Ceftazidime abryl

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ceftazidime Abryl Ceftazidime Abryl

Composition:

Active substance: ceftazidime;

1 vial contains 500 mg or 1000 mg of ceftazidime (as ceftazidime pentahydrate);

Excipient: sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white to light yellow powder.

Pharmacotherapeutic group.

Antibacterial agent for systemic use. Third-generation cephalosporins.

ATC code J01D D02.

Pharmacological properties.

Pharmacodynamics.

Ceftazidime is a bactericidal cephalosporin antibiotic whose mechanism of action is related to inhibition of bacterial cell wall synthesis.

Acquired resistance to the antibiotic varies across different regions and may change over time, with significant differences possible among individual strains. It is advisable to use local (regional) data on antibiotic susceptibility, especially when treating severe infections.

Susceptible microorganisms

Gram-positive aerobes: Streptococcus pyogenes, Streptococcus agalactiae.

Gram-negative aerobes: Citrobacter koseri, Escherichia coli, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Proteus mirabilis, Proteus spp., Providencia spp.

Strains with possible acquired resistance

Gram-negative aerobes: Acinetobacter baumannii, Burkholderia cepacia, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Klebsiella spp., Pseudomonas aeruginosa, Serratia spp., Morganella morganii.

Gram-positive aerobes: Staphylococcus aureus, Staphylococcus pneumoniae.

Gram-positive anaerobes: Clostridium perfringens, Peptococcus spp., Peptostreptococcus spp.

Gram-negative anaerobes: Fusobacterium spp.

Resistant microorganisms

Gram-positive aerobes: Enterococcus spp., including E. faecalis and E. faecium, Listeria spp.

Gram-positive anaerobes: Clostridium difficile.

Gram-negative anaerobes: Bacteroides spp., including B. fragilis.

Others: Chlamydia spp., Mycoplasma spp., Legionella spp.

Pharmacokinetics.

After intramuscular injection of 500 mg and 1000 mg, mean peak plasma concentrations of 18 and 37 mg/L, respectively, are rapidly achieved in patients. Within 5 minutes after intravenous bolus administration of 500 mg, 1000 mg, or 2000 mg, mean serum concentrations of 46, 87, or 170 mg/L, respectively, are achieved. Therapeutically effective concentrations persist in serum for up to 8–12 hours after intravenous or intramuscular administration. Plasma protein binding is approximately 10%. Concentrations of ceftazidime exceeding the minimum inhibitory concentration (MIC) for most common pathogenic microorganisms are achieved in tissues and fluids such as bone, heart, bile, sputum, intraocular, synovial, pleural, and peritoneal fluids. Ceftazidime rapidly crosses the placenta and is excreted into breast milk. The drug poorly penetrates the intact blood-brain barrier; in the absence of inflammation, drug concentrations in the central nervous system (CNS) are low. However, during meningitis, ceftazidime concentrations in the CNS range from 4 to 20 mg/L or higher, which corresponds to therapeutic levels.

Ceftazidime is not metabolized in the body. After parenteral administration, high and sustained serum concentrations of ceftazidime are achieved. The elimination half-life is approximately 2 hours. The drug is excreted unchanged, in active form, in urine via glomerular filtration; approximately 80–90% of the dose is recovered in urine within 24 hours. In patients with impaired renal function, elimination of ceftazidime is reduced, and dosage adjustment is required. Less than 1% of the drug is excreted in bile, significantly limiting the amount reaching the intestine.

Clinical characteristics.

Indications.

Treatment of the following infections in adults and children, including newborns:

• hospital-acquired pneumonia;
• respiratory tract infections in patients with cystic fibrosis;
• bacterial meningitis;
• chronic suppurative otitis media;
• malignant external otitis;
• complicated urinary tract infections;
• complicated skin and soft tissue infections;
• complicated intra-abdominal infections;
• bone and joint infections;
• peritonitis associated with dialysis in patients undergoing continuous ambulatory peritoneal dialysis.

Treatment of bacteremia arising in patients as a result of any of the above-mentioned infections.

Ceftazidime may be used for the treatment of patients with neutropenia and fever caused by bacterial infection.

