Merrem (Meropenem) - Indications and Dosage

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MERREM I.V. and other antibacterial drugs, MERREM I.V. should only be used to treat or prevent 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.

MERREM I.V. is indicated as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms:

Skin and Skin Structure Infections

Complicated skin and skin structure infections due to Staphylococcus aureus (β-lactamase and non-β-lactamase producing, methicillin susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci , Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species.

Intra-abdominal Infections

Complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species.

Bacterial Meningitis (Pediatric patients > 3 months only)

Bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae (β-lactamase and non-β-lactamase-producing isolates), and Neisseria meningitidis.

‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established.

MERREM I.V. 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 PRECAUTIONS - Pediatrics ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections.

Appropriate cultures should usually be performed before initiating antimicrobial treatment in order to isolate and identify the organisms causing infection and determine their susceptibility to MERREM I.V.

MERREM I.V. is useful as presumptive therapy in the indicated condition (i.e., intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity.

Antimicrobial therapy should be adjusted, if appropriate, once the results of culture(s) and antimicrobial susceptibility testing are known.

DOSAGE AND ADMINISTRATION

Adults

The recommended dose of MERREM I.V. is 500 mg given every 8 hours for skin and skin structure infections and 1 g given every 8 hours for intra-abdominal infections. MERREM I.V. should be administered by intravenous infusion over approximately 15 to 30 minutes. Doses of 1 g may also be administered as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Use in Adults with Renal Impairment

Dosage should be reduced in patients with creatinine clearance less than 51 mL/min. (see dosing table below).

Recommended MERREM I.V. Dosage Schedule for Adults With Impaired Renal Function

Creatinine Clearance (mL/min)	Dose (dependent on type of infection)	Dosing Interval
≥51	Recommended dose (500 mg cSSSI and 1 g Intra-abdominal)	Every 8 hours
26-50	Recommended dose	Every 12 hours
10-25	One-half recommended dose	Every 12 hours
<10	One-half recommended dose	Every 24 hours

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)⁵ 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

There is inadequate information regarding the use of MERREM I.V. in patients on hemodialysis.

There is no experience with peritoneal dialysis.

Use in Adults With Hepatic Insufficiency

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

Use in Elderly Patients

No dosage adjustment is required for elderly patients with creatinine clearance values above 50 mL/min.

Use in Pediatric Patients

For pediatric patients from 3 months of age and older, the MERREM I.V. dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered MERREM I.V. at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 g every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis. MERREM I.V. should be given as intravenous infusion over approximately 15 to 30 minutes or as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Recommended MERREM I.V. Dosage Schedule for Pediatrics with Normal Renal Function

Type of Infection	Dose (mg/kg)	Up to Maximum Dose	Dosing Interval
Complicated skin and skin structure	10	500 mg	Every 8 hours
Intra-abdominal	20	1 g	Every 8 hours
Meningitis	40	2 g	Every 8 hours

There is no experience in pediatric patients with renal impairment.

PREPARATION OF SOLUTION

For Intravenous Bolus Administration

Constitute injection vials (500 mg and 1g) with sterile Water for Injection. (See table below.) Shake to dissolve and let stand until clear.

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

For Infusion

Infusion vials (500 mg and 1g) may be directly constituted with a compatible infusion fluid (See COMPATIBILITY AND STABILITY.) Alternatively, an injection vial may be constituted, then the resulting solution added to an I.V. container and further diluted with an appropriate infusion fluid. (See COMPATIBILITY AND STABILITY.)

WARNING:    Do not use flexible container in series connections.

COMPATIBILITY AND STABILITY

Compatibility of MERREM I.V. with other drugs has not been established. MERREM I.V. should not be mixed with or physically added to solutions containing other drugs.

Freshly prepared solutions of MERREM I.V. should be used whenever possible. However, constituted solutions of MERREM I.V. maintain satisfactory potency at controlled room temperature 15-25ºC (59-77°F) or under refrigeration at 4°C (39°F) as described below. Solutions of intravenous MERREM I.V. should not be frozen.

