Meropenem for Injection: Indications, Dosage, Precautions, Adverse Effects
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Meropenem for Injection - Product Information

Manufacture: Fresenius Kabi USA, LLC
Country: United States
Condition: Intraabdominal Infection, Meningitis, Nosocomial Pneumonia, Skin and Structure Infection, Skin or Soft Tissue Infection, Urinary Tract Infection
Class: Carbapenems
Form: Liquid solution, Intravenous (IV)
Ingredients: Meropenem Trihydrate

Indications and Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection, USP (I.V.) and other antibacterial drugs, Meropenem for injection, USP (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.

Meropenem for injection, USP (I.V.) is useful as presumptive therapy in the indicated condition (e.g. intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity.  For information regarding use in pediatric patients see Indications and Usage, Dosage and Administration, Adverse Reactions, and Clinical Pharmacology .

Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only)

Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections 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.

Intra-abdominal Infections (Adult and Pediatric Patients)

Meropenem for injection, USP (I.V.) is indicated as a single agent therapy 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.

Bacterial Meningitis (Pediatric Patients 3 Months of age and older only)

Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, 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.

Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.

Dosage and Administration

Adult Patients

The recommended dose of Meropenem for injection (I.V.) 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 (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.

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)5 may be used to estimate creatinine clearance.

Females: 0.85 x above value

Recommended Meropenem for injection (I.V.) 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
Greater than 25 to 50 Recommended dose Every 12 hours
10 to 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 (I.V.) in patients on hemodialysis or peritoneal dialysis.

Use in Pediatric Patients

Pediatric Patients 3 Months of Age and Older

For pediatric patients from 3 months of age and older, the Meropenem for injection (I.V.) 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 (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered Meropenem for injection (I.V.) at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 gram every 8 hours for intra-abdominal infections and 2 grams every 8 hours for meningitis. Meropenem for injection (I.V.) should be given as 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.

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 10 500 mg Every 8 hours
Intra-abdominal 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 complicated skin and skin structure infections 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 intra-abdominal infections, the Meropenem for injection (I.V.) dose is based on gestational age (GA) and postnatal age (PNA). (See dosing table below). Meropenem for injection (I.V.) should be given as intravenous infusion over 30 minutes.  

Recommended Meropenem for injection (I.V.) 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 

Preparation of Solution

For Intravenous Bolus Administration

Constitute injection vials (500 mg and 1 gram) 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 gram 20 20 50

For Infusion

Infusion vials (500 mg and 1 gram) may be directly constituted with a compatible infusion fluid. Alternatively, an injection vial may be constituted, then the resulting solution added to an intravenous container and further diluted with an appropriate infusion fluid [see Dosage and Administration].

WARNING: Do not use flexible container in series connections.

Compatibility

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

Stability and Storage

Freshly prepared solutions of Meropenem should be used. However, 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 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) 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) constituted with Dextrose Injection 5% should be used immediately.

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

Dosage Forms and Strengths

Single use clear glass vials containing 500 mg or 1 gram (as the trihydrate blend with anhydrous sodium carbonate for constitution) of sterile meropenem powder.

Contraindications

Meropenem for injection (I.V.) is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to β-lactams.

Warnings and Precautions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with β-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens.

There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another β-lactam. Before initiating therapy with Meropenem for injection (I.V.), it is important to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other β-lactams, and other allergens. If an allergic reaction to Meropenem for injection (I.V.) occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation. Other therapy may also be administered as indicated.

Seizure Potential

Seizures and other adverse CNS experiences have been reported during treatment with Meropenem for injection (I.V.). These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function [see Adverse Reactions and Drug Interactions ].

