity of infection, the known or suspected susceptibility of the pathogen(s) and the condition of the patient. In children over 50 kg weight, adult dosage should be used.

Exceptions.

1. Febrile episodes in neutropenic patients: the dose should be 20 mg/kg every 8 hours.
2. Meningitis: the dose should be 40 mg/kg every 8 hours.
Meropenem should be given as an I.V. bolus over approximately 5 minutes or by intravenous infusion over approximately 15 to 30 minutes. There is limited safety data available to support the administration of a 40 mg/kg bolus dose.
There is no experience in children with renal impairment.

Constitution and compatibility.

Meropenem to be used for bolus I.V. injection should be constituted with sterile water for injections (10 mL per 500 mg meropenem). This provides an approximate available concentration of 50 mg/mL. Constituted solutions are both clear and colourless to pale yellow.
Meropenem for I.V. infusion may be directly constituted with either 0.9% sodium chloride solution for infusion or 5% glucose (dextrose) solution for infusion and then further diluted (50 to 200 mL) with the compatible infusion fluid (final concentration of 1 to 20 mg/mL).

Pharmaceutical precautions.

Shake constituted solution before use. All vials are for single use only. Standard aseptic technique should be employed during constitution and administration.
Meropenem should not be mixed with or physically added to solutions containing other medicines.

Stability after constitution and dilution.

After reconstitution.

The reconstituted solutions for intravenous injection or infusion should be used immediately. The time interval between the beginning of reconstitution and the end of intravenous injection or infusion should not exceed one hour.
Solutions of Meropenem should not be frozen. For single use in one patient only. Discard any unused solution.

4.3 Contraindications

Meropenem is contraindicated in patients who have demonstrated hypersensitivity to this product.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving therapy with β-lactams. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. There have been reports of patients with a history of penicillin hypersensitivity who have experienced severe hypersensitivity when treated with another β-lactam. Before initiating treatment with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, or other β-lactam antibiotics. If an allergic reaction occurs to meropenem then discontinue the medicine. Serious hypersensitivity reactions may require adrenaline and other emergency measures.
As with other β-lactam antibiotics, strains of Pseudomonas aeruginosa may develop resistance on treatment with meropenem. Development of resistance has been reported in pseudomonal hospital acquired lower respiratory tract infections. In such cases, meropenem should be used with caution and repeat sensitivity testing is recommended.
As with other antibiotics, overgrowth of non-susceptible organisms may occur and repeated evaluation of each patient is necessary.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta lactam antibiotics (see Section 4.8 Adverse Effects (Undesirable Effects)). When SCAR is suspected, meropenem should be discontinued immediately and an alternative treatment should be considered.

Gastrointestinal disease.

History of colitis: Antibiotics should be prescribed with care for individuals with a history of gastrointestinal disease, especially ulcerative colitis, regional enteritis, or antibiotic associated colitis.
Rarely, pseudomembranous colitis has been reported with meropenem as with practically all antibiotics and may vary in severity from slight to life threatening. Therefore, antibiotics should be prescribed with care for individuals with a history of gastrointestinal complaints, particularly colitis. It is important to consider the diagnosis of pseudomembranous colitis in the case of patients who develop diarrhoea when using an antibiotic. Although studies indicate that a toxin produced by Clostridium difficile is one of the main causes of antibiotic associated colitis, other causes should be considered. Mild cases usually respond to medicine discontinuation alone. However, in moderate to severe cases appropriate therapy such as oral antibacterial agents effective against Clostridium difficile should be considered.
Fluids, electrolytes and protein replacement should be provided when indicated. Medicines which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.

Seizures.

Seizures have infrequently been reported during treatment with carbapenems, including meropenem.

Sodium.

This medicinal product contains sodium which should be taken into consideration for patients on a controlled sodium diet.

Use in severe meningitis.

Neurological sequelae were reported following treatment of severe meningitis with meropenem. In clinical trials these adverse events were reported in 23 of 148 patients treated with meropenem and in 17 of 144 patients treated with comparator antibiotics.

Use with valproic acid/sodium valproate.

The concomitant use of valproic acid/sodium valproate and meropenem is not recommended. Meropenem may reduce serum valproic acid levels. Subtherapeutic levels may be reached in some patients (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic impairment.

Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytosis). Patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem.

Use in renal impairment.

See Section 4.2 Dose and Method of Administration.

Use in the elderly.

See Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties.

Paediatric use.

Efficacy and tolerability in infants under 3 months of age have not been established; therefore, meropenem is not recommended for use below this age.

Effects on laboratory tests.

A positive or indirect Coombs' test may develop.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Meropenem has been administered concomitantly with many other medications without apparent adverse interaction. However, no specific medicine interaction studies other than with probenecid were conducted.

Probenecid.

Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. As the potency and duration of action of meropenem dosed without probenecid are adequate the coadministration of probenecid with meropenem is not recommended. The potential effect of meropenem on the protein binding of other medicines or metabolism has not been studied. However, the protein binding is so low (approximately 2%) that no interactions with other compounds would be expected on the basis of this mechanism.

Valproic acid/sodium valproate.

A clinically significant reduction in serum valproic acid concentration has been reported when it is coadministered with carbapenem agents resulting in a 60 -100% decrease in valproic acid levels in about two days. Due to the rapid onset and the extent of the decrease, co-administration of meropenem for IV injection in patients stabilised on valproic acid/sodium valproate is not considered to be manageable and therefore should be avoided (see Section 4.4 Special Warnings and Precautions for Use; Section 6.2 Incompatibilities).
The concomitant use of meropenem and valproic acid/sodium valproate/valpromide is not recommended.

Oral anticoagulants.

Simultaneous administration of antibiotics with warfarin may augment its anticoagulant effects. There have been many reports of increases in the anticoagulant effects of orally administered anticoagulant agents, including warfarin, in patients who are concomitantly receiving antibacterial agents. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of the antibiotic to the increase in INR (international normalized ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after co-administration of antibiotics with an oral anticoagulant agent.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility was not impaired in rats with exposures (based on AUC) slightly greater than those observed in patients at the recommended intravenous dose.
(Category B2)
Reproduction studies conducted with meropenem in rats have shown no embryotoxicity or teratogenicity at plasma exposures (based on AUC values) approximately equal to those observed in patients at the recommended intravenous dose. In a teratology study in cynomolgus monkeys given daily intravenous injections meropenem showed no evidence of teratogenicity at dose levels up to 360 mg/kg/day.
There are however, no adequate or well controlled trials of meropenem in pregnant women. Because reproduction studies are not always predictive of human response, meropenem should not be used in pregnancy unless the potential benefit justifies the potential risk to the foetus.
 Meropenem has been reported to be excreted in human breast milk. Meropenem should not be used in breastfeeding women unless the potential benefit justifies the potential risk to the baby.

4.7 Effects on Ability to Drive and Use Machines

No studies on the ability to drive and use machines have been performed. However, when driving or operating machines it should be taken into account that headache, paraesthesiae and convulsions have been reported for meropenem.

4.8 Adverse Effects (Undesirable Effects)

Meropenem is generally well tolerated.
In clinical trials, adverse events lead to cessation of treatment in less than 1% of patients. Serious adverse events are rare. See Tables 2 and 3.
Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients taking beta lactam antibiotics.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems or contact Apotex Medical Information enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

The pharmacological properties and mode of administration make it unlikely that intentional overdose will occur. Accidental overdosage could occur during therapy, particularly in patients with renal impairment. Treatment of overdosage should be symptomatic. In normal individuals rapid renal elimination will occur. In subjects with renal impairment haemodialysis will remove meropenem and its metabolite.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Meropenem is a carbapenem antibiotic for parenteral use, that is stable to human dehydropeptidase-1 (DHP-1).
Meropenem exerts its bactericidal action by interfering with vital bacterial cell wall synthesis. The ease with which it penetrates bacterial cell walls, its high level of stability to all serine β-lactamases and its marked affinity for multiple penicillin binding proteins (PBPS) explain the potent bactericidal action of meropenem against a broad spectrum of aerobic and anaerobic bacteria. Bactericidal concentrations are commonly the same as the minimum inhibitory concentrations (MICs).

Susceptibility testing.

Localised clusters of infections due to carbapenem resistant bacteria have been reported in some regions.
The susceptibility to meropenem of a given clinical isolate should be determined by standard methods. Interpretation of test results should be made in accordance with local infectious diseases and clinical microbiology guidelines.
Meropenem is stable in susceptibility tests and these tests can be performed using normal routine methods. In vitro tests show that meropenem acts synergistically with various antibiotics. It has been demonstrated both in vitro and in vivo that meropenem has a postantibiotic effect.
Meropenem is usually active, in vitro and in clinical infections, against the strains of bacteria shown below:
Commonly susceptible species.

Gram positive aerobes.

Enterococcus faecalis (note that E. faecalis can naturally display intermediate susceptibility), Staphylococcus aureus (methicillin susceptible strains only: methicillin resistant Staphylococci including MRSA are resistant to meropenem), Staphylococcus species including Staphylococcus epidermidis (methicillin susceptible strains only: methicillin resistant Staphylococci including MRSE are resistant to meropenem), Streptococcus agalactiae (group B Streptococcus), Streptococcus mitis, Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius), Streptococcus pneumoniae, Streptococcus pyogenes (group A Streptococcus).

Gram negative aerobes.

Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Neisseria meningitidis, Proteus mirabilis, Serratia marcescens.

Gram positive anaerobes.

