Instructions for use Esomer gastro-resistant tablets 40 mg blister No. 28
Composition
active ingredient: esomeprazole;
1 tablet contains esomeprazole magnesium dihydrate 43.38 mg equivalent to esomeprazole 40 mg;
excipients: cellulose and mannitol mixture (Avicel®), glycerol monostearate, mannitol, methacrylate copolymer (type A), paraffin, polyvinylpyrrolidone, polysorbate 80, sodium stearyl fumarate, spherical sugar, triethyl citrate;
film coating: hypromellose, iron oxide yellow (E 172), iron oxide red (E 172), macrogol (PEG 4000), talc, titanium dioxide (E 171).
Dosage form
Gastro-resistant tablets.
Main physicochemical properties: pink, oval-shaped tablets, film-coated.
Pharmacotherapeutic group
Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.
ATX code A02B C05.
Pharmacological properties
Pharmacodynamics
Esomeprazole is the S-isomer of omeprazole, which reduces gastric acid secretion by a specifically targeted mechanism of action. It is a specific inhibitor of the proton pump in the parietal cell. The R- and S-isomers of omeprazole have the same pharmacodynamic activity.
Esomeprazole is a weak base, it concentrates and converts to the active form in the highly acidic environment of the secretory tubules of the parietal cell, where it inhibits the enzyme H+K+-ATPase - the proton pump, and also suppresses basal and stimulated acid secretion.
After oral administration of 20 mg and 40 mg esomeprazole, the effect is observed within one hour. After repeated administration of 20 mg esomeprazole once daily for 5 days, the mean peak acid output after pentagastrin stimulation is reduced by 90% when measured 6–7 hours after the dose on day 5.
After 5 days of oral administration of esomeprazole 20 mg and 40 mg, gastric pH was >4 for a mean of 13 and 17 hours, respectively, and >24 hours in patients with symptomatic reflux esophagitis. The proportion of patients with gastric pH >4 for 8, 12, and 16 hours after 20 mg esomeprazole was 76%, 54%, and 24%, respectively. The corresponding proportions for 40 mg esomeprazole were 97%, 92%, and 56%.
When using AUC as an indirect indicator of plasma concentration, the dependence of acid secretion inhibition on drug exposure was demonstrated.
Therapeutic effects of inhibition of hydrochloric acid secretion.
Treatment of reflux esophagitis with esomeprazole 40 mg was successful in approximately 70% of patients after 4 weeks of treatment and in 93% after 8 weeks of treatment.
Esomeprazole 20 mg twice daily for one week, together with appropriate antibiotics, resulted in successful eradication of Helicobacter pylori in approximately 90% of patients. After one week of treatment, no further antisecretory monotherapy was required for successful ulcer healing and symptom relief in uncomplicated duodenal ulcers.
Other effects associated with inhibition of hydrochloric acid secretion.
During the period of use of antisecretory drugs, plasma gastrin concentration increases in response to decreased acid secretion. Chromogranin A (CgA) also increases due to decreased gastric acidity.
It is possible that the increase in the number of ECL cells is associated with an increase in plasma gastrin levels, which has been observed in some patients with long-term use of esomeprazole.
There have been reports of a slight increase in the incidence of gastric granular cysts with long-term use of antisecretory drugs. These phenomena are a physiological consequence of prolonged inhibition of acid secretion and are benign and reversible.
The reduction in gastric acidity caused by any proton pump inhibitor increases the number of bacteria normally present in the gastrointestinal tract in the stomach. Treatment with proton pump inhibitors may increase the risk of gastrointestinal infections caused by, for example, Salmonella or Campylobacter, and in hospitalized patients, possibly also Clostridium difficile.
Pharmacokinetics
Absorption.
Esomeprazole is rapidly absorbed, with peak plasma concentrations occurring approximately 1–2 hours after dosing. Absolute bioavailability is 64% after a single 40 mg dose and increases to 89% after repeated once-daily dosing. For 20 mg esomeprazole, the corresponding values are 50% and 68%.
Food intake slows down and reduces the absorption of esomeprazole, but does not affect the effect of esomeprazole on gastric acidity.
Distribution.
The volume of distribution in healthy volunteers at steady state is 0.22 l/kg body weight. Esomeprazole is 97% bound to plasma proteins.
Metabolism.
Esomeprazole is completely metabolized by the cytochrome P450 (CYP) system. The main part of the metabolism of esomeprazole depends on the polymorphic CYP2C19, which is responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The rest depends on a second specific isoform, CYP3A4, which is responsible for the formation of esomeprazole sulfone, the main metabolite in blood plasma.
