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Meropenem for Injection

[ Usual Diluents ] [ Standard Dilution ] [ Storage and Stability ]
DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither NewMedicalTerms Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  

Drug UPDATES:   [Drug information (pdf)]  

 

Usual Diluents top of page

NS (preferred - greater stability),      D5W (must be used immediately)

Standard Dilutions   [Amt of drug] [Infusion vol] [Infusion rate] top of page

 DUPLEX® Containers or dilution of powder for injection:
[ 0.5 grams]   [50 ml ]  [15-30 minutes]
[ 1 gram]   [50 ml ]  [15-30 minutes]

Bolus administration (see preparation below - powder for injection):
[ 0.5 grams]   [10 ml ]  [3 to 5 minutes]
[ 1 gram]   [20 ml ]  [3 to 5 minutes]

For Intravenous Bolus Administration
Re-constitute injection vials (500 mg and 1 gram) with sterile Water for Injection (see table 4 below). Shake to dissolve and let stand until clear.

Table 4: Volume of Sterile Water for Injection for Reconstitution of Injection Vials

Vial size Amount of Diluent Added (mL) Approximate Withdrawable Volume (mL) Approximate Average Concentration (mg/mL)
500 mg 10 10 50
1 gram 20 20 50

Stability:
DUPLEX® Containers

  • 500 mg Meropenem for Injection USP and 50 mL Sodium Chloride Injection 0.9% USP in DUPLEX® Container 
  • 1 gram Meropenem for Injection USP and 50 mL Sodium Chloride Injection 0.9% USP in DUPLEX® Container

Freshly prepared solutions of Meropenem for Injection USP and Sodium Chloride Injection USP should be used. Following reconstitution (activation) in the DUPLEX® Container, the product maintains satisfactory potency for 1 hour at up to 25ºC (77ºF) or for 15 hours at up to 5ºC (41ºF). Solutions of intravenous Meropenem for Injection USP and Sodium Chloride Injection USP should not be frozen.

Meropenem injection, powder, for solution

Freshly prepared solutions of Meropenem should be used. However, re-constituted solutions of Meropenem maintain satisfactory potency under the conditions described below. Solutions of intravenous Meropenem should not be frozen.

Intravenous Bolus Administration:  Meropenem injection vials re-constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of Meropenem) may be stored for up to 3 hours at up to 25°C (77°F) or for 13 hours at up to 5°C (41°F).

Intravenous Infusion Administration:  Solutions prepared for infusion (Meropenem concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Sodium Chloride Injection 0.9% may be stored for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F).

Solutions prepared for infusion (Meropenem concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Dextrose Injection 5% should be used immediately.

WARNINGS  top of page

See warnings and precautions below.

DESCRIPTION  top of page

Description:

Meropenem for injection is a sterile, pyrogen-free, synthetic, carbapenem antibacterial drug for intravenous administration. Meropenem is (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-ene-2-carboxylic acid trihydrate. Its empirical formula is C17H25N3O5S•3H2O with a molecular weight of 437.52.

Meropenem for injection is a white to pale yellow crystalline powder containing meropenem trihydrate and sodium carbonate. The constituted solution varies from colorless to yellow depending on the concentration. The pH of freshly constituted solutions is between 7.3 and 8.3. Meropenem is soluble in 5% monobasic potassium phosphate solution, sparingly soluble in water, very slightly soluble in hydrated ethanol, and practically insoluble in acetone or ether.

Meropenem for Injection USP and Sodium Chloride Injection USP is supplied as a sterile, nonpyrogenic, single-use packaged combination of meropenem (drug chamber) and 50 mL of sodium chloride (diluent) in the DUPLEX® sterile container. When reconstituted as instructed, each 1 gram Meropenem for injection in the DUPLEX® Container will deliver 1 gram of meropenem and a total sodium content of 290.2 mg (12.6 mEq). Each 500 mg Meropenem for injection in the DUPLEX® Container will deliver 500 mg of meropenem and a total sodium content of 245.1 mg (10.7 mEq) [see Dosage and Administration (2.4)]. The osmolality of the reconstituted solution of Meropenem for Injection USP and Sodium Chloride Injection USP is approximately 356 mOsmol/kg for the 500 mg dose and approximately 417 mOsmol/kg for the 1 gram dose.

