Upasarin upasa with vitamin c

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT UPSARIN UPSA WITH VITAMIN C

Composition:

Active substances: 1 effervescent tablet contains 330 mg of acetylsalicylic acid, 200 mg of ascorbic acid (vitamin C);

Excipients: sodium hydrogen carbonate, anhydrous citric acid, povidone, sodium benzoate (E 211).

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white tablets with a score line, beveled edges, water-soluble with effervescence.

Pharmacotherapeutic group.

Analgesics and antipyretics. Acetylsalicylic acid, combinations without psycholeptics.

ATC code N02B A51.

Pharmacological properties.

Pharmacodynamics.

Acetylsalicylic acid belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesic, antipyretic, and anti-inflammatory properties. Its mechanism of action involves irreversible inhibition of the enzyme cyclooxygenase, which participates in the synthesis of prostaglandins.

Acetylsalicylic acid also inhibits platelet aggregation by blocking platelet synthesis of thromboxane A2.

Pharmacokinetics.

Acetylsalicylic acid is rapidly and almost completely absorbed after oral administration. Maximum plasma concentrations are reached within 15–40 minutes.

The bioavailability of acetylsalicylic acid depends on the dose: it is approximately 60% for doses below 500 mg and 90% for doses above 1 g, due to saturation of hepatic hydrolysis.

Acetylsalicylic acid undergoes rapid hydrolysis to form salicylic acid (a metabolite that is also active).

Acetylsalicylic and salicylic acids are quickly distributed in all tissues. These acids cross the placental barrier and are excreted into breast milk.

Salicylic acid is highly bound to plasma proteins (90%).

The elimination half-life from plasma is 15–20 minutes for acetylsalicylic acid and 2–4 hours for salicylic acid.

Acetylsalicylic acid is primarily metabolized in the liver. It is mainly excreted in urine as salicylic acid and glucuronide conjugates, as well as in the form of salicyluric acid and gentisic acid.

Ascorbic acid is well absorbed in the gastrointestinal tract. If its intake exceeds the body's requirements, the excess is excreted in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain and/or fever.

Contraindications.

Hypersensitivity to acetylsalicylic acid, other salicylates, ascorbic acid, or to any component of the drug.

Bronchial asthma induced by salicylates or other NSAIDs in medical history.

Peptic ulcers.

Hemorrhagic diathesis.

Risk of bleeding.

Severe renal diseases, pronounced renal failure.

Nephrolithiasis.

Pronounced hepatic insufficiency.

Pronounced heart failure.

Predisposition to thrombosis, thrombophlebitis.

Diabetes mellitus.

Combination with methotrexate at doses of 20 mg/week or higher (see section "Interaction with other medicinal products and other types of interactions").

Third trimester of pregnancy at doses exceeding 100 mg per day.

Combination of oral anticoagulants with anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day) or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid.

Interaction with other medicinal products and other types of interactions.

Risks of interactions associated with the platelet antiaggregant effect.

When the drug is used in combination with agents having platelet antiaggregant properties (abciximab, aspirin, clopidogrel, epoprostenol, eptifibatide, iloprost and iloprost tromethamine, tirofiban and ticlopidine), the risk of bleeding increases.

The use of multiple platelet antiaggregants increases the risk of bleeding, as does their combination with heparin and molecules related to oral anticoagulants and other thrombolytics. This must be taken into account when using the drug. The patient must be under constant medical supervision.

Contraindicated combinations (see section "Contraindications").

Oral anticoagulants

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day), or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid, due to increased risk of bleeding, especially in case of history of gastroduodenal ulcer.

Methotrexate, when administered at doses greater than 20 mg/week

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day), or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid, due to increased toxicity, particularly hematological, of methotrexate (reduced renal clearance of methotrexate by anti-inflammatory agents).

Not recommended combinations.

Oral anticoagulants

Use of analgesic or antipyretic doses of acetylsalicylic acid (≥500 mg per dose and/or <3 g per day), even in the absence of history of gastroduodenal ulcer, as it may increase the risk of bleeding.

