Merop

Meropenem Trihydrate (MEROP) Injection is a sterile, pyrogen-free, synthetic, broad-spectrum, carbapenem antibiotic for intravenous administration. Meropenem Trihydrate (MEROP) Injection is a white to pale yellow depending on the concentration. The pH of freshly constituted solutions is between 7.3 and 8.3. Meropenem Trihydrate (MEROP) Injection is soluble in 5% monobasic potassium phosphate solution, sparingly soluble in water, very lightly soluble in hydrated ethanol, and practically insoluble in acetone or ether.
500 mg: Each vial contains: Meropenem Trihydrate, USP equivalent to anhydrous Meropenem 500 mg.
Also contains Sodium as Sodium Carbonate 45.1 mg (1.96 mEq).
1 g: Each vial contains: Meropenem Trihydrate, USP equivalent to anhydrous Meropenem 1 gram.
Also contains Sodium as Sodium Carbonate 90.2 mg (3.92 mEq).

Antibacterial.
Pharmacology: Pharmacodynamics: Mode of Action: Meropenem Trihydrate (MEROP) Injection is a carbapenem antibiotic structurally similar to imipenem for parenteral use, that is relatively stable to human dehydropeptidase-1 (DHP-1) and therefore does not require the addition of an inhibitor of DHP-1. Meropenem Trihydrate (MEROP) Injection exerts its bactericidal action by interfering with vital bacterial cell wall synthesis. The ease with which it penetrates bacterial cell walls, its high level of stability to all serine beta-lactamases and its marked affinity for the Penicillin Binding Proteins (PBPs) explain the potent bactericidal action of Meropenem Trihydrate (MEROP) Injection against a broad spectrum of aerobic and anaerobic bacteria.
Minimum bactericidal concentrations (MBC) are commonly the same as the minimum inhibitory concentrations (MIC). For 76% of the bacteria tested, the MBC: MIC ratios were 2 or less. The in vitro antibacterial spectrum of Meropenem Trihydrate (MEROP) Injection includes the majority of clinically significant Gram-positive and Gram-negative, aerobic and anaerobic strains of H bacteria, as shown as follows: Gram-positive aerobes: Bacillus spp., Corynebacterium diphtheriae, Enterococcus faecalis, Lactobacillus spp., Staphylococcus aureus (penicillinase negative and positive), Staphylococci-coagulase-negative; including Staphylococcus epidermis, Staphylococcus saprophyticus, Staphylococcus intermedius, Streptococcus pneumoniae (penicillin susceptible and resistant), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus bovis, Streptococcus viridans.
Gram-negative aerobes: Acinetobacter baumannii, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae (including beta-lactamase positive and ampicillin resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Neisseria gonorrhoeae (including beta-lactamase positive, penicillin resistant and spectinomycin resistant strains), Klebsiella pneumoniae, Klebsiella aerogenes, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella spp., Vibrio cholerae.
Anaerobic bacteria: Bacteroides fragilis, Bacteroides coagulans, Bacteroides uniformis, Clostridium perfringens, Clostridium sporogenes, Clostridium innocuum, Fusobacterium mortiferum, Fusobacterium varium, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptococcus saccharolyticus, Propionibacterium acnes, Propionibacterium avidum, Enterococcus faecium and methicillin-resistant staphylococci have been found to be resistant to meropenem.
Pharmacokinetics: A 30-minute intravenous infusion of a single dose of Meropenem Trihydrate (MEROP) Injection in healthy volunteers results in peak plasma levels of approximately 23 microgram/mL for the 500 mg dose and 49 microgram/mL for the 1 g dose.
After an IV dose of 500 mg, plasma levels of Meropenem Trihydrate (MEROP) Injection decline to values of 1 microgram/mL or less, 6 hours after administration.
When multiple doses are administered at 8 hourly intervals to subjects with normal renal function, accumulation of Meropenem Trihydrate (MEROP) Injection does not occur. In subjects with normal renal function, Meropenem Trihydrate (MEROP) Injection's elimination half-life is approximately 1 hour. Plasma protein binding of Meropenem Trihydrate (MEROP) Injection is approximately 2%.
Meropenem Trihydrate (MEROP) Injection penetrates well into most body fluids and tissues including cerebrospinal fluid of patients with bacterial meningitis, achieving concentrations in excess of those required to inhibit most bacteria.
Studies in children have shown that the pharmacokinetics of Meropenem Trihydrate (MEROP) Injection in children is similar to those in adults. The elimination half-life for Meropenem Trihydrate (MEROP) Injection was approximately 1.5 hours in pediatric patients of age 3 months to 2 years and the pharmacokinetics are linear over the dose range of 10 to 40 mg/kg. Pharmacokinetic studies in patients with renal insufficiency have shown the plasma clearance of Meropenem Trihydrate (MEROP) Injection correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment. Pharmacokinetic studies in the elderly have shown a reduction in plasma clearance of Meropenem Trihydrate (MEROP) Injection, which correlated with age-associated reduction in creatinine clearance. Pharmacokinetic studies in patients with liver disease have shown no effects of liver disease on the pharmacokinetics of Meropenem Trihydrate (MEROP) Injection.