The DUPLEX® Container is a flexible dual chamber container. After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is hyperosmotic and is intended for single intravenous use. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene ethylene copolymer that contains no plasticizers.

Not made with natural rubber latex, PVC or Di(2-ethylhexyl)phthalate (DEHP).

CLINICAL PHARMACOLOGY: top of page

Mechanism of Action:

The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Meropenem binds to PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus. Bactericidal concentrations (defined as a 3 log10 reduction in cell counts within 12 to 24 hours) are typically 1-2 times the bacteriostatic concentrations of meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed.

Meropenem has significant stability to hydrolysis by beta-lactamases, both penicillinases and cephalosporinases produced by Gram-positive and Gram-negative bacteria.

Meropenem does not have in-vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE).

Resistance
There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of Gram-negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target PBPs, 3) increased expression of efflux pump components, and 4) production of antibacterial drug-destroying enzymes (carbapenemases, metallo-beta-lactamases).

Cross-Resistance
Cross-resistance is sometimes observed with isolates resistant to other carbapenems.

Interaction with Other Antimicrobials
In vitro tests show meropenem to act synergistically with aminoglycoside antibacterial drugs against some isolates of Pseudomonas aeruginosa.

Antimicrobial Activity
Meropenem has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].

Gram-positive bacteria

Enterococcus faecalis (vancomycin-susceptible isolates only)
Staphylococcus aureus (methicillin-susceptible isolates only)
Streptococcus agalactiae
Streptococcus pneumoniae (penicillin-susceptible isolates only)
Streptococcus pyogenes
Viridans group streptococci

Gram-negative bacteria

Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Neisseria meningitidis
Proteus mirabilis
Pseudomonas aeruginosa

Anaerobic bacteria

Bacteroides fragilis
Bacteroides thetaiotaomicron
Peptostreptococcus species

INDICATIONS AND USAGE  top of page

INDICATIONS AND USAGE:

1.1 Complicated Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older requiring the full adult dose only)

Meropenem for Injection USP and Sodium Chloride Injection USP is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species.

1.2 Complicated Intra-abdominal Infections (Adult Patients and Pediatric Patients 3 Months of age and older requiring the full adult dose only)

Meropenem for Injection USP and Sodium Chloride Injection USP is indicated for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species.

1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older requiring the full adult dose only)

Meropenem for Injection USP and Sodium Chloride Injection USP is indicated for the treatment of bacterial meningitis caused by Haemophilus influenzae, Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae.

Meropenem has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.

For information regarding use in pediatric patients (3 months of age and older) [see Indications and Usage (1.1), (1.2) or (1.3); Dosage and Administration (2.3), and Adverse Reactions (6.1)].

1.4 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for Injection USP and Sodium Chloride Injection USP and other antibacterial drugs, Meropenem for Injection USP and Sodium Chloride Injection USP should only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS top of page

Contraindications:

  • Known hypersensitivity to product components or anaphylactic reactions to beta-lactams.
  • Contraindicated where the administration of sodium or chloride could be clinically detrimental.

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS:

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactams.
  • Seizures and other adverse CNS experiences have been reported during treatment.
  • Co-administration of Meropenem for Injection with valproic acid or divalproex sodium reduces the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures.
  • Clostridium difficile-associated diarrhea (ranging from mild diarrhea to fatal colitis) has been reported. Evaluate if diarrhea occurs.
  • In patients with renal dysfunction, thrombocytopenia has been observed.
  • Solutions containing sodium ions should be used with great care, if at all, in patients where the administration of sodium could be detrimental.

ADVERSE REACTIONS top of page

ADVERSE REACTIONS:
Most common adverse reactions (greater than or equal to 2%) are: headache, nausea, constipation, diarrhea, anemia, vomiting, and rash

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information (pdf)

DOSAGE AND ADMINISTRATION  top of page

DOSAGE AND ADMINISTRATION:

2.1 Adult Patients

Meropenem for Injection USP and Sodium Chloride Injection USP in the DUPLEX® Container should be used only in patients who require the entire 500 mg or 1 gram dose and not any fraction thereof. The recommended dose of Meropenem for Injection USP and Sodium Chloride Injection USP is 500 mg given every 8 hours for skin and skin structure infections and 1 gram given every 8 hours for intra-abdominal infections. When treating complicated skin and skin structure infections caused by P. aeruginosa, a dose of 1 gram every 8 hours is recommended.

