Consumer medicine information

Ertapenem Kabi

Ertapenem

BRAND INFORMATION

Brand name

Ertapenem Kabi

Active ingredient

Ertapenem

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ertapenem Kabi.

SUMMARY CMI

ERTAPENEM KABI

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 being given ERTAPENEM KABI?

ERTAPENEM KABI contains the active ingredient ertapenem. ERTAPENEM KABI is used to treat infections caused by bacteria (germs). These infections include: infections within the abdomen (stomach), pelvic infections, diabetic foot infections in patients without osteomyelitis.

For more information, see Section 1. Why am I being given ERTAPENEM KABI? in the full CMI.

2. What should I know before I am given ERTAPENEM KABI?

You should not be given ERTAPENEM KABI if you have ever had an allergic reaction to ERTAPENEM KABI 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 am given ERTAPENEM KABI? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ERTAPENEM KABI 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 be given ERTAPENEM KABI?

ERTAPENEM KABI is given as a slow injection into a vein, known as intravenous infusion.

ERTAPENEM KABI must only be given by a doctor or nurse.

More instructions can be found in Section 4. How will I be given ERTAPENEM KABI? in the full CMI.

5. What should I know while being given ERTAPENEM KABI?

Things you should doCall your doctor straight away if you:
  • Develop severe diarrhoea
  • Develop a severe skin reaction such as painful red areas, fluid filled bumps, large blisters, or peeling layers of skin whilst being given ERTAPENEM KABI.
Driving or using machines
  • ERTAPENEM KABI may cause dizziness or sleepiness in some patients. Make sure you know how you react to ERTAPENEM KABI before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or sleepy.
Looking after your medicine
  • ERTAPENEM KABI will usually be stored in the pharmacy or on the ward.
  • The powder for injection should be kept in a cool dry place where the temperature stays before 25°C.

For more information, see Section 5. What should I know while being given ERTAPENEM KABI? in the full CMI.

6. Are there any side effects?

Common side effects of ERTAPENEM KABI include diarrhoea, inflammation of the vein, nausea, and 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

ERTAPENEM KABI

Active ingredient: Ertapenem

Consumer Medicine Information (CMI)

This leaflet provides important information about using ERTAPENEM KABI. 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 ERTAPENEM KABI.

Where to find information in this leaflet:

1. Why am I being given ERTAPENEM KABI?
2. What should I know before I am given ERTAPENEM KABI?
3. What if I am taking other medicines?
4. How will I be given ERTAPENEM KABI?
5. What should I know while being given ERTAPENEM KABI?
6. Are there any side effects?
7. Product details

1. Why am I being given ERTAPENEM KABI?

ERTAPENEM KABI contains the active ingredient ertapenem.

ERTAPENEM KABI belongs to a class of antibiotics called carbapenems. It works by killing the bacteria calling your infection.

ERTAPENEM KABI is used to treat infections caused by bacteria (germs). These infections include:

  • Infections within the abdomen (stomach)
  • Pelvic infections
  • Diabetic foot infections in patients without osteomyelitis.

ERTAPENEM KABI may also be used in patients not responding to, or unable to tolerate, other antibiotics.

Your doctor may have prescribed ERTAPENEM KABI for another reason.

Ask your doctor if you have any questions about why ERTAPENEM KABI has been prescribed for you.

2. What should I know before I am given ERTAPENEM KABI?

Warnings

ERTAPENEM KABI should not be given if:

  • you are allergic to ertapenem, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • You have an allergy to other antibiotics in the same class as ERTAPENEM KABI
  • You have had a serious allergic reaction (anaphylaxis) to beta-lactam antibiotics, including penicillins or cephalosporins
  • The vial cap shows signs of tampering
  • The expiry date printed on the pack has passed.

Check with your doctor if you:

  • have any other medical conditions, especially the following:
    - seizures or fits, or a predisposition to seizures (e.g. brain scarring)
    - kidney disease, or are undergoing dialysis
    - bowel problems while using antibiotics or after finishing them, including severe abdominal or stomach cramps, or watery and severe diarrhoea
  • have allergies to other antibiotics, in particular penicillins and cephalosporins.
    - If you are allergic to any of them you may be allergic to ERTAPENEM KABI.
  • Are pregnant or intend to become pregnant
  • Are breastfeeding or intend to breastfeed
  • Have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes
  • Are taking a medicine containing valproic acid

If you have not told your doctor or any of the above, tell them before you are given ERTAPENEM KABI.

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

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

Like most medicines, the use of ERTAPENEM KABI is generally not recommended during pregnancy. However, if there is a need to consider using ERTAPENEM KABI during pregnancy, your doctor will discuss the possible risks and benefits to you and your unborn baby.

Breastfeeding

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Like most medicines, the use of ERTAPENEM KABI is generally not recommended while breastfeeding. ERTAPENEM KABI is secreted into human milk.

  • This refers to any medical condition-specific, medicine-specific, and/or age-specific subheading(s) relevant for inclusion for certain categories/groups of users, as applicable to the medicine.

Children

Do not use ERTAPENEM KABI in children under 3 months of age.

The safety and effectiveness in children younger than 3 months of age have not been established.

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 ERTAPENEM KABI may interfere with each other.

These include:

  • Sodium valproate, used to control different types of epilepsy and mania

These medicines may be affected by ERTAPENEM KABI 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 will decide whether you should use ERTAPENEM KABI in combination with this medicine.

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

4. How will I be given ERTAPENEM KABI?

How is it given

ERTAPENEM KABI is given as a slow injection into a vein, known as intravenous infusion.

ERTAPENEM KABI will be prepared and given to you by a doctor or other healthcare professional.

