Diaprazol

INSTRUCTIONS for medical use of the medicinal product Diaprazole (DIAprazolE)

Composition:

Active substance: omeprazole;

1 vial contains sodium omeprazole equivalent to omeprazole 40 mg;

Excipient: anhydrous sodium carbonate.

Pharmaceutical form. Lyophilisate for solution for injection.

Main physicochemical properties: lyophilized powder from white to light yellow color, without visible inclusions.

Pharmacotherapeutic group.

Agents for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. Omeprazole. ATC code A02BC01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Omeprazole, a racemic mixture of two enantiomers, reduces gastric hydrochloric acid secretion through a highly targeted mechanism of action. Omeprazole inhibits gastric acid secretion by specifically acting on the proton pump in parietal cells. When administered once daily, the drug acts rapidly and provides control through reversible inhibition of gastric acid secretion.

Omeprazole is a weak base that accumulates and is converted into its active form in the highly acidic environment of the intracellular canaliculi of parietal cells, where it inhibits the H⁺, K⁺-ATPase enzyme (proton pump). This effect on the final step of gastric acid production is dose-dependent and results in highly effective suppression of both basal and stimulated acid secretion, regardless of the type of stimulation.

Pharmacodynamic effects

All pharmacodynamic effects can be explained by the influence of omeprazole on gastric acid secretion.

Effect on gastric acid secretion

Intravenous administration of omeprazole causes a dose-dependent inhibition of gastric acid secretion in humans. To achieve an immediate reduction in intragastric acidity equivalent to that obtained with repeated oral doses of 20 mg, an initial intravenous dose of 40 mg is recommended. This results in an immediate reduction of intragastric acidity and sustained suppression, averaging 90% over 24 hours, both after intravenous injection and intravenous infusion.

Inhibition of acid secretion correlates with the area under the plasma concentration-time curve (AUC) of omeprazole and does not depend on the actual plasma concentration of omeprazole at any given moment.

No signs of tachyphylaxis have been observed during omeprazole treatment.

Effect on Helicobacter pylori (H. pylori)

H. pylori is associated with the development of peptic ulcer disease, including duodenal and gastric ulcers. H. pylori is the primary factor in the development of gastritis. H. pylori, together with gastric hydrochloric acid, is a major contributor to peptic ulcer disease. H. pylori is the main factor in the development of atrophic gastritis, which is associated with an increased risk of gastric cancer.

Eradication of H. pylori using omeprazole in combination with antimicrobial agents is associated with high rates of ulcer healing and prolonged remission.

Other effects related to inhibition of gastric acid secretion

During treatment with antisecretory agents, serum gastrin levels increase in response to reduced acid secretion. Additionally, due to decreased gastric acidity, chromogranin A (CgA) levels rise. Elevated CgA levels may interfere with diagnostic testing for neuroendocrine tumors. It has been reported that treatment with proton pump inhibitors (PPIs) should be discontinued 5–14 days before measuring CgA levels. Testing should be repeated if levels have not normalized by that time.

An increase in ECL-cell numbers, possibly related to elevated serum gastrin levels, has been observed in both children and adults during long-term omeprazole therapy. These findings are considered to have no clinical significance.

During prolonged treatment, a slightly increased frequency of gastric fundic gland polyps has been reported. These changes are a physiological consequence of pronounced inhibition of gastric acid secretion; the process is benign and likely reversible.

Reduction of gastric acidity by any means, including PPIs, increases the number of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing agents slightly increases the risk of gastrointestinal infections caused by Salmonella and Campylobacter.

Pharmacokinetics.

Distribution

The estimated volume of distribution is approximately 0.3 L/kg body weight. Omeprazole is approximately 97% bound to plasma proteins.

Metabolism and elimination

Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The majority of its metabolism depends on the polymorphically expressed CYP2C19, which is responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. The remainder depends on another specific isoenzyme (CYP3A4), responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, there is a potential for competitive inhibition and metabolic drug-drug interactions with other CYP2C19 substrates. However, due to its low affinity for CYP3A4, omeprazole lacks the ability to inhibit the metabolism of other CYP3A4 substrates. Furthermore, omeprazole does not exert inhibitory effects on major CYP enzymes.

Approximately 3% of individuals of Caucasian descent and 15–20% of individuals of Mongoloid descent lack functional CYP2C19 enzyme; they are classified as "poor metabolizers." In these individuals, omeprazole metabolism may be predominantly catalyzed by CYP3A4. After repeated administration of omeprazole 20 mg once daily, the mean AUC in poor metabolizers is 5–10 times higher than in individuals with functional CYP2C19 (i.e., "extensive metabolizers"). Mean maximum plasma concentrations are also 3–5 times higher. However, these findings do not affect omeprazole dosing.