Meropenem for Injection USP and Sodium Chloride Injection USP should be administered by intravenous infusion over approximately 15 to 30 minutes.

Additional comments for meropenem injection, powder, for solution (pdf)

Meropenem for injection (I.V.) should be administered by intravenous infusion over approximately 15 minutes to 30 minutes. Doses of 1 gram may also be administered as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes to 5 minutes.

2.2 Use in Adult Patients with Renal Impairment

Dosage should be reduced in patients with creatinine clearance of 50 mL/min or less. (See dosing table below.)

Dosage should be reduced in renal failure if less than a full dose (1 gram or 500 mg) is required and an alternative formulation should be used to avoid risk of overdose.

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)2 may be used to estimate creatinine clearance.

Males: Creatinine Clearance (mL/min) =

Weight (kg) x (140 - age) 
 72 x serum creatinine (mg/dL)

Females: 0.85 x above value

Table 1: Recommended Meropenem for Injection Dosage Schedule for Adult Patients With Renal Impairment

Creatinine Clearance (mL/min)   Dose (dependent on type of infection)  Dosing Interval
greater than 50  Recommended dose (500 mg cSSSI and 1 gram Intra-abdominal infection)  Every 8 hours
 26-50  Recommended dose  Every 12 hours
 10-25  One-half recommended dose  Every 12 hours
less than 10  One-half recommended dose  Every 24 hours

There is inadequate information regarding the use of meropenem for injection in patients on hemodialysis or peritoneal dialysis.

2.3 Use in Pediatric Patients (3 Months of age and older only)

  • Meropenem for Injection USP and Sodium Chloride Injection USP in the DUPLEX® Container is designed to deliver a 500 mg or 1 gram dose of meropenem. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the full adult dose of meropenem.  Meropenem is not to be used in pediatric patients aged less than three months. For pediatric patients 3 months of age and older, the Meropenem for Injection USP and Sodium Chloride Injection USP dose is 10 mg/kg, 20 mg/kg or 40 mg/kg every 8 hours (maximum dose is 2 grams every 8 hours), depending on the type of infection (cSSSI, cIAI, intra-abdominal infection or meningitis). See dosing table 2 below. [see Use in Specific Populations (8.4)].  
  • For pediatric patients weighing over 50 kg administer Meropenem for Injection USP and Sodium Chloride Injection USP at a dose of 500 mg every 8 hours for cSSSI, 1 gram every 8 hours for cIAI and 2 grams every 8 hours for meningitis.
  • Administer Meropenem for Injection USP and Sodium Chloride Injection USP as an intravenous infusion over approximately 15 minutes to 30 minutes.

Table 2: Recommended Meropenem for injection (I.V.) Dosage Schedule for Pediatric Patients 3 Months of Age and Older With Normal Renal Function

 Type of Infection  Dose (mg/kg)  Up to a Maximum Dose  Dosing Interval
 Complicated Skin and Skin Structure Infections  10  500 mg  Every 8 hours
 Complicated Intra-abdominal Infections  20  1 gram  Every 8 hours
 Meningitis  40  2 grams Every 8 hours 

There is no experience in pediatric patients with renal impairment.

When treating cSSSI caused by P. aeruginosa, a dose of 20 mg/kg (or 1 gram for pediatric patients weighing over 50 kg) every 8 hours is recommended.

2.4 Preparation and Administration of Meropenem for Injection USP and Sodium Chloride Injection USP in DUPLEX® Container

Important Administration Instructions

  • Do not use in series connections. Such use would result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.
  • Do not introduce additives into the DUPLEX® Container.
  • Administer Meropenem for Injection USP and Sodium Chloride Injection USP intravenously over approximately 15 to 30 minutes.

This reconstituted solution is for intravenous use only. Additional info - DUPLEX® Container

Additional comments for meropenem injection, powder, for solution (pdf)

Important Administration Instructions:

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For Intravenous Bolus Administration

Re-constitute injection vials (500 mg and 1 gram) with sterile Water for Injection (see table 4 below). Shake to dissolve and let stand until clear.