When is it given

  • Your doctor will decide what dose and how long you will receive ERTAPENEM KABI. This depends on your condition and other factors, such as your kidney function. No dose adjustment is necessary if you are elderly.

If you are given too much ERTAPENEM KABI

As this product is administered by a doctor or healthcare professional, it is unlikely you will be given too much ERTAPENEM KABI.

However, if you have any concerns, you should immediately:

  • contact a healthcare professional, your doctor, or
  • phone the Poisons Information Centre
    (by calling 13 11 26), 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 being given ERTAPENEM KABI?

Things you should do

Call your doctor straight away if you:

  • Develop severe diarrhoea
    Do this even if it occurs several weeks after ERTAPENEM KABI has been stopped.
    Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.
    This is because antibiotics such as ERTAPENEM KABI can change the type of bacteria in the bowel. As a result, this allows bacteria, normally present in the bowel and normally harmless, to multiply and cause the above symptoms.
    Do not take any diarrhoea medicine without first checking with your doctor.
  • Develop a severe skin reaction such as painful red areas, fluid filled bumps, large blisters, or peeling layers of skin whilst being given ERTAPENEM KABI. You may need urgent medical care.

Remind any doctor, dentist or pharmacist that you visit that you are using ERTAPENEM KABI.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ERTAPENEM KABI affects you.

ERTAPENEM KABI may cause dizziness or sleepiness in some patients. Make sure you know how you react to ERTAPENEM KABI before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or sleepy.

Looking after your medicine

It is unlikely that you will be asked to store ERTAPENEM KABI yourself. It will usually be stored in the pharmacy on the ward.

Solutions of ERTAPENEM KABI should not be frozen.

Solutions of ERTAPENEM KABI should be used as soon as possible after reconstitution and further dilution. If storage is unavoidable, the solution should be stored in the refrigerator where the temperature is kept between 2°C to 8°C, for not more than 24 hours, and used as soon as practicable within 4 hours after removal from the refrigerator.

As ERTAPENEM KABI does not contain a preservative, there is a risk that any prepared solution that has not been stored in a refrigerator may be contaminated with germs and cause an infection.

Getting rid of any unwanted medicine

A doctor, nurse or pharmacist will dispose of any unused ERTAPENEM KABI.

Any unused vials containing solution of ERTAPENEM KABI which has been prepared, but not used, should be discarded.

Vials of ERTAPENEM KABI are intended for single-use only. They do not contain a preservative and there is a possibility of contamination with repeated use.

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.

Common side effects

Common side effectsWhat to do
Tell your doctor or nurse if you notice any of the following and they worry you:
  • Discomfort of the vein where you had the injection, for example, pain, tenderness, redness, swelling or firm swelling.
  • Swelling, clotting, tenderness, swelling and inflammation
  • Headache
  • Nausea, vomiting
  • Diarrhoea
  • Vaginal itching or redness
  • Alteration in some laboratory blood tests, and a combination of high fever, feeling unwell, and skin rash
Speak to your doctor if you have any of these common side effects and they worry you.

These are the more common side effects of ERTAPENEM KABI. For the most part, these have been mild.

Rare side effects

Rare side effectsWhat to do
Tell your doctor or nurse immediately if you notice any of the following:
  • Severe abdominal cramps or stomach cramps
  • Watery and severe diarrhoea, which may also be bloody
  • High temperature, also called fever
  • Seizures or fits
  • Shortness of breath
  • Chest pain
  • Slow heart rate
  • Skin rash, redness, itchiness or hives
  • Severe skin reactions, such as painful red areas, fluid-filled bumps, large blisters, or peeling of layers of skin have been reported for the beta-lactam class of antibiotics
  • Formation of lump and warmth at injection site
  • Strange or disturbing thoughts or moods (including agitation, aggression, severe confusion, disorientation, mental status changes)
  • Tremors or uncontrollable twitching, jerking or writhing movements
  • Decreased consciousness

These may be serious side effects of ERTAPENEM KABI. You may need urgent medical attention. Serious side effects are rare.
Also, tell your doctor if you notice:
  • Dizziness, light-headedness, or unsteady walking
  • Unusual tiredness or weakness
  • Sore, creamy-yellow, raised patches in the mouth (oral thrush)
  • Teeth staining
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these rare side effects.

Very rare side effects

Very rare side effectsWhat to do
A few people may be allergic to some medicines. Tell your doctor or nurse immediately if you notice any of the following. These are examples of acute allergy:
  • Throat or chest tightness, difficulty breathing
  • Swelling of the mouth, lips, eyes or face
  • Flushing (sudden redness) of the face
  • Vomiting
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very rare side effects.

If you have these, you may have had a serious allergic reaction to ERTAPENEM KABI. You may need urgent medical attention. These side effects are very rare.

Rare side effects after finishing ERTAPENEM KABI

Common side effectsWhat to do
Tell your doctor or nurse if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with ERTAPENEM KABI:
  • Severe abdominal cramps or stomach cramps
  • Watery and severe diarrhoea, which may also be bloody
  • Fever, in combination with one or both of the above
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very rare side effects.

These are rare but serious side effects. You may have a serious condition affecting your bowel.

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 ERTAPENEM KABI contains

Active ingredient
(main ingredient)		Ertapenem 1 g
Other ingredients
(inactive ingredients)		Sodium bicarbonate
Sodium hydroxide

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

What ERTAPENEM KABI looks like

ERTAPENEM KABI is a sterile, white to yellowish powder in a glass vial. Each vial is packaged within a carton (AUST R 294975).

