Merapin 2000 mg

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ME RAPIN 2000 mg (MERAPIN 2000 mg)

Composition:

Active substance: meropenem;

One vial contains meropenem trihydrate equivalent to meropenem 2000 mg;

Excipients: sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: crystalline powder, white to slightly yellow.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Carbapenems. ATC code J01D H02.

Pharmacological properties.

Pharmacodynamics.

Meropenem exerts bactericidal activity by inhibiting bacterial cell wall synthesis in both Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins (PBPs).

As with other β-lactam antibacterial agents, the duration of time during which meropenem concentrations exceed the minimum inhibitory concentrations (MICs) (T>MIC) correlates strongly with efficacy. In preclinical models, meropenem demonstrated activity when plasma concentrations exceeded the MIC for the infecting microorganisms for approximately 40% of the dosing interval. This target value has not been clinically established.

Bacterial resistance to meropenem may arise due to:

• Reduced outer membrane permeability in Gram-negative bacteria (due to decreased porin production);
• Reduced affinity for target PBPs;
• Increased expression of efflux pump components;
• Production of β-lactamases capable of hydrolyzing carbapenems.

In the European Union, outbreaks of infection caused by carbapenem-resistant bacteria have been reported.

Cross-resistance between meropenem and medicinal products belonging to the classes of quinolones, aminoglycosides, macrolides, and tetracyclines, with respect to the target microorganisms, is absent. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the underlying mechanism involves reduced membrane permeability and/or the presence of efflux pump(s).

The MIC breakpoints established during clinical trials by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are available at the following link: https://www.ema.europa.eu/documents/other/minimum-inhibitory-concentration-mic-breakpoints_en.xlsx

The prevalence of acquired resistance may vary geographically and over time for individual species; therefore, it is advisable to refer to local data on microbial resistance, especially when treating severe infections. If necessary, when the local prevalence of microbial resistance is such that the benefit of using the medicinal product, at least for certain types of infections, is questionable, expert consultation should be sought.

The following pathogenic microorganisms are listed based on clinical experience and therapeutic treatment guidelines.

Usually susceptible species

Gram-positive aerobes

Enterococcus faecalis⁷

Staphylococcus aureus (methicillin-susceptible)⁸

Staphylococcus species (methicillin-susceptible), including Staphylococcus epidermidis

Streptococcus agalactiae (Group B)

Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius)

Streptococcus pneumoniae

Streptococcus pyogenes (Group A)

Gram-negative aerobes

Citrobacter freundii

Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii

Neisseria meningitidis

Proteus mirabilis

Proteus vulgaris

Serratia marcescens

Gram-positive anaerobes

Clostridium perfringens

Peptoniphilus asaccharolyticus

Peptostreptococcus species (including P. micros, P. anaerobius, P. magnus)

Gram-negative anaerobes

Bacteroides caccae

Bacteroides fragilis group

Prevotella bivia

Prevotella disiens

Species for which acquired resistance may be a problem

Gram-positive aerobes

Enterococcus faecium^7,9

Gram-negative aerobes

Acinetobacter species

Burkholderia cepacia

Pseudomonas aeruginosa

Inherently resistant microorganisms

Gram-negative aerobes

Stenotrophomonas maltophilia

Legionella species

Other microorganisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetii

Mycoplasma pneumoniae

⁷ Species exhibiting intrinsic intermediate susceptibility.

⁸ All methicillin-resistant staphylococci are resistant to meropenem.

⁹ Resistance rate > 50% in one or more EU countries.

Glanders and melioidosis: the use of meropenem in humans is based on in vitro susceptibility data for B. mallei and B. pseudomallei and limited human data. Physicians should refer to national and/or international consensus documents regarding the treatment of glanders and melioidosis.

Pharmacokinetics.

In healthy individuals, the mean plasma half-life is approximately 1 hour; the mean volume of distribution is about 0.25 L/kg (11–27 L); the mean clearance is 287 mL/min with a 250 mg dose, decreasing to 205 mL/min with a 2 g dose. After administration of 500 mg, 1000 mg, and 2000 mg doses as 30-minute infusions, mean C_max values are approximately 23, 49, and 115 µg/mL, respectively; corresponding AUC values are 39.3, 62.3, and 153 µg×h/mL. After 5-minute infusions, C_max values are 52 and 112 µg/mL for 500 mg and 1000 mg doses, respectively. With multiple dosing every 8 hours in patients with normal renal function, accumulation of meropenem was not observed.