It is used in the treatment of susceptible infections including intra-abdominal infections, meningitis, respiratory tract infections (including cystic fibrosis patients), septicemia, skin infection, urinary tract infections and infections in immunocompromised patients.

Adults: 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: See Table 1.

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Dosage Schedule for Adults with Impaired Renal Function: Dosage should be reduced in patients with creatinine clearance less than 51 mL/min, as scheduled as follows. (See Table 2.)

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Meropenem Trihydrate (MEROP) Injection is cleared by hemodialysis; if continued treatment with Meropenem Trihydrate (MEROP) Injection is necessary, it is recommended that the unit dose (based on the type and severity of infection) be administered at the completion of the hemodialysis procedure to restore therapeutically effective plasma concentrations.
There is no experience with the use of Meropenem Trihydrate (MEROP) Injection in patients under peritoneal dialysis.
Dosage in Adults with Hepatic Insufficiency: No dosage adjustment is necessary in patients with hepatic insufficiency.
Elderly Patients: No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 mL/min.
Children: For children over 3 months and up to 12 years of age the recommended dose is 10 to 20 mg/kg every 8 hours depending on type and severity of infection, susceptibility of the pathogen and the condition of the patient. In children over 50 kg weight, adult dosage should be used.
For children aged 4 to 18 years with cystic fibrosis, doses ranging from 25 to 40 mg/kg every 8 hours. There is no experience in children with renal impairment.
Preparation of Solution: For Intravenous Bolus Administration: Meropenem Trihydrate (MEROP) Injection (500 mg and 1 gram) is compatible with the following infusion fluids: Sterile Water for Injection.
Sodium Chloride Injection (0.9% w/v).
Dextrose Injection (5% w/v).
Dextrose Injection (10% w/v).
Dextrose and Sodium Chloride Injection (5% w/v & 0.9% w/v).
Ringer's Lactate Injection.
Use freshly prepared solutions of Meropenem Trihydrate (MEROP) Injection for IV Injection and Infusion.
As shown as follows, the following diluents maintain satisfactory potency at room temperature (15°C to 25°C) or under refrigerated temperature (4°C). (See Table 3.)

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For Infusion: Infusion vials (500 mg and 1 g) may be directly constituted with a compatible infusion fluid. Alternatively, an injection vial may be constituted, then the resulting solution added to an I.V. container and further diluted with an appropriate infusion fluid.
Method of Administration: Meropenem Trihydrate (MEROP) Injection to be used for bolus intravenous injection should be constituted with sterile water for injections (10 mL per 500 mg meropenem). This provides an approximate concentration of 50 mg/mL. Constituted solutions are clear, and colorless or pale yellow.
Meropenem Trihydrate (MEROP) Injection for intravenous infusion may be constituted with compatible infusion fluids (50 to 200 mL).
When constituted as instructed (see Preparation of Solution as previously mentioned), each 1 gram Meropenem Trihydrate (MEROP) Injection vial will deliver 1 g of meropenem and 90.2 mg of sodium as sodium carbonate (3.92 mEq).