Ceftazidime may be used for prophylaxis of urinary tract infections during urological procedures (transurethral resection of the prostate).

When prescribing ceftazidime, its antibacterial spectrum, primarily directed against aerobic Gram-negative bacteria, should be taken into account.

Ceftazidime should be used in combination with other antibacterial agents if microorganisms causing the infection are expected to be outside the spectrum of ceftazidime activity.

The drug should be prescribed in accordance with current official guidelines on the use of antibacterial agents.

Contraindications.

Hypersensitivity to ceftazidime or to any of the excipients of the medicinal product.

Hypersensitivity to other cephalosporin antibiotics.

History of severe hypersensitivity (e.g., anaphylactic reactions) to other β-lactam antibiotics (penicillins, monobactams, and carbapenems).

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of high doses of the drug with nephrotoxic medicinal products may adversely affect renal function.

Chloramphenicol is an in vitro antagonist of ceftazidime and other cephalosporins. The clinical significance of this phenomenon is unknown; however, if concomitant use of Ceftazidime Abryl with chloramphenicol is considered, the possibility of antagonism should be taken into account.

Like other antibiotics, Ceftazidime Abryl may affect intestinal flora, leading to reduced reabsorption of estrogens and decreased efficacy of combined oral contraceptives.

Ceftazidime does not interfere with enzymatic methods for glucose in urine testing; however, a minor interference may be observed when using copper reduction methods (Benedict, Fehling, Clinistix).

Ceftazidime does not interfere with the alkaline picrate method for creatinine determination.

Special precautions for use

Severe skin adverse reactions (SSARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported during treatment with ceftazidime. These reactions may be life-threatening or fatal and occur with an "unknown" frequency.

Patients should be informed about the signs and symptoms, and closely monitored for skin reactions.

If signs or symptoms suggestive of these reactions occur, ceftazidime should be discontinued immediately, and alternative therapy should be considered.

If a serious reaction such as SJS, TEN, DRESS, or AGEP develops during treatment with ceftazidime, ceftazidime therapy must never be restarted.

As with other β-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, ceftazidime therapy should be discontinued immediately and appropriate emergency measures initiated.

Prior to initiating therapy, patients should be questioned about previous hypersensitivity reactions to ceftazidime, cephalosporin antibiotics, or other β-lactam antibiotics. The drug should be administered with caution to patients who have experienced non-severe hypersensitivity reactions to other β-lactam antibiotics (see section "Contraindications").

Ceftazidime has a limited antibacterial spectrum. It is not an appropriate agent for monotherapy of certain types of infections, except when the causative pathogen is known to be susceptible to this drug or when there is a high likelihood that the likely pathogen will be susceptible to ceftazidime. This is particularly important when considering treatment of patients with bacteremia, bacterial meningitis, skin and soft tissue infections, or bone and joint infections. Additionally, ceftazidime is susceptible to hydrolysis by certain extended-spectrum β-lactamases. Therefore, when selecting ceftazidime for treatment, information on the prevalence of microorganisms producing extended-spectrum β-lactamases should be taken into account.

Concomitant administration of high doses of cephalosporins and nephrotoxic agents such as aminoglycosides or potent diuretics (e.g., furosemide) may adversely affect renal function. Clinical experience with ceftazidime has shown that this phenomenon is unlikely when recommended dosages are followed. There are no data indicating that ceftazidime at usual therapeutic doses adversely affects renal function.

Ceftazidime is eliminated by the kidneys; therefore, the dose should be reduced according to the degree of renal impairment. Cases of neurological complications have been reported when the dose was not appropriately reduced.

As with other broad-spectrum antibiotics, prolonged treatment with Ceftazidime Abryl may result in overgrowth of non-susceptible microorganisms (e.g., Candida, Enterococci); in such cases, discontinuation of therapy or other necessary interventions may be required. Careful ongoing monitoring of the patient is essential.

Cases of pseudomembranous colitis, ranging in severity from mild to life-threatening, have been reported with antibiotic use. It is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic therapy. In cases of persistent or severe diarrhea, or if abdominal cramps occur, treatment should be discontinued immediately, further diagnostic evaluation performed, and specific therapy for Clostridium difficile initiated if necessary. Medicinal products that inhibit intestinal motility should not be administered.

