Merovex 500/Merovex 1000

Merovex 500/Merovex 1000

meropenem

Manufacturer:

Venus Remedies

Distributor:

VE Pharma
Full Prescribing Info
Contents
Meropenem trihydrate.
Description
Merovex 500: Each vial contains: Meropenem Trihydrate USP Eq. to Meropenem Anhydrous 500 mg, Sodium Carbonate USP Eq. to Sodium 45.1 mg (As sterile blend of meropenem & sodium Carbonate).
Merovex 1000: Each vial contains: Meropenem Trihydrate USP Eq. to Meropenem Anhydrous 1000 mg, Sodium Carbonate USP Eq. to Sodium 90.2 mg (As sterile blend of meropenem & sodium Carbonate).
Meropenem is a white to slightly yellow crystalline powder, soluble in dimethylformamide and in 5% monobasic potassium phosphate solution, sparingly soluble in water, very slightly soluble in alcohol, practically insoluble in acetone and in ether. And Meropenem is described chemically as 1-Azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, 3-[[5-[(dimethylamino) carbonyl]-3-pyrrolidinyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo, trihydrate, [4R-[3(3S*,5S*), 4α, 5β, 6β(R*)]]-(4R, 5S, 6S)-3-[[(3S, 5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl] thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-carboxylic acid, trihydrate. The molecular formula is C17H25N3O5S·3H20 and the molecular weight is 437.52.
Action
Pharmacological Classification: Carbapenem derivative, Antibiotic.
Pharmacology: Pharmacodynamics: Mode of action: Meropenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis in Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins (PBPs).
Pharmacokinetics: In healthy subjects the mean plasma half-life is approximately 1 hour; the mean volume of distribution is approximately 0.25 l/kg (11-27 l) and the mean clearance is 287 ml/min at 250 mg falling to 205 ml/min at 2 g. Doses of 500 mg, 1 mg and 2 mg doses infused over 30 minutes give mean Cmax values of approximately 23, 49 and 115 μg/ml respectively, corresponding AUC values were 39.3, 62.3 and 153 μg.h/ml. After infusion over 5 minutes Cmax values are 52 and 112 μg/ml after 500 and 1 g doses respectively. When multiple doses are administered 8-hourly to subjects with normal renal function, accumulation of meropenem does not occur.
A study of 12 patients administered meropenem 1 g 8 hourly post-surgically for intra-abdominal infections showed a comparable Cmax and half-life to normal subjects but a greater volume of distribution 271.
Distribution: The average plasma protein binding of meropenem was approximately 2% and was independent of concentration. After rapid administration (5 minutes or less) the pharmacokinetics are biexponential but this is much less evident after 30 minutes infusion. Meropenem has been shown to penetrate well into several body fluids and tissues: including lung, bronchial secretions, bile, cerebrospinal fluid, gynaecological tissues, skin, fascia, muscle, and peritoneal exudates.
Metabolism: Meropenem is metabolised by hydrolysis of the beta-lactam ring generating a microbiologically inactive metabolite. In vitro meropenem shows reduced susceptibility to hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem and there is no requirement to co-administer a DHP-I inhibitor.
Adult patients: Pharmacokinetic studies performed in patients have not shown significant pharmacokinetic differences versus healthy subjects with equivalent renal function. A population model developed from data in 79 patients with intra-abdominal infection or pneumonia, showed a dependence of the central volume on weight and the clearance on creatinine clearance and age.
Toxicology: Preclinical safety data: Animal studies indicate that meropenem is well tolerated by the kidney. Histological evidence of renal tubular damage was seen in mice and dogs only at doses of 2 g/kg and above after a single administration and above and in monkeys at 500 mg/kg in a 7-day study.
Meropenem is generally well tolerated by the central nervous system. Effects were seen in acute toxicity studies in rodent at doses exceeding 1 g/kg.
The IV LD50 of meropenem in rodents is greater that 2 g/kg.
In repeat dose studies of up to 6 months duration only minor effects were seen including a decrease in red cell parameters in dogs.
Indications/Uses
Meropenem is indicated for the treatment of the following infections in adults and children over 3 months of age: Pneumonia, including community acquired pneumonia and nosocomial pneumonia.
Broncho-pulmonary infections in cystic fibrosis.
Complicated urinary tract infections.
Complicated intra-abdominal infections.
Intra- and post-partum infections.
Complicated skin and soft tissue infections.
Acute bacterial meningitis.
Meropenem may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Dosage/Direction for Use
The tables as follows provide general recommendations for dosing.
The dose of meropenem administered and the duration of treatment should take into account the type of infection to be treated, including its severity, and the clinical response.
A dose of up to 2 g three times daily in adults and adolescents and a dose of up to 40 mg/kg three times daily in children may be particularly appropriate when treating some types of infections, such as nosocomial infections due to Pseudomonas aeruginosa or Acinetobacter spp.
Additional considerations for dosing are needed when treating patients with renal insufficiency (see further follows).
Adults and Adolescents: See Table 1.