Clostridium perfringens, Peptostreptococcus spp. (including P. micros, P. anaerobius, P. magnus).

Gram negative anaerobes.

Bacteroides caccae, Bacteroides fragilis.
Species for which acquired resistance may be a problem.

Gram positive aerobes.

Enterococcus faecium (E. faecium can naturally display intermediate susceptibility even without acquired resistance mechanisms); Staphylococcus aureus (methicillin-resistant staphylococci including MRSA are resistant to meropenem); Staphylococcus epidermidis (methicillin-resistant staphylococci including MRSE are resistant to meropenem).

Gram negative aerobes.

Acinetobacter species, Burkholderia cepacia, Pseudomonas aeruginosa.
Inherently resistant organisms.

Gram negative aerobes.

Stenotrophomonas (Xanthomonas) maltophilia, Legionella species.

Other inherently resistant organisms.

Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.
The published medical microbiology literature describes in vitro meropenem susceptibilities of many other bacterial species. However, the clinical significance of such in vitro findings is uncertain. Advice on the clinical significance of in vitro findings should be obtained from local infectious diseases and clinical microbiology experts and local professional guidelines.
The prevalence of acquired 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

The pharmacokinetics are linear over the dose range of 10 to 40 mg/kg.

Absorption.

A 30 minute intravenous infusion of a single dose of meropenem in normal volunteers results in peak plasma levels of approximately 11 microgram/mL for the 250 mg dose, 23 microgram/mL for the 500 mg dose, 49 microgram/mL for the 1 g dose and 115 microgram/mL following the 2 g dose.
A 5 minute intravenous bolus injection of meropenem in normal volunteers results in peak plasma levels of approximately 52 microgram/mL for the 500 mg dose and 112 microgram/mL for the 1 g dose.
Intravenous infusions over 2 minutes, 3 minutes and 5 minutes of a 1 g dose of meropenem were compared in a three way crossover trial. These durations of infusion resulted in peak plasma levels of 110, 91 and 94 microgram/mL, respectively.
After an intravenous dose of 500 mg, plasma levels of meropenem decline to values of 1 microgram/mL or less, 6 hours after administration.

Distribution.

When multiple doses are administered at 8 hourly intervals to subjects with normal renal function, accumulation of meropenem does not occur.
Plasma protein binding of meropenem is approximately 2%.
Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid of patients with bacterial meningitis, achieving concentrations in excess of those required to inhibit most bacteria.

Metabolism.

The only metabolite of meropenem is microbiologically inactive.
In subjects with normal renal function, meropenem's elimination half-life is approximately one hour.

Excretion.

Approximately 70% of the intravenous administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 microgram/mL are maintained for up to 5 hours at the 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in volunteers with normal renal function.
Studies in children have shown that the pharmacokinetics of meropenem in children are essentially similar to those in adults. The elimination half-life for meropenem was approximately 1.5 hours in children under the age of 2 years.
Pharmacokinetic studies in patients with renal insufficiency have shown the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment.
Pharmacokinetic studies in the elderly have shown a reduction in plasma clearance of meropenem which correlated with age associated reduction in creatinine clearance.
Pharmacokinetic studies in patients with liver disease have shown no effects of liver disease on the pharmacokinetics of meropenem.

5.3 Preclinical Safety Data

Genotoxicity.

Meropenem, with and without metabolic activation as appropriate, was not genotoxic in assays for gene mutations (Salmonella typhimurium, E. coli and Chinese hamster ovary cells) and chromosomal damage (mouse micronucleus assay and human lymphocytes in vitro).

Carcinogenicity.

The carcinogenic potential of meropenem has not been investigated.

6 Pharmaceutical Particulars

6.1 List of Excipients

Meropenem powder for injection contains 222.5 mg sodium carbonate for each gram of meropenem (anhydrous potency). See Table 4.

6.2 Incompatibilities

Meropenem should only be mixed with products within Section 4.2 Dose and Method of Administration.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Prior to constitution, store meropenem powder for injection packs below 30°C. See Constitution and compatibility for storage of prepared solutions.

6.5 Nature and Contents of Container

20 mL vial.

Vial packs (glass, with rubber stopper, sealed with aluminium-plastic cap) of 10 vials (AUST R 218843).

30 mL vial.

Vial packs (glass, with rubber stopper, sealed with aluminium-plastic cap) of 10 vials (AUST R 218840).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

White to slightly yellow powder.

Chemical structure.


Chemical Name: (4R,5S,6S)-3-[[(3S,5S)-5-[(dimethylamino) carbonyl]pyrrolidin-3-yl]sulfanyl]-6-[(1R)-1-hydroxy-ethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid trihydrate.
Molecular Formula: C17H25N3O5S.3H2O.
Molecular Weight: 437.52.

CAS number.

119478-56-7 meropenem trihydrate.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes