Consumer medicine information

Meropenem Ranbaxy

Meropenem

BRAND INFORMATION

Brand name

Meropenem Ranbaxy

Active ingredient

Meropenem

Schedule

SUMMARY CMI

Meropenem Ranbaxy

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Meropenem Ranbaxy?

Meropenem Ranbaxy contains the active ingredient meropenem. Meropenem Ranbaxy is used to treat infections of the lungs (pneumonia or bronchitis), infection of the bladder or kidney (urinary tract infection), infection of tissues around the stomach or gut, infections of the ovaries, vagina or womb, skin infections, infections of the membranes surrounding the brain and spinal cord (meningitis), infections of the blood (septicaemia), high fever and significant reduction in white blood cells resulting decreased resistance to infection (febrile neutropenia).

For more information, see Section 1. Why am I using Meropenem Ranbaxy? in the full CMI.

2. What should I know before I use Meropenem Ranbaxy?

Do not use if you have ever had an allergic reaction to meropenem or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Meropenem Ranbaxy? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Meropenem Ranbaxy and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Meropenem Ranbaxy?

The dose of Meropenem Ranbaxy is based on your condition, age and type and severity of infection.

Your doctor will decide how much Meropenem Ranbaxy to give you. The usual dose is 500 mg to 1g injected every 8 hours. If you have meningitis you may require more. If you have kidney problems, a smaller dose may be given. Children also require lower doses.

More instructions can be found in Section 4. How do I use Meropenem Ranbaxy? in the full CMI.

5. What should I know while using Meropenem Ranbaxy?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Meropenem Ranbaxy Call you doctor straight away if you develop severe diarrhoea
Driving or using machines	Meropenem may cause headache, tingling or prickling skin and convulsions/seizures (fits) in some people. If you have any of these symptoms, do not drive, operate machinery or do anything that could be dangerous.
Looking after your medicine	Meropenem Ranbaxy is store below 25°C

For more information, see Section 5. What should I know while using Meropenem Ranbaxy? in the full CMI.

6. Are there any side effects?

Common side effects include pain with redness and/or swelling at the site of injection, feeling sick (nausea), being sick (vomiting), loose stool (diarrhoea), skin problems such as rash or itching, headache.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Meropenem Ranbaxy

Active ingredient(s): meropenem

Consumer Medicine Information (CMI)

This leaflet provides important information about using Meropenem Ranbaxy. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Meropenem Ranbaxy.

Where to find information in this leaflet:

1. Why am I using Meropenem Ranbaxy?
2. What should I know before I use Meropenem Ranbaxy?
3. What if I am taking other medicines?
4. How do I use Meropenem Ranbaxy?
5. What should I know while using Meropenem Ranbaxy?
6. Are there any side effects?
7. Product details

1. Why am I using Meropenem Ranbaxy?

Meropenem Ranbaxy contains the active ingredient meropenem. Meropenem Ranbaxy belongs to a group of medicines called carbapenem antibiotics. These medicines fight bacteria that cause infections in the body. Meropenem will not work against viral (such as colds and flu) or fungal diseases.

Meropenem Ranbaxy may have been prescribed to you or your child (aged 3 months or above) for the treatment of the following bacterial infections:

Infections of the lungs (pneumonia or bronchitis)
Infection of the bladder or kidney (urinary tract infection)
Infection of tissues around the stomach or gut
Infections of the ovaries, vagina or womb
Skin infections
Infections of the membranes surrounding the brain and spinal cord (meningitis)
Infections of the blood (septicaemia)
High fever and significant reduction in white blood cells resulting decreased resistance to infection (febrile neutropenia).

Meropenem Ranbaxy is given by injection, usually in hospitals, and its available only with a doctor's prescription.

Meropenem Ranbaxy is not addictive.

2. What should I know before I use Meropenem Ranbaxy?

Warnings

When you must not be given Meropenem Ranbaxy:

you are allergic to meropenem
you are allergic to any of the ingredients listed at the end of this leaflet
you are allergic to other similar antibiotics (e.g. other carbapenems like imipenem; or beta-lactam antibiotics like penicillin, amoxicillin, ampicillin, ceftriaxone, cefotaxime etc).