As with other broad-spectrum cephalosporins and penicillins, some previously susceptible strains of Enterobacter spp. and Serratia spp. may become resistant during ceftazidime therapy. In such cases, periodic susceptibility testing should be performed.

Ceftazidime Abryl contains sodium (one vial containing 500 mg ceftazidime contains 26 mg sodium; one vial containing 1000 mg ceftazidime contains 52 mg sodium), which should be taken into account when treating patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Data on ceftazidime use in pregnant women are limited. The drug should be administered during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.

Ceftazidime is excreted in breast milk in small amounts, but no effect on the breastfed infant is expected with therapeutic doses. Ceftazidime may be used during breastfeeding.

Ability to influence reaction speed when driving or operating machinery

No specific studies have been conducted. However, adverse reactions such as dizziness may affect the ability to drive or operate machinery (see section "Adverse reactions").

Method of administration and dosage.

Adults and children ≥ 40 kg

Table 1

Intermittent administration
Infection	Dose administered
respiratory tract infections in patients with cystic fibrosis	100-150 mg/kg body weight per day every 8 hours, up to a maximum of 9000 mg per day1
febrile neutropenia	2000 mg every 8 hours
hospital-acquired pneumonia
bacterial meningitis
bacteremia*
bone and joint infections	1000-2000 mg every 8 hours
complicated skin and soft tissue infections
complicated intra-abdominal infections
peritonitis associated with continuous ambulatory peritoneal dialysis
complicated urinary tract infections	1000-2000 mg every 8 or 12 hours
prophylaxis of infectious complications during prostate surgery (transurethral resection)	1000 mg during anesthesia induction, 1000 mg at the time of catheter removal
chronic otitis media	1000-2000 mg every 8 hours
malignant external otitis
Continuous infusion
Infection	Dose administered
febrile neutropenia	A loading dose of 2000 mg is administered, followed by continuous infusion of 4000 mg to 6000 mg every 24 hours1
hospital-acquired pneumonia
respiratory tract infections in patients with cystic fibrosis
bacterial meningitis
bacteremia*
bone and joint infections
complicated skin and soft tissue infections
complicated intra-abdominal infections
peritonitis associated with continuous ambulatory peritoneal dialysis
1 In adult patients with normal renal function, 9000 mg per day has been used without adverse reactions.

Children < 40 kg

Table 2

Infants and children aged > 2 months and body weight < 40 kg	Infection	Usual dose
Intermittent administration
	complicated urinary tract infections	100–150 mg/kg body weight per day in 3 divided doses, maximum 6000 mg per day
	chronic otitis media
	malignant external otitis
	neutropenia in children	150 mg/kg body weight per day in 3 divided doses, maximum 6000 mg per day
	respiratory tract infections in patients with cystic fibrosis
	bacterial meningitis
	bacteraemia*
	bone and joint infections	100–150 mg/kg body weight per day in 3 divided doses, maximum 6000 mg per day
	complicated skin and soft tissue infections
	complicated intra-abdominal infections
	peritonitis associated with continuous ambulatory peritoneal dialysis
Continuous infusion
	febrile neutropenia	A loading dose of 60–100 mg/kg body weight is administered, followed by continuous infusion of 100–200 mg/kg body weight per day, up to a maximum of 6000 mg per day
	hospital-acquired pneumonia
	respiratory tract infections in patients with cystic fibrosis
	bacterial meningitis
	bacteraemia*
	bone and joint infections
	complicated skin and soft tissue infections
	complicated intra-abdominal infections
	peritonitis associated with continuous ambulatory peritoneal dialysis
Infants aged ≤ 2 months	Infection	Usual dose
Intermittent administration
	Most infections	25–60 mg/kg body weight per day in 2 divided doses1
1In infants and children aged ≤ 2 months, the serum half-life may be 2–3 times longer than in adults

* If this is related to the infections listed in the section "Indications" or if such infections are suspected.

Children

The safety and efficacy of administering Ceftazidime Abryl by continuous intravenous infusion to infants and children ≤ 2 months of age have not been established.

Geriatric patients

Due to reduced ceftazidime clearance, the daily dose for elderly patients with acute infections should generally not exceed 3000 mg, particularly in patients aged 80 years and older.

Hepatic impairment

Dosage adjustment is not required for patients with mild to moderate hepatic impairment. Clinical studies in patients with severe hepatic impairment have not been conducted. Careful medical monitoring is recommended.

Renal impairment

Ceftazidime is excreted unchanged by the kidneys. Therefore, the dose should be reduced in patients with impaired renal function.

The initial dose should be 1000 mg. The maintenance dose should be based on glomerular filtration rate.

Recommended maintenance doses of ceftazidime in renal impairment – intermittent administration

Adults and children ≥ 40 kg body weight

Table 3

Creatinine clearance, mL/min	Approximate serum creatinine level, µmol/L (mg/dL)	Recommended single dose of ceftazidime, mg	Dosing interval, hours
50-31	150-200 (1.7-2.3)	1000	12
30-16	200-350 (2.3-4)	1000	24
15-6	350-500 (4-5.6)	500	24
< 5	> 500 (> 5.6)	500	48

For patients with severe infections, the single dose may be increased by 50% or the frequency of administration correspondingly increased. For such patients, monitoring of serum ceftazidime levels is recommended.

In children, creatinine clearance should be adjusted according to body surface area or body weight.

Children < 40 kg

Table 4

Creatinine clearance, mL/min**	Approximate serum creatinine level*, µmol/L (mg/dL)	Recommended individual dose mg/kg body weight	Dosing frequency, hours
50-31	150-200 (1.7-2.3)	25	12
30-16	200-350 (2.3-4)	25	24
15-6	350-500 (4-5.6)	12.5	24
< 5	> 500 (> 5.6)	12.5	48

* Serum creatinine levels calculated according to recommendations may not precisely reflect the degree of renal function impairment in all patients with renal insufficiency.

** Creatinine clearance calculated based on body surface area or measured.

Close medical monitoring is recommended.

Recommended maintenance doses of ceftazidime in renal insufficiency – continuous infusion

Adults and children ≥ 40 kg body weight

Table 5

Creatinine clearance, ml/min	Approximate serum creatinine level, µmol/L (mg/dL)	Dosing frequency (hours)
50–31	150–200 (1.7–2.3)	A loading dose of 2000 mg is administered, followed by continuous infusion of 1000 mg to 3000 mg every 24 hours
30–16	200–350 (2.3–4)	A loading dose of 2000 mg is administered, followed by continuous infusion of 1000 mg every 24 hours
≤ 15	> 350 (4–5.6)	Not studied

Dose selection should be cautious. Careful medical monitoring is recommended.

Children < 40 kg

The safety and efficacy of administering Ceftazidime Abri by continuous intravenous infusion in children with body weight < 40 kg and impaired renal function have not been established. Careful medical monitoring is recommended.

If continuous intravenous infusion of the drug is required in children with impaired renal function, creatinine clearance should be adjusted according to the child's body surface area or body weight.

Hemodialysis

The serum half-life of ceftazidime during hemodialysis ranges from 3 to 5 hours.

A maintenance dose of ceftazidime, as recommended in Table 6, should be administered after each hemodialysis session.

Peritoneal dialysis

Ceftazidime can be used during peritoneal dialysis, including continuous ambulatory peritoneal dialysis (CAPD).

In addition to intravenous administration, ceftazidime may be added to the dialysis fluid (usually 125 to 250 mg per 2 L of dialysis solution).

For patients with renal insufficiency undergoing prolonged arteriovenous hemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 1000 mg daily as a single dose or divided doses. For low-flux hemofiltration, doses should be adjusted as in renal impairment.

For patients undergoing venovenous hemofiltration and venovenous hemodialysis, dosing recommendations are provided in Tables 6 and 7.