Elimination

Total plasma clearance is approximately 30–40 L/hour after a single dose. The elimination half-life of omeprazole in plasma is generally less than 1 hour, both after single and repeated once-daily administration. Omeprazole is completely cleared from plasma between doses, with no tendency for accumulation when administered once daily. Nearly 80% of an omeprazole dose is excreted in urine as metabolites, and the remainder is excreted in feces, primarily via biliary secretion.

The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a nonlinear relationship between AUC and dose after repeated dosing. This time- and dose-dependent relationship is due to reduced presystemic metabolism and systemic clearance, possibly caused by inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone). No effects of any metabolites on gastric acid secretion have been observed.

Special patient populations

Patients with hepatic impairment

Omeprazole metabolism is slowed in patients with impaired liver function, leading to increased AUC. However, with once-daily administration, no tendency for drug accumulation has been observed.

Patients with renal impairment

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function.

Elderly patients

The rate of omeprazole metabolism is slightly reduced in elderly patients (75–79 years of age).

Clinical characteristics.

Indications.

Intravenous omeprazole is indicated as an alternative to oral therapy in the following cases.

Adults

Treatment of duodenal ulcer.

Prevention of recurrence of duodenal ulcer.

Treatment of gastric ulcer.

Prevention of recurrence of gastric ulcer.

In combination with appropriate antibiotics for eradication of Helicobacter pylori (H. pylori) in peptic ulcer disease.

Treatment of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Prevention of gastric and duodenal ulcers associated with NSAID use in patients at risk.

Treatment of reflux esophagitis.

Long-term treatment of patients with inactive reflux esophagitis.

Treatment of symptomatic gastroesophageal reflux disease.

Treatment of Zollinger–Ellison syndrome.

Contraindications.

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any of the excipients of the medicinal product.

Omeprazole, like other PPIs, should not be used concomitantly with nelfinavir and atazanavir.

Interaction with other medicinal products and other forms of interactions.

Effect of omeprazole on the pharmacokinetics of other medicinal products

Medicinal products whose absorption is pH-dependent

Suppression of gastric secretion during treatment with omeprazole and other PPIs may reduce or increase the absorption of medicinal products whose absorption is pH-dependent. As with other agents that reduce gastric acidity, absorption of drugs such as ketoconazole, itraconazole, and also erlotinib may be reduced, whereas absorption of drugs such as digoxin may be increased during omeprazole treatment. Concomitant administration of omeprazole (20 mg once daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10% (in two out of ten subjects by up to 30%).

Nelfinavir, atazanavir

Plasma levels of nelfinavir and atazanavir are reduced when administered concomitantly with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated.

Concomitant use of omeprazole (40 mg once daily) reduced the average exposure to nelfinavir by approximately 40%, and the average exposure to its pharmacologically active metabolite M8 was reduced by approximately 75–90%. This interaction may also be due to inhibition of CYP2C19 activity.

Concomitant use of omeprazole with atazanavir is not recommended.

Concomitant use of omeprazole (40 mg once daily) with atazanavir 300 mg or ritonavir 100 mg resulted in a 75% reduction in atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Concomitant use of omeprazole (20 mg once daily) with atazanavir 400 mg or ritonavir 100 mg in healthy volunteers resulted in approximately a 30% reduction in atazanavir exposure compared to atazanavir 300 mg or ritonavir 100 mg once daily.

Digoxin

Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10%. Cases of digoxin toxicity have been rarely reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Therapeutic drug monitoring of digoxin should be intensified. When used concomitantly with digoxin, patients should be under close medical supervision.

Clopidogrel

In a study, clopidogrel (loading dose 300 mg followed by 75 mg daily) was administered alone and together with omeprazole (80 mg given simultaneously with clopidogrel) for 5 days. When clopidogrel and omeprazole were used together, exposure to the active metabolite of clopidogrel was reduced by 46% (day 1) and by 42% (day 5). Mean inhibition of platelet aggregation was reduced by 47% (after 24 hours) and by 30% (day 5) when clopidogrel and omeprazole were administered together. In another study, administration of clopidogrel and omeprazole at different times did not prevent their interaction, likely due to the inhibitory effect of omeprazole on CYP2C19. Conflicting data on the clinical significance of this pharmacokinetic/pharmacodynamic interaction regarding major cardiovascular events have been reported in observational and clinical studies. Therefore, concomitant use of omeprazole and clopidogrel should be avoided.