Accidental overdosage could occur during therapy, particularly in patients with renal impairment. Treatment of overdosage should be symptomatic. In normal individuals, rapid renal elimination will occur; in subjects with renal impairment, haemodialysis will remove Meropenem trihydrate for Injection USP MEROP and its metabolite.

Meropenem Trihydrate (MEROP) Injection is contraindicated in patients who have demonstrated hypersensitivity to this product.

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 Trihydrate (MEROP) Injection careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.
Meropenem Trihydrate (MEROP) Injection should be used with caution in patients with such a history. If an allergic reaction for Meropenem Trihydrate (MEROP) Injection occurs, the drug should be discontinued and appropriate measures taken.
Use in Children: Efficacy and tolerability in infants under 3 months old have not been established; therefore, Meropenem Trihydrate (MEROP) Injection is not recommended for use below this age. There is no experience in children with altered hepatic or renal function.

Pregnancy: The safety of Meropenem Trihydrate (MEROP) Injection in human pregnancy has not been evaluated. Animal studies have not shown any adverse effect on the developing fetus. The only adverse effect observed in animal reproductive studies was an increased incidence of abortions in monkeys at 13 times the expected exposure in man. Meropenem Trihydrate (MEROP) Injection should not be used in pregnancy unless the potential benefit justifies the potential risk to the fetus. In every case, it should be used under the direct supervision of the physician.
Lactation: Meropenem Trihydrate (MEROP) Injection is detectable at very low concentrations in animal breast milk. Meropenem Trihydrate (MEROP) Injection should not be used in breast-feeding women unless the potential benefit justifies the potential risk to the baby.

Infections and Infestations: Uncommon: Oral and vaginal candidiasis.
Blood and Lymphatic System Disorders: Common: Thrombocythemia.
Uncommon: Eosinophilia, thrombocytopenia, leukopenia, neutropenia.
Rare: Agranulocytosis.
Very Rare: Hemolytic anemia.
Nervous System Disorders: Common: Headache.
Uncommon: Paresthesia.
Rare: Convulsions.
Gastrointestinal Disorders: Common: Diarrhea, vomiting, nausea.
Very Rare: Pseudomembranous colitis.
Hepatobiliary Disorders: Common: Increased alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, blood lactate dehydrogenase, γ-glutamyltransferase.
Uncommon: Increased blood bilirubin.
Skin and Subcutaneous Tissue Disorders: Common: Rash, pruritus.
Uncommon: Urticaria.
Very Rare: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.
General Disorders and Administration Site Conditions: Common: Inflammation, pain.
Uncommon: Thrombophlebitis.
Immune System Disorders: Very Rare: Angioedema, manifestations of anaphylaxis.

Probenecid competes with Meropenem Trihydrate (MEROP) Injection for active tubular secretion and thus inhibits the renal excretion, with the effect of increasing the elimination half-life and plasma concentration of Meropenem Trihydrate (MEROP) Injection. As the potency and duration of action of Meropenem Trihydrate (MEROP) Injection dosed without Probenecid are adequate, the co-administration of Probenecid with Meropenem Trihydrate (MEROP) Injection is not recommended.
Meropenem Trihydrate (MEROP) Injection has been administered concomitantly with other medications without adverse pharmacological interactions. However, no other specific data regarding potential drug interactions is available (apart from probenecid as previously mentioned).

Store at temperatures not exceeding 30°C.
Shelf-Life: Meropenem Trihydrate (MEROP) Injection has a shelf life of 24 months.

Other Beta-Lactams

J01DH02 - meropenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.

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