The parameters listed below mainly reflect pharmacokinetics in individuals with a functional CYP2C19 enzyme (extensive metabolizers).
Total plasma clearance is approximately 17 l/h after a single dose and approximately 9 l/h after repeated dosing. The plasma elimination half-life is approximately 1.3 h after repeated once-daily dosing. Esomeprazole is completely eliminated from plasma between doses without any tendency for accumulation with once-daily dosing.
The main metabolites of esomeprazole do not affect gastric secretion. Approximately 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the feces. Less than 1% of the parent drug is recovered in the urine.
Special patient groups.
Slow metabolizers.
Approximately 2.9 ± 1.5% of the population lack a functional CYP2C19 enzyme (they are called poor metabolisers). In these individuals, esomeprazole is mainly metabolised by CYP3A4. After repeated once-daily dosing with 40 mg esomeprazole, the mean area under the plasma concentration-time curve in poor metabolisers is approximately 100% higher than in individuals with a functional CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentration is increased by approximately 60%. These findings have no impact on the dosage of esomeprazole.
Patients with impaired liver function.
The metabolism of esomeprazole in patients with mild to moderate hepatic dysfunction may be impaired. The rate of metabolism is reduced in patients with severe hepatic impairment, resulting in a 2-fold increase in the area under the plasma concentration-time curve. Therefore, the maximum dose for patients with severe hepatic impairment is 20 mg. Esomeprazole and its metabolites do not tend to accumulate when administered once daily.
Patients with impaired renal function.
Studies in this category of patients have not been conducted. Since the kidneys are responsible for the excretion of esomeprazole metabolites, and not the main parent compound, no changes in metabolism are expected in patients with impaired renal function.
Elderly patients.
The metabolism of esomeprazole does not undergo significant changes in elderly patients (71 to 80 years).
Pediatric patients.
After multiple doses of 20 mg and 40 mg esomeprazole, the overall exposure and time to peak plasma concentrations in children aged 12–18 years were similar to those in adults.
Gender characteristics.
After a single dose of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was 30% higher in women than in men. No gender-related differences were observed with repeated once-daily dosing. These findings do not impact the dosing of esomeprazole.
Indication
Adults.
Gastroesophageal reflux disease (GERD):
- treatment of erosive reflux esophagitis;
Prevention of recurrent bleeding from peptic ulcers of the stomach or duodenum after intravenous treatment with esomeprazole.
Treatment of Zollinger-Ellison syndrome.
Children aged 12 and over.
Gastroesophageal reflux disease (GERD):
– treatment of erosive reflux esophagitis.
Contraindication
Hypersensitivity to esomeprazole, substituted benzimidazoles or to any of the excipients. Concomitant use with nelfinavir is contraindicated. Do not use concomitantly with atazanovir.
Interaction with other medicinal products and other types of interactions
Effect of esomeprazole on the pharmacokinetics of other drugs.
Warfarin.
When esomeprazole 40 mg was administered to patients taking warfarin, coagulation times were within normal limits. However, after the widespread introduction of the drug into medical practice, there were several reports of a clinically significant increase in coagulation times, therefore, with the simultaneous use of esomeprazole and warfarin (or other coumarin derivatives), coagulation parameters should be monitored.
Voriconazole.
Omeprazole, like esomeprazole, acts as an inhibitor of CYP 2C19. Co-administration of omeprazole (40 mg once daily) resulted in an increase in Cmax and AUC of voriconazole (a CYP2C19 substrate) by 15% and 41%, respectively.
Diazepam.
Concomitant use of 30 mg esomeprazole results in a 45% decrease in the clearance of the CYP2C19 substrate diazepam.
Omeprazole has been reported to interact with some protease inhibitors (antiretroviral drugs). The clinical significance and mechanisms of such interactions are not always known. The increase in gastric pH during omeprazole use may alter the absorption of protease inhibitors. Other mechanisms of interaction may be related to inhibition of CYP 2C19. In the case of some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels of the latter have been observed when administered with omeprazole. Therefore, concomitant use of omeprazole and drugs such as atazanavir and nelfinavir is not recommended. The use of omeprazole (40 mg once daily) with atazanavir 300 mg and ritonavir 100 mg in healthy volunteers resulted in a significant decrease in the exposure of atazanavir (approximately 75% decrease in AUC, Cmax, Cmin). Increasing the dose of atazanavir to 400 mg did not compensate for the effect of omeprazole on the efficacy of atazanavir. Increased plasma levels of other antiretroviral agents, such as saquinavir, have been reported. There are also other antiretroviral agents (darunavir, aprenavir, lopinavir) whose plasma levels were unchanged when co-administered with omeprazole.