Oral anticoagulants

Use of antiplatelet doses of acetylsalicylic acid (from 50 to 375 mg per day) in cases of history of gastroduodenal ulcer, due to increased risk of bleeding, particularly in case of history of gastroduodenal ulcer. Monitoring, including bleeding time, is required.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day), or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid – increased risk of ulcer formation and gastrointestinal bleeding.

Clopidogrel (except for approved indications for this combination in the acute phase of coronary syndrome)

Increased risk of bleeding due to summation of antiplatelet effects.

Glucocorticoids (except hydrocortisone as replacement therapy)

Anti-inflammatory doses of acetylsalicylic acid (≥1 g per dose and/or ≥3 g per day) – increased risk of bleeding.

Low molecular weight heparins (and similar) and unfractionated heparins: use of therapeutic doses and/or administration to elderly patients

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day) or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid – increased risk of bleeding (inhibition of platelet function) and damage to gastric and duodenal mucosa by acetylsalicylic acid.

It is recommended to use another anti-inflammatory, analgesic or antipyretic medicinal product.

Pemetrexed

In patients with mild to moderate renal function (creatinine clearance of 45–80 mL/min), there is a risk of increased pemetrexed toxicity (reduced renal clearance of pemetrexed by acetylsalicylic acid in anti-inflammatory doses, i.e., ≥1 g per dose and/or ≥3 g per day).

Ticlopidine

Increased risk of bleeding due to summation of antiplatelet effects. If such a combination cannot be avoided, strict clinical monitoring is required.

Uricosurics (benzbromarone, probenecid)

Reduced uricosuric effect due to competition in renal tubular excretion of uric acid.

Combinations requiring caution in use.

Clopidogrel (in approved indications for this combination in the acute phase of coronary syndrome)

Increased risk of bleeding due to summation of antiplatelet effects. Clinical monitoring is required.

Diuretics

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day) or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid: possible acute renal failure in a dehydrated patient due to reduced glomerular filtration, secondary to decreased synthesis of renal prostaglandins. Possible reduction in antihypertensive effect.

Fluid loss in the patient should be compensated and renal function should be monitored at the beginning of treatment.

Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day) or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid: possible acute renal failure in a dehydrated patient due to reduced glomerular filtration, secondary to decreased synthesis of renal prostaglandins. Possible reduction in antihypertensive effect. Fluid loss in the patient should be compensated and renal function should be monitored at the beginning of treatment.

Methotrexate administered at doses less than or equal to 20 mg/week

Anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day) or analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day) of acetylsalicylic acid – increased toxicity of methotrexate, particularly hematological (reduced renal clearance of methotrexate by anti-inflammatory agents).

Weekly blood count monitoring is required during the first weeks of combined treatment, intensified medical supervision of the patient, and in case of any (even minor) renal function impairment and in elderly patients.

Methotrexate administered at doses greater than or equal to 20 mg/week

When antiplatelet doses of acetylsalicylic acid (from 50 to 375 mg per day) are used – increased toxicity of methotrexate, particularly hematological (reduced renal clearance of methotrexate by anti-inflammatory agents).

Weekly blood count monitoring is required during the first weeks of combined treatment, intensified medical supervision of the patient, and in case of any (even minor) renal function impairment and in elderly patients.

Pemetrexed

In patients with normal renal function, there is a risk of increased pemetrexed toxicity (reduced renal clearance of pemetrexed when acetylsalicylic acid is used in anti-inflammatory doses, i.e., ≥1 g per dose and/or ≥3 g per day). Biological monitoring of renal function is required.

Local gastrointestinal agents, antacids and charcoal

Reduced gastrointestinal absorption of acetylsalicylic acid.

Use of antacids or activated charcoal is possible with a time interval of at least 2 hours after administration of acetylsalicylic acid.

Combinations to be considered.

Oral anticoagulants

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg/day).