Symptoms of allergic reaction may include skin rash, itchiness or hives, shortness of breath, wheezing or difficulty breathing, swelling of the face, tongue, lips or other parts of the body.

Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

have any other medical conditions especially the following:
- liver problems
- kidney problems, including dialysis
- disease of the stomach or intestines (in particular inflammation of intestine)

Your doctor will discuss with you the benefits and risks of taking it.

have allergies to any other medicines, including antibiotics (such as other carbapenems, penicillins, cephalosporins or monobactams).
have allergies to any foods, preservatives or dyes.
are on a controlled sodium diet.
- Meropenem Ranbaxy contains sodium (90 mg per 1 g of meropenem).

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Do not breast-feed if you are being given this medicine.

The active ingredient in Meropenem Ranbaxy passes into the breast milk. Your doctor may discuss the risk and benefits if you need this medicine while you are breast feeding.

Children

Safety and effectiveness of Meropenem Ranbaxy in children younger than 3 months of age have not been established. It is not recommended for use in these children.

Ask you doctor if you have any questions about why this medicine has been prescribed for you or your child.

Your doctor may have prescribed it for another reason.

3. What if I am taking other medicines?

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

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

Probenecid (a medicine used to treat gout)
Sodium valproate (a medicine used to treat fit/seizure or mania)

These medicines may be affected by Meropenem Ranbaxy, or may affect how well it works. You may need different amounts of your medicine, or you may need to take difference medicines. Your doctor will advise you.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Meropenem Ranbaxy.

4. How do I use Meropenem Ranbaxy?

How much will you be given

The dose of Meropenem Ranbaxy is based on your condition, age and type and severity of infection.

Meropenem Ranbaxy should not be given to babies less than three months of age or babies and children with kidney problems.

How Meropenem Ranbaxy is given

Meropenem Ranbaxy should only be injected into a vein (intravenous injection). It must always be given by a doctor or a nurse. It can be given either as a slow injection or as a slow drip over 15 to 30 minutes.

Your doctor will decide which is best for you.

How long you will be given Meropenem Ranbaxy

Meropenem Ranbaxy will be given as a number of injections over several days. You doctor will decide how long you will need to have Meropenem Ranbaxy.

If you use too much Meropenem Ranbaxy

As Meropenem is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience any severe side effects after being given Meropenem, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Meropenem Ranbaxy?

Things you should do

Call your doctor straight away if you:

Develop severe diarrhoea, even if it occurs several weeks after you have been given Meropenem Ranbaxy.

You may have developed a serious bowel condition called antibiotic-associated colitis and you need urgent medical attention. Do not take any medicine for your diarrhoea without checking with your doctor first.

Remind any doctor, dentist or pharmacist you visit that you are using Meropenem Ranbaxy.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Meropenem Ranbaxy affects you.

Meropenem may cause headache, tingling or prickling skin and convulsions/seizures (fits) in some people. If you have any of these symptoms, do not drive, operate machinery or do anything that could be dangerous. Children should be careful when undertaking activities requiring attention such as riding bicycles or climbing.

If you are about to have any blood tests, tell your doctor that you are being treated with Meropenem Ranbaxy.

It may interfere with results of some tests.

Looking after your medicine

The hospital staff will keep Meropenem Ranbaxy in a safe place below 25°C. They will also make sure that the expiry date has not passed.

Getting rid of any unwanted medicine

The hospital staff will dispose of any unused Meropenem Ranbaxy.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
pain with redness and/or swelling at the site of injection feeling sick (nausea), being sick (vomiting) loose stool (diarrhoea) skin problems such as rash or itching headache.	Speak to your doctor if you have any of these less serious side effects and they worry you.

These are common side effects of meropenem, and are usually mild and short-lived.

