Gemtero

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GEMTERO (GEMTERO)

Composition:

Active substance: gemcitabine hydrochloride;

One vial contains gemcitabine hydrochloride equivalent to 200 mg or 1.0 g of gemcitabine;

Excipients: mannitol (E 421); sodium acetate, trihydrate.

Pharmaceutical form. Lyophilisate for solution for infusion.

Main physicochemical properties: white or almost white lyophilisate in vials made of colorless glass.

Pharmacotherapeutic group. Antineoplastic agents. Antimetabolites. Pyrimidine analogues. ATC code L01B C05.

Pharmacological Properties.

Pharmacodynamics.

Gemcitabine exhibits cell cycle specificity, primarily causing cell death during DNA synthesis (S-phase), as well as blocking cell growth at the G1/S-phase boundary of the cycle.

Gemcitabine (dFdC) undergoes intracellular metabolism via nucleoside kinases to form diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic effect of gemcitabine results from the combined action of diphosphate and triphosphate metabolites, leading to inhibition of DNA synthesis. First, the diphosphate metabolite inhibits ribonucleotide reductase, the enzyme responsible for catalyzing the formation of deoxyribonucleotide triphosphates required for DNA synthesis. Inhibition of this enzyme by dFdCDP leads to decreased concentrations of deoxyribonucleotides, including dCTP. Second, dFdCTP competes with dCTP during DNA synthesis (self-potentiation).

Thus, reduced intracellular dCTP concentration facilitates the incorporation of gemcitabine triphosphate metabolites into the DNA chain. DNA epsilon polymerases are unable to remove gemcitabine or repair the newly synthesized DNA strands. After incorporation of intracellular gemcitabine metabolites into DNA, one additional nucleotide is added to the growing DNA chain, resulting in complete inhibition of further DNA synthesis ("masked chain termination") and programmed cell death known as apoptosis.

Pharmacokinetics.

Distribution. Maximum plasma concentration (measured within 5 minutes after the end of infusion) ranges from 3.2 to 45.5 mcg/mL.

Volume of distribution in the central compartment is 12.4 L/m² in women and 17.5 L/m² in men. Volume of distribution in the peripheral compartment is 47.4 L/m² (similar in both women and men). Clearance in women is approximately 25% lower than in men.

Half-life. Half-life ranges from 42 to 94 minutes, depending on patient gender and age. With the recommended dosing schedule, elimination of gemcitabine should be complete within 5–11 hours after the start of infusion. Weekly administration does not result in drug accumulation.

Metabolism. Gemcitabine is rapidly metabolized in the liver, kidneys, blood, and other tissues by cytidine deaminase.

During intracellular metabolism, mono-, di-, and triphosphates of gemcitabine (dFdCMP, dFdCDP, and dFdCTP) are formed, of which dFdCDP and dFdCTP are pharmacologically active. These intracellular metabolites are not detectable in plasma or urine.

The primary metabolite, 2’-deoxy-2’,2’-difluorouridine (dFdU), is inactive and is detectable in blood and urine.

Elimination. Systemic clearance of gemcitabine ranges from 29.2 to 92.2 L/h/m², depending on patient gender and age (inter-individual variability of 52.2%). Drug clearance in women is approximately 25% lower than in men. Gemcitabine clearance decreases with age in both women and men, although it remains relatively rapid. When gemcitabine is administered at the recommended dose of 1000 mg/m² body surface area via 30-minute intravenous infusions, dose adjustments are not required for women or men with lower clearance.

Renal excretion. Less than 10% of the administered dose is excreted unchanged in urine. Renal clearance ranges from 2 to 7 L/h/m².

Within one week after gemcitabine administration, 92–98% of the dose is eliminated from the body, with 99% excreted in urine (primarily as dFdU) and 1% in feces.

Kinetics of dFdCTP. This metabolite is detectable in peripheral blood mononuclear cells; therefore, the data below refer to these cells. Following administration of gemcitabine at doses ranging from 35 to 350 mg/m² body surface area via 30-minute intravenous infusions, steady-state intracellular concentrations of dFdCTP increase proportionally from 0.4 to 5 mcg/mL. When plasma gemcitabine concentration exceeds 5 mcg/mL, dFdCTP concentrations in mononuclear cells do not increase further, indicating saturation of the metabolic process.