Increased risk of bleeding, especially in case of gastroduodenal ulcer.

Nonsteroidal anti-inflammatory drugs

When antiplatelet doses of acetylsalicylic acid (from 50 to 375 mg/day) are used – increased risk of ulcer development and gastrointestinal bleeding.

Glucocorticoids (except hydrocortisone as replacement therapy)

When analgesic or antipyretic doses of acetylsalicylic acid (≥500 mg per dose and/or <3 g per day) are used – possible increased risk of bleeding.

Low molecular weight heparins (and similar) and unfractionated heparins: use of therapeutic doses and/or administration to elderly patients

When antiplatelet doses of acetylsalicylic acid (from 50 to 375 mg/day) are used – increased risk of bleeding (inhibition of platelet function) and damage to gastric and duodenal mucosa by acetylsalicylic acid.

Low molecular weight heparins (and similar) and unfractionated heparins: prophylactic doses

Combined use of drugs acting at different levels of hemostasis increases the risk of bleeding. This must be taken into account when using acetylsalicylic acid in combination with heparins in prophylactic doses (low molecular weight and similar or unfractionated heparins) regardless of dose, in patients under 65 years of age. Clinical and laboratory monitoring is also required.

Selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

Increased risk of bleeding.

Thrombolytics

Increased risk of bleeding.

Concomitant use of ibuprofen interferes with the irreversible inhibition of platelets by acetylsalicylic acid. Treatment with ibuprofen in patients at risk of cardiovascular diseases may limit the cardioprotective effect of acetylsalicylic acid.

Ascorbic acid reduces the toxicity of sulfonamide drugs, reduces the effect of heparin and indirect anticoagulants, promotes iron absorption, increases penicillin absorption, enhances the side effects of salicylates (risk of crystaluria).

Quinolone derivatives, calcium chloride, salicylates, glucocorticosteroids with prolonged use reduce the body's vitamin C stores. When used concomitantly, ascorbic acid reduces the chronotropic effect of isoprenaline; when used in high doses – increases mexiletine renal excretion. Barbiturates and primidone increase the urinary excretion of ascorbic acid. Ascorbic acid reduces the therapeutic effect of neuroleptics (phenothiazine derivatives), tubular reabsorption of amphetamine and tricyclic antidepressants. Taking ascorbic acid together with deferoxamine increases tissue iron toxicity, especially in the myocardium, which may lead to circulatory decompensation. Ascorbic acid can be taken 2 hours after deferoxamine injection. At high doses, ascorbic acid affects vitamin B12 resorption. Ascorbic acid enhances oxalate excretion in urine, thus increasing the risk of oxalate stone formation in urine.

Special precautions for use.

The drug should be used with caution in:

• Circulatory disorders (e.g., renal vascular disease, congestive heart failure, reduced circulating blood volume, major surgical procedures, sepsis, or significant blood loss), as acetylsalicylic acid may further increase the risk of kidney damage and cause acute renal failure. In patients with glucose-6-phosphate dehydrogenase deficiency, acetylsalicylic acid may cause hemolysis or hemolytic anemia. Factors increasing the risk of hemolysis include, for example, high-dose therapy, fever, or acute infections. Ascorbic acid should be used with caution in patients predisposed to calcium oxalate nephrolithiasis or those suffering from recurrent kidney stone disease;
• Hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents, as well as in the presence of allergy to other substances;
• History of gastrointestinal ulcers, including chronic or recurrent peptic ulcer disease or gastrointestinal bleeding. Gastrointestinal bleeding or ulcers/perforations may occur at any time during treatment with acetylsalicylic acid, without prior symptoms or history. The relative risk increases in elderly patients and in patients with low body weight;
• Concomitant use of anticoagulants;
• Impaired renal and/or hepatic function.

In patients with allergic complications, including bronchial asthma, allergic rhinitis, urticaria, skin itching, mucosal swelling, nasal polyps, as well as in combination with chronic respiratory tract infections, and in patients with hypersensitivity to NSAIDs, bronchospasm or an attack of bronchial asthma may develop during treatment.