Who distributes ERTAPENEM KABI

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Telephone: 1300 732 001

This leaflet was prepared in October 2022.

Published by MIMS December 2022

BRAND INFORMATION

Brand name

Ertapenem Kabi

Active ingredient

Ertapenem

Schedule

S4

 

1 Name of Medicine

Ertapenem sodium.

2 Qualitative and Quantitative Composition

Each vial contains 1.046 grams ertapenem sodium, equivalent to 1 gram ertapenem, as the active ingredient; the inactive ingredients are sodium bicarbonate and sodium hydroxide. The sodium content is approximately 137 mg (approximately 6.0 mEq).

3 Pharmaceutical Form

Ertapenem Kabi is supplied as a white to yellowish sterile lyophilized powder for intravenous (IV) infusion after reconstitution with appropriate diluent (see Section 4.2 Dose and Method of Administration).

4 Clinical Particulars

4.1 Therapeutic Indications

Ertapenem is indicated for the treatment of patients, aged 3 months or more, with moderate to severe infections (except meningitis, see Section 4.4 Special Warnings and Precautions for Use) caused by susceptible strains of microorganisms which are suspected or proven to be resistant to all other antibiotics, or for patients unable to tolerate other antibiotics.
Ertapenem is also indicated for initial empiric therapy for the treatment of complicated intra-abdominal infections and acute pelvic infections including post-partum endomyometritis, septic abortion and post-surgical gynaecological infections.
Ertapenem is also indicated for the treatment of diabetic foot infections, which require parenteral antibiotic therapy and are caused by susceptible bacterial pathogens which are suspected or proven to be resistant to all other registered antibiotics, or for patients unable to tolerate other antibiotics.
Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to ertapenem. Therapy with ertapenem may be initiated empirically before the results of these tests are known; once these results become available, antimicrobial therapy should be adjusted accordingly.

4.2 Dose and Method of Administration

The usual dose of ertapenem in patients 13 years of age and older is 1 g given once a day. The usual dose of ertapenem in patients 3 months to 12 years of age is 15 mg/kg twice daily (not to exceed 1 g/day).
Ertapenem Kabi is administered by IV infusion over a period of 30 minutes.
The usual duration of therapy with ertapenem is 3-14 days, but varies by the type of infection and causative pathogen(s) (see Section 4.1 Therapeutic Indications). When clinically indicated, a switch to an appropriate oral antimicrobial may be implemented if clinical improvement has been observed.
In controlled clinical studies, patients were treated 3-14 days. Total treatment duration was determined by the treating physician based on site and severity of the infection, and on the patient's clinical response. In some studies, treatment was converted to oral therapy at the discretion of the treating physician after clinical improvement had been demonstrated.

Patients with renal insufficiency.

Ertapenem may be used for the treatment of infections in adult patients with renal insufficiency. In patients whose creatinine clearance is > 30 mL/min/1.73 m2, no dosage adjustment is necessary. Adult patients with advanced renal insufficiency (creatinine clearance ≤ 30 mL/min/1.73 m2), including those on haemodialysis, should receive 500 mg daily. There are no data in paediatric patients with renal insufficiency.

Patients on haemodialysis.

In a clinical study in adults, following a single 1 g IV dose of ertapenem given immediately prior to a haemodialysis session, approximately 30% of the dose was recovered in the dialysate. When patients on haemodialysis are given the recommended daily dose of 500 mg of ertapenem within 6 hours prior to haemodialysis, a supplementary dose of 150 mg is recommended following the haemodialysis session. If ertapenem is given at least 6 hours prior to haemodialysis, no supplementary dose is needed. There are no data in paediatric patients undergoing haemodialysis. There are no data in adult and paediatric patients undergoing peritoneal dialysis or haemofiltration.
When only the serum creatinine is available, the following formula1 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function. See Equation 1.
No dosage adjustment is recommended in patients with impaired hepatic function (see Section 5.2 Pharmacokinetic Properties, Pharmacokinetics in special populations, Hepatic impairment).
In patients 13 years of age and older, the recommended dose of ertapenem can be administered without regard to age or gender.
1 Cockcroft and Gault equation: Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976.

Instructions for use/handling.

Preparation for IV administration. Do not mix or co-infuse Ertapenem Kabi with other medications, other than heparin or potassium chloride.
Do not use diluents containing glucose.
Ertapenem Kabi must be reconstituted and then diluted prior to administration.

Patients 13 years of age and older.

1. Reconstitute the contents of a 1 g vial of Ertapenem Kabi with 10 mL of one of the following: Water for Injections or 0.9% Sodium Chloride Injection.
2. Shake well to dissolve and immediately transfer the contents of the reconstituted vial to 50 mL of 0.9% Sodium Chloride Injection. The resulting solution is chemically and physically stable only if used within 6 hours at room temperature or stored for 24 hours at 2-8°C and used within 4 hours after removal from refrigeration.
3. To ensure adequate potency and to avoid microbiological hazard, the ertapenem solution should be used as soon as practicable after reconstitution and further dilution. If storage is unavoidable, the solution should be held at 2-8°C for not more than 24 hours and used as soon as practicable within 4 hours after removal from refrigeration. The solution should not be frozen.
4. The solution should be infused over a period of 30 minutes.

Paediatric patients 3 months to 12 years of age.