Terminal half-life of dFdCTP ranges from 0.7 to 12 hours.

Kinetics of dFdU.

Maximum plasma concentration of dFdU is reached 3–15 minutes after completion of a 30-minute infusion at a dose of 1000 mg/m² body surface area and ranges from 28 to 52 mcg/mL.

Minimum plasma concentration of dFdU when gemcitabine is administered once weekly ranges from 0.07 to 1.12 mcg/mL, with no evidence of accumulation.

The decline in plasma dFdU concentration follows a triphasic pattern, with a mean terminal half-life of 65 hours (range: 33–84 hours).

91–98% of gemcitabine is converted into dFdU.

Mean volume of distribution of dFdU in the central compartment is 18 L/m² (range: 11–22 L/m²).

Mean volume of distribution at steady state (Vss) for dFdU is 150 L/m² (range: 96–228 L/m²).

Tissue distribution – extensive.

Mean clearance of dFdU is 2.5 L/h/m² (range: 1–4 L/h/m²).

Excretion in urine – complete.

Combination therapy with gemcitabine and paclitaxel

When gemcitabine and paclitaxel are used in combination, the pharmacokinetics of both drugs remain unchanged.

Combination therapy with gemcitabine and carboplatin

When gemcitabine and carboplatin are used in combination, the pharmacokinetics of gemcitabine remain unchanged.

Renal impairment

Mild to moderate renal impairment (creatinine clearance 30–80 mL/min) does not significantly affect the pharmacokinetics of gemcitabine.

Clinical Characteristics.

Indications.

Bladder cancer. Gemcitabine is indicated for the treatment of locally advanced or metastatic bladder cancer in combination with cisplatin.

Pancreatic cancer. Gemcitabine is indicated for the treatment of locally advanced adenocarcinoma of the pancreas.

Non-small cell lung cancer. Gemcitabine is indicated in combination with cisplatin as first-line therapy for patients with locally advanced or metastatic non-small cell lung cancer. The possibility of using gemcitabine as monotherapy may be considered for elderly patients or patients with an ECOG performance status of 2.

Ovarian cancer. Gemcitabine in combination with carboplatin is indicated for the treatment of locally advanced or metastatic epithelial ovarian cancer in patients who have relapsed after a treatment-free interval of at least 6 months following platinum-based first-line therapy.

Breast cancer. Gemcitabine in combination with paclitaxel is indicated for the treatment of patients with unresectable locally recurrent or metastatic breast cancer who have experienced recurrence after prior adjuvant/neoadjuvant chemotherapy. Prior chemotherapy, in the absence of clinical contraindications, should have included anthracyclines.

Contraindications.

Hypersensitivity to gemcitabine or to any of the excipients; breastfeeding period.

Special precautions.

Special handling for solution preparation for infusion

As with other cytotoxic agents, great care should be taken in the preparation and administration of the infusion solution. The solution should be prepared in a biological safety cabinet using gloves and protective gowns. If work in a safety cabinet is not possible, a mask and protective goggles must be used.

Contact of the solution with the eyes may cause severe irritation. In such a case, the eyes should be immediately and thoroughly flushed with water. If irritation persists, medical advice should be sought. In case of contact with the skin, the skin should be immediately washed with water.

Interaction with other medicinal products and other forms of interaction.

Specific studies on gemcitabine interactions have not been conducted.

Radiotherapy

Concomitant radiotherapy (administered simultaneously or ≤ 7 days apart). The toxicity associated with combined modality therapy depends on multiple factors, including the dose of gemcitabine, frequency of infusions, radiation dose, technique used, and the volume and site of irradiation.

Preclinical and clinical studies have demonstrated that gemcitabine has radiosensitizing activity. In one trial, gemcitabine at a dose of 1000 mg/m² was administered over a period of up to 6 weeks concurrently with thoracic radiotherapy in patients with non-small cell lung cancer, and significant toxicity was observed in the form of severe and potentially life-threatening mucositis, particularly esophagitis and pneumonitis, especially in patients who received high-dose radiotherapy (median irradiated volume of 4795 cm³). In subsequent studies, it has been suggested that lower doses of gemcitabine should be used with concomitant radiotherapy to achieve expected toxicity, as demonstrated in a phase II study of non-small cell lung cancer, where thoracic irradiation at 66 Gy was administered together with gemcitabine (600 mg/m², 4 doses) and cisplatin (80 mg/m², 2 doses) over 6 weeks. The optimal regimen for safe use of gemcitabine with therapeutic radiation doses has not yet been established for all tumor types.