Dosing recommendations for ceftazidime in patients undergoing prolonged

venovenous hemofiltration

Table 6

Residual renal function (creatinine clearance, ml/min)	Maintenance dose (mg) according to ultrafiltration rate (ml/min)a
	5	16.7	33.3	50
0	250	250	500	500
5	250	250	500	500
10	250	500	500	750
15	250	500	500	750
20	500	500	500	750

The maintenance dose should be administered every 12 hours.

Dosing recommendations for ceftazidime in patients undergoing prolonged
venovenous hemodialysis

Table 7

Residual renal function (creatinine clearance, mL/min)	Supplementary dose (mg) for dialysate at flow rate (mL/min)a
	1 L/h			2 L/h
	Ultrafiltration rate (L/h)			Ultrafiltration rate (L/h)
	0.5	1	2	0.5	1	2
0	500	500	500	500	500	750
5	500	500	750	500	500	750
10	500	500	750	500	750	1000
15	500	750	750	750	750	1000
20	750	750	1000	750	750	1000

The maintenance dose should be administered every 12 hours.

Administration.

Ceftazidime Abryl should be administered intravenously by injection or infusion, or by deep intramuscular injection. Recommended sites for intramuscular administration are the upper outer quadrant of the gluteus maximus muscle or the lateral part of the thigh.

Solutions of ceftazidime may be administered directly into the vein or into an intravenous infusion system, if the patient is receiving parenteral fluids.

The dosage depends on the severity of the disease, susceptibility, site and type of infection, as well as on the patient's age and renal function.

Acquired resistance to the antibiotic varies in different regions and may change over time, and may differ significantly for individual strains. It is advisable to use local data on antibiotic susceptibility, especially when treating severe infections.

Instructions for Preparation

Ceftazidime Abryl is compatible with most commonly used intravenous infusion solutions. However, sodium bicarbonate for injection should not be used as a solvent (see section "Incompatibilities").

Flasks of all sizes are produced under reduced pressure. As the drug dissolves, carbon dioxide is released and pressure in the flask increases. Small bubbles of carbon dioxide in the dissolved preparation can be disregarded.

Table 8

Dose administered		Required amount of solvent (ml)	Approximate concentration (mg/ml)
500 mg	Intramuscular Intravenous bolus	1.5 5	260 90
1000 mg	Intramuscular Intravenous bolus Intravenous infusion	3 10 50*	260 90 20

* Reconstitution should be carried out in two steps (see text).

The solution color varies from light yellow to amber depending on concentration, diluent, and storage conditions. When recommendations are followed, the drug's efficacy is not affected by variations in its coloration.

Ceftazidime at concentrations from 1 mg/mL to 40 mg/mL is compatible with the following solutions: 0.9% sodium chloride solution; M/6 sodium lactate solution; Hartmann's solution; 5% glucose solution; 0.225% sodium chloride and 5% glucose solution; 0.45% sodium chloride and 5% glucose solution; 0.9% sodium chloride and 5% glucose solution; 0.18% sodium chloride and 4% glucose solution; 10% glucose solution; 10% glucose 40 and 0.9% sodium chloride solution; 10% glucose 40 and 5% glucose solution; 6% dextran 70 and 0.9% sodium chloride solution; 6% dextran 70 and 5% glucose solution.

Ceftazidime at concentrations from 0.05 mg/mL to 0.25 mg/mL is compatible with peritoneal dialysis fluid (lactate).

Ceftazidime for intramuscular administration may be dissolved in 0.5% or 1% lidocaine hydrochloride solution.

The stability of both drugs is maintained when ceftazidime at a concentration of 4 mg/mL is mixed with the following agents: hydrocortisone (hydrocortisone sodium phosphate) 1 mg/mL in 0.9% sodium chloride injection or 0.5% glucose solution; cefuroxime (cefuroxime sodium) 3 mg/mL in 0.9% sodium chloride injection; cloxacillin (cloxacillin sodium) 4 mg/mL in 0.9% sodium chloride injection; heparin 10 IU/mL or 50 IU/mL in 0.9% sodium chloride injection; potassium chloride 10 mEq/L or 40 mEq/L in 0.9% sodium chloride injection.

The contents of the vial of Abryl Ceftazidime 500 mg, reconstituted with 1.5 mL of water for injection, may be added to a solution of metronidazole (500 mg in 100 mL), and both drugs retain their activity.

