Coact

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KOACT (Koact)

Composition:

Active substances: amoxicillin and clavulanic acid;

One film-coated tablet contains amoxicillin (equivalent to amoxicillin trihydrate) 500 mg and clavulanic acid (equivalent to potassium clavulanate) 125 mg;

Excipients: sodium starch glycolate (type A), microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate, Opadry white 06B58855(HIS): (hypromellose 5 cP, titanium dioxide (E 171), polyethylene glycol PEG 400, hypromellose 15 cP), isopropyl alcohol, methylene chloride, purified water.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: white or almost white oval film-coated tablets with the imprint “A” on one side and “64” on the other side.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Beta-lactam antibiotics, penicillins. Combinations of penicillins with beta-lactamase inhibitors. ATC code J01CR02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Amoxicillin is a semisynthetic antibiotic of the penicillin class (a beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins (PBPs)) involved in the biosynthesis of bacterial peptidoglycan, an essential structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which typically results in cell lysis and death.

Amoxicillin is susceptible to beta-lactamases produced by resistant bacteria and is degraded by them; therefore, the spectrum of activity of amoxicillin does not include microorganisms that produce these enzymes.

Clavulanic acid has a beta-lactam structure similar to that of penicillins. It inactivates certain beta-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid itself does not possess clinically significant antibacterial activity.

Pharmacokinetic/pharmacodynamic relationship

The duration of time during which the drug concentration remains above the minimum inhibitory concentration (T> MIC) is considered the primary factor determining the efficacy of amoxicillin.

Mechanisms of resistance

The two main mechanisms of resistance to amoxicillin/clavulanic acid are:

• Inactivation by bacterial beta-lactamases mentioned above, which are not inhibited by clavulanic acid, including enzymes of class B, C, and D;
• Modification of PBPs, leading to reduced affinity of the antibacterial agent for its target.

Impermeability of bacteria or efflux pump mechanisms may contribute to or cause bacterial resistance, particularly in Gram-negative bacteria.

Breakpoints

The minimum inhibitory concentration (MIC) breakpoints for amoxicillin/clavulanic acid established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Microorganisms	Breakpoints of sensitivity (μg/ml)
	Sensitive	Intermediate	Resistant
Haemophilus influenzae 1	≤ 1	-	> 1
Moraxella catarrhalis 1	≤ 1	-	> 1
Staphylococcus aureus 2	≤ 2	-	> 2
Coagulase-negative staphylococci 2	≤ 0.25		> 0.25
Enterococcus 1	≤ 4	8	> 8
Streptococcus A, B, C, G 5	≤ 0.25	-	> 0.25
Streptococcus pneumoniae 3	≤ 0.5	1–2	> 2
Enterobacteriaceae 1, 4	-	-	> 8
Gram-negative anaerobic bacteria 1	≤ 4	8	> 8
Gram-positive anaerobic bacteria 1	≤ 4	8	> 8
Breakpoints not specific to individual species 1	≤ 2	4–8	> 8
1 The reported values are for amoxicillin concentration. For susceptibility testing, the concentration of clavulanic acid is set at 2 mg/L. 2 The reported values are for oxacillin concentration. 3 The breakpoints listed in the table are derived from ampicillin breakpoints. 4 The resistance breakpoint R>8 mg/L means that all strains with resistance mechanisms are classified as resistant. 5 The breakpoints listed in the table are derived from benzylpenicillin breakpoints.

The prevalence of resistance may vary geographically and over time for individual species, so local susceptibility data should be obtained, especially when treating severe infections. Expert consultation should be sought if local resistance prevalence is at a level where the benefit of using the drug is questionable, at least for certain types of infections.

Commonly susceptible organisms

Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible)£, Coagulase-negative staphylococci (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-haemolytic streptococci, Streptococcus viridans group. Gram-negative aerobes: Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae2, Moraxella catarrhalis, Pasteurella multocida. Anaerobes: Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp.