Non-concomitant radiotherapy (administered with an interval >7 days). Data analysis has not revealed increased toxicity when gemcitabine is administered more than 7 days before or after radiotherapy, except in cases of "radiation recall" phenomena. Data indicate that gemcitabine may be initiated after acute radiation effects have resolved or at least one week after radiotherapy.

Tissue damage in previously irradiated areas (e.g., esophagitis, colitis, and pneumonitis) has been reported following radiotherapy when gemcitabine was administered either concomitantly or non-concomitantly.

Other

The concurrent use of live attenuated vaccines, including yellow fever vaccine, is not recommended due to the risk of systemic, potentially fatal disease, particularly in immunosuppressed patients.

Special precautions for use.

Prolonged infusion duration and increased dosing frequency increase toxicity.

Hematological toxicity

Gemcitabine may suppress bone marrow function, manifesting as leukopenia, thrombocytopenia, and anemia.

In patients receiving gemcitabine, platelet, white blood cell, and granulocyte counts should be monitored before each dose. The dose of gemcitabine may be reduced or administration delayed in case of myelosuppression. Nevertheless, myelosuppression is usually short-lived and most often does not require dose reduction or discontinuation of therapy.

Peripheral blood cell counts may decrease even after discontinuation of gemcitabine therapy. Patients with impaired bone marrow function should be treated with caution. As with other cytotoxic agents, the risk of cumulative bone marrow suppression should be considered when gemcitabine is used in combination with other chemotherapeutic agents.

Hepatic impairment

The drug should be administered with caution in patients with hepatic or renal impairment, as clinical studies have not provided sufficient data to recommend precise dosing for such patients. Administration of gemcitabine in the presence of liver metastases, hepatitis, history of alcoholism, or hepatic cirrhosis may lead to worsening of liver dysfunction. Laboratory assessment of renal and hepatic function (including virological testing) should be performed periodically.

Concomitant radiotherapy

Toxicity has been reported during concomitant radiotherapy (simultaneously or ≤ 7 days after).

Live vaccines

Administration of the yellow fever vaccine and other live attenuated vaccines is not recommended in patients receiving gemcitabine therapy.

Reversible posterior leukoencephalopathy syndrome

Cases of reversible posterior leukoencephalopathy syndrome with potentially severe outcomes have been reported in patients receiving gemcitabine either as monotherapy or in combination with other chemotherapeutic agents. Most patients who developed reversible posterior leukoencephalopathy syndrome while receiving gemcitabine experienced acute hypertension and epileptic seizures, as well as other symptoms such as headache, lethargy, confusion, and visual loss.

This syndrome is diagnosed by magnetic resonance imaging (MRI). Reversible posterior leukoencephalopathy syndrome is a reversible condition if appropriate supportive therapy is initiated. If reversible posterior leukoencephalopathy syndrome develops during gemcitabine therapy, treatment should be discontinued and supportive measures initiated, including blood pressure control and anticonvulsant therapy.

Cardiovascular system

Due to the risk of cardiac or vascular disorders associated with gemcitabine use, special attention should be given to patients with a history of cardiovascular disease.

Capillary leak syndrome

Capillary leak syndrome has been reported in patients receiving gemcitabine either as monotherapy or in combination with other chemotherapeutic agents. With early detection and appropriate treatment, capillary leak syndrome is usually manageable, but fatal outcomes have been reported. This condition arises from increased systemic vascular permeability, leading to leakage of fluid and proteins from the intravascular space into the interstitium. Clinical manifestations include generalized edema, weight gain, hypoalbuminemia, severe hypotension, acute renal failure, and pulmonary edema. Drug administration should be discontinued at the first signs of capillary leak syndrome, and appropriate therapy initiated. Capillary leak syndrome may occur in later treatment cycles and is often associated with adult respiratory distress syndrome.