1. Reconstitute the contents of a 1 g vial of Ertapenem Kabi with 10 mL of one of the following: Water for Injections or 0.9% Sodium Chloride Injection.
2. Shake well to dissolve and immediately withdraw a volume equal to 15 mg/kg of body weight and dilute in 0.9% Sodium Chloride Injection to a final concentration of 20 mg/mL or less. The resulting solution is chemically and physically stable only if used within 6 hours at room temperature, or stored for 24 hours at 2-8°C and used within 4 hours after removal from refrigeration.
3. To ensure adequate potency and to avoid microbiological hazard, the ertapenem solution should be used as soon as practicable after reconstitution and further dilution. If storage is unavoidable, the solution should be held at 2-8°C for not more than 24 hours, and used as soon as practicable within 4 hours after removal from refrigeration. The solution should not be frozen.
4. The solution should be infused over a period of 30 minutes.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to use, whenever solution and container permit. Solutions of Ertapenem Kabi range from colourless to pale yellow. Variations of colour within this range do not affect the potency of the product.
Product is for single use in one patient only. Discard any residue.

Compatibility.

Compatibility of Ertapenem Kabi with intravenous solutions containing heparin sodium or potassium chloride has been demonstrated.

4.3 Contraindications

Ertapenem Kabi is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with ertapenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens. If an allergic reaction to ertapenem occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment.
As with other antibiotics, prolonged use of ertapenem may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including ertapenem. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with ertapenem use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. In moderate to severe cases appropriate therapy such as oral antibacterial agents effective against Clostridium difficile should be considered. Fluid, electrolytes and protein replacement should be provided when indicated.
Seizure and other central nervous system (CNS) adverse experiences have been reported during treatment with ertapenem (see Section 4.8 Adverse Effects (Undesirable Effects)). During clinical investigations in adult patients treated with ertapenem (1 g once a day), seizures, irrespective of drug relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period. These experiences have occurred most commonly in patients with CNS disorders (e.g. brain lesions or history of seizures) and/or compromised renal function. Close adherence to the recommended dosage regimen is urged, especially in patients with known factors that predispose to convulsive activity. Anticonvulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus or seizures occur, patients should be evaluated neurologically and the dosage of ertapenem re-examined to determine whether it should be decreased or discontinued.

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), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, ertapenem should be discontinued immediately and an alternative treatment should be considered.

Use in CNS infections.

Ertapenem is not recommended in the treatment of meningitis or other CNS infections in the paediatric population due to a lack of sufficient CSF penetration to cover all relevant pathogens.

Use in renal impairment.

A dosage adjustment is recommended for adult patients with advanced or end-stage renal insufficiency (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

In clinical studies, the efficacy and safety of ertapenem in the elderly (≥ 65 years) was comparable to that seen in younger patients (< 65 years).

Paediatric use.

Safety and effectiveness of ertapenem in paediatric patients 3 months to 17 years of age are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in paediatric patients and additional data from comparator-controlled studies in paediatric patients 3 months to 17 years of age and 2-17 years of age in intra-abdominal infection and acute pelvic infection2 comparator-controlled studies (see Section 4.1 Therapeutic Indications; Section 5.1 Pharmacodynamic Properties). There are no data in paediatric patients with renal insufficiency.
Ertapenem is not recommended in infants under 3 months of age as no data are available.
2 Acute pelvic infection is not the same entity as pelvic inflammatory disease.

Effects on laboratory tests.

Adult patients.

Clinically Significant Laboratory Abnormalities that were measured during parenteral therapy in ≥ 1.0% of patients treated with ertapenem in clinical studies are presented in Table 1.
The most frequently observed drug-related laboratory abnormalities during parenteral therapy in patients receiving ertapenem were elevations in ALT, AST, alkaline phosphatase and platelet count.
In the majority of clinical studies, parenteral therapy was followed by a switch to an appropriate oral antimicrobial (see Section 5.1 Pharmacodynamic Properties, Clinical trials). During the entire treatment period and a 14-day post-treatment follow-up period, drug-related laboratory abnormalities in patients treated with ertapenem were no different than those listed above.
Other drug-related laboratory abnormalities included the following: increases in direct serum bilirubin, total serum bilirubin, eosinophils, indirect serum bilirubin, PTT, urine bacteria, BUN, serum creatinine, serum glucose, monocytes, urine epithelial cells, urine red blood cells; decreases in segmented neutrophils, white blood cells, haematocrit, haemoglobin and platelet count.
In a clinical study for the treatment of diabetic foot infections in which 289 adult diabetic patients were treated with ertapenem, the drug related laboratory adverse experience profile was generally similar to that seen with previous clinical trials.

Paediatric patients.

The overall laboratory adverse experience profile is comparable to that in adults. Table 2 shows the incidence of laboratory adverse experiences reported in ≥ 1.0% of paediatric patients in clinical studies.
Additional drug-related laboratory adverse experiences that were reported during parenteral therapy in > 0.5% but < 1.0% of paediatric patients treated with ertapenem in clinical studies include: increase in eosinophils.
Other drug-related laboratory abnormalities during the entire treatment period plus 14-day follow-up included the following: elevations in ALT, elevations in AST, decreases in white blood cells.