Organisms for which resistance development may be a concern

Gram-positive aerobes: Enterococcus faecium$. Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris.

Naturally resistant microorganisms

Gram-negative aerobes: Acinetobacter spp., Citrobacter freundii, Enterobacter spp., Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia. Other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.

$ Natural moderate susceptibility in the absence of acquired resistance mechanisms. £ All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid. 1 Streptococcus pneumoniae resistant to penicillin should not be treated with this formulation of amoxicillin/clavulanic acid (see sections "Special precautions for use" and "Dosage and administration"). 2 Strains with reduced susceptibility have been reported in certain EU countries with a frequency greater than 10%.

Pharmacokinetics.

Absorption. Amoxicillin and clavulanic acid are completely dissociated in aqueous solutions at physiological pH levels. Both components are rapidly and well absorbed following oral administration.

The bioavailability of amoxicillin and clavulanic acid is approximately 70% after oral administration. The plasma profiles of both components are identical, and the time to reach maximum plasma concentration (Tmax) for each component is approximately one hour.

Serum concentrations of amoxicillin and clavulanic acid achieved after administration of amoxicillin/clavulanic acid are identical to those achieved following oral administration of equivalent doses of amoxicillin or clavulanic acid given separately.

Distribution. Approximately 25% of total clavulanic acid in plasma and 18% of total amoxicillin in plasma are protein-bound. The apparent volume of distribution is approximately 0.3–0.4 L/kg for amoxicillin and about 0.2 L/kg for clavulanic acid.

After intravenous administration, amoxicillin and clavulanic acid have been detected in the gallbladder, abdominal tissue, skin, adipose tissue, muscle tissue, synovial and peritoneal fluids, bile, and pus. Amoxicillin does not distribute adequately into cerebrospinal fluid.

Animal studies have not revealed any evidence of significant retention of substances derived from any component of the drug in body tissues. Amoxicillin, like most penicillins, may be detected in breast milk. A small amount of clavulanic acid may also be detected in breast milk (see section "Use during pregnancy or breastfeeding").

It has been demonstrated that both amoxicillin and clavulanic acid cross the placental barrier (see section "Use during pregnancy or breastfeeding").

Biological transformation. Amoxicillin is partially excreted in urine as inactive penicilloic acid in amounts equivalent to 10–25% of the initial dose. Clavulanic acid is extensively metabolized in the human body and is excreted in urine and feces, as well as in the form of carbon dioxide in expired air.

Elimination. The primary route of elimination for amoxicillin is renal, whereas clavulanic acid is eliminated both via the kidneys and through extrarenal mechanisms.

In healthy volunteers, the mean elimination half-life of amoxicillin/clavulanic acid is approximately one hour, and the mean total clearance is approximately 25 L/hour.

Various studies have shown that urinary excretion amounts to 50–85% for amoxicillin and 27–60% for clavulanic acid over a 24-hour period. In the case of clavulanic acid, the greatest amount of the substance is excreted within the first 2 hours after administration.

Concomitant administration of probenecid slows the elimination of amoxicillin but does not affect the renal excretion of clavulanic acid (see section "Interaction with other medicinal products and other forms of interaction").

Age. The elimination half-life of amoxicillin is identical in children aged 3 months to 2 years, older children, and adults. For neonates (including premature infants) during the first week of life, the dosing frequency should not exceed twice daily due to immaturity of the renal elimination pathway. Since elderly patients are more likely to have decreased renal function, dosage should be selected with caution, and monitoring of renal function is recommended.

Renal impairment. Total serum clearance of amoxicillin/clavulanic acid decreases proportionally with decreasing renal function. The reduction in clearance is more pronounced for amoxicillin than for clavulanic acid, as a larger fraction of amoxicillin is eliminated by the kidneys. In renal impairment, dosing should prevent excessive accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section "Method of administration and dosage").

