Meropenem (Page 2 of 8)

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) a nd (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 25ºC (77ºF) or for 13 hours at up to 5ºC (41ºF).

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 25ºC (77ºF) or 15 hours at up to 5ºC (41ºF).

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.

3 DOSAGE FORMS AND STRENGTHS

Single dose clear glass vials of Meropenem for Injection, USP containing 500 mg or 1 gram (as the trihydrate blended with anhydrous sodium carbonate for re-constitution) of sterile meropenem powder.

4 CONTRAINDICATIONS

Meropenem for Injection 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 beta (β)-lactams.

5 WARNINGS AND PRECAUTIONS

5.1 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, 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 occurs, discontinue the drug immediately.

5.2 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving Meropenem for Injection [see Adverse Reactions (6.2)]. If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment should be considered.

5.3 Seizure Potential

Seizures and other adverse CNS experiences have been reported during treatment with Meropenem for Injection. 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 (6.1)and Drug Interactions (7.2)].

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 adult patients with creatinine clearance of 50 mL/min or less [see Dosage and Administration (2.2) ].

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 re-examine the dosage of Meropenem for Injection to determine whether it should be decreased or discontinued.

5.4 Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid

The concomitant use of meropenem and valproic acid or divalproex sodium is generally not recommended. 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. Consider administration of antibacterial drugs other than carbapenems to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of Meropenem for Injection is necessary, consider supplemental anti-convulsant therapy [see Drug Interactions (7.2) ].

5.5 Clostridium d ifficile -associated Diarrhea

Clostridium difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Meropenem for Injection, 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.

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