4.5 Interactions with Other Medicines and Other Forms of Interactions

When ertapenem is administered with probenecid, probenecid competes for active tubular secretion and thus inhibits the renal excretion of ertapenem. This leads to small but statistically significant increases in the elimination half-life (19%) and in the AUC (25%). No dosage adjustment is necessary when ertapenem is given with probenecid. Because of the small effect on half-life, the co-administration with probenecid to extend the half-life of ertapenem is not recommended.
In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport. In vitro studies in human liver microsomes indicate ertapenem does not inhibit metabolism mediated by any of the six major cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Drug interactions caused by inhibition of P-glycoprotein-mediated drug clearance or CYP-mediated drug clearance are unlikely (see Section 5 Pharmacological Properties).
Other than with probenecid, no specific clinical drug interaction studies have been conducted.
The concomitant use of ertapenem and valproic acid/semisodium valproate is generally not recommended. Anti-bacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or semisodium valproate. If administration of ertapenem is necessary, supplemental anti-convulsant therapy should be considered.
Case reports in the literature have shown that co-administration of carbapenems, including ertapenem, to patients receiving valproic acid or semisodium valproate results in a reduction of valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Increasing the dose of valproic acid or semisodium valproate may not be sufficient to overcome this interaction. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Ertapenem had no adverse effect on fertility of either male or female rats at doses up to 700 mg/kg/day IV, which was associated with a plasma AUC level similar to the anticipated human value at the clinically recommended dose.
(Category B3)
In mice and rats given IV doses of up to 700 mg/kg/day (for rats, similar to human exposure at the recommended dose of 1 g based on plasma AUCs; no exposure data were available for mice), there was no evidence of developmental toxicity as assessed by external, visceral and skeletal examination of the fetuses. However, in mice given 700 mg/kg/day, slight decreases in average fetal weights, and an associated decrease in the average number of ossified sacrocaudal vertebrae, were observed. Ertapenem crosses the placental barrier in rats.
There are no adequate and well-controlled studies in pregnant women. Ertapenem should not be used in pregnant women, unless the expected therapeutic benefit to the mother clearly outweighs the potential risk to the mother and fetus.
 Ertapenem is excreted in human milk (see Section 5.2 Pharmacokinetic Properties, Distribution). In rats given IV doses of up to 700 mg/kg/day (similar to human exposure at the recommended dose of 1 g based on plasma AUCs) there was no evidence of post-natal toxicity. Ertapenem should not be used in a breastfeeding woman, unless the expected therapeutic benefit to the mother clearly outweighs the potential risk to the infant.

4.7 Effects on Ability to Drive and Use Machines

Dizziness and somnolence can occur which may affect some patients' ability to drive and/or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Adult patients.

The total number of patients treated with ertapenem in clinical studies was over 1,900 of which over 1,850 received a 1 g dose of ertapenem. Most adverse experiences reported in these clinical studies were described as mild to moderate in severity. Drug-related adverse experiences were reported in approximately 20% of patients treated with ertapenem. Ertapenem was discontinued due to adverse experiences thought to be drug-related in 1.3% of patients.
The most common drug-related adverse experiences reported during parenteral therapy in patients treated with ertapenem were diarrhoea (4.3%), infused vein complication (3.9%), nausea (2.9%) and headache (2.1%).
The following drug-related adverse experiences were reported during parenteral therapy in ≥ 1.0% of patients treated with ertapenem. See Table 3.
Additional drug-related adverse experiences that were reported during parenteral therapy with ertapenem with an incidence > 0.1% but < 1.0% within each body system are listed below.

Body as a whole.

Asthenia/fatigue, candidiasis, oedema/swelling, fever, pain, abdominal pain, chest pain.

Cardiovascular system.

Extravasation, hypotension, bradycardia.

Digestive system.

Acid regurgitation, anorexia, oral candidiasis, constipation, C. difficile-associated diarrhoea, dry mouth, dyspepsia.

Nervous system and psychiatric.

Confusion, dizziness, insomnia, somnolence.

Respiratory system.

Dyspnoea.

Skin and skin appendage.

Erythema, pruritus.

Special senses.

Taste perversion.

Urogenital system.

Vaginal pruritus.
In clinical studies, seizure was reported during parenteral therapy in 0.2% of patients treated with ertapenem, 0.3% of patients treated with piperacillin/tazobactam and 0% of patients treated with ceftriaxone.
In the majority of clinical studies, parenteral therapy was followed by a switch to an appropriate oral antimicrobial (see Section 5.1 Pharmacodynamic Properties, Clinical trials). During the entire treatment period and a 14-day post-treatment follow-up period, drug-related adverse experiences in patients treated with ertapenem included those listed above as well as rash and vaginitis at an incidence of ≥ 1.0% (common) and allergic reactions, malaise and fungal infections at an incidence of > 0.1% but < 1.0% (uncommon).
In a clinical study for the treatment of diabetic foot infections in which 289 adult diabetic patients were treated with ertapenem, the drug-related adverse experience profile was generally similar to that seen in previous clinical trials.

Paediatric patients.

Clinical studies enrolled 384 paediatric patients treated with ertapenem. The overall adverse experience profile is comparable to that in adult patients. Table 4 shows the incidence of drug-related adverse experiences reported during parenteral therapy in ≥ 1.0% of paediatric patients in these studies.
In the paediatric clinical studies, the majority of the patients had parenteral therapy followed by a switch to an appropriate oral antimicrobial (see Section 5.1 Pharmacodynamic Properties, Clinical trials). During the entire treatment period and a 14-day post-treatment follow-up period, drug-related adverse experiences reported with an incidence of ≥ 1.0% in patients treated with ertapenem were no different than those listed in Table 4.
Additional drug-related adverse experiences that were reported during parenteral therapy with ertapenem with an incidence > 0.5% but < 1.0% within each body system are listed below.

General disorders and administration site conditions.

Infusion site induration, infusion site pruritus, infusion site warmth.

Vascular disorders.

Phlebitis.

Post-marketing experience.

The following post-marketing adverse experiences have been reported.

Immune system.

Anaphylaxis including anaphylactoid reactions.

Psychiatric disorders.

Altered mental status (including agitation, aggression, delirium, disorientation, mental status changes).

Nervous system disorders.