During surgical procedures (including dental procedures), the use of drugs containing acetylsalicylic acid may increase the likelihood of bleeding or exacerbation of bleeding due to inhibition of platelet aggregation for some time after administration of acetylsalicylic acid. Use with caution in women with metrorrhagia or menorrhagia (risk of increased volume and duration of menstruation).

When using low doses of acetylsalicylic acid, excretion of uric acid may be reduced. This may lead to the development of gout in patients with impaired uric acid excretion.

1 effervescent tablet contains 485 mg of sodium, which should be considered in patients on a low-salt diet.

When high doses are used or the drug is administered long-term, renal function, blood pressure, and pancreatic function should be monitored. The drug should be used with caution in patients with a history of mild to moderate kidney disease. Since ascorbic acid enhances iron absorption, its use in high doses may be hazardous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, or sideroblastic anemia.

Patients with high iron content in the body should use the drug at minimal doses.

Concomitant intake of the drug with alkaline drinks reduces absorption of ascorbic acid; therefore, tablets should not be taken with alkaline mineral water. Absorption of ascorbic acid may also be impaired in intestinal dyskinesia, enteritis, and achylia.

As a reducing agent, ascorbic acid may affect laboratory test results, for example, blood glucose, bilirubin, transaminase activity, lactate dehydrogenase activity.

Since ascorbic acid has a mild stimulating effect, the drug is not recommended to be taken late in the day.

Long-term use of high-dose ascorbic acid may accelerate its own metabolism, potentially leading to paradoxical hypovitaminosis after discontinuation of treatment.

Do not exceed the recommended dose. Do not use simultaneously with other drugs containing acetylsalicylic acid and vitamin C. Use with caution in polycythemia and leukemia.

Prolonged use of analgesics may lead to the development of headache.

Fecal occult blood tests may yield false-negative results.

Use during pregnancy or breastfeeding.

The drug may be used during pregnancy only if other medicinal products are ineffective. Salicylates may be used during pregnancy only after careful assessment of the risk-benefit ratio.

During the first and second trimesters of pregnancy, drugs containing acetylsalicylic acid should not be prescribed except in cases of extreme necessity. If women planning pregnancy, as well as pregnant women during the first and second trimesters, require treatment with acetylsalicylic acid, doses should be as low as possible and treatment duration as short as possible. Use of salicylates during the first trimester has been associated in some retrospective epidemiological studies with an increased risk of congenital malformations (cleft palate, heart defects, gastroschisis). However, with long-term use of therapeutic doses exceeding 150 mg/day, this risk has been found to be low: a study involving 32,000 mother-child pairs showed no association between drug use and increased risk of congenital malformations.

According to previous assessments, during long-term use, acetylsalicylic acid should not be taken in doses exceeding 150 mg/day.

During the third trimester of pregnancy, high-dose salicylate use (over 300 mg/day) may lead to prolonged gestation and weakened labor contractions, as well as cardiopulmonary toxicity in the fetus (premature closure of the ductus arteriosus) or impaired fetal renal function, which may progress to renal failure with reduced amniotic fluid volume. Prostaglandin synthesis inhibitors used at the end of pregnancy may cause prolonged bleeding time in both mother and fetus due to anti-aggregatory effects, which may occur even with very low doses.

High-dose acetylsalicylic acid use shortly before delivery may lead to intracranial hemorrhage, particularly in premature infants.

Therefore, except in extremely rare cases justified by cardiovascular or obstetric medical indications with special monitoring, the use of acetylsalicylic acid during the third trimester of pregnancy is contraindicated.

Since acetylsalicylic acid passes into breast milk, the use of this medicinal product is not recommended during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

No effects on the ability to drive vehicles or operate machinery have been reported.

Method of Administration and Dosage

For oral use.

Completely dissolve the tablet in a large glass of water and drink immediately.