Hepatic impairment. The drug should be used with caution in patients with hepatic impairment, and regular monitoring of liver function is recommended.

Clinical characteristics.

Indications.

Treatment of bacterial infections in adults and children caused by microorganisms sensitive to the drug, such as:

• acute bacterial sinusitis (confirmed);
• acute otitis media;
• confirmed exacerbation of chronic bronchitis;
• community-acquired pneumonia;
• cystitis;
• pyelonephritis;
• skin and soft tissue infections, including cellulitis, animal bites, severe dentoalveolar abscesses with spreading cellulitis;
• bone and joint infections, including osteomyelitis.

Contraindications.

Hypersensitivity to the components of the drug Coact or to any agent from the penicillin group.

History of severe hypersensitivity reactions (including anaphylactoid reactions) associated with the use of other beta-lactam agents (including cephalosporins, carbapenems, or monobactams).

History of jaundice or hepatic dysfunction associated with the use of amoxicillin and clavulanic acid.

Interaction with other medicinal products and other forms of interaction.

Oral anticoagulants

Oral anticoagulants and penicillin-class antibiotics are commonly used together in clinical practice, with no widespread reports of interaction. However, cases of increased international normalized ratio (INR) have been reported in patients receiving acenocoumarol or warfarin who were prescribed a course of amoxicillin therapy. If concomitant use of these drugs is necessary, prothrombin time or INR should be closely monitored when initiating or discontinuing amoxicillin. Additionally, dosage adjustment of oral anticoagulants may be required (see sections "Special precautions for use" and "Adverse reactions").

Methotrexate

Penicillins may reduce methotrexate excretion, potentially leading to increased toxicity.

Probenecid

Concomitant use of probenecid is not recommended. Probenecid reduces renal tubular secretion of amoxicillin. Concurrent administration may result in elevated and prolonged blood levels of amoxicillin.

Mycophenolate mofetil

In patients receiving mycophenolate mofetil, initiation of oral amoxicillin with clavulanic acid may reduce the pre-dose concentration of the active metabolite mycophenolic acid by approximately 50%. This change in pre-dose levels may not fully reflect changes in total exposure to mycophenolic acid. Therefore, dosage adjustment of mycophenolate mofetil is usually not required unless there is clinical evidence of graft dysfunction. However, close monitoring is necessary during concomitant use and for some time after completion of antibiotic therapy.

Special precautions for use.

Before initiating therapy with amoxicillin/clavulanic acid, careful information should be obtained regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam agents (see sections "Contraindications" and "Side effects").

Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid reactions and severe skin reactions) have been reported in patients receiving penicillin therapy. Hypersensitivity reactions may also progress to DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) — a severe allergic reaction that may lead to myocardial infarction (see section "Side effects"). Such reactions are more likely in patients with a history of penicillin hypersensitivity and in those with atopic diseases. If an allergic reaction occurs, amoxicillin/clavulanic acid should be discontinued immediately and appropriate alternative therapy initiated.

Cases of drug-induced enterocolitis syndrome (DIES), predominantly in children receiving amoxicillin/clavulanic acid, have been reported (see section "Side effects"). Drug-induced enterocolitis syndrome is an allergic reaction characterized primarily by persistent vomiting (occurring 1–4 hours after drug administration) in the absence of allergic skin or respiratory symptoms. Additional symptoms may include abdominal pain, diarrhea, hypotension, or leukocytosis with neutrophilia. Severe cases have been documented, including progression to shock.

If infection is confirmed to be caused by microorganism(s) sensitive to amoxicillin alone, switching from amoxicillin/clavulanic acid to amoxicillin should be considered according to established guidelines.

This medicinal product should not be used when there is a high risk of pathogens with reduced susceptibility or resistance to beta-lactam agents not mediated by beta-lactamases that are sensitive to inhibition by clavulanic acid. This product should not be used for treatment of infections caused by penicillin-resistant S. pneumoniae strains.