Respiratory system

Pulmonary toxicity, sometimes severe (such as pulmonary edema, interstitial pneumonitis, or adult respiratory distress syndrome (ARDS)), has been reported. If such events occur, discontinuation of gemcitabine therapy should be considered. Early symptomatic intervention may improve the condition.

Urinary and reproductive system

Hemolytic-uremic syndrome (HUS)

HUS has been rarely reported in the post-marketing period in patients receiving gemcitabine. HUS is potentially life-threatening. Drug administration should be discontinued at the first signs of microangiopathic hemolytic anemia, such as rapid decline in hemoglobin levels accompanied by thrombocytopenia, increased serum bilirubin, serum creatinine, blood urea, or lactate dehydrogenase. Renal failure may be irreversible even after discontinuation of therapy, and dialysis may become necessary.

Fertility

Fertility studies showed that gemcitabine caused hypospermatogenesis in male mice. Therefore, men receiving gemcitabine therapy should not plan conception during treatment and for 6 months after therapy. Due to the potential for loss of fertility following gemcitabine therapy, men are advised to consider sperm preservation prior to starting treatment.

Severe skin adverse reactions (SSARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis, have been observed during gemcitabine therapy, which may lead to fatal outcomes. Patients should be informed about the signs and symptoms of SSARs and closely monitored for skin reactions. If symptoms suggestive of these reactions occur, gemcitabine should be discontinued immediately.

Sodium

One vial of gemcitabine 200 mg contains 3.5 mg (< 1 mmol) of sodium, i.e., sodium is practically absent.

One vial of gemcitabine 1.0 g contains 17.5 mg (< 1 mmol) of sodium, i.e., sodium is practically absent.

Use during pregnancy or breastfeeding.

Pregnancy

There are no adequate data on the use of gemcitabine in pregnant women. Animal studies have shown reproductive toxicity. Considering the results of animal studies and the mechanism of action, gemcitabine should not be used during pregnancy unless clearly necessary. Women should be advised to avoid pregnancy during gemcitabine therapy or to inform their physician if they become pregnant while receiving gemcitabine.

Breastfeeding

It is unknown whether gemcitabine is excreted in human milk, and adverse reactions in breastfed infants cannot be excluded; therefore, breastfeeding should be discontinued during gemcitabine therapy.

Fertility

Fertility studies showed that gemcitabine caused hypospermatogenesis in male mice. Therefore, men receiving gemcitabine therapy should not plan conception during treatment and for 6 months after therapy. Due to the potential for loss of fertility following gemcitabine therapy, men are advised to consult specialists regarding sperm cryopreservation prior to starting treatment.

Ability to affect reaction speed when driving or operating machinery.

No studies on the effect of the drug on the ability to drive or operate machinery have been conducted. Since gemcitabine may cause mild to moderate somnolence, especially when combined with alcohol, patients should avoid operating machinery or driving vehicles until this effect subsides.

Administration and Dosage

HEMTERO should only be prescribed by a physician experienced in the use of anticancer chemotherapy.

Route of administration. For intravenous use after reconstitution of the lyophilisate. The solution should be colorless or slightly yellow.

Gemcitabine infusions are generally well tolerated by patients, allowing administration in an outpatient setting. In case of extravasation, the infusion must be stopped immediately and administration of the drug resumed into another vein. After gemcitabine administration, the patient must remain under close medical supervision.

Bladder cancer (combination therapy)

The recommended dose of gemcitabine is 1000 mg/m² administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle in combination with cisplatin. Cisplatin should be administered at a recommended dose of 70 mg/m² either on day 1 after gemcitabine or on day 2 of each 28-day cycle. This 4-week cycle is then repeated. Dose reductions, either between cycles or during a cycle, may be necessary depending on the degree of toxicity experienced by the patient.

Pancreatic cancer

HEMTERO should be administered as a 30-minute intravenous infusion at a dose of 1000 mg/m² once weekly for 7 weeks, followed by a one-week rest period. Subsequent cycles should consist of infusions administered once weekly for 3 weeks, followed by a one-week rest every 4 weeks. Dose adjustments may be made during any cycle depending on the degree of toxicity experienced by the patient.