The medication is intended for adults and children over 15 years of age.

Adults and children with body weight over 50 kg (approximately 15 years and older): The maximum recommended daily dose is 3 g of acetylsalicylic acid, i.e., 9 effervescent tablets per day.

The single dose is 2 effervescent tablets. If necessary, the dose may be repeated after 4 hours.

Elderly patients.

The recommended maximum daily dose is 2 g of acetylsalicylic acid, i.e., 6 effervescent tablets per day.

The single dose is 1 effervescent tablet. If necessary, the dose may be repeated no sooner than 4 hours later. In cases of more severe pain or fever, 2 effervescent tablets may be taken, but the total daily dose must not exceed 6 effervescent tablets.

Frequency of administration.

Regular dosing helps prevent fluctuations in the intensity of pain and fever:

• In children aged 15 years, a regular interval between doses should be maintained both during the day and night, preferably 6 hours, but not less than 4 hours;
• In adults, the interval between doses should be at least 4 hours.

The duration of treatment is determined individually by a physician. It is important to remember that acetylsalicylic acid should not be used for more than 3 days for the treatment of fever and not more than 5 days for the treatment of pain.

Children.

The medication may be used in children aged 15 years and older. Medications containing acetylsalicylic acid should not be used in children with acute respiratory viral infections (ARVI), whether accompanied by fever or not. In certain viral diseases, particularly influenza A, influenza B, and varicella (chickenpox), there is a risk of developing Reye's syndrome—a very rare but life-threatening condition requiring immediate medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant medication, although a causal relationship has not been definitively established. If these conditions are accompanied by persistent vomiting, this may be a sign of Reye's syndrome.

Overdose.

Salicylate overdose may occur due to chronic intoxication resulting from prolonged therapy (administration of more than 100 mg/kg/day for over 2 days may cause toxic effects), or due to acute, life-threatening intoxication (overdose), which may result, for example, from accidental ingestion by children or unintentional overdose.

Chronic salicylate poisoning may have an insidious onset, as its symptoms are nonspecific. Moderate chronic intoxication, or salicylism, typically occurs only after ingestion of large doses.

Symptoms. Mild intoxication may be accompanied by increased respiratory rate, hyperventilation, respiratory alkalosis, alkaline urine reaction, increased sweating, nausea, and vomiting. Moderate to severe intoxication is characterized by respiratory alkalosis followed by compensatory metabolic acidosis, acidemia, aciduria, hyperpyrexia; respiratory system effects ranging from hyperventilation and non-cardiogenic pulmonary edema to respiratory arrest and asphyxia; cardiovascular system effects ranging from cardiac arrhythmias and arterial hypotension to cardiac arrest; dehydration, oliguria, renal failure, impaired glucose metabolism, ketosis, gastrointestinal bleeding; hematological changes ranging from inhibition of platelet aggregation to coagulopathy; nervous system effects including toxic encephalopathy and central nervous system (CNS) depression, which may manifest as lethargy, decreased consciousness, coma, and epileptic seizures.

Acute and chronic overdoses caused by ascorbic acid have been reported in the literature. Ascorbic acid overdose may lead to oxidative hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, disseminated intravascular coagulation, and elevated oxalate levels in blood serum and urine. Elevated oxalate levels have been found to cause calcium deposition in patients undergoing dialysis. Additionally, there are several reports indicating that high doses of vitamin C, whether administered orally or intravenously, may trigger the formation of calcium oxalate kidney stones, calcium oxalate crystalluria in patients predisposed to salt crystallization, tubulointerstitial nephropathy, and acute renal failure due to kidney stone formation.

Other symptoms include impaired balance, dizziness, tinnitus, hearing loss, headache, and confusion. These symptoms can be managed by reducing the dose. Tinnitus may occur at plasma salicylate concentrations exceeding 150–300 µg/mL. More serious adverse reactions occur at plasma salicylate concentrations above 300 µg/mL.