Serious side effects

Serious side effects

What to do

severe diarrhoea, even if it occurs several weeks after you have been given Meropenem Ranbaxy
allergic reactions, including shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue or other parts of the body; skin rash, itchiness or hives.
chest pain or discomfort
fast or irregular hearbeat; or changes in the rhythm or rate of the heartbeat
convulsions/ seizures (fit)
unexpected breathlessness and /or red/brown urine - this may indicate damage to your red blood cells
muscle discomfort such as swelling, weakness, tender or sore muscles.

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Meropenem Ranbaxy contains

Active ingredient (main ingredient)	meropenem
Other ingredients (inactive ingredients)	Sodium carbonate anhydrous
Potential allergens	-

Do not take this medicine if you are allergic to any of these ingredients.

What Meropenem Ranbaxy looks like

Meropenem Ranbaxy 500 mg/20 mL vial (Aust R 167025) and 1 g/vial (AUST R 167024) is a sterile white to pale yellow powder supplied in a glass vial. The hospital staff make it up into a solution before injection.

Who distributes Meropenem Ranbaxy

Sun Pharma ANZ Pty Ltd
12 Waterloo Road
Macquarie Park Sydney NSW 2113 Australia
Tel: 1800 726 229
Email: [email protected]

Douglas Pharmaceuticals Ltd
P O Box 45 027
Auckland 0651
New Zealand
Phone: (09) 835 0660

This leaflet was prepared in May 2024.

Published by MIMS July 2024

BRAND INFORMATION

Brand name

Meropenem Ranbaxy

Active ingredient

Meropenem

Schedule

1 Name of Medicine

Meropenem trihydrate.

2 Qualitative and Quantitative Composition

Meropenem powder for injection or infusion is a white to pale yellow crystalline sterile powder for reconstitution. One vial contains meropenem trihydrate equivalent to meropenem 500 mg or 1000 mg. The inactive ingredient sodium carbonate 104 mg or 208 mg respectively. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Meropenem Ranbaxy is supplied as a sterile lyophilised powder for intravenous infusion available in single dose clear glass vials. The product is a white to pale yellow crystalline powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Meropenem Ranbaxy is indicated for the 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 of Meropenem Ranbaxy is 500 mg to 1 g by intravenous administration every eight hours depending on type and severity of infection, the known or suspected susceptibility of the pathogen(s) and the condition of the patient.
Exceptions.

Febrile episodes in neutropenic patients.

The dose should be 1 g every eight hours.

Meningitis.

The dose should be 2 g every eight 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 Ranbaxy should be given as an intravenous bolus injection over approximately five minutes or by intravenous infusion over approximately 15 to 30 minutes. 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 Ranbaxy 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 elderly patients with normal renal function or creatinine clearance values above 50 mL/minute.

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 eight hours depending on the 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.

Febrile episodes in neutropenic patients.

The dose should be 20 mg/kg every eight hours.

Meningitis.

The dose should be 40 mg/kg every eight hours.
Meropenem Ranbaxy should be given as an intravenous bolus over approximately five 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.

Method of administration.

For intravenous bolus administration.

Constitute injection vials (500 mg or 1 g) with sterile water for injection. (See Table 2.) Shake to dissolve and let stand until clear. Constituted solutions are clear and colourless to pale yellow.

For infusion.

Infusion vials (500 mg or 1 g) may be directly constituted with a compatible infusion fluid and then further diluted with an appropriate infusion fluid. (See Compatibility and stability.)
Shake constituted solution before use. All vials are for single use only. Standard aseptic technique should be employed during constitution and administration.

Compatibility and stability.

Meropenem Ranbaxy is compatible with the following infusion fluids: 0.9% sodium chloride intravenous infusion, 5% or 10% glucose intravenous infusion, 5% glucose intravenous infusion with 0.02% sodium bicarbonate, 5% glucose with 0.9% sodium chloride intravenous infusion, 5% glucose with 0.225% sodium chloride intravenous infusion, 5% glucose with 0.15% potassium chloride intravenous infusion, 2.5% and 10% mannitol intravenous infusion, Normosol-M in 5% glucose intravenous infusion.

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 injection should not be frozen.

4.3 Contraindications

Meropenem Ranbaxy is contraindicated in patients who are hypersensitive to meropenem or beta-lactam antibiotic (including carbapenem, penicillin) or any component of this product.