Other medicinal products

Absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly reduced, thus clinical efficacy may be diminished. Concomitant use of the medicinal product with posaconazole and erlotinib should be avoided.

Medicinal products metabolized by CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme responsible for omeprazole metabolism. Therefore, metabolism of concomitantly administered medicinal products that are also metabolized by CYP2C19 may be reduced, and systemic exposure to these agents may be increased. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/maintenance dose 75 mg daily) and omeprazole (80 mg daily orally, i.e., a dose four times higher than the standard daily dose), resulting in a mean reduction of 46% in exposure to the active metabolite of clopidogrel and a mean reduction of 16% in maximum inhibitory effect (ADP-induced) on platelet aggregation. As a precaution, concomitant use of omeprazole and clopidogrel should be avoided.

However, the clinical relevance of this interaction remains unclear.

Cilostazol

In healthy volunteers, administration of omeprazole 40 mg increased Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively.

Phenytoin

Plasma concentration monitoring of phenytoin is recommended during the first 2 weeks after initiation of omeprazole treatment; if phenytoin dosage adjustment is required, monitoring and further dosage adjustments should continue after discontinuation of omeprazole.

Unknown interaction mechanism

Saquinavir

Concomitant use of omeprazole with saquinavir/ritonavir resulted in an increase in saquinavir plasma levels by approximately 70%, which was associated with acceptable tolerability in HIV-infected patients.

Tacrolimus

Increased serum levels of tacrolimus have been reported with concomitant use of omeprazole. Intensified monitoring of tacrolimus concentration and renal function (creatinine clearance) is required, and dosage adjustment of tacrolimus may be necessary.

Methotrexate

Elevated methotrexate levels have been reported in some patients when co-administered with PPIs. When high-dose methotrexate therapy is required, temporary discontinuation of omeprazole should be considered.

Effect of other medicinal products on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4

Since omeprazole is metabolized by CYP2C19 and CYP3A4 enzymes, medicinal products known to inhibit the activity of CYP2C19 or CYP3A4, or both enzymes (such as clarithromycin and voriconazole), may cause an increase in omeprazole plasma levels due to slowed metabolism. Concomitant administration of voriconazole resulted in more than a two-fold increase in omeprazole exposure. Since high doses of omeprazole are generally well tolerated, dose adjustment of omeprazole is usually not required. However, dose adjustment should be considered for patients with severe hepatic impairment and in cases where long-term treatment is indicated.

Omeprazole is partially metabolized by CYP3A4 as well, but does not inhibit this enzyme. Thus, omeprazole does not affect the metabolism of drugs metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide.

Inducers of CYP2C19 and/or CYP3A4

Medicinal products known to induce the activity of CYP2C19 or CYP3A4, or both enzymes (such as rifampicin and St. John’s wort), may cause a decrease in omeprazole plasma levels due to accelerated metabolism.

Special precautions for use

In the presence of any alarming symptom (e.g., significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, or melena) or suspicion or presence of gastric ulcer, malignancy must be excluded, as treatment may mask symptoms and delay diagnosis.

Concomitant use of atazanavir with proton pump inhibitors (PPIs) is not recommended. If co-administration of atazanavir with a PPI cannot be avoided, careful clinical monitoring (e.g., viral load) is recommended, along with increasing the atazanavir dose to 400 mg with 100 mg ritonavir; the omeprazole dose should not exceed 20 mg.

Omeprazole, like all drugs that suppress gastric acid secretion, may reduce absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered when treating patients with cachexia or risk factors for reduced vitamin B12 absorption during long-term therapy.

Omeprazole is an inhibitor of CYP2C19. At the initiation or discontinuation of omeprazole therapy, potential interactions with drugs metabolized by CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

PPI therapy is associated with a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

The use of PPIs, particularly at high doses and over long durations (>1 year), is associated with a slightly increased risk of fractures of the hip, wrist, and spine, primarily in elderly patients or those with other risk factors. According to study data, PPIs increase the overall fracture risk by 10–40%. In some cases, this is associated with the presence of other risk factors in the patient. Patients at risk of osteoporosis should receive appropriate treatment and adequate supplementation with vitamin D and calcium.

As with any long-term therapy, especially when omeprazole treatment exceeds one year, patients require medical supervision and regular laboratory monitoring of serum magnesium and calcium levels.

In patients taking PPIs, including omeprazole, for at least 3 months, significant hypomagnesemia may occur (in most cases, patients had been taking the drug for approximately 1 year).

