ADMINISTRATION ROUTES:
IV
ALTERNATIVE NAMES:
Meropenem-AFT, DBL Meropenem
ICU INDICATIONS:
- Treatment of infections caused by susceptible organisms
- Broad spectrum cover of hospital-acquired infections (particularly in the setting of intra-abdominal sepsis)
PRESENTATION AND ADMINISTRATION:
IV:
1 g vials of white powder
Note: Meropenem should be administered by continuous infusion in ICU. Give loading dose then start continuous infusion as indicated below. See DOSAGE below for details.
Reconstitution:
Reconstitute each vial with 19 mL of water for injection to make a total volume of 20 mL (approximate concentration 50 mg/mL). Initial reconstitution should be prepared as soon as possible before use. Solutions reconstituted with water for injection are stable for 3 hours at 25 degrees.
Load / Intermittent IV dose:
Add dose to 50 – 100 mL of compatible fluid and administer over 15 – 30 minutes. Alternatively, inject reconstituted solution slowly over 5 minutes.
For subsequent continuous infusion:
Make up the prescribed dose to 100 mL of compatible fluid and administer over 8 hours as per table below.
Diluted doses are stable for up to 8 hours at room temperature. Make up infusion immediately before use.
| Prescribed dose | Volume to remove from a 100 mL bag | Volume of reconstituted drug solution to add to bag | Final volume | Infusion rate for an 8 hour infusion |
|---|---|---|---|---|
| 2 g | 40 mL | 40 mL | 100 mL | 12.5 mL/hr |
| 1.33 g | 26.6 mL | 26.6 mL | 100 mL | 12.5 mL/hr |
| 1 g | 20 mL | 20 mL | 100 mL | 12.5 mL/hr |
| 660 mg | 13.2 mL | 13.2 mL | 100 mL | 12.5 mL/hr |
| 330 mg | 6.6 mL | 6.6 mL | 100 mL | 12.5 mL/hr |
-
If the infusion is paused for less than 4 hours, the rate should be increased so it completes within 8 hours of when it was initially commenced. If necessary, any remaining antibiotic that has not been infused at the 8 hour mark can be administered as a bolus.
-
If the infusion is paused for 4 hours or more, a loading dose appropriate for the indication and patient's renal function (or CRRT) should be administered, and the infusion restarted after the appropriate timing interval has passed (follow advice in DOSAGE section below). In this scenario, the bag should be discarded and replaced with a new one.
Compatible with the following IV fluids:
Sodium chloride 0.9% ONLY for continuous infusions
Sodium chloride 0.9%, glucose 5% for load/intermittent dosing
Store at room temperature
DOSAGE:
IV:
STANDARD vs HIGH Dosing
HIGH dose indications are
- CNS Infections
- Septic shock: use HIGH dose for septic shock for first 48 hours, then switch to STANDARD dose (adjusted for renal function or CRRT) if the patient is clinically improving
- Pseudomonas aeruginosa infection (confirmed or suspected)
- Other infections (particularly ones caused by bacteria with high minimum inhibitory concentration) may require HIGH dose under Infectious Disease clinical guidance
All other patients receive STANDARD dosing
Meropenem can be administered via either continuous or intermittent IV infusion at both HIGH and STANDARD dose. In ICU most patients receive continuous infusion. Intermittent dosing may be utilised in some situations (see 'Intermittent Dose' section below).
ICU CONTINUOUS IV INFUSION:
STANDARD Dose
1 g load
1 g TDS via 8-hourly infusions
Start 4 hours after loading dose
HIGH Dose
2 g load
2 g TDS via 8-hourly infusions
Start 4 hours after loading dose
Convert continuous infusions to intermittent IV doses when patient cleared for discharge from ICU or as appropriate. Give first intermittent dose as soon as the continuous infusion is stopped.
ICU INTERMITTENT IV DOSING:
Treatment can be started with intermittent IV dosing for patients who are likely to be discharged from ICU soon after initiation. It should also be considered for patients who have difficult IV access (discuss with ICU pharmacist first as meropenem may be compatible for Y-site administration with other infusions).
STANDARD Dose
1 g TDS
HIGH Dose
2 g TDS
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
In renal impairment or continuous renal replacement therapy (CRRT), meropenem can be administered by either continuous infusion or by intermittent IV dosing.
Continuous Infusion Dose in Renal Impairment/CRRT
| STANDARD DOSE | STANDARD DOSE | HIGH DOSE | HIGH DOSE | |
|---|---|---|---|---|
| GFR (ml/min) or CRRT mode | Load | Subsequent Continuous Infusion | Load | Subsequent Continuous Infusion |
| >25-50 | 1 g | 660 mg TDS via 8-hour infusions. Start 6 hours after loading dose | 2 g | 1.33 g TDS via 8-hour infusions. Start 6 hours after loading dose |
| >10-≤25 or CVVHDF | 1 g | 660 mg TDS via 8-hour infusions. Start 6 hours after loading dose | 1 g | 660 mg TDS via 8-hour infusions. Start 6 hours after loading dose |
| ≤10 | 1 g | 330 mg TDS via 8-hour infusions. Start 12 hours after loading dose | 1 g | 330 mg TDS via 8-hour infusions. Start 12 hours after loading dose |
For other modes of renal replacement therapy (intermittent haemodialysis, peritoneal dialysis) see intermittent IV dosing below.