In a study involving 12 patients receiving 1000 mg meropenem every 8 hours after surgery for intra-abdominal infections, C_max and half-life values were consistent with those in healthy individuals, but the volume of distribution was larger (27 L).

Distribution

The mean plasma protein binding of meropenem is approximately 2% and is independent of drug concentration. After rapid administration (5 minutes or less), the pharmacokinetics are biexponential, but this is much less evident after a 30-minute infusion. Meropenem has been shown to penetrate well into various body fluids and tissues, including lungs, bronchial secretions, bile, cerebrospinal fluid, female genital tissues, skin, fascia, muscle, and peritoneal exudates.

Metabolism

Meropenem is metabolized by hydrolysis of the β-lactam ring, forming a microbiologically inactive metabolite. In vitro, meropenem shows reduced susceptibility to hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem, and therefore co-administration with a DHP-I inhibitor is not required.

Elimination

Meropenem is primarily eliminated unchanged by the kidneys; approximately 70% (50–75%) of the administered dose is excreted unchanged within 12 hours. An additional 28% is excreted as the microbiologically inactive metabolite. Fecal excretion accounts for only about 2% of the dose. Measured renal clearance and the effect of probenecid indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment

Renal dysfunction results in higher plasma AUC values and a prolonged half-life for meropenem. AUC increased 2.4-fold in patients with moderate renal impairment (creatinine clearance (CrCl) 33–74 mL/min), 5-fold in patients with severe renal impairment (CrCl 4–23 mL/min), and 10-fold in patients on hemodialysis (CrCl <2 mL/min), compared to healthy subjects (CrCl >80 mL/min). AUC values for the microbiologically inactive open-ring metabolite were also significantly increased in patients with renal impairment. Dose adjustment is recommended for patients with moderate and severe renal impairment (see section "Posology and method of administration").

Meropenem is removed by hemodialysis, with a clearance during hemodialysis approximately 4 times higher than in anuric patients.

Hepatic impairment

Studies in patients with alcoholic cirrhosis show no effect of liver disease on the pharmacokinetics of meropenem after repeated dosing.

Adult patients

Pharmacokinetic studies in patients have not revealed significant pharmacokinetic differences compared to healthy individuals with similar renal function. A population model developed from data in 79 patients with intra-abdominal infection or pneumonia showed dependence of key parameters on body weight, creatinine clearance, and age.

Children

Pharmacokinetic studies in infants and children with infection, receiving doses of 10, 20, and 40 mg/kg, demonstrated C_max values approaching those observed in adults after 500, 1000, and 2000 mg doses, respectively. Comparison revealed pharmacokinetic characteristics across doses and half-lives similar to those in adults, except in the youngest patients (<6 months, t_1/2 1.6 hours). Mean meropenem clearance values were 5.8 mL/min/kg (6–12 years), 6.2 mL/min/kg (2–5 years), 5.3 mL/min/kg (6–23 months), and 4.3 mL/min/kg (2–5 months). Approximately 60% of the dose is excreted in urine within 12 hours as meropenem, and an additional 12% as the metabolite. Meropenem concentrations in cerebrospinal fluid in children with meningitis are approximately 20% of simultaneous plasma concentrations, although considerable inter-individual variability exists.

Pharmacokinetics of meropenem in neonates receiving antibacterial treatment showed higher clearance in neonates with greater chronological or gestational age, with an overall mean half-life of 2.9 hours. Monte Carlo simulations based on the population pharmacokinetic model indicated that with a dosing regimen of 20 mg/kg every 8 hours, T>MIC of 60% against P. aeruginosa was achieved in 95% of preterm neonates and 91% of term neonates.

Elderly patients

Pharmacokinetic studies in healthy elderly individuals (65–80 years) showed reduced plasma clearance, correlating with age-related decline in creatinine clearance, and a slight reduction in non-renal clearance. Dose adjustment is not required in elderly patients, except in cases of moderate or severe renal impairment.

Clinical characteristics.

Indications.

The drug is indicated for the treatment of the following infections in adults and children aged 3 months and older:

• severe pneumonia, including hospital-acquired and ventilator-associated pneumonia;
• bronchopulmonary infections in cystic fibrosis;
• complicated urinary tract infections;
• complicated intra-abdominal infections;
• obstetrical infections and postpartum infections;
• complicated skin and soft tissue infections;
• acute bacterial meningitis.

The drug may be used for treatment of patients with neutropenia and fever suspected to be caused by bacterial infection.

Treatment of patients with bacteremia associated or potentially associated with any of the above-mentioned infections.

Official recommendations regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the drug.

Hypersensitivity to any other antibacterial agent of the carbapenem group.

