lifecarebiosciences

Merocare SE

MEROCARE SE available in 1.5 g strength as a white to off-white sterile, dry powder consisting of Meropenam/Disodium Edetate/Sulbactam Sodium packaged in tubular glass vials. The product does not contain any preservative and is for single use only. It is administered as intravenous injection. Each single dose 1.5 g vial of MEROCARE SE contains Meropenam 1000 mg, Sulbactam Sodium Ph. Eur. equivalent to Sulbactam 500 mg, Disodium Edetate Ph. Eur. 37 mg.

Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Meropenam in MEROCARE SE exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which lead to cell death.

Disodium Edetate is a non-antibiotic adjuvant entity and membrane permeability enhancer, chelator with a high affinity for calcium, zinc & other divalent ions. It does not have antimicrobial property of its own but acts as a potentiator. It also inhibits Efflux pump by altering genes expression responsible for OMPs expression. Due to its chelation property it chelates divalent ions of lipopolysaccharide layer and makes biofilm porous and thus breaks existing biofilm and prevents biofilm formation.
Sulbactam sodium is a β-lactamase inhibitor with weak antibacterial action. Sulbactam is an irreversible inhibitor of β-lactamase; it binds the enzyme and does not allow it to interact with the antibiotic, thus extending their spectrum activity.

MEROCARE SE, a novel antibiotic adjuvant entity comprising Meropenam, Sulbactam & Disodium edetate powder for solution for injection/Infusion is a synergistic antimicrobial antibiotic. Presence of Disodium Edetate may synergizes the activity of meropenam and sulbactam as it helps in opening porin channels and allows more drug to enter periplasmic space resulting in enhanced killing.

Pharmacokinetics: 

Absorption: MEROCARE SE is to be administered intravenously.
Absorption Peak Concentration: Meropenam is dependent on dose, renal function, and administration technique The time to peak concentration following intravenous administration is approximately 1 hour (range: 0.5 – 1.5 hours) after the start of the infusion, while that of Sulbactam sodium is 19.287 (SD ± 5.685 µg/ml) and is reached approximately 0.521 hour (SD ± 0.102) in healthy volunteers after the dose.
Distribution: Plasma protein binding of meropenem is approximately 2%. Meropenem achieves concentrations that match or exceed those required to inhibit most susceptible bacteria in most body fluids and tissues including cerebrospinal fluid. Peak concentrations in body fluids were mostly achieved in 1 hour following intravenous infusion The volume of distribution is 12 to 20 L, while sulbactam reaches its half life in 0.94 hours. Sulbactam has been found to be approximately 38% reversibly bound to human serum protein.
Metabolism: Extrarenal, 20% to 25% Increases up to 50% in patients with creatinine clearance of less than 20 mL/minute . There is one metabolite, which is inactive, ICI-213689. Disodium Edetate molecule is not metabolized in the body, it thus passes very rapidly into the urine carrying its metallic ion with it. Disodium Edetate molecule leave the body intact. Sulbactam is not metabolised, but is excreted primarily in the urine (glomerular filtration and tubular secretion) with a small amount being recovered in bile and faeces.
Elimination: Approximately 70% of a meropenem dose administered intravenously is recovered unchanged in the urine over 12 hours. The clearance of meropenem from plasma correlates with the creatinine clearance. There is no accumulation of repeated doses of meropenem 500 mg every 8 hours or 1 gram every 6 hours in patients with normal renal function. Dose adjustments are necessary in patients with renal impairment and 70-80% of Sulbactam is eliminated as an unchanged active substance in the urine

Indications/Uses

• Pneumonias and Nosocomial pneumonias
• Urinary Tract Infections
• Intra-abdominal Infections
• Gynaecological Infections, such as endometritis and pelvic inflammatory disease
• Bacterial Meningitis 
• Septicaemia
• Empiric treatment, for presumed infections in patients with febrile neutropenia, used as

monotherapy or in combination with anti-viral or anti-fungal agents.

Meropenem has proved efficacious alone or in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Dosage/Direction for Use

The dosage and duration of therapy shall be established depending on type and severity of infection and the condition of the patient.

The recommended daily dosage is as follows:-

500 mg IV every 8 hours in the treatment of pneumonia, UTI and gynaecological infections such as endometritis.

1 g IV every 8 hours in the treatment of hospital acquired pneumonias, peritonitis, presumed infections in febrile neutropenic patients, septicaemia.

In meningitis the recommended dosage is 2g every 8 hours.

Dosage Schedule for Adults with Impaired Renal Function Dosage should be reduced in patients with creatinine clearance less than 51 ml/min, as scheduled below:

Creatinine Clearance (ml/min)            Dose (based on unit doses of 500mg, 1g, 2g)           Frequency

26-50                                                               one unit dose                                                   every 12 hours

10-25                                                               one-half unit dose                                            every 12 hours

<10                                                                  one-half unit dose                                           every 24 hours

Contraindications

• anaphylactic reaction to beta-lactam antibiotics
• hypersensitivity to meropenem or any component of the product or other drugs in the same class (carbapenems)

Precautions

There is some clinical and laboratory evidence of partial cross-allergenicity between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. As with all beta-lactam antibiotics, rare hypersensitivity reactions have been reported. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. Meropenem should be used with caution in patients with such a history. If an allergic reaction to meropenem occurs, the drug should be discontinued and appropriate measures taken.

Use In Pregnancy & Lactation

Pregnancy The safety of Meropenem in human pregnancy has not been evaluated. Animal studies have not shown any adverse effect on the developing foetus. Meropenem should not be used in pregnancy unless the potential benefit justifies the potential risk to the foetus. In every case, it should be used under the direct supervision of the physician.

Lactation Meropenem is detectable at very low concentrations in animal breast milk. Meropenem should not be used in breast-feeding women unless the potential benefit justifies the potential risk to the baby

Storage

MEROCARE SE (Meropenam/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) is to be stored below 30°C. Protect from direct sunlight.
Shelf-life: 24 months.

References:

• Meropenam PI
• Elores PI