Non-small cell lung cancer (monotherapy)

The recommended dose of gemcitabine is 1000 mg/m² administered as a 30-minute intravenous infusion once weekly for 3 weeks, followed by a one-week rest. This 4-week cycle is repeated. Dose reductions between cycles or within a cycle may be necessary depending on the degree of toxicity experienced by the patient.

Non-small cell lung cancer (combination therapy with cisplatin)

The recommended dose of gemcitabine is 1250 mg/m² body surface area administered as a 30-minute intravenous infusion on days 1 and 8 of a 21-day cycle. Dose adjustments may be made during any cycle depending on the degree of toxicity experienced by the patient.

Cisplatin has been used at doses of 75–100 mg/m² once every 3 weeks.

Breast cancer (combination therapy)

HEMTERO in combination with paclitaxel is recommended as follows: paclitaxel (175 mg/m²) is administered on day 1 via a 3-hour intravenous infusion, followed by gemcitabine (1250 mg/m²) administered via a 30-minute intravenous infusion on days 1 and 8 of each 21-day cycle. The dose may be reduced between cycles or within a cycle depending on the degree of toxicity experienced by the patient. Patients must have an absolute granulocyte count of at least 1.5 x 10⁹/L prior to initiation of combination therapy with gemcitabine and paclitaxel.

Ovarian cancer (combination therapy)

HEMTERO in combination with carboplatin is recommended at a dose of 1000 mg/m² administered as a 30-minute intravenous infusion on days 1 and 8 of a 21-day cycle. On day 1 of the cycle, carboplatin is administered after gemcitabine at a dose providing an AUC of 4 mg/mL/min. The dose may be reduced between cycles or within a cycle depending on the degree of toxicity experienced by the patient.

Monitoring for toxic effects and dose adjustment

Dose adjustments due to non-hematological toxicity

To manage non-hematological toxicity, patients should be monitored regularly, and liver and kidney function should be assessed. The dose of gemcitabine may be reduced (across cycles or within a cycle) depending on the severity of toxic effects. Generally, in the event of severe (grade 3 or 4) non-hematological toxicity, except for nausea/vomiting, gemcitabine therapy should be withheld or the dose reduced at the physician’s discretion. Gemcitabine treatment may only be resumed after resolution of toxic effects.

Dose adjustments due to hematological toxicity

At the beginning of treatment. Regardless of indication, platelet and granulocyte counts must be determined before each administration. Treatment may be initiated if granulocyte count is ≥1,500 (x10⁶/L) and platelet count is ≥100,000 (x10⁶/L).

During treatment. Gemcitabine dose adjustments should be made according to the recommendations below.

Table 1

Gemcitabine dose adjustments during treatment of patients with bladder cancer, NSCLC, or pancreatic cancer receiving monotherapy or combination therapy with cisplatin

* Continuation of gemcitabine administration within a treatment cycle is possible only after achieving an absolute neutrophil count ≥0.5 (x10⁹/l) and platelet count ≥50 (x10⁹/l).

Table 2

Gemcitabine dose adjustment during the treatment cycle for patients with breast cancer receiving combination therapy with paclitaxel

* Treatment within a cycle is not resumed. Therapy is restarted on the first day of the next cycle, provided that the absolute granulocyte count is ≥1.5 (x10⁹/l) and platelet count is ≥100 (x10⁹/l).

Table 3

Dose adjustment of gemcitabine during treatment cycle in patients with ovarian cancer receiving combination therapy with carboplatin

* Treatment within a cycle is not resumed. Therapy should be restarted on the first day of the next cycle, provided that the absolute granulocyte count is ≥1.5 (x10⁹/l) and platelet count is ≥100 (x10⁹/l).

Dose adjustments due to hematological toxicity in subsequent cycles, for all indications

The dose of gemcitabine should be reduced by 75% of the initial dose of the cycle in the event of the following manifestations of hematological toxicity:

− absolute granulocyte count < 0.5 x 10⁹/l for more than 5 days;

− absolute granulocyte count < 0.1 x 10⁹/l for more than 3 days;

− febrile neutropenia;

− platelets < 25 x 10⁹/l;

− delay of cycle by more than 1 week due to toxicity development.