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Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes.
Paediatric population: Children under 3 months of age: The safety and efficacy of meropenem in children under 3 months of age have not been established and the optimal dose regimen has not been identified. However, limited pharmacokinetic data suggest that 20 mg/kg every 8 hours may be an appropriate regimen.
Children from 3 months to 11 years of age and up to 50 kg body weight: The recommended dose regimens are shown in the table as follows: See Table 2.

Click on icon to see table/diagram/image

Children over 50 kg body weight: The adult dose should be administered.
Preparation of Solution: For Intravenous Administration: Constitute injection vials (500 mg and 1 g) with sterile Water for Injection. Shake to dissolve and let stand until clear. (See Table 3.)

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A solution for bolus injection is prepared by dissolving the drug product in water for injection to a final concentration of 50 mg/ml. Chemical and physical in-use stability for a prepared solution for bolus injection has been demonstrated for 3 hours at up to 25°C (77°F) or 12 hours under refrigerated conditions 2°C-8°C (36°F-46°F).
A solution for infusion is prepared by dissolving the drug product in either 0.9% sodium chloride solution for infusion or 5% dextrose solution for infusion to a final concentration of 1 to 20 mg/ml. Chemical and physical in-use stability for a prepared solution for infusion using 0.9% sodium chloride solution has been demonstrated for 3 hours at up to 25°C (77°F) or 24 hours under refrigerated conditions 2°C-8°C (36°F-46°F).
Overdosage
Relative overdose may be possible in patients with renal impairment if the dose is not adjusted as described in Dosage & Administration. Limited post-marketing experience indicates that if adverse reactions occur following overdose, they are consistent with the adverse reaction profile described in Adverse Reactions are generally mild in severity and resolve on withdrawal or dose reduction. Symptomatic treatments should be considered.
In individuals with normal renal function, rapid renal elimination will occur.
Haemodialysis will remove meropenem and its metabolite.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to any other carbapenem antibacterial agent.
Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of betalactam antibacterial agent (e.g. penicillins or cephalosporins).
Warnings
The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.
As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity reactions have been reported.
Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.
If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken.
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of meropenem. Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered.
Medicinal products that inhibit peristalsis should not be given.
Adverse Reactions
CNS: Headache, Syncope, Insomnia, Agitation, Delirium, Confusion, Fever, Dizziness, Pain, Seizures, Nervousness, Paresthesia, Hallucinations, Somnolence, Anxiety, Depression.
CV: Heart Failure, Cardiac arrest, MI, Pulmonary Embolism, Tachycardia, Chest pain, Hypertension, Bradycardia, Hypotension.
GI: Diarrhea, Nausea, Vomiting, Constipation, Abdominal Pain or Enlargement, Oral candidiasis, Anorexia.
GU: Dysuria, Kidney failure.
Hematologic: Bleeding events, Anemia.
Hepatic: Hepatic failure, Cholestatic jaundice, jaundice, flatulence, ileus.
Musculoskeletal: Back pain.
Respiratory: Apnea, Hypoxia, Respiratory disorder, Dyspnea.
Skin: Rash; Pruritus; Urticaria; Sweating; Inflammation; Pain, Edema, Phlebitis, or Thrombophlebitis at injection site.
Other: Hypersensitivity reactions, Anaphylaxis, Sepsis, Shock, Peripheral Edema.
Drug Interactions
No specific medicinal product interaction studies other than probenecid were conducted.
Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. Caution is required if probenecid is co-administered with meropenem.
The potential effect of meropenem on the protein binding of other medicinal products or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected on the basis of this mechanism.
Decreases in blood levels of valproic acid have been reported when it is co-administered with carbapenem agents resulting in a 60-100% decrease in valproic acid levels in about two days. Due to the rapid onset and the extent of the decrease, co-administration of valproic acid with carbapenem agents is not considered to be manageable and therefore should be avoided.
Oral anti-coagulants: Simultaneous administration of antibiotics with warfarin may augment its anti-coagulant effects. There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of the antibiotic to the increase in INR (international normalised ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after co-administration of antibiotics with an oral anti-coagulant agent.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
Shelf Life: Two years from the date of Manufacturing.
MIMS Class
ATC Classification
J01DH02 - meropenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Presentation/Packing
Merovex 500: Powd for inj (vial) (white to yellowish powder) 500 mg x 20 mL x 1's.
Merovex 1000: Powd for inj (vial) (white to yellowish powder) 1 g x 20 mL x 1's.
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