2 DOSAGE AND ADMINISTRATION 500 mg every 8 hours by intravenous infusion over 15 to 30 minutes for complicated skin and skin structure infections (cSSSI) for adult patients. When treating infections caused by Pseudomonas aeruginosa , a dose of 1 gram every 8 hours is recommended. ( 2.1 ) 1 gram every 8 hours by intravenous infusion over 15 minutes to 30 minutes for intra-abdominal infections for adult patients. ( 2.1 ) 1 gram every 8 hours by intravenous bolus injection (5 mL to 20 mL) over 3 minutes to 5 minutes for adult patients. ( 2.1 ) Dosage should be reduced in adult patients with renal impairment. ( 2.2 ) 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) 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 Pediatric patients 3 months of age and older Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients 3 Months of Age and Older with Normal Renal Function (2.3) Type of Infection Dose (mg/kg) Up to a Maximum Dose Dosing Interval Complicated skin and skin structure* 10 500 mg Every 8 hours Intra-abdominal 20 1 gram Every 8 hours Meningitis 40 2 gram Every 8 hours - Intravenous infusion is to be given over approximately 15 minutes to 30 minutes. - Intravenous bolus injection (5 mL to 20 mL) is to be given over approximately 3 minutes to 5 minutes. - There is no experience in pediatric patients with renal impairment. *20 mg/kg (or 1 gram for pediatric patients weighing over 50 kg) every 8 hours is recommended when treating complicated skin and skin structure infections caused by P. aeruginosa. (2.3) Pediatric patients less than 3 months of age Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-Abdominal Infections and Normal Renal Function (2.3) Age Group Dose (mg/kg) Dose Interval Infants less than 32 weeks GA and PNA less than 2 weeks 20 Every 12 hours Infants less than 32 weeks GA and PNA 2 weeks and older 20 Every 8 hours Infants 32 weeks and older GA and PNA less than 2 weeks 20 Every 8 hours Infants 32 weeks and older GA and PNA 2 weeks and older 30 Every 8 hours - Intravenous infusion is to be given over 30 minutes. - There is no experience in pediatric patients with renal impairment. GA: gestational age and PNA: postnatal age 2.1 Adult Patients The recommended dose of meropenem for injection 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 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 1 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 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) 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 Pediatric Patients 3 Months of Age and Older For pediatric patients 3 months of age and older, the Meropenem for Injection 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 meropenem for injection 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 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 Meropenem for Injection 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. 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 meropenem for injection dose is based on gestational age (GA) and postnatal age (PNA). See dosing Table 3 below. Meropenem for injection should be given as intravenous infusion over 30 minutes. Table 3: Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-abdominal Infections and Normal Renal Function Age Group Dose (mg/kg) Dose Interval Infants less than 32 weeks GA and PNA less than 2 weeks 20 Every 12 hours Infants less than 32 weeks GA and PNA 2 weeks and older 20 Every 8 hours Infants 32 weeks and older GA and PNA less than 2 weeks 20 Every 8 hours Infants 32 weeks and older GA and PNA 2 weeks and older 30 Every 8 hours There is no experience in pediatric patients with renal impairment. 2.4 Preparation and Administration of Meropenem for Injection 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 with other drugs has not been established. Meropenem for injection 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 should be used. However, re-constituted solutions of meropenem for injection maintain satisfactory potency under the conditions described below. Solutions of intravenous meropenem for injection should not be frozen. Intravenous Bolus Administration Meropenem for injection vials re-constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of meropenem for injection) 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 for injection 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 for injection concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Dextrose Injection 5% should be used immediately.