Intermittent Dosing in Renal Impairment or Dialysis (any mode)
| GFR (ml/min) / CRRT Mode | STANDARD Dose | HIGH Dose |
|---|---|---|
| >25-50 | 1 g BD | 2 g BD |
| >10-≤25 or CVVHDF | 1 g BD | 1 g BD |
| ≤10 | 1 g OD | 1 g OD |
For other dialysis modalities such as Continuous Ambulatory Peritonal Dialysis (CAPD) or Intermittent Haemodialysis (HD), intermittent IV dosing is used. The STANDARD dose is used for these patients, irrespective of the indication.
| RRT Modality | Dose |
|---|---|
| CAPD | 1 g OD |
| HD | 1 g OD. On dialysis days, administer dose after dialysis session |
DOSAGE IN PAEDIATRICS:
IV:
20-40 mg/kg TDS
CLINICAL PHARMACOLOGY:
Meropenem is a carbapenem antibiotic. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections:
Aerobes, Gram-Positive:
- Enterococcus faecalis (excluding vancomycin-resistant isolates)
- Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing, methicillin- susceptible isolates only)
- Streptococcus agalactiae
- Streptococcus pneumoniae (penicillin-susceptible isolates only)
- Streptococcus pyogenes
- Viridans group streptococci.
Aerobes, Gram-Negative:
- Escherichia coli
- Haemophilus influenzae (beta-lactamase and non-beta-lactamase-producing)
- Klebsiella pneumoniae
- Neisseria meningitidis
- Pseudomonas aeruginosa
- Proteus mirabilis.
Anaerobes:
- Bacteroides fragilis
- Bacteroides thetaiotaomicron
- Peptostreptococcus species
CONTRAINDICATIONS:
- Hypersensitivity to carbapenems
WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more apt to occur in patients 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 reactions when treated with another beta-lactam. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens.
PRECAUTIONS:
General:
Seizures and other adverse CNS experiences have been reported during treatment with meropenem. These experiences have occurred most commonly in patients with CNS disorders (e.g. brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function. This risk of seizures is lower than the risk with imipenem.
In patients with renal dysfunction, thrombocytopaenia has been observed but no clinical bleeding reported.
Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytosis). Patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem.
Laboratory Tests:
No tests in addition to routine ICU tests are required
Drug/Laboratory Test Interactions:
None noted
IMPORTANT DRUG INTERACTIONS IN ICU:
Meropenem significantly reduces serum levels of valproic acid to subtherapeutic. This interaction is complex, persistent and not resolved by valproate dose increases. Concomitant use should be avoided and an alternative antibiotic should be used. However, if a patient has received even a single dose of meropenem while also taking valproic acid – follow advice below.
For patients taking valproic acid for seizure control:
Adult patients: Commence adjunctive antiepileptic cover with levetiracetam
- Give 1 g as a loading dose
- Then give 500 mg BD, starting 12 hours after the loading dose
- Continue levetiracetam throughout the meropenem treatment, and for 14 days after the treatment is stopped
Paediatric patients:
- Maintain the usual valproic acid dose and consult paediatric neurology for advice on appropriate adjunctive antiepileptic cover
Consult neurology for patients:
- taking valproic acid for epilepsy but are intolerant or allergic to levetiracetam'
- already taking levetiracetam before meropenem was initiated
- with a history of refractory epilepsy
- who have a seizure while receiving adjunctive levetiracetam for the above reason
For patients taking valproic acid for other indications (e.g. migraine prophylaxis, mania), consult with the relevant specialist team for advice. Levetiracetam should not be prescribed for these patients as it is unlikely to provide any benefit.
ADVERSE REACTIONS:
General:
Nausea and vomiting; pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain
Cardiovascular: Heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope, peripheral oedema, peripheral vascular disease, shock
Gastrointestinal
Oral moniliasis, anorexia, diarrhoea, nausea/vomiting, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction
Hepatobiliary:
Cholestatic jaundice/jaundice, hepatic failure,
Haematological:
Haemolytic anaemia, hypochromic anaemia, thrombocythaemia, eosinophilia, leucopenia, thrombocytopenia, neutropenia
Metabolic/Nutritional:
Peripheral oedema, hypoglycaemia
Nervous system:
Insomnia, agitation/delirium, confusion, dizziness, seizure (see PRECAUTIONS), nervousness, paraesthesia, hallucinations, somnolence, anxiety, depression, asthenia, headache
Respiratory:
Respiratory disorder, dyspnoea, pleural effusion, asthma, increased cough, pulmonary oedema, hypoxia, pharyngitis, pleural effusion, apnoea
Skin and appendages:
Urticaria, sweating, skin ulceration, pruritus, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Urogenital system:
Dysuria, kidney failure, vaginal moniliasis, urinary incontinence