4.4 Special Warnings and Precautions for Use

Serious, and occasionally fatal, hypersensitivity reactions have been reported in patients receiving therapy with beta-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 beta-lactam. Before initiating treatment with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins or other beta-lactam antibiotics. If an allergic reaction to meropenem occurs, discontinue the drug. Serious hypersensitivity reactions may require adrenaline and other emergency measures.
Rhabdomyolysis has been reported with the use of meropenem. If signs or symptoms of rhabdomyolysis are observed, meropenem should be discontinued and appropriate therapy initiated.
As with other antibiotics, overgrowth of non-susceptible organisms may occur and repeated evaluation of each patient is necessary.
As with other beta-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.
Rarely, pseudomembranous colitis has been observed 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 drug 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. Drugs that delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil), may prolong and/or worsen the condition and should not be used.
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.
A positive or indirect Coombs' test may develop.
The concomitant use of valproic acid/ sodium valproate and Meropenem Ranbaxy is not recommended. Meropenem Ranbaxy 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).
This medicine contains sodium (90 mg per 1 g of meropenem). This should be taken into consideration by patients on a controlled sodium diet.

Skin and subcutaneous tissue disorders.

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 receiving meropenem [see Section 4.8 Adverse Effects (Undesirable Effects)]. If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment should be considered.

Use in hepatic impairment.

Patients with pre-existing liver disorders should have liver function monitored during treatment with Meropenem Ranbaxy.

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 drug 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 drugs 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.

Decreases in blood levels of valproic acid have 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, coadministration of Meropenem Ranbaxy 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).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility was not impaired in rats with exposures (based on area under the curve (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 Ranbaxy 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 Ranbaxy.

4.8 Adverse Effects (Undesirable Effects)

Meropenem is generally well tolerated. In clinical trials, adverse events led to cessation of treatment in less than 1% of patients. Serious adverse events are rare.

Common events.

General disorders and administration site conditions.

Inflammation, thrombophlebitis, pain.

Gastrointestinal disorders.

Nausea, vomiting, diarrhoea.

Blood and lymphatic system disorders.

Thrombocythaemia.

Nervous system disorders.

Headache.

Skin and subcutaneous tissue disorders.

Rash, pruritus.

Hepatobiliary disorders.

Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, gamma-glutamyltransferase increased and blood bilirubin increased alone or in combination, have been reported.

Adverse reactions reported at a frequency < 1%.

Immune system disorders.

Systemic allergic reactions (hypersensitivity) may occur following administration of meropenem. These reactions may include angioedema and manifestations of anaphylaxis.

Skin and subcutaneous tissue disorders.

Urticaria (uncommon). Severe skin reactions, such as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed. Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalised exanthematous pustulosis (AGEP) (not known).

Musculoskeletal and connective tissue disorders.

Rhabdomyolysis (not known).

Gastrointestinal disorders.

Pseudomembranous colitis. Jaundice and hepatic failure have been reported but a causal link with meropenem has not been established.

Blood and lymphatic system disorder.

Uncommon: eosinophilia, leucopenia, thrombocytopenia and neutropenia. Rare: agranulocytosis. Very rare: haemolytic anaemia.
A positive direct or indirect Coombs' test may develop.

Cardiovascular.

Cardiac failure has been reported but a causal link with meropenem has not been established.

Nervous system disorders.

Uncommon: paraesthesiae, convulsions.

Psychiatric disorders.

Delirium and hallucinations have been reported but a causal link with meropenem has not been established.

Respiratory, thoracic and mediastinal disorders.

Pneumonia and respiratory failure have been reported but a causal link with meropenem has not been established.

Renal and urinary disorders.

Renal impairment.

Whole body.

Fever and septicaemia have been reported but a causal link with meropenem has not been established.

Infections and infestations.

Oral candidiasis and vaginal candidiasis (uncommon).

Description of selected adverse reactions.

Kounis syndrome.