Seizures may occur in patients with impaired renal function and in those receiving high doses of the drug (see section "Side effects").

Amoxicillin/clavulanic acid should be avoided in suspected infectious mononucleosis, as administration of amoxicillin has been associated with the development of a maculopapular rash.

Concomitant administration of allopurinol during amoxicillin therapy increases the likelihood of allergic skin reactions.

Prolonged use may occasionally lead to overgrowth of microorganisms not susceptible to the drug.

The early onset of fever-associated generalized erythema with pustule formation during treatment may indicate acute generalized exanthematous pustulosis (AGEP) (see section "Side effects"). This reaction requires immediate discontinuation of Coact and constitutes a contraindication to further use of amoxicillin.

Amoxicillin/clavulanic acid should be used with caution in patients showing signs of impaired liver function (see sections "Contraindications", "Dosage and administration", and "Side effects").

Hepatic complications have been reported, primarily in males and elderly patients, which may be associated with prolonged treatment. Reports in children are very rare. In all patient groups, symptoms usually occur during or shortly after treatment, although in some cases they may appear several weeks after completion of therapy. These events are usually reversible. Hepatic complications may be severe and, in exceptionally rare cases, fatal. Such events have almost always occurred in patients with severe underlying disease or those receiving concomitant medications known to have potential hepatotoxic effects (see section "Side effects").

Antibiotic-associated colitis, with severity ranging from mild to life-threatening, has been reported with nearly all antibacterial agents, including amoxicillin (see section "Side effects"). Therefore, this diagnosis must be considered in patients presenting with diarrhea during or after antibiotic use. In case of suspected antibiotic-associated colitis, Coact should be discontinued immediately, medical advice sought, and appropriate treatment initiated. Antiperistaltic agents are contraindicated in such cases.

During prolonged therapy, periodic monitoring of organ system functions, including renal, hepatic, and hematopoietic function, is recommended.

Rare cases of prolonged prothrombin time have been reported in patients receiving amoxicillin/clavulanic acid. Appropriate monitoring is required when anticoagulants are co-administered. Dose adjustment of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections "Interaction with other medicinal products and other forms of interaction" and "Side effects").

Dosage adjustment is required in patients with impaired renal function depending on the degree of impairment (see section "Dosage and administration").

Crystalluria (including acute kidney injury) has been very rarely observed in patients with reduced urine output, primarily during parenteral therapy. Adequate fluid intake and diuresis should be maintained when high doses of amoxicillin are administered to reduce the risk of amoxicillin crystalluria. In patients with urinary catheters, catheter patency should be checked regularly (see sections "Side effects" and "Overdose").

During amoxicillin therapy, enzymatic methods using glucose oxidase should be used for urine glucose testing, as non-enzymatic methods may yield false-positive results.

The presence of clavulanic acid in Coact may lead to non-specific binding of IgG and albumin to red blood cell membranes, resulting in false-positive direct Coombs test results.

Positive results in the Platelia Aspergillus immunoassay (Bio-Rad Laboratories) have been reported in patients receiving amoxicillin/clavulanic acid, despite subsequent confirmation of absence of Aspergillus infection. Cross-reactions with polysaccharides and polyfuranoses from non-Aspergillus species have also been reported with the Platelia Aspergillus immunoassay (Bio-Rad Laboratories).

Therefore, positive test results in patients receiving amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

This medicinal product contains less than 1 mmol per dose of sodium, i.e., essentially sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy. Reproductive studies in animals with oral and parenteral forms of amoxicillin/clavulanic acid revealed no teratogenic effects. In one study involving women with premature rupture of membranes, prophylactic use of amoxicillin/clavulanic acid was associated with an increased risk of necrotizing enterocolitis in newborns. As with other medicinal products, use during pregnancy, especially in the first trimester, should be avoided unless considered necessary by the physician.