After discontinuation of the drug, serum magnesium levels returned to normal. Clinical features of hypomagnesemia include increased neuromuscular excitability, manifesting as carpopedal spasms, motor agitation; tachycardia, cardiac arrhythmias, elevated blood pressure; and dystrophic disorders such as trophic skin erosions and ulcers. The diagnostic criterion for hypomagnesemia is a serum magnesium concentration below 1 mEq/L. Additionally, cases have been reported where hypomagnesemia led to hypocalcemia due to suppressed parathyroid hormone secretion in the context of low magnesium levels in the body. In some patients, severe hypocalcemia and hypomagnesemia occurred, leading to convulsive syndrome, cardiac arrhythmias, tetany, mental disturbances, and severe vomiting, resulting in electrolyte imbalance.

During treatment with antisecretory drugs, plasma gastrin concentration increases due to reduced gastric acid secretion. As a result of reduced acid secretion, chromogranin A (CgA) levels increase. Elevated CgA levels may interfere with diagnostic tests for neuroendocrine tumors. To avoid this interference, PPIs should be discontinued at least 5 days before measuring CgA levels. If CgA and gastrin levels do not return to reference values after initial measurements, the test should be repeated 14 days after stopping PPI therapy.

Subacute cutaneous lupus erythematosus (SCLE)

The use of PPIs may be associated with very rare cases of SCLE. If skin lesions occur, particularly in sun-exposed areas, and are accompanied by arthralgia, the patient should seek immediate medical attention, and the healthcare provider should consider discontinuing omeprazole. A history of SCLE following previous PPI treatment increases the risk of developing SCLE upon treatment with other PPIs.

Renal function impairment

Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking omeprazole and may occur at any time during omeprazole therapy (see section "Adverse reactions"). Acute tubulointerstitial nephritis may progress to renal failure. If ATIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.

This medicinal product contains 1.93 mmol (or 44.52 mg)/dose of sodium. Caution should be exercised when administering this product to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Epidemiological studies involving more than 1000 pregnant women who had successful deliveries indicate no adverse effects of omeprazole on pregnancy or fetal/neonatal health. Omeprazole may be used during pregnancy only if, in the opinion of the physician, the expected benefit to the mother outweighs the potential risk to the fetus.

Omeprazole is excreted in breast milk in small amounts, but its effect on the infant is unknown. Therefore, breastfeeding should be discontinued during treatment with this medicinal product.

Ability to affect reaction speed when driving or operating machinery

It is unlikely that the drug affects the ability to drive or operate machinery.

However, considering that adverse reactions (e.g., dizziness, somnolence, hallucinations, reversible confusion, etc.) may occur in sensitive patients during treatment, such patients should refrain from driving or operating machinery requiring concentration during treatment.

Method of Administration and Dosage

Dosage

Alternative to Oral Therapy

For patients for whom oral administration of the drug is unsuitable, intravenous administration of omeprazole 40 mg once daily is recommended. For patients with Zollinger-Ellison syndrome, the recommended initial intravenous dose is 60 mg per day. Higher daily doses may be required; therefore, the dose should be individually adjusted. If the daily dose exceeds 60 mg, it should be divided equally into two parts and administered twice daily.

The drug must be administered intravenously only and must not be given by any other route.

The solution should be used immediately after preparation, but no later than 3 hours after preparation. The diluted omeprazole solution must not be stored in the refrigerator. Any unused solution should be discarded.

Instructions for Reconstitution Prior to Administration

For intravenous injections: the contents of each vial containing 40 mg omeprazole should be dissolved in 10 mL of sterile water for injections. The solution for intravenous injection should be administered slowly over 5 minutes.

For intravenous infusions: the contents of each vial containing 40 mg omeprazole should be reconstituted with 10 mL of diluent and further diluted to 100 mL with 0.9% sodium chloride solution or 5% glucose solution. The stability of omeprazole depends on the pH of the infusion solution; therefore, other diluents or volumes should not be used.

The intravenous infusion should be administered over 20–30 minutes.

The solution should be used immediately after preparation, but no later than 3 hours after preparation. The diluted omeprazole solution must not be stored in the refrigerator.

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

Special Patient Populations

Renal Impairment

Dose adjustment is not required in patients with renal impairment.

Hepatic Impairment

In patients with hepatic impairment, a daily dose of 10–20 mg may be sufficient.

Elderly Patients (> 65 years)

Dose adjustment is not required in elderly patients.