Severe hypersensitivity (e.g., anaphylactic reactions, severe skin reactions) to any other type of β-lactam antibacterial agent (e.g., penicillins or cephalosporins).

Interaction with other medicinal products and other forms of interaction.

Studies on interaction of the drug with other medicinal products, except probenecid, have not been conducted.

Probenecid competes with meropenem for active tubular secretion and thereby inhibits renal excretion of meropenem, resulting in prolonged elimination half-life and increased plasma concentration of meropenem. Caution should be exercised when probenecid is administered concomitantly with meropenem.

The potential effect of meropenem on protein binding or metabolism of other drugs has not been studied. However, since protein binding is minimal, interactions with other compounds via this mechanism are unlikely.

Decreased serum levels of valproic acid have been reported when co-administered with carbapenems, resulting in approximately 60–100% reduction within about 2 days. Due to the rapid onset and extent of this reduction, concomitant administration of valproic acid/sodium valproate/valpromide and carbapenems is considered non-adjustable; therefore, such interaction should be avoided (see section "Special precautions for use").

Oral anticoagulants

Concomitant administration of antibiotics with warfarin may enhance its anticoagulant effect. Numerous reports have documented increased anticoagulant effect of oral anticoagulants, including warfarin, in patients receiving antibiotics concomitantly. The risk may vary depending on the type of underlying infection, age, and general condition of the patient, thus making it difficult to assess the exact contribution of antibiotics to the increase in INR (International Normalized Ratio). Frequent monitoring of INR levels is recommended during and immediately after concomitant use of antibiotics with oral anticoagulants.

Children

All drug interaction studies have been conducted in adults only.

Special precautions for use

When selecting meropenem as a treatment option, consideration should be given to the appropriateness of using a carbapenem-class antibacterial agent, taking into account factors such as the severity of infection, prevalence of resistance to other suitable antibacterial agents, and the risk of selecting carbapenem-resistant bacteria.

Resistance in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter

In the European Union, resistance to penems among Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter varies. Local resistance patterns of these bacteria to penems should be considered when prescribing the drug.

Hypersensitivity reactions

As with other β-lactam antibiotics, serious, and sometimes fatal, hypersensitivity reactions have been reported (see sections "Contraindications" and "Side effects").

Patients with a history of hypersensitivity to carbapenems, penicillins, or other β-lactam antibiotics may also exhibit hypersensitivity to meropenem. A careful patient history regarding previous hypersensitivity reactions to β-lactam antibiotics should be obtained prior to initiating meropenem therapy.

If a severe allergic reaction occurs, the drug should be discontinued immediately and appropriate measures initiated.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, and acute generalized exanthematous pustulosis, have been reported in patients receiving meropenem therapy (see section "Side effects"). If signs or symptoms suggestive of these reactions occur, meropenem should be discontinued immediately and alternative therapy considered.

Hypersensitivity reactions to other beta-lactam antibiotics have been reported to progress to Kounis syndrome (acute allergic coronary artery spasm that may lead to myocardial infarction; see section "Side effects").

Rhabdomyolysis

Cases of rhabdomyolysis have been reported during meropenem use. If signs or symptoms of rhabdomyolysis occur, meropenem should be discontinued and appropriate therapy initiated (see section "Side effects").

Antibiotic-associated colitis

Cases of antibiotic-associated colitis and pseudomembranous colitis, with severity ranging from mild to life-threatening, have been reported with nearly all antibacterial agents, including meropenem. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or following meropenem therapy (see section "Side effects"). Discontinuation of meropenem and initiation of specific therapy directed against Clostridium difficile should be considered. Medicinal products that suppress intestinal peristalsis should not be prescribed.

Seizures

Seizures have been reported rarely during treatment with carbapenems, including meropenem (see section "Side effects").

Drug-induced liver injury (DILI)

Liver function should be closely monitored during meropenem therapy due to the risk of drug-induced liver injury (DILI) (see section "Side effects"). If severe DILI develops, discontinuation of treatment should be considered if clinically appropriate. Re-administration of meropenem should only be considered if its use is deemed clearly necessary.

Use in patients with hepatic disease: Liver function should be closely monitored in patients with pre-existing liver disease during meropenem therapy. Dose adjustment is not required (see section "Dosage and administration").

Seroconversion in the direct antiglobulin test (Coombs test)

Meropenem therapy may result in a positive direct and/or indirect Coombs test.

Concomitant use of meropenem and valproic acid/sodium valproate/valpromide is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

The product contains approximately 4.0 mEq of sodium per 1 g dose, which should be taken into account when prescribing the drug to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of meropenem in pregnant women are limited or lacking.