Breastfeeding period. Both active components are excreted in breast milk (no information is available on the effect of clavulanic acid on breastfed infants). Diarrhea and fungal mucosal infections may therefore occur in the breastfed infant, and breastfeeding should be discontinued. The possibility of allergic reactions should also be considered.

Coact may be used during breastfeeding only if, in the physician’s opinion, the benefit outweighs the risk.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of the medicinal product on the ability to drive or operate machinery have not been conducted. However, side effects (e.g., allergic reactions, dizziness, seizures) may occur that could impair the ability to drive or operate machinery (see section "Side effects").

Dosage and Administration

The drug should be used in accordance with official recommendations on antibiotic therapy and local antibiotic susceptibility data. Susceptibility to amoxicillin/clavulanate varies across regions and may change over time. Local susceptibility data should be consulted when necessary, and microbiological identification and susceptibility testing should be performed if indicated.

When necessary, consider using alternative formulations of Coact (i.e., those providing higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) (see sections "Pharmacodynamics" and "Special Instructions").

The recommended dosage range depends on the expected pathogens and their susceptibility to antibacterial agents, the severity of the infection, the site of infection, as well as the patient's age, body weight, and renal function.

For adults and children with body weight ≥40 kg, the total daily dose is 1500 mg of amoxicillin/375 mg of clavulanic acid (3 tablets), administered as described below.

For children aged 6 years and older with body weight between 25 and 40 kg, the maximum daily dose is 2400 mg of amoxic游戏副本

Body weight (kg)	40	35	30	25	Recommended single dose [mg/kg body weight] (see above)
Amoxicillin [mg/kg body weight] per single dose (1 film-coated tablet)	12.5	14.3	16.7	20.0	6.67–20
Clavulanic acid [mg/kg body weight] per single dose (1 film-coated tablet)	3.1	3.6	4.2	5.0	1.67–5

Elderly patients

Dose adjustment is not required for elderly patients. If necessary, the dose is adjusted according to renal function.

Dosing in renal impairment

Dosing is based on calculated peak levels of amoxicillin. There is no need to adjust the dose in patients with creatinine clearance > 30 mL/min.

Adults and children with body weight ≥ 40 kg

Creatinine clearance 10–30 mL/min	500 mg/125 mg twice daily
Creatinine clearance < 10 mL/min	500 mg/125 mg once daily
Hemodialysis	500 mg/125 mg every 24 hours plus 500 mg/125 mg during dialysis and repeated at the end of dialysis (since plasma concentrations of amoxicillin and clavulanic acid are reduced)

Children aged 6 years and older with body weight between 25 and 40 kg

Since the tablet cannot be divided, this formulation of Coact is not prescribed to children with body weight between 25 and 40 kg and creatinine clearance below 30 mL/min or to children undergoing hemodialysis.

Dosing in hepatic impairment

Use with caution; liver function should be monitored regularly.

The tablet should be swallowed whole without chewing. If necessary, to facilitate swallowing, the tablet may be split in half and the halves swallowed without chewing.

The medication should be taken with food to minimize potential gastrointestinal intolerance.

The duration of treatment is determined individually. Treatment should not be continued for more than 14 days without reassessment of the patient's condition.

Treatment may be initiated parenterally and then continued orally.

Children

This formulation of Coact may be used in children aged 6 years and older with body weight of at least 25 kg.

Overdose

Symptoms

Gastrointestinal disturbances and disturbances in fluid and electrolyte balance may occur. Crystalluria associated with amoxicillin administration has been observed, which in some cases led to renal failure (see section "Special precautions").

Seizures may occur in patients with impaired renal function and in patients receiving high doses of the drug.

Amoxicillin precipitation in urinary bladder catheters has been reported, primarily after high-dose intravenous administration. Catheter patency should be checked regularly (see section "Special precautions").

Amoxicillin crystalluria has been observed, which in some cases led to renal failure (see section "Special precautions").