Depressed level of consciousness, dyskinesia, gait disturbance, hallucinations, myoclonus, tremor, encephalopathy (recovery may be prolonged in patients with renal impairment). Seizures (very rare). Seizures occurred most frequently in elderly patients and those with pre-existing CNS disorders (e.g. brain lesions or history of seizures) and/or compromised renal function (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal disorders.

Teeth staining.

Skin and subcutaneous tissue disorders.

Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), urticaria, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) and acute generalised exanthematous pustulosis (AGEP) have been reported with beta-lactam antibiotics, hypersensitivity vasculitis.

Musculoskeletal and connective tissue disorders.

Muscular weakness.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

No specific information is available on the treatment of overdosage with ertapenem. Intentional overdosing of ertapenem is unlikely. Intravenous administration of ertapenem at a 3 g daily dose for 8 days to healthy adult volunteers did not result in significant toxicity. In clinical studies in adults, inadvertent administration of up to 3 g in a day did not result in clinically important adverse experiences. In paediatric clinical studies, a single IV dose of 40 mg/kg up to a maximum of 2 g did not result in toxicity.
In the event of an overdose, ertapenem should be discontinued and general supportive treatment given until renal elimination takes place.
Ertapenem can be removed by haemodialysis; however, no information is available on the use of haemodialysis to treat overdosage.
Contact the Poisons Information Centre on 13 11 26 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. Ertapenem has in vitro activity against a wide range of gram positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Ertapenem has significant stability against hydrolysis by most classes of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases, but not metallo-beta-lactamases.
Ertapenem has been shown to be active against most strains of the following microorganisms in vitro and in clinical infections:

Aerobic and facultative anaerobic gram-positive microorganisms.

Staphylococcus aureus (including penicillinase-producing strains), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Note.

Methicillin-resistant staphylococci are resistant to ertapenem. Many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant.

Aerobic and facultative anaerobic gram-negative microorganisms.

Escherichia coli, Haemophilus influenzae (including beta-lactamase producing strains), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.

Anaerobic microorganisms.

Bacteroides fragilis and other species in the B. fragilis group, Clostridium species (excluding C. difficile), Eubacterium species, Peptostreptococcus species, Porphyromonas asaccharolytica, Prevotella species.
The following in vitro data are available, but their clinical significance is unknown.
Ertapenem exhibits in vitro minimum inhibitory concentrations (MICs) of ≤ 1 microgram/mL against most (≥ 90%) strains of Streptococcus species including Streptococcus pneumoniae, ≤ 0.5 microgram/mL against most (≥ 90%) strains of Haemophilus species, ≤ 2 microgram/mL against most (≥ 90%) strains of the other aerobic and facultative anaerobic microorganisms and ≤ 4 microgram/mL against most (≥ 90%) strains of the strict anaerobic microorganisms in the following list; however, the safety and effectiveness of ertapenem in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical studies:

Aerobic and facultative anaerobic gram-positive microorganisms.

Staphylococcus species, coagulase negative, methicillin susceptible, Streptococcus pneumoniae, penicillin resistant, Viridans streptococci.

Note.

Methicillin-resistant staphylococci are resistant to ertapenem. Many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant.

Aerobic and facultative anaerobic gram-negative microorganisms.

Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli producing ESBLs, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae producing ESBLs, Morganella morganii, Proteus vulgaris, Serratia marcescens.

Note.

Many strains of the above organisms that are multiply resistant to other antibiotics e.g. penicillins, cephalosporins (including third-generation) and aminoglycosides, are susceptible to ertapenem.

Anaerobic microorganisms.

Fusobacterium species.

Clinical trials.3

Adult patients.

Complicated intra-abdominal infections.

Ertapenem was evaluated in adults for the treatment of complicated intra-abdominal infections in a randomised, multicentre, double-blind, controlled clinical trial. This study compared ertapenem (1 g IV once a day) with piperacillin/tazobactam (3.375 g IV every 6 hours) for 5-14 days and enrolled 665 patients. In this study, complicated intra-abdominal infections were defined as those requiring surgical intervention and which extend beyond the hollow viscus into the peritoneal space. Patients were stratified at baseline into two groups: localised complicated appendicitis (stratum 1) and any other complicated intra-abdominal infection including colonic, small intestinal, and biliary infections and generalised peritonitis (stratum 2). At 1-2 weeks post-therapy, the clinical and microbiological success rates were 89.6% (190/212) for ertapenem and 82.7% (162/196) for piperacillin/tazobactam; at 4-6 weeks post-therapy (test of cure), success rates were 86.7% (176/203) for ertapenem and 81.3% (157/193) for piperacillin/tazobactam. At the test of cure for patients in stratum 1, the success rates were 90.4% (85/94) for ertapenem and 90.1% (82/91) for piperacillin/tazobactam, and for patients in stratum 2 the success rates were 83.5% (91/109) for ertapenem and 73.5% (75/102) for piperacillin/tazobactam. The clinical success rates at the test of cure by pathogen in the microbiologically evaluable patients are presented in Table 5.
In patients with E. coli bacteraemia, 100% (3/3) were treated successfully with ertapenem.
3 Reported cure rates are based on assessable subjects (excludes indeterminate and missing values).

Acute pelvic infections including postpartum endomyometritis, septic abortion and postsurgical gynaecologic infections.

Ertapenem was evaluated in adults for the treatment of acute pelvic infections in a randomised, multicentre, double-blind, controlled clinical trial. This study compared ertapenem (1 g IV once a day) with piperacillin/tazobactam (3.375 g IV every 6 hours) for 3-10 days and enrolled 412 patients including 350 patients with obstetric/postpartum infections and 45 patients with septic abortion. The clinical success rates at 2-4 weeks post-therapy (test of cure) were 93.9% (153/163) for ertapenem and 91.5% (140/153) for piperacillin/tazobactam. The clinical success rates at the test of cure by pathogen in the microbiologically evaluable patients are presented in Table 6.
In patients with E. coli bacteraemia, 100% (6/6) were treated successfully with ertapenem.

Bacterial septicaemia.

In a composite analysis of data from pivotal and supportive studies 172 evaluable patients were bacteremic. Overall, 69/86 (80.2%) patients in the ertapenem group and 72/86 (83.7%) patients in the combined ceftriaxone and piperacillin/tazobactam groups had a favourable response assessment (test of cure). The primary efficacy response rates at the test of cure by pathogen in the evaluable patients are presented in Table 7.

Diabetic foot infections.

Ertapenem was evaluated in adults for the treatment of diabetic foot infections in a randomised, multicenter, double-blind, controlled clinical trial. This study compared ertapenem (1 g IV once a day) with piperacillin/tazobactam (3.375 g IV every 6 hours) and enrolled 586 patients. Both regimens allowed the option to switch to oral amoxicillin/clavulanate for a total of 5-28 days of treatment (parenteral and oral). Adults with Type I or Type II diabetes with moderate to severe diabetic foot infections requiring parenteral antibiotic therapy were enrolled. Subjects with suspected osteomyelitis were excluded. Efficacy analyses took into consideration the investigator's assessment of the severity of the baseline wound. For the primary analysis, 94.2% of patients in the ertapenem group and 92.2% of patients in the piperacillin/tazobactam group had a favourable response assessment at the discontinuation of IV therapy assessment (DCIV) visit. The clinical success rates at 10 days post-therapy were 87.4% (180/206) for ertapenem and 82.7% (162/196) for piperacillin/tazobactam. The clinical success rates for both the DCIV assessment and 10-day post-treatment follow-up assessment (FUA) are presented in Table 8.
The clinical success rates at the post-therapy visit by pathogen in the clinically evaluable patients are presented in Table 9.
Paediatric patients. Ertapenem was evaluated in paediatric patients in a study which enrolled 112 patients and compared ertapenem (15 mg/kg IV every 12 hours in patients 2-12 years of age, and 1 g IV once a day in patients 13-17 years of age) to ticarcillin/clavulanate (50 mg/kg for patients < 60 kg or 3.0 g for patients > 60 kg, 4 or 6 times a day) up to 14 days for the treatment of complicated intra-abdominal infections and acute pelvic infections. The response rates for the EPP population are presented in Table 10.
Paediatric experience in intra-abdominal infections and acute pelvic infections is limited to children 2 years and older, and bacterial septicaemia has not been studied in this population.
A second study assessing the effect of ertapenem in additional infections not approved in adults included paediatric patients, recruitment criteria age range, 3 months to 17 years of age. This study enrolled 404 patients and compared ertapenem (15 mg/kg IV every 12 hours in patients 3 months to 12 years of age, and 1 g IV once a day in patients 13-17 years of age) to ceftriaxone (50 mg/kg/day IV in two divided doses in patients 3 months to 12 years of age and 50 mg/kg/day IV as a single daily dose in patients 13-17 years of age) for the treatment of complicated urinary tract infection, skin and soft tissue infection or community-acquired pneumonia. Both regimens allowed the option to switch to oral amoxicillin/clavulanate for a total of up to 14 days of treatment (parenteral and oral).

5.2 Pharmacokinetic Properties

Absorption.

Average plasma concentrations (microgram/mL) of ertapenem following a single 30-minute IV infusion of a 1 g dose in healthy young adults are presented in Table 11.
Area under the plasma concentration curve (AUC) of ertapenem in adults increases nearly dose-proportionally over the 0.5-2 g dose range.
There is no accumulation of ertapenem in adults following multiple IV doses ranging 0.5-2 g daily.
Average plasma concentrations (microgram/mL) of ertapenem in paediatric patients are presented in Table 12.

Distribution.

Ertapenem is highly bound to human plasma proteins. In healthy young adults, the protein binding of ertapenem decreases as plasma concentrations increase, from approximately 95% bound at an approximate plasma concentration of < 100 microgram/mL to approximately 85% bound at an approximate plasma concentration of 300 microgram/mL.
The volume of distribution (Vdss) of ertapenem in adults is approximately 8 litres (0.11 L/kg), approximately 0.2 L/kg in paediatric patients 3 months to 12 years of age and approximately 0.16 L/kg in paediatric patients 13-17 years of age.
Ertapenem penetrates into suction-induced skin blisters. Concentrations of ertapenem achieved in skin blister fluid at each sampling point on the third day of 1 g once daily IV doses are presented in Table 13. The ratio of AUC in skin blister fluid to AUC in plasma is 0.61.
The level of ertapenem in breast milk of five lactating women was measured at random time points daily for five consecutive days following the last 1 g dose of IV therapy. The measured concentration of ertapenem in breast milk on the last day of therapy (5-14 days postpartum) in all five women was < 0.38 microgram/mL; peak concentrations were not assessed. By Day 5 after discontinuation of therapy, the level of ertapenem was undetectable in the breast milk of four women and was detected at trace levels (< 0.13 microgram/mL) in one woman.
In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Metabolism.

In healthy young adults, after IV infusion of radiolabelled 1 g ertapenem, the plasma radioactivity consists predominantly (94%) of ertapenem. The major metabolite of ertapenem is the ring-opened derivative formed by hydrolysis of the beta-lactam ring.
In vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism mediated by any of the six major cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Excretion.