Animal studies have not shown direct or indirect reproductive toxicity. As a precautionary measure, it is advisable to avoid using meropenem during pregnancy.

Breastfeeding

A small amount of meropenem passes into human breast milk. Meropenem may be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant.

Ability to affect reaction speed when driving or operating machinery.

Studies on the influence of the drug on the ability to drive vehicles or operate machinery have not been conducted.

When driving or operating machinery, caution should be exercised due to the possibility of developing headache, paresthesia, or seizures, which have been reported during meropenem use.

Dosage and Administration

Dosage

The tables below provide general recommendations for dosage of the medicinal product.

The dose of meropenem and duration of treatment depend on the type of causative pathogen, severity of the infection, and the patient's response to therapy.

The use of the drug at a dose of up to 2 g three times daily in adults and children with body weight over 50 kg, and up to 40 mg/kg three times daily in children, may be particularly appropriate for the treatment of certain infections caused by less susceptible bacterial species (e.g. Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.) or in cases of severe infections.

Additional dosage recommendations must be followed when treating patients with renal impairment (see below).

Table 1. Recommended doses for adults and children with body weight over 50 kg

Infection	Single dose administered every 8 hours
Severe pneumonia, including hospital-acquired and ventilator-associated pneumonia	500 mg or 1 g
Respiratory tract infections in cystic fibrosis	2 g
Complicated urinary tract infections	500 mg or 1 g
Complicated intra-abdominal infections	500 mg or 1 g
Infections during childbirth and postpartum infections	500 mg or 1 g
Complicated skin and soft tissue infections	500 mg or 1 g
Acute bacterial meningitis	2 g
Treatment of febrile neutropenic patients	1 g

The drug should usually be administered as an intravenous infusion over 15 to 30 minutes.

Additionally, doses of up to 1 g may be given as an intravenous bolus injection over approximately 5 minutes. Safety data supporting administration of a 2 g dose as an intravenous bolus injection in adults are limited.

Renal impairment

Table 2. Recommended doses of the drug for adults and children weighing more than 50 kg when the patient's creatinine clearance is less than 51 ml/min

Creatinine clearance (ml/min)	Single dose (see Table 1)	Frequency
26-50	full single dose	every 12 hours
10-25	half the single dose	every 12 hours
<10	half the single dose	every 24 hours

Data supporting the use of the doses of the drug indicated in Table 2, adjusted per 2 g dose unit, are limited.

Meropenem is eliminated by hemodialysis and hemofiltration; therefore, the required dose of the drug should be administered after completion of the hemodialysis procedure.

There are no recommendations regarding established dosing for patients receiving peritoneal dialysis.

Hepatic impairment

Dose adjustment of the drug is not required for patients with hepatic impairment (see section "Special precautions").

Dosing in elderly patients

Dose adjustment is not required for elderly patients with normal renal function or with creatinine clearance values above 50 mL/min.

Children under 3 months of age

There are no data on the safety and efficacy of meropenem in children under 3 months of age, and the optimal dosing regimen has not been established. Limited pharmacokinetic data support the use of a meropenem dose of 20 mg/kg every 8 hours (see section "Pharmacokinetics").

Table 3. Recommended doses of the drug for children aged from 3 months to 11 years and with body weight below 50 kg

Infection	Single dose administered every 8 hours
Severe pneumonia, including hospital-acquired and ventilator-associated pneumonia	10 or 20 mg/kg body weight
bronchopulmonary infections in cystic fibrosis	40 mg/kg body weight
Complicated urinary tract infections	10 or 20 mg/kg body weight
Complicated intra-abdominal infections	10 or 20 mg/kg body weight
Complicated skin and soft tissue infections	10 or 20 mg/kg body weight
Acute bacterial meningitis	40 mg/kg body weight
Treatment of patients with febrile neutropenia	20 mg/kg body weight

Children with body weight more than 50 kg

The dose should be applied as for adult patients.

There is no experience with the use of the drug in children with impaired renal function.

Method of administration

The drug is usually administered as an intravenous infusion lasting from 15 to 30 minutes. Additionally, doses of meropenem up to 20 mg/kg may be administered as an intravenous bolus injection over approximately 5 minutes. Safety data supporting administration of the drug as an intravenous bolus injection at a dose of 40 mg/kg in children are limited.

Preparation for intravenous bolus injection

The solution for bolus injection should be prepared by dissolving the medicinal product in water for injections to obtain a concentration of 50 mg/mL.