Due to the similarity of pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, the concomitant use of esomeprazole with atazanavir is not recommended. The concomitant use of esomeprazole with nelfinavir is contraindicated.
Clopidogrel.
In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and esomeprazole (40 mg daily orally), resulting in a mean 40% decrease in exposure to the active metabolite of clopidogrel and a mean 14% decrease in maximal inhibitory activity (ADP-induced) against platelet aggregation.
In a study in healthy volunteers, in which clopidogrel was co-administered with a combination of 20 mg esomeprazole and 81 mg acetylsalicylic acid compared with clopidogrel alone, a decrease in exposure to the active metabolite of clopidogrel by almost 40% was observed. However, the maximum inhibitory activity (ATP-induced) on platelet aggregation in these subjects was the same in the groups receiving clopidogrel alone and clopidogrel + combination (esomeprazole + acetylsalicylic acid), which is probably explained by the concomitant administration of low-dose acetylsalicylic acid.
Several observational and clinical studies on PK/PD interactions have shown conflicting results as to whether the risk of major cardiovascular events is increased when a patient receives clopidogrel with a PPI (proton pump inhibitor). As a precaution, it is recommended to avoid the concomitant use of clopidogrel with PPIs.
Drugs metabolized by CYP2C19.
Esomeprazole inhibits CYP2C19, the main enzyme that metabolizes esomeprazole. Therefore, when esomeprazole is used in combination with drugs that are metabolized by CYP2C19 (such as diazepam, citalopram, imipramine, clomipramine, phenytoin), the plasma concentrations of these drugs may be increased, and a dose reduction may be necessary. This should be taken into account, especially when prescribing esomeprazole on an “as needed” basis.
Drugs whose absorption depends on pH.
Reduced gastric acidity during the use of esomeprazole may increase or decrease the absorption of medicinal substances if their absorption depends on the acidity of gastric juice.
As with other drugs that reduce gastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib may be reduced, while the absorption of drugs such as digoxin may be increased during treatment with esomeprazole. Concomitant administration of omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10% (in two out of ten subjects by 30%). Digoxin toxicity has been reported rarely. However, caution should be exercised when esomeprazole is administered at high doses to elderly patients. Increased therapeutic drug monitoring of digoxin should be performed.
Methotrexate.
Increased blood levels of methotrexate have been reported in some patients when co-administered with proton pump inhibitors. If high doses of methotrexate are required, temporary withdrawal of esomeprazole should be considered.
Tacrolimus.
Increased plasma levels of tacrolimus have been reported with concomitant use of esomeprazole. Renal function (creatinine clearance) and tacrolimus plasma levels should be monitored and the dose of tacrolimus adjusted if necessary.
Cisapride.
In healthy volunteers, co-administration of 40 mg esomeprazole with cisapride resulted in a 32% increase in area under the concentration-time curve (AUC) and a 31% increase in elimination half-life (t1/2), but no significant increase in peak plasma levels of cisapride. A moderate prolongation of the QT interval was observed after administration of cisapride alone and was not increased by subsequent administration of cisapride in combination with esomeprazole.
Omeprazole, like esomeprazole, acts as an inhibitor of CYP 2C19. The use of omeprazole at a dose of 40 mg in healthy volunteers during a study resulted in an increase in Cmax and area under the concentration-time curve (AUC) for cilostazol by 18% and 26%, respectively, and for one of its active metabolites by 29% and 69%, respectively.
Phenytoin.
Concomitant use of 40 mg esomeprazole results in a 13% increase in phenytoin plasma levels in epileptic patients. It is recommended to monitor phenytoin plasma levels when initiating or discontinuing esomeprazole therapy.
Investigational medicinal products without clinically significant interactions
Amoxicillin and quinidine
It was noted that esomeprazole had no clinically significant effect on the pharmacokinetics of amoxicillin or quinidine.
Naproxen or rofecoxib
No pharmacokinetic interactions were observed during short-term studies of concomitant use of esomeprazole with naproxen or rofecoxib.
Effect of other drugs on the pharmacokinetics of esomeprazole.
Drugs that inhibit CYP2C19, CYP3A4, or both enzymes.
Esomeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and the CYP3A4 inhibitor clarithromycin (500 mg twice daily) resulted in a two-fold increase in esomeprazole exposure (AUC).
Concomitant use of esomeprazole and a combined CYP2C19 and CYP3A4 inhibitor may result in more than a doubling of esomeprazole exposure. Voriconazole (a CYP2C19 and CYP3A4 inhibitor) increased omeprazole AUC by 280%. In such situations, dose adjustment of esomeprazole is not always necessary. However, dose adjustment should be considered in patients with severe hepatic impairment or in the case of long-term treatment.