Special patient groups

Patients with hepatic and renal impairment. The drug should be administered with caution in patients with hepatic and renal impairment, as insufficient data are available from clinical studies to recommend specific doses for such patients.

Elderly patients (˃65 years). Gemcitabine is well tolerated in patients aged 65 years and older. There is no evidence to suggest that dose adjustment is required in elderly patients beyond what is already recommended for all patients.

Children. Gemcitabine is not recommended for use in children due to insufficient data on efficacy and safety in this patient group.

Instructions for solution preparation (if further dilution is required)

The only permitted diluent for reconstitution of sterile gemcitabine powder is 9 mg/ml (0.9%) sodium chloride injection solution (without preservatives). To reconstitute, add 5 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution (without preservatives) to a vial containing 200 mg of gemcitabine, or 25 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution (without preservatives) to a vial containing 1000 mg. The total volume after reconstitution is 5.26 ml (for the 200 mg vial) or 26.3 ml (for the 1000 mg vial), respectively. This results in a solution concentration of 38 mg/ml, accounting for the volume displacement of the lyophilized powder. Shake well to dissolve. Further dilution may be performed using sterile 9 mg/ml (0.9%) sodium chloride injection solution (without preservatives). The prepared solution is a clear, colorless or pale straw-colored solution. Parenteral medicinal products should be visually inspected for particulate matter and discoloration prior to administration. If particulate matter is observed, the solution must not be administered. The prepared solution should be stored for no more than 24 hours.

Unused medicinal product or waste materials must be disposed of in accordance with local requirements.

Children.

GEMTERO is not recommended for use in children due to insufficient data on safety and efficacy.

Overdose.

There is no known antidote for gemcitabine overdose. Clinically tolerable toxicity has been observed with doses up to 5.7 g/m² administered as a 30-minute intravenous infusion every 2 weeks. In case of suspected overdose, the patient should be closely monitored, including appropriate blood count monitoring, and supportive therapy should be administered as necessary.

Adverse Reactions

The most commonly reported adverse reactions associated with gemcitabine treatment are nausea, with or without vomiting, and elevated levels of liver transaminases (ALT and AST) as well as alkaline phosphatase, observed in approximately 60% of patients; proteinuria and hematuria, observed in approximately 50% of patients; dyspnea, observed in 10–40% of patients (with the highest frequency in patients with lung cancer); and allergic skin rashes, observed in 25% of patients, of which 10% were accompanied by pruritus.

The frequency and severity of adverse reactions depend on the dose, rate of infusion, and intervals between doses. Dose-dependent adverse reactions include decreased levels of thrombocytes, leukocytes, and granulocytes.

The following table of adverse reactions and their frequency is derived from clinical studies of gemcitabine. Within each category, adverse reactions are listed in decreasing order of frequency: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10000 and < 1/1000), very rare (<1/10000), frequency not known (cannot be estimated based on available data).

Combination use in breast cancer

The frequency of hematological toxicity grade III and IV, particularly neutropenia, increases when gemcitabine is used in combination with paclitaxel, although the increased frequency of these adverse reactions is not associated with a higher incidence of infections or hemorrhagic events. Weakness and febrile neutropenia are observed more frequently with the combination of gemcitabine and paclitaxel. Weakness, not associated with anemia, usually resolves after the first cycle of therapy.

* Grade 4 neutropenia lasting more than 7 days was observed in 12.6% of patients receiving combination therapy and in 5% of patients receiving paclitaxel alone.

Combination therapy in bladder cancer

Combined use in ovarian cancer

The phenomenon of sensory neuropathy was also observed more frequently with combination therapy compared to carboplatin used alone.

Shelf life. 3 years.

Storage conditions. Store in the original packaging, protected from light, at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Packaging. 200 mg or 1 g per vial; 1 vial per cardboard box.

Prescription status. Prescription only.

Manufacturer. HETERO LABS LIMITED.

HETERO LABS LIMITED.

Manufacturer's address and place of business.
Unit-VI, TSIIC, Formulation SEZ,
Sy No. 410 & 411, Polepally Village, Jadcherla Mandal, Mahaboobnagar-District, Telangana,
Pin-509301, India.