Acute intoxication is indicated by significant disturbances in acid-base balance, which may vary depending on age and severity of intoxication. The most common finding in children is metabolic acidosis. The severity of the condition cannot be assessed solely based on plasma salicylate concentration. Absorption of acetylsalicylic acid may be delayed due to delayed gastric emptying, formation of gastric concretions, or ingestion of enteric-coated tablets.

Treatment. Management of intoxication due to acetylsalicylic acid overdose depends on the severity and clinical symptoms and follows standard procedures used for poisoning. All measures should aim to accelerate drug elimination and restore electrolyte and acid-base balance. Administer activated charcoal and forced alkaline diuresis. Infuse electrolyte solutions as needed based on acid-base and electrolyte status. Hemodialysis is indicated in severe cases of poisoning.

Adverse Reactions.

Gastrointestinal disorders: dyspepsia, epigastric and abdominal pain, heartburn, diarrhea, nausea, vomiting, stomach cramps; in isolated cases – gastrointestinal tract inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which in rare instances may lead to gastrointestinal bleeding and perforations, with corresponding laboratory and clinical manifestations.

Rarely – transient hepatic insufficiency with increased liver transaminase levels.

Blood system: increased risk of bleeding: intraoperative hemorrhages, hematomas, bleeding from the genitourinary organs, epistaxis, gingival bleeding, purpura; rarely or very rarely – severe bleeding such as gastrointestinal hemorrhage (hematemesis, melena) and cerebral hemorrhage (particularly in patients with uncontrolled arterial hypertension and/or concomitant use of antihemostatic agents), which in isolated cases could potentially be life-threatening.

Bleeding may lead to acute and chronic post-hemorrhagic anemia/iron-deficiency anemia (due to so-called occult microbleeding), with corresponding laboratory findings and clinical symptoms such as asthenia, pallor of the skin, hypoperfusion.

Allergic reactions: rash, urticaria, Quincke's edema, pruritus, rhinitis, nasal congestion, eczema, and very rarely – anaphylactic shock, non-cardiogenic pulmonary edema, Reye’s syndrome.

In patients with bronchial asthma, increased frequency of bronchospasm may occur; allergic reactions ranging from mild to moderate severity potentially affecting the skin, respiratory system, gastrointestinal tract, and cardiovascular system.

Nervous system: headache, vertigo, increased fatigue, sensation of hearing loss, dizziness and tinnitus, which may indicate overdose.

Other: sensation of warmth.

With prolonged use at high doses the following are possible: damage to the glomerular apparatus of the kidneys, formation of urate and/or oxalate kidney stones and urinary tract stones, renal failure; damage to the islet apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the development of diabetes mellitus; myocardial dystrophy; thrombocytosis, hyperprothrombinemia, erythrocytopenia, neutrophilic leukocytosis, hemolytic anemia; decreased capillary permeability (possible worsening of tissue trophism, increased blood pressure); oral dysbiosis; disturbances in zinc and copper metabolism. In patients with severe glucose-6-phosphate dehydrogenase deficiency, hemolysis and development of hemolytic anemia have been reported.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in a tightly closed tube to prevent moisture penetration.

Keep out of reach of children.

Packaging.

10 tablets in a tube, 1 or 2 tubes in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

UPSA SAS, France / UPSA SAS, France.

Manufacturer’s address and location of business activity.

979, avenue des Pyrenees, 47520 Le Passage, France / 979, avenue de Pyrenees, 47520 Le Passage, France;

304, avenue du Docteur Jean Bru, 47000 Agen, France / 304, avenue Docteur Jean Bru, 47000 Agen, France.

Date of last review.

For any questions regarding the safety of the medicinal product, please contact the applicant's representative:

Representative Office "Delta Medical Promotions AG"

43 Chornovola Street, Vyshneve, Kyiv region, 08132, Ukraine.

Tel.: 044 593 33 55,

Fax: 044 593 33 54.

Email: [email protected]