Table 4: Volume of Sterile Water for Injection for Reconstitution of Injection Vials

Vial size

Amount of Diluent Added (mL) Approximate Withdrawable Volume (mL) Approximate Average Concentration (mg/mL)
500 mg 10 10 50
1 gram 20 20 50

For Infusion

  • Injection vials (500 mg and 1 gram) may be directly re-constituted with a compatible infusion fluid.
  • Alternatively, an injection vial may be re-constituted, then the resulting solution added to an intravenous container and further diluted with an appropriate infusion fluid [ see Dosage and Administration (2.5) and ( 2.6)].
  • Do not use flexible container in series connections.

2.5 Compatibility

Compatibility of Meropenem for Injection USP and Sodium Chloride Injection USP with other drugs has not been established. Meropenem for Injection USP and Sodium Chloride Injection USP should not be mixed with or physically added to solutions containing other drugs.

2.6 Stability and Storage

Freshly prepared solutions of Meropenem for Injection USP and Sodium Chloride Injection USP should be used. Following reconstitution (activation) in the DUPLEX® Container, the product maintains satisfactory potency for 1 hour at up to 25ºC (77ºF) or for 15 hours at up to 5ºC (41ºF). Solutions of intravenous Meropenem for Injection USP and Sodium Chloride Injection USP should not be frozen.

Additional comments for meropenem injection, powder, for solution (pdf)

Freshly prepared solutions of Meropenem should be used. However, re-constituted solutions of Meropenem maintain satisfactory potency under the conditions described below. Solutions of intravenous Meropenem should not be frozen.

Intravenous Bolus Administration

Meropenem injection vials re-constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of Meropenem) may be stored for up to 3 hours at up to 25°C (77°F) or for 13 hours at up to 5°C (41°F).

Intravenous Infusion Administration

Solutions prepared for infusion (Meropenem concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Sodium Chloride Injection 0.9% may be stored for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F).

Solutions prepared for infusion (Meropenem concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Dextrose Injection 5% should be used immediately.

HOW SUPPLIED  top of page

DOSAGE FORMS AND STRENGTHS:

  • 500 mg Meropenem for Injection USP and 50 mL Sodium Chloride Injection 0.9% USP in DUPLEX® Container 
  • 1 gram Meropenem for Injection USP and 50 mL Sodium Chloride Injection 0.9% USP in DUPLEX® Container
  • Single dose clear glass vials of Meropenem for Injection (I.V.) containing 500 mg or 1 gram (as the trihydrate blended with anhydrous sodium carbonate for re-constitution) of sterile meropenem powder.

Storage and Stability top of page

DUPLEX® Container:

Meropenem for Injection USP and Sodium Chloride Injection USP in the DUPLEX® Container is a flexible dual chamber container supplied in two concentrations. The diluent chamber contains approximately 50 mL of 0.9% Sodium Chloride Injection USP. After reconstitution, the delivered doses are equivalent to 5001 mg and 11 gram meropenem.

Meropenem for Injection USP and Sodium Chloride Injection USP is supplied sterile and nonpyrogenic in the DUPLEX® Container packaged 24 units per case.

 NDC  REF  Dose  Volume
 0264-3183-11  3183-11  500 mg  50 mL
 0264-3185-11  3185-11  1 gram  50 mL

Store the unactivated unit at 20–25°C (68–77°F). Excursion permitted to 15-30°C. [See USP Controlled Room Temperature.] Protect from freezing.

Use only if prepared solution is clear and free from particulate matter.

------------------------
meropenem injection, powder, for solution

Meropenem for injection, USP (I.V.) is supplied in 20 mL and 30 mL injection vials containing sufficient meropenem to deliver 500 mg or 1 gram for intravenous administration, respectively. The dry powder should be stored at controlled room temperature 20º to 25ºC (68º to 77ºF) [see USP].

Product No. NDC No. Strength
PRX350725 63323-507-25 500 mg/vial Injection Vial packaged in cartons of 25
PRX350825 63323-508-25 1 g/vial Injection Vial packaged in cartons of 25

Meropenem (merrem ®)