Preparation of solutions for intramuscular or intravenous bolus injection

1. Insert the needle of the syringe through the vial stopper and add the recommended volume of diluent.
2. Remove the syringe needle and shake the vial until a clear solution is obtained.
3. Invert the vial. With the syringe plunger fully depressed, insert the needle into the vial. Withdraw the entire solution into the syringe, keeping the needle tip submerged in the solution at all times. Small bubbles of carbon dioxide may be disregarded.

Preparation of solutions for intravenous infusion (1000 mg vials)

1. Insert the needle of the syringe through the vial stopper and add 10 mL of diluent.
2. Remove the syringe needle and shake the vial until a clear solution is obtained.
3. Do not insert an air vent needle through the stopper until the drug is completely dissolved. Insert an air vent needle through the stopper into the vial to relieve internal pressure.
4. Without removing the air vent needle, adjust the total volume to 50 mL. Remove the air vent needle, shake the vial, and set up the infusion system as usual.

To ensure sterility of the preparation, it is essential not to insert the air vent needle through the stopper before the drug is fully dissolved.

The prepared solution may be stored for up to 24 hours at temperatures below 25°C or for up to 7 days at temperatures up to 4°C.

Children.

May be administered to children from the first days of life.

Overdose.

Overdose may lead to neurological complications such as encephalopathy, seizures, and coma. Symptoms of overdose may occur in patients with renal impairment if the dose is not appropriately reduced (see sections "Dosage and Administration" and "Special Warnings and Precautions for Use"). Serum concentrations of ceftazidime can be reduced by hemodialysis or peritoneal dialysis.

Adverse reactions.

Infections and infestations: candidiasis (including vaginitis and aphthous stomatitis).

Blood system disorders: eosinophilia, thrombocytosis, leukopenia, neutropenia, thrombocytopenia, lymphocytosis, hemolytic anemia, and agranulocytosis.

Immune system disorders: anaphylaxis (including bronchospasm and/or arterial hypotension).

Nervous system disorders: dizziness, headache, paresthesia.

Neurological complications such as tremor, myoclonia, seizures, encephalopathy, and coma have been reported in patients with renal impairment who did not receive appropriately reduced doses of ceftazidime.

Cardiovascular system disorders: phlebitis or thrombophlebitis at the injection site.

Gastrointestinal disorders: diarrhea, nausea, vomiting, abdominal pain, and colitis, taste disturbances.

As with other cephalosporins, colitis may be related to Clostridium difficile and may manifest as pseudomembranous colitis.

Renal and urinary disorders: interstitial nephritis, acute renal failure.

Hepatobiliary disorders: transient elevation of one or more liver enzymes (ALT, AST, LDH, GGT, alkaline phosphatase), jaundice.

Skin and subcutaneous tissue disorders: maculopapular rash or urticaria, pruritus, angioneurotic edema, polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP).

General disorders and administration site conditions: pain and/or inflammation at the site of intramuscular injection, fever.

Laboratory findings: positive Coombs test; as with some other cephalosporins, transient elevations in blood urea, blood urea nitrogen, and/or serum creatinine have occasionally been observed.

A positive Coombs test occurs in approximately 5% of patients and may interfere with blood grouping.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Incompatibilities.

Ceftazidime Abryl is less stable in solutions of injectable sodium bicarbonate than in other intravenous infusion solutions and therefore is not recommended as a solvent.

Ceftazidime and aminoglycosides should not be mixed in the same infusion system or syringe.

Instances of precipitate formation have been observed when vancomycin was added to a solution of ceftazidime. Therefore, it is recommended to flush infusion systems and intravenous catheters between administration of these two agents.

Packaging.

1 vial per cardboard pack.

Prescription status. Prescription only.

Manufacturer.

Nectar Lifesciences Limited.

Manufacturer's address and location of business operations.

Unit-VI, Village Bhatolikalan, near Jharmajri E.P.I.P., P.O. Barotiwala, Tehsil Nalagarh, District Solan, Himachal Pradesh, 173205, India.