During clinical investigations, 2,904 immunocompetent adult patients were treated for non-CNS infections with the overall seizure rate being 0.7% (based on 20 patients with this adverse event). All meropenem-treated patients with seizures had pre-existing contributing factors. Among these are included prior history of seizures or CNS abnormality and concomitant medications with seizure potential. Dosage adjustment is recommended in patients with advanced age and/or reduced renal function. [see Dosage and Administration ]

Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity. Continue anti-convulsant therapy in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, evaluate neurologically, placed on anti-convulsant therapy if not already instituted, and the dosage of Meropenem for injection (I.V.) re-examined to determine whether it should be decreased or the antibacterial drug discontinued.

Interaction with Valproic Acid

Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. The concomitant use of meropenem and valproic acid or divalproex sodium is generally not recommended. Antibacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of Meropenem for injection (I.V.) is necessary, supplemental anti-convulsant therapy should be considered [see Drug Interactions ].

Clostridium Difficile-associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Meropenem for injection (I.V.), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Development of Drug-Resistant Bacteria

Prescribing Meropenem for injection (I.V.) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Overgrowth of Nonsusceptible Organisms

As with other broad-spectrum antibacterial drugs, prolonged use of meropenem may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient is essential. If superinfection does occur during therapy, appropriate measures should be taken.

Laboratory Tests

While Meropenem for injection (I.V.) possesses the characteristic low toxicity of the beta-lactam group of antibacterial drugs, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.

Patients with Renal Impairment

In patients with renal impairment, thrombocytopenia has been observed but no clinical bleeding reported [see Dosage and Administration , Adverse Reactions, Use In Specific Populations and Clinical Pharmacology ].

Dialysis

There is inadequate information regarding the use of Meropenem for injection (I.V.) in patients on hemodialysis or peritoneal dialysis.

Potential for Neuromotor Impairment

Patients receiving Meropenem for injection (I.V.) on an outpatient basis may develop adverse events such as seizures, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment. Until it is reasonably well established that Meropenem for injection (I.V.) is well tolerated, patients should not operate machinery or motorized vehicles [see Adverse Reactions].

Adverse Reactions

The following are discussed in greater detail in other sections of labeling:

  • Hypersensitivity Reactions [see Warnings and Precautions]
  • Seizure Potential [see Warnings and Precautions]
  • Interaction with Valproic Acid [see Warnings and Precautions]
  • Clostridium difficile – associated Diarrhea [see Warnings and Precautions]
  • Development of Drug-Resistant Bacteria [see Warnings and Precautions ]
  • Overgrowth of Nonsusceptible Organisms [see Warnings and Precautions ]
  • Laboratory Tests [see Warnings and Precautions
  • Patients with Renal Impairment [see Warnings and Precautions ]
  • Dialysis [see Warnings and Precautions ]
  • Potential for Neuromotor Impairment [see Warnings and Precautions ]

Adverse Reactions from Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adult Patients

During clinical investigations, 2,904 immunocompetent adult patients were treated for non-CNS infections with Meropenem for injection (I.V.) (500 mg or 1 gram every 8 hours). Deaths in 5 patients were assessed as possibly related to meropenem; 36 (1.2%) patients had meropenem discontinued because of adverse events. Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies. In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem for injection (I.V.).

The following adverse reaction frequencies were derived from the clinical trials in the 2904 patients treated with Meropenem for injection (I.V.)

Local Adverse Reactions

Local adverse reactions that were reported irrespective of the relationship to therapy with Meropenem for injection (I.V.) were as follows:

Inflammation at the injection site 2.4%

Injection site reaction 0.9%

Phlebitis/thrombophlebitis 0.8%

Pain at the injection site 0.4%

Edema at the injection site 0.2%

Systemic Adverse Reactions

Systemic adverse reactions that were reported irrespective of the relationship to Meropenem for injection (I.V.) occurring in greater than 1% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%).

Additional systemic adverse reactions that were reported irrespective of relationship to therapy with Meropenem for injection (I.V.) and occurring in less than or equal to 1% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency:

Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%), summing to 1.2%.

Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain

Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope

Digestive System: oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction

Hemic/Lymphatic: anemia, hypochromic anemia, hypervolemia

Metabolic/Nutritional: peripheral edema, hypoxia

Nervous System: insomnia, agitation/delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia [see Warnings and Precautions]

Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema

Skin and Appendages: urticaria, sweating, skin ulcer

Urogenital System: dysuria, kidney failure, vaginal moniliasis, urinary incontinence

Adverse Laboratory Changes

Adverse laboratory changes that were reported irrespective of relationship to Meropenem for injection (I.V.) and occurring in greater than 0.2% of the patients were as follows:

Hepatic: increased SGPT (ALT), SGOT (AST), alkaline phosphatase, LDH, and bilirubin

Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased WBC, shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia

Renal: increased creatinine and increased BUN

NOTE: For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported irrespective of relationship to Meropenem for injection (I.V.), increased in patients with moderately severe renal impairment (creatinine clearance greater than 10 to 26 mL/min) [see Dosage and Administration , Warnings and Precautions , Use In Specific Populations and , and Clinical Pharmacology ].

Urinalysis: presence of red blood cells

Complicated Skin and Skin Structure Infections

In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above. The most common adverse events occurring in greater than 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7%), diarrhea (7%), anemia), and pain). Adverse events with an incidence of greater than 1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia.

Pediatric Patients

Clinical Adverse Reactions

Meropenem for injection (I.V.) was studied in 515 pediatric patients (3 months to less than 13 years of age) with serious bacterial infections (excluding meningitis, see next section) at dosages of 10 mg/kg to 20 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for injection (I.V.) and their rates of occurrence as follows:

Diarrhea 3.5%

Rash 1.6%

Nausea and Vomiting 0.8%

Meropenem for injection (I.V.) was studied in 321 pediatric patients (3 months to less than 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for injection (I.V.) and their rates of occurrence as follows:

Diarrhea 4.7%

Rash (mostly diaper area moniliasis) 3.1%

Oral Moniliasis 1.9%

Glossitis 1%

In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). In the Meropenem for injection (I.V.) treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.

Meropenem for injection (I.V.) was studied in 200 neonates and infants less than 3 months of age. The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse reactions were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse reactions to Meropenem for injection (I.V.).

The clinical adverse reactions seen in these patients that were reported (regardless of investigator assessment of causality) and their rates of occurrence are as follows:

Convulsion 5%

Hyperbilirubinemia (conjugated) 4.5%

Vomiting 2.5%

Adverse Laboratory Changes

Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Meropenem for injection (I.V.). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions section of this product label and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity. Hematologic - agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia. Skin–toxic epidermal necrolysis, Stevens-Johnson Syndrome, angioedema, and erythema multiforme.

Drug Interactions

Probenecid

Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem. Co-administration of probenecid with meropenem is not recommended.

Valproic Acid

Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid’s glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. If administration of Meropenem for injection (I.V.) is necessary, then supplemental anti-convulsant therapy should be considered [see Warnings and Precautions].

Use in Specific Populations

Pregnancy

Pregnancy Category B. Reproductive studies have been performed with meropenem in rats at doses of up to 1,000 mg/kg/day, and cynomolgus monkeys at doses of up to 360 mg/kg/day (on the basis of AUC comparisons, approximately 1.8 times and 3.7 times, respectively, to the human exposure at the usual dose of 1 gram every 8 hours). These studies revealed no evidence of impaired fertility or harm to the fetus due to meropenem, although there were slight changes in fetal body weight at doses of 250 mg/kg/day (on the basis of AUC comparisons, 0.4 times the human exposure at a dose of 1 gram every 8 hours) and above in rats. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Meropenem has been reported to be excreted in human milk. Caution should be exercised when Meropenem for injection (I.V.) is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Meropenem for injection (I.V.) have been established for pediatric patients 3 months of age and older with complicated skin and skin structure infections and bacterial meningitis, and for pediatric patients of all ages with complicated intra-abdominal infections.