Intravenous Bolus Administration

MERREM I.V. injection vials constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of MERREM I.V.) may be stored for up to 2 hours at controlled room temperature 15-25°C (59-77°F) or for up to 12 hours at 4°C (39°F).

Intravenous Infusion Administration

Stability in Infusion Vials: MERREM I.V. infusion vials constituted with Sodium Chloride Injection 0.9% (MERREM I.V. concentrations ranging from 2.5 to 50 mg/mL) are stable for up to 2 hours at controlled room temperature 15-25°C (59-77°F) or for up to 18 hours at 4°C (39°F). Infusion vials of MERREM I.V. constituted with Dextrose Injection 5% (MERREM I.V. concentrations ranging from 2.5 to 50 mg/mL) are stable for up to 1 hour at controlled room temperature 15-25°C (59-77°F) or for up to 8 hours at 4°C (39°F).

Stability in Plastic I.V. Bags: Solutions prepared for infusion (MERREM I.V. concentrations ranging from 1 to 20 mg/mL) may be stored in plastic intravenous bags with diluents as shown below:

	Number of Hours Stable at Controlled Room Temperature 15-25°C (59-77°F)	Number of Hours Stable at 4°C (39°F)
Sodium Chloride Injection 0.9%	4	24
Dextrose Injection 5.0%	1	4
Dextrose Injection 10.0%	1	2
Dextrose and Sodium Chloride Injection 5.0%/0.9%	1	2
Dextrose and Sodium Chloride Injection 5.0%/0.2%	1	4
Potassium Chloride in Dextrose Injection 0.15%/5.0%	1	6
Sodium Bicarbonate in Dextrose Injection 0.02%/5.0%	1	6
Dextrose Injection 5.0% in Normosol®-M	1	8
Dextrose Injection 5.0% in Ringers Lactate Injection	1	4
Dextrose and Sodium Chloride Injection 2.5%/0.45%	3	12
Mannitol Injection 2.5%	2	16
Ringers Injection	4	24
Ringers Lactate Injection	4	12
Sodium Lactate Injection 1/6 N	2	24
Sodium Bicarbonate Injection 5.0%	1	4

Stability in Baxter Minibag Plus: Solutions of MERREM I.V. (MERREM I.V. concentrations ranging from 2.5 to 20 mg/mL) in Baxter Minibag Plus bags with Sodium Chloride Injection 0.9% may be stored for up to 4 hours at controlled room temperatures 15-25°C (59-77°F) or for up to 24 hours at 4°C (39°F). Solutions of MERREM I.V. (MERREM I.V. concentrations ranging from 2.5 to 20 mg/mL) in Baxter Minibag Plus bags with Dextrose Injection 5.0% may be stored up to 1 hour at controlled room temperatures 15-25°C (59-77°F) or for up to 6 hours at 4°C (39°F).

Stability in Plastic Syringes, Tubing and Intravenous Infusion Sets: Solutions of MERREM I.V. (MERREM I.V. concentrations ranging from 1 to 20 mg/mL) in Water for Injection or Sodium Chloride Injection 0.9% (for up to 4 hours) or in Dextrose Injection 5.0% (for up to 2 hours) at controlled room temperatures 15-25°C (59-77°F) are stable in plastic tubing and volume control devices of common intravenous infusion sets.

Solutions of MERREM I.V. (MERREM I.V. concentrations ranging from 1 to 20 mg/mL) in Water for Injection or Sodium Chloride Injection 0.9% (for up to 48 hours) or in Dextrose Injection 5% (for up to 6 hours) are stable at 4ºC (39ºF) in plastic syringes.

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

HOW SUPPLIED

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

500 mg Injection Vial (NDC 0310-0325-20)

1 g Injection Vial (NDC 0310-0321-30)