Kounis syndrome (acute coronary syndrome associated with an allergic reaction) has been reported with other 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 https://www.tga.gov.au/reporting-problems in Australia or https://nzphvc.otago.ac.nz/reporting/ in New Zealand.

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 131126 in Australia.
For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766), in New Zealand.

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-I). 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 beta-lactamases and its marked affinity for the 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).
Meropenem is stable in susceptibility tests which 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.

Mechanisms of resistance.

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.
The antibacterial spectrum of meropenem includes the following species, based on clinical experience.
Commonly susceptible species.

Gram positive aerobes.

Streptococcus mitis, Streptococcus sanguis, Streptococcus viridans. 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 milleri group (S. anginosus, S. constellatus, and S. intermedius), Streptococcus pneumoniae, Streptococcus pyogenes (Group A streptococcus).

Gram negative aerobes.

Citrobacter spp., including Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, and other Enterobacter spp., Escherichia coli, Haemophilus influenzae (including beta-lactamase-positive strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Klebsiella pneumoniae and other Klebsiella spp., Morganella morganii, Proteus mirabilis, Citrobacter koseri, Klebsiella oxytoca, Serratia marcescens.

Anaerobic bacteria.

Bacteroides thetaiotaomicron, and other Bacteroides spp., Eubacterium lentum, Fusobacterium spp., Mobiluncus curtisii, Peptococcus spp.

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).

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

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 five 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 two minutes, three minutes and five 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.

Distribution.

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.
Plasma protein binding of meropenem is approximately 2%.

Metabolism.

The only metabolite of meropenem is microbiologically inactive.

Excretion.

Six hours after administration of an intravenous dose of 500 mg, plasma levels of meropenem decline to values of 1 microgram/mL or less.
When multiple doses are administered at eight-hourly intervals to subjects with normal renal function, accumulation of meropenem does not occur.
In subjects with normal renal function, meropenem's elimination half-life is approximately one hour.
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 five hours at the 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every eight hours or 1 g administered every six hours in volunteers with normal renal function.

Special populations.

Use in hepatic impairment.

Pharmacokinetic studies in patients with liver disease have shown no effects of liver disease on the pharmacokinetics of meropenem.

Use in renal impairment.

Pharmacokinetic studies in patients with renal insufficiency have shown that the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment.

Use in the elderly.

Pharmacokinetic studies in the elderly have shown a reduction in plasma clearance of meropenem which correlated with age-associated reduction in creatinine clearance.

Paediatric use.

Studies in children have shown that 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. The pharmacokinetics are linear over the dose range of 10 to 40 mg/kg.

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

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Compatibility of meropenem with other drugs has not been established. Meropenem Ranbaxy should not be mixed with or physically added to solutions containing other drugs.

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

It is recommended to use freshly prepared solutions of meropenem for intravenous injection and infusion. Reconstituted product should be used immediately on one patient. If necessary, it must be stored for not more than 24 hours at 2 to 8°C. For detailed information, see Table 3.
Solutions of meropenem injection should not be frozen.
Use on one patient on one occasion only. Discard any residue.

Storage conditions.

Before reconstitution - Store below 25°C. Do not freeze.

6.5 Nature and Contents of Container

Clear type 1 glass vials with grey rubber stopper and flip off seal, containing meropenem 500 mg (equivalent to meropenem trihydrate 570 mg) or 1 g (equivalent to meropenem trihydrate 1.14 g).
Vial stopper not made with natural rubber latex.
Available in packs of 1, 5 and 10* vials.
* Not marketed in Australia.

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

Meropenem is soluble in dimethylformamide and 5% dibasic potassium phosphate solution, sparingly soluble in water and 5% monobasic potassium phosphate solution, practically insoluble in alcohol, acetone and ether. The pH of freshly constituted solutions is between 7.3 and 8.3.

Chemical structure.

Chemical name: (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylcarbamoyl)-3-pyrrolidinyl]thio]- 6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo- 1-azabicyclo[3.2.0]hept-2-enecarboxylic acid, trihydrate.

CAS number.

CAS Number: 119478-56-7.

7 Medicine Schedule (Poisons Standard)

S4.

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