Chemical and physical stability of the prepared solution for bolus injection has been demonstrated for 3 hours at temperatures up to 25 °C or for 12 hours under refrigeration (2–8 °C).

From a microbiological standpoint, if the method of opening/reconstitution/dilution does not exclude the risk of microbial contamination, the medicinal product should be used immediately.

If the medicinal product is not used immediately, the storage period and conditions of the prepared solution should be carefully controlled.

Preparation for intravenous infusion

The infusion solution should be prepared by dissolving the medicinal product in 0.9% sodium chloride infusion solution or in 5% glucose (dextrose) infusion solution to obtain a concentration of 1–20 mg/mL.

Chemical and physical stability of the prepared infusion solution using 0.9% sodium chloride solution has been demonstrated for 3 hours at 25 °C or for 24 hours under refrigeration (2–8 °C). From a microbiological standpoint, the medicinal product should be used immediately. If the medicinal product is not used immediately, the storage period and conditions of the prepared solution should be carefully controlled.

The solution prepared with 5% glucose (dextrose) should be used immediately.

Prepared solutions should not be frozen.

Children

The drug may be administered to children aged from 3 months.

Overdose

Relative overdose is possible in patients with impaired renal function if the dose of the drug is not adjusted as described in the section "Dosage and administration". Limited post-marketing experience with the drug suggests that if adverse reactions occur after overdose, they are consistent with the profile of the adverse reactions listed in the section "Adverse reactions" and are generally mild in severity and resolve after discontinuation or dose reduction of the drug. Symptomatic treatment should be considered.

In individuals with normal renal function, the drug is rapidly eliminated by the kidneys.

Haemodialysis removes meropenem and its metabolites from the body.

Adverse Reactions

In the review of data from 4872 out of 5026 patients regarding the impact of meropenem treatment, the most frequently reported adverse reactions associated with meropenem use were diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), and injection site inflammation (1.1%). The most commonly reported laboratory abnormalities associated with meropenem use were thrombocytosis (1.6%) and elevated liver enzymes (1.5–4.3%).

In the table below, all adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations – uncommon: oral and vaginal candidiasis.

Blood and lymphatic system disorders – common: thrombocytosis; uncommon: eosinophilia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system disorders – uncommon: angioedema, anaphylactic reaction (see sections “Contraindications” and “Special precautions”).

Nervous system disorders – common: headache; uncommon: paraesthesia; rare: seizures (see section “Special precautions”).

Psychiatric disorders – rare: delirium.

Gastrointestinal disorders – common: diarrhea, vomiting, nausea, abdominal pain; uncommon: antibiotic-associated colitis (see section “Special precautions”).

Hepatobiliary and pancreatic disorders – common: increased transaminase levels, increased alkaline phosphatase levels in blood, increased lactate dehydrogenase levels in blood; uncommon: increased blood bilirubin levels; uncommon: drug-induced liver injury (DILI)*.

Metabolism and nutrition disorders – uncommon: hypokalemia.

Skin and subcutaneous tissue disorders – common: rash, pruritus; uncommon: urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme; frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (see section “Special precautions”).

Musculoskeletal and connective tissue disorders – frequency not known: rhabdomyolysis.

Renal and urinary disorders – uncommon: increased blood creatinine levels, increased blood urea levels.

General disorders and administration site conditions – common: inflammation, pain; uncommon: thrombophlebitis, injection site pain.

*DILI includes hepatitis and liver failure.

There are no data suggesting an increased risk of adverse reactions in children based on the limited available data. All reported cases corresponded to adverse reactions observed in adult patients.

Description of selected adverse reactions

Kounis syndrome

Cases of acute coronary syndrome associated with allergic reaction (Kounis syndrome) have been reported during treatment with other beta-lactam antibiotics (see section “Special precautions”).

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children. Do not freeze the reconstituted solution.

Each vial is for single use only.

Standard aseptic techniques should be used during solution preparation and administration.

The solution should be shaken before use.

Any unused product or waste material must be disposed of in accordance with local requirements.

Incompatibilities. The medicinal product must not be mixed or combined with other medicinal products.

The preparation intended for intravenous bolus injection should be reconstituted with sterile water for injection.

Meropenem in vials for intravenous infusion may be directly reconstituted in 0.9% sodium chloride solution or 5% glucose solution for infusion.

Packaging. 1 vial per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Venus Remedies Limited.

Manufacturer's address and site of operation.

Hill Top Industrial Estate, Jarmajri, EPIC Phase-I (Ext), Bhatoli Kalan, Baddi, Distt. Solan, Himachal Pradesh, 173205, India.