Children

Experience with intravenous administration of omeprazole in pediatric practice is limited; therefore, the drug should not be administered to this patient group.

Overdose

Information on the consequences of omeprazole overdose in humans is limited. Cases of omeprazole administration at doses up to 560 mg have been reported. There have also been isolated reports of single oral doses of omeprazole reaching 2400 mg (120 times higher than the usual recommended clinical dose). Symptoms such as nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache have been observed. In isolated cases, lethargy, depression, and confusion have also been reported.

The described symptoms were transient, and no reports of serious outcomes have been received. The elimination rate of the drug did not change (first-order kinetics) with increasing doses.

In clinical studies, intravenous administration of up to 270 mg in a single day and up to 650 mg over three days did not result in any dose-dependent adverse reactions.

Treatment: There is no specific antidote. The drug is poorly removed by dialysis. Gastric lavage may be indicated, along with symptomatic and supportive therapy.

Adverse reactions.

The most common adverse reactions are headache, abdominal pain, constipation, diarrhea, flatulence, and nausea/vomiting.

The undesirable effects listed below were identified during clinical studies. None of these events were considered dose-dependent.

System Organ Classes	Adverse Reactions
Blood and lymphatic system	leukopenia, thrombocytopenia, agranulocytosis, pancytopenia
Immune system	hypersensitivity reactions, including fever, angioneurotic edema, and anaphylactic reactions/shock
Metabolism and nutrition	hyponatremia, hypomagnesemia; severe hypomagnesemia may lead to hypocalcemia; hypomagnesemia may also cause hypokalemia
Psychiatric	insomnia, anxiety, mild disorientation, agitation, confusion, depression, aggression, hallucinations
Nervous system	headache, dizziness, paresthesia, sleep disturbances, feeling of weakness, somnolence, taste disturbances
Eye disorders	blurred vision, visual disturbances
Ear and labyrinth disorders	vertigo
Respiratory, thoracic and mediastinal disorders	sudden wheezing or shortness of breath (bronchospasm)
Gastrointestinal disorders	abdominal pain, constipation, diarrhea, flatulence, nausea/vomiting, dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis, fundic gland polyps (benign)
Hepatobiliary disorders	increased liver enzymes, hepatitis with or without jaundice, hepatic failure, encephalopathy in patients with pre-existing liver disease
Skin and subcutaneous tissue	dermatitis, erythema, pruritus, rash, urticaria, alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), subacute cutaneous lupus erythematosus (see section "Special precautions")
Musculoskeletal, connective tissue and bone disorders	arthralgia, myalgia, fracture of femur, wrist or spine, muscle weakness
Renal and urinary disorders	tubulointerstitial nephritis (with possible progression to renal failure), darkening of urine
Reproductive system and breast disorders	impotence, gynecomastia
General disorders and administration site conditions	malaise, peripheral edema, increased sweating

In isolated cases, irreversible vision impairment has been reported in seriously ill patients receiving omeprazole as intravenous injection, particularly at high doses; however, a causal relationship has not been established.

The adverse event profile observed in children is consistent with that in adults, both during short-term and long-term therapy.

Shelf life. 2 years.

Vials containing powder (without cardboard box) may be stored under normal lighting conditions for up to 24 hours.

Reconstituted solution:

chemical and physical stability has been demonstrated for 12 hours at 25 °C after reconstitution with 0.9% sodium chloride solution and for 6 hours at 25 °C after reconstitution with 5% glucose solution.

From a microbiological standpoint, the medicinal product should be used immediately, unless reconstitution has been carried out under controlled and aseptic conditions validated by appropriate methods.

Storage conditions.

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

Keep out of reach of children.

Incompatibilities. This medicinal product must not be mixed with other solvents except those specified in the section "Directions for use and dosage".

Packaging.

The medicinal product is placed into vials made of dark glass, stoppered with a rubber stopper and sealed with an aluminum crimp cap fitted with a flip-off cap ensuring first-opening control.

One vial per cardboard pack.

Prescription status. Prescription only.

Manufacturer.

Naprod Life Sciences Pvt. Ltd.

NAPROD LIFE SCIENCES Pvt. Ltd.

Manufacturer's address and location of manufacturing site.

G-17/1, M.I.D.C., Tarapur, Boisar, Dist-Thane 401 506, Maharashtra State, India

G-17/1, M.I.D.C., Tarapur, Boisar, Dist-Thane 401 506, Maharashtra State, India

Marketing Authorization Holder.

M.Biotech Ltd

M.Biotech Ltd

Address of the Marketing Authorization Holder.

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom