MERREM IV Solution for injection Ref.[50733] Active ingredients: Meropenem

2.1 Adult Patients

The recommended dose of MERREM IV 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.

MERREM IV 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.)

When only serum creatinine is available, the following formula (Cockcroft and Gault equation) ¹ may be used to estimate creatinine clearance.

Males: Creatinine Clearance (mL/min) =

Weight (kg) × (140 – age) / 72 × serum creatinine (mg/dL)

Females: 0.85 × above value

Table 1. Recommended MERREM IV Dosage Schedule for Adult Patients with Renal Impairment:

There is inadequate information regarding the use of MERREM IV in patients on hemodialysis or peritoneal dialysis.

2.3 Use in Pediatric Patients

Pediatric Patients 3 Months of Age and Older

• For pediatric patients 3 months of age and older, the MERREM IV 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.
• For pediatric patients weighing over 50 kg administer MERREM IV 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 MERREM IV as an intravenous infusion over approximately 15 minutes to 30 minutes or as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes to 5 minutes.
• There is limited safety data available to support the administration of a 40 mg/kg (up to a maximum of 2 grams) bolus dose.

Table 2. Recommended MERREM IV Dosage Schedule for Pediatric Patients 3 Months of Age and Older with Normal Renal Function:

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.

Pediatric Patients Less Than 3 Months of Age

For pediatric patients (with normal renal function) less than 3 months of age, with complicated intra-abdominal infections, the MERREM IV dose is based on gestational age (GA) and postnatal age (PNA). See dosing table 3 below. MERREM IV should be given as intravenous infusion over 30 minutes.

Table 3. Recommended MERREM IV Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-abdominal Infections and Normal Renal Function:

There is no experience in pediatric patients with renal impairment.

2.4 Preparation and Administration of MERREM IV

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:

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 MERREM IV with other drugs has not been established. MERREM IV should not be mixed with or physically added to solutions containing other drugs.

2.6 Stability and Storage

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

Intravenous Bolus Administration:

MERREM IV injection vials re-constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of MERREM IV) 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 (MERREM IV 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 (MERREM IV concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Dextrose Injection 5% should be used immediately.

In mice and rats, large intravenous doses of meropenem (2200 mg/kg to 4000 mg/kg) have been associated with ataxia, dyspnea, convulsions, and mortalities.

Intentional overdosing of MERREM IV is unlikely, although accidental overdosing might occur if large doses are given to patients with reduced renal function. The largest dose of meropenem administered in clinical trials has been 2 grams given intravenously every 8 hours. At this dosage, no adverse pharmacological effects or increased safety risks have been observed.

Limited postmarketing experience indicates that if adverse events occur following overdosage, they are consistent with the adverse event profile described in the Adverse Reactions section and are generally mild in severity and resolve on withdrawal or dose reduction. Consider symptomatic treatments. In individuals with normal renal function, rapid renal elimination takes place. Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis; however, no information is available on the use of hemodialysis to treat overdosage.

The dry powder should be stored at controlled room temperature 20°–25°C (68°–77°F) [see USP].