Ertapenem is eliminated primarily by the kidneys. The mean plasma half-life in healthy young adults and patients 13-17 years of age is approximately 4 hours and approximately 2.5 hours in paediatric patients 3 months to 12 years of age.
Following administration of a 1 g radiolabelled IV dose of ertapenem to healthy young adults, approximately 80% is recovered in urine and 10% in faeces. Of the 80% recovered in urine, approximately 38% is excreted as unchanged drug and approximately 37% as the ring-opened metabolite.
In healthy young adults given a 1 g IV dose, average concentrations of ertapenem in urine exceed 984 microgram/mL during the period 0-2 hours post-dose and exceed 52 microgram/mL during the period 12-24 hours post-dose.

Pharmacokinetics in special populations.

Gender.

Following administration of a 1 g IV dose over 30 minutes, the plasma concentrations (AUC) of ertapenem, both total and unbound, were similar in healthy male and female subjects (total drug AUC was 570.0 microgram.hr/mL for men vs 566.8 microgram.hr/mL for women).

Elderly.

Following a 1 g IV dose of ertapenem, AUC increases by approximately 39% in elderly subjects (≥ 65 years) relative to young adults (< 65 years). No dosage adjustment is necessary in elderly patients.

Paediatric patients.

Plasma concentrations of ertapenem are comparable in paediatric patients 13-17 years of age and adults following a 1 g once daily IV dose.
Following the 20 mg/kg dose (up to a maximum dose of 1 g), the pharmacokinetic parameter values in patients 13-17 years of age were generally comparable to those in healthy young adults. Three out of six patients 13-17 years of age received less than a 1 g dose. To provide an estimate of the pharmacokinetic data if all patients in this age group were to receive a 1 g dose, the pharmacokinetic data were calculated adjusting for a 1 g dose, assuming linearity. A comparison of results shows that a 1 g once daily dose of ertapenem achieves a pharmacokinetic profile in patients 13-17 years of age comparable to that of adults. The ratios (13-17 years/Adults) for AUC, the end of infusion concentration and the concentration at the midpoint of the dosing interval were 0.99, 1.20 and 0.84, respectively.
Plasma concentrations at the midpoint of the dosing interval following a single 15 mg/kg IV dose of ertapenem in patients 3 months to 12 years of age are comparable to plasma concentrations at the midpoint of the dosing interval following a 1 g once daily IV dose in adults (see Section 5.2 Pharmacokinetic Properties, Distribution). The plasma clearance (mL/min/kg) of ertapenem in patients 3 months to 12 years of age is approximately 2-fold higher as compared to that in adults. At the 15 mg/kg dose, the AUC value (doubled to model a twice daily dosing regimen, i.e. 30 mg/kg/day exposure) in patients 3 months to 12 years of age was comparable to the AUC value in young healthy adults receiving a 1 g IV dose of ertapenem.

Hepatic impairment.

The pharmacokinetics of ertapenem in patients with hepatic insufficiency have not been established. Due to the limited extent of hepatic metabolism of ertapenem, its pharmacokinetics are not expected to be affected by hepatic impairment. Therefore, no dosage adjustment is necessary in patients with hepatic impairment.

Renal impairment.

Following a single 1 g IV dose of ertapenem in adults, AUC is similar in patients with mild renal insufficiency (Clcr 60-90 mL/min/1.73 m2) compared with healthy subjects (ages 25-82 years). AUC is increased in patients with moderate renal insufficiency (Clcr 31-59 mL/min/1.73 m2) approximately 1.5-fold compared with healthy subjects. AUC is increased in patients with advanced renal insufficiency (Clcr 5-30 mL/min/1.73 m2) approximately 2.6-fold compared with healthy subjects. AUC is increased in patients with end-stage renal insufficiency (Clcr < 10 mL/min/1.73 m2) approximately 2.9-fold compared with healthy subjects. Following a single 1 g IV dose given immediately prior to a haemodialysis session, approximately 30% of the dose is recovered in the dialysate. There are no data in paediatric patients with renal insufficiency.

5.3 Preclinical Safety Data

Genotoxicity.

Ertapenem was not genotoxic, as assessed in vitro for gene mutations, chromosomal aberrations and DNA strand breaks in cultured mammalian cells. An in vivo assay of chromosomal damage (micronucleus test in mice) was also negative.

Carcinogenicity.

The carcinogenic potential of ertapenem has not been examined in long term animal studies.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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

Store below 25°C.

6.5 Nature and Contents of Container

Each vial of un-reconstituted Ertapenem Kabi contains a white to yellowish powder containing 1 g ertapenem (as sodium).
Vials (Type I clear, colourless glass, chlorobutyl rubber stopper, aluminium cap): packs of 1s and 10s.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Ertapenem sodium is a white to off-white hygroscopic, weakly crystalline powder. It is soluble in water and 0.9% sodium chloride solution, practically insoluble in ethanol, and insoluble in isopropyl acetate and tetrahydrofuran. Ertapenem sodium is a 1-β methyl-carbapenem that is structurally related to beta-lactam antibiotics, such as penicillins and cephalosporins.

Chemical structure.


Chemical Name: [4R-[3(3S*,5S*),4α,5β,6β(R*)]]- 3-[[5-[[(3-carboxyphenyl) amino] carbonyl]-3-pyrrolidinyl] thio]- 6-(1-hydroxyethyl)-4-methyl-7-oxo -1-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid monosodium salt.

CAS number.

153773-82-1 (ertapenem sodium).
Molecular Formula: C22H24N3NaO7S.
Molecular Weight: 497.497.

7 Medicine Schedule (Poisons Standard)

Australia: S4 - Prescription Only Medicine.
New Zealand: Prescription Medicine.

Summary Table of Changes