Merrem I.V. (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 strains of the designated microorganisms:

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 ((beta)-lactamase and non-(beta)-lactamase-producing strains), and Neisseria meningitidis.

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 ADMINI-STRATION 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: One gram (1 g) by intravenous administration every 8 hours. MERREM I.V. should be given by intravenous infusion, over approximately 15 to 30 minutes or 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.)

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)⁴ may be used to estimate creatinine clearance.

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 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered MERREM I.V. at a dose of 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.

There is no experience in pediatric patients with renal impairment.

PREPARATION OF SOLUTION

FOR INTRAVENOUS BOLUS ADMINISTRATION

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

FOR INFUSION

Infusion vials (500 mg and 1 g) 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.)

NOTE: ADD-VANTAGE VIALS ARE NOT TO BE USED IN THIS MANNER.

FOR ADD-VANTAGE VIALS

ADD-Vantage vials of MERREM I.V. are to be constituted only with Sodium Chloride Injection 0.45%, Sodium Chloride Injection 0.9% or Dextrose Injection 5% in the 50, 100, and 250 mL Abbott ADD-Vantage^® flexible diluent containers. MERREM I.V. supplied in single-use ADD-Vantage vials should be prepared as directed.

DIRECTIONS FOR USE OF MERREM I.V. (MEROPENEM FOR INJECTION) IN ADD-VANTAGE VIALS:

To Open Diluent Container: Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble ADD-Vantage Vial and Flexible Diluent Container: (Use Aseptic Technique)

1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
   
   1. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (see Figure 1), then pull straight up to remove the cap. (See Figure 2.)
      
      NOTE: Once the breakaway cap has been removed, do not access vial with syringe.
   2. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (See Figure 3.)
   
   
   
2. Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (See Figure 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go.
   NOTE: ONCE VIAL IS SEATED, DO NOT ATTEMPT TO REMOVE.
   
3. Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
4. Label appropriately.

To Prepare Admixture:

1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
2. With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (See Figure 5.)
   
3. Pull the inner cap from the drug vial. (See Figure 6.) Verify that the rubber stopper has been pulled out and invert the system several times, allowing the drug and diluent to mix.
   
4. Mix contents thoroughly and use within the specified time.

PREPARATION FOR ADMINISTRATION: (USE ASEPTIC TECHNIQUE)

1. Confirm the activation and admixture of vial contents.
2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
3. Close flow control clamp of administration set.
4. Remove cover from outlet port at bottom of container.
5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated.
   NOTE: See full directions on administration set carton.
6. Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
7. Squeeze and release drip chamber to establish proper fluid level in chamber.
8. Open flow control clamp and clear air from set. Close clamp.
9. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
10. Regulate rate of administration with flow control clamp.

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 15-25°C (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 (55-77°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:

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 4°C (39°F) in plastic syringes.

ADD-Vantage Vials: ADD-Vantage vials diluted in Sodium Chloride Injection 0.45% (MERREM I.V. concentrations ranging from 5 to 20 mg/mL) may be stored for up to 6 hours at controlled room temperature 15-25°C (59-77°F) or for 24 hours at 4°C (39°F). ADD-Vantage vials diluted in Sodium Chloride Injection 0.9% (MERREM I.V. concentrations ranging from 1-20 mg/mL) may be stored for up to 4 hours at controlled room temperature 15-25°C (59-77°F) or for 24 hours at 4°C (39°F). ADD-Vantage vials diluted with Dextrose Injection 5.0% (MERREM I.V. concentrations ranging from 1-20 mg/mL) may be stored for up to 1 hour at controlled room temperature 15-25°C (59-77°F) or for 8 hours at 4°C (39°F).

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. MERREM I.V. is supplied in 100 mL infusion vials containing sufficient meropenem to deliver 500 mg or 1 g for intravenous administration. The dry powder should be stored at controlled room temperature 20-25°C (68-77°F) [see USP].

MERREM I.V. is also supplied as ADD-Vantage Vials containing sufficient meropenem to deliver 500 mg or 1 g for intravenous administration.