Skin and Skin Structure Infections

Use of Meropenem for injection (I.V.) in pediatric patients 3 months of age and older with complicated skin and skin structure infections is supported by evidence from an adequate and well-controlled study in adults and additional data from pediatric pharmacokinetics studies [see Indications and Usage , Dosage and Administration , Adverse Reactions, Clinical Pharmacology and Clinical Studies].

Intra-abdominal Infections

Use of Meropenem for injection (I.V.) in pediatric patients 3 months of age and older with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetics studies and controlled clinical trials in pediatric patients. Use of Meropenem for injection (I.V.) in pediatric patients less than 3 months of age with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from a pediatric pharmacokinetic and safety study [see Indications and Usage ,Dosage and Administration , Adverse Reactions, Clinical Pharmacology  and Clinical Studies].

Bacterial Meningitis

Use of Meropenem for injection (I.V.) in pediatric patients 3 months of age and older with bacterial meningitis is supported by evidence from adequate and well-controlled studies in the pediatric population [see Indications and Usage , Dosage and Administration , Adverse Reactions, Clinical Pharmacology  and Clinical Studies].

Geriatric Use

Of the total number of subjects in clinical studies of Meropenem for injection (I.V.), approximately 1,100 (30%) were 65 years of age and older, while 400 (11%) were 75 years and older. Additionally, in a study of 511 patients with complicated skin and skin structure infections, 93 (18%) were 65 years of age and older, while 38 (7%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; spontaneous reports and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Meropenem is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

A pharmacokinetic study with Meropenem for injection (I.V.) in elderly patients has shown a reduction in the plasma clearance of meropenem that correlates with age-associated reduction in creatinine clearance [see Clinical Pharmacology ].

Patients with Renal Impairment

Dosage adjustment is necessary in patients with creatinine clearance 50 mL/min or less [see Dosage and Administration , Warnings and Precautions, and Clinical Pharmacology ].

Overdosage

In mice and rats, large intravenous doses of meropenem (2,200 mg/kg to 4,000 mg/kg) have been associated with ataxia, dyspnea, convulsions, and mortalities.

Intentional overdosing of Meropenem for injection (I.V.) 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 post-marketing 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.

How Supplied/Storage And Handling

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 20 to 25ºC (68 to 77ºF) [see USP].

Product No. NDC No. Strength
NP350720 63323-507-21 500 mg/vial Injection Vial packaged in cartons of 10
NP350830 63323-508-31 1 g/vial Injection Vial packaged in cartons of 10

The container closure is not made with natural rubber latex.

Patient Counseling Information

  • Counsel patients that antibacterial drugs including Meropenem for injection (I.V.) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Meropenem for injection (I.V.) is prescribed to treat a bacterial infection, tell patients that although it is common to feel better early in the course of therapy, take the medication exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Meropenem for injection (I.V.) or other antibacterial drugs in the future.
  • Counsel patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions].
  • Counsel patients to inform their physician if they are taking valproic acid or divalproex sodium. Valproic acid concentrations in the blood may drop below the therapeutic range upon co-administration with Meropenem for injection (I.V.). If treatment with Meropenem for injection (I.V.) is necessary and continued, alternative or supplemental anti-convulsant medication to prevent and/or treat seizures may be needed [see Warnings and Precautions]
  • Patients receiving Meropenem for injection (I.V.) on an outpatient basis may develop adverse events such as seizures, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment. Until it is reasonably well established that Meropenem for injection (I.V.) is well tolerated, patients should not operate machinery or motorized vehicles [see Warnings and Precautions]

NORMOSOL is a registered trademark of Hospira Inc.

N+ and NOVAPLUS are registered trademarks of Novation, LLC.

Manufactured For

Fresenius Kabi USA, LLC

Lake Zurich, IL 60047

Revised: July 2015