Treatment

Gastrointestinal disturbances can be treated symptomatically, with attention to fluid/electroly balance.

Amoxicillin/clavulanic acid can be removed from the bloodstream by hemodialysis.

Side effects

The most commonly reported adverse reactions to the drug are diarrhea, nausea, and vomiting.

The list of adverse drug reactions known from clinical trials of amoxicillin/clavulanic acid and post-marketing surveillance, classified by MedDRA system organ class, is provided below.

The following frequency classification of adverse effects is applied:

very common ≥ 1/10;
common ≥ 1/100 and < 1/10;
uncommon ≥ 1/1,000 and < 1/100;
rare ≥ 1/10,000 and < 1/1,000;
very rare < 1/10,000;
not known (frequency cannot be estimated from available data).

Infections and infestations

Common: candidiasis of skin and mucous membranes.
Frequency not known: overgrowth of microorganisms not sensitive to the drug.

Blood and lymphatic system disorders

Rare: reversible leukopenia (including neutropenia) and thrombocytopenia.
Frequency not known: reversible agranulocytosis and hemolytic anemia; prolonged bleeding time and prothrombin time(^1).

Immune system disorders(^{10})

Frequency not known: angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis.

Nervous system disorders

Uncommon: dizziness, headache.
Frequency not known: reversible hyperactivity and convulsions(^2), aseptic meningitis.

Gastrointestinal disorders

Common: diarrhea, nausea(^3), vomiting.
Uncommon: gastrointestinal disturbances.
Frequency not known: antibiotic-associated colitis(^4), "black hairy tongue", discoloration of tooth enamel(^{11}). Drug-induced enterocolitis syndrome (DIES), acute pancreatitis.

Hepatobiliary disorders

Uncommon: increased levels of AST and/or ALT(^5).
Frequency not known: hepatitis(^6) and cholestatic jaundice(^6).

Skin and subcutaneous tissue disorders(^7)

Uncommon: skin rashes, pruritus, urticaria.
Rare: erythema multiforme.
Frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis(^9), drug reaction with eosinophilia and systemic symptoms (DRESS). Linear IgA disease.

Renal and urinary disorders

Very rare: interstitial nephritis.
Frequency not known: crystalluria(^8) (including acute kidney injury).

Cardiac disorders

Frequency not known: Coombs' syndrome.

(^1) See section "Special precautions for use".
(^2) See section "Special precautions for use".
(^3) Nausea is more frequently associated with higher oral doses of the drug. Gastrointestinal reactions may be reduced in severity by taking the drug with food.
(^4) Including pseudomembranous colitis and hemorrhagic colitis (see section "Special precautions for use").
(^5) Mild elevations in AST and/or ALT levels have been more frequently observed in patients receiving beta-lactam antibiotics, but the clinical significance of these findings is unknown.
(^6) These events have been observed with other penicillin and cephalosporin antibiotics (see section "Special precautions for use").
(^7) If hypersensitivity reactions (dermatitis) occur, the drug should be discontinued (see section "Special precautions for use").
(^8) See section "Overdose".
(^9) See section "Special precautions for use".
(^{10}) See sections "Contraindications" and "Special precautions for use".
(^{11}) Tooth enamel discoloration has been very rarely reported in children. This phenomenon can be prevented by proper oral hygiene, as it is reversible with tooth brushing.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug authorization is an important step. It allows continuous monitoring of the benefit-risk ratio of the medicinal product.

Healthcare professionals are required to report any suspected adverse reactions via the pharmacovigilance system of Ukraine.

Shelf life. 2 years.

Storage conditions. Store in a dry place, out of reach of children, at a temperature not exceeding 25 °C.

Packaging. 5 tablets per blister, 3 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. Aurobindo Pharma Limited, Unit-XII.

Manufacturer's address and place of business.
Survey No. 314, Bachupally Village, Kuthpally Mandal, Ranga Reddy District, Hyderabad, Telangana State, 500090, India.