Drugs that induce CYP2C19, CYP3A4, or both enzymes.
Drugs that induce CYP2C19, CYP3A4 or both enzymes (such as rifampicin or St. John's wort) may lead to decreased plasma levels of esomeprazole by accelerating its metabolism.
Application features
In the presence of alarming symptoms (such as significant weight loss, nausea, dysphagia, haematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as the use of esomeprazole may alter symptoms and delay the correct diagnosis.
Patients who use the drug for a long time (especially more than a year) should be under regular supervision.
Patients taking the drug on an "as needed" basis should notify their doctor if their symptoms change.
The use of proton pump inhibitors may slightly increase the risk of gastrointestinal infections such as Salmonella and Campylobacter.
The use of esomeprazole, as with all drugs that inhibit acid secretion, may lead to reduced absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account in patients with reduced body stores or risk factors for reduced absorption of vitamin B12 during long-term therapy.
Severe hypomagnesaemia has been reported with proton pump inhibitors (PPIs) (including esomeprazole) in patients taking them for at least 3 months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmias may occur. The latter may have an abrupt and insidious onset. Hypomagnesaemia has resolved after magnesium replacement therapy and discontinuation of the PPI. In patients who are expected to be on long-term treatment or who are taking PPIs with digoxin or medicinal products that may cause hypomagnesaemia (e.g. diuretics), plasma magnesium levels should be monitored before starting PPI treatment and periodically during treatment.
Proton pump inhibitors, especially at high doses and for long periods (> 1 year), may modestly increase the risk of hip, wrist, or spine fractures, predominantly in elderly patients or those with other relevant risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fractures by 10–40%. Some fractures may be associated with other risk factors. Patients at risk of osteoporosis should be screened and treated according to current clinical guidelines, and adequate vitamin D and calcium intake should be ensured.
Concomitant use of esomeprazole and atazanavir is not recommended. If the combination of atazanavir with proton pump inhibitors cannot be avoided, close monitoring of the patient in a hospital setting is recommended, as well as an increase in the dose of atazanavir to 400 mg with 100 mg ritonavir; the dose of esomeprazole should not exceed 20 mg.
When prescribing esomeprazole, it is necessary to take into account its interaction with other drugs that may affect the concentration of esomeprazole in the blood plasma.
Elevated chromogranin A (CgA) levels may interfere with testing for neuroendocrine tumors. To avoid false results, esomeprazole treatment should be discontinued at least 5 days before CgA measurement.
Saccharose
This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Impact on laboratory test results
Due to increased levels of chromogranin A (CgA), laboratory tests for the detection of neuroendocrine tumours may be affected. To avoid this effect, treatment with esomeprazole should be discontinued at least 5 days before measuring CgA levels (see section 5.1).
Use during pregnancy or breastfeeding
Pregnancy.
Clinical data on the use of esomeprazole in pregnant women are limited. The results of studies on a large number of pregnant women who took the racemic mixture of omeprazole indicate the absence of malformative (impaired fetal development) and fetotoxic effects. Animal studies with esomeprazole did not show direct or indirect negative effects on embryonal/fetal development. Animal studies with the racemic mixture did not show direct or indirect negative effects on pregnancy, childbirth and postnatal development. The drug should be prescribed with caution during pregnancy.
Breastfeeding period.
No studies have been conducted in breast-feeding women. It is not known whether esomeprazole is excreted in breast milk. Therefore, esomeprazole should not be used during breast-feeding.
Fertility.
Animal studies of the racemic mixture of omeprazole have not shown any effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Esomeprazole has minimal influence on the ability to drive and use machines. Adverse reactions such as dizziness (uncommon) and blurred vision (rare) have been reported (see section 4.8). If such disorders occur, patients should not drive or use machines.
Method of administration and doses
The drug is intended for oral use in adults and children over 12 years of age. The tablets should be taken whole 1 hour before meals and washed down with sufficient water. The tablets should not be chewed or crushed. The duration of the course of treatment is usually determined by the doctor.
Adults
Gastroesophageal reflux disease (GERD)
Treatment of erosive reflux esophagitis: 40 mg once daily for 4 weeks. An additional 4 weeks are recommended for patients whose esophagitis has not been cured or whose symptoms persist.
Prevention of recurrent bleeding from gastric or duodenal ulcers after intravenous treatment with esomeprazole: 40 mg once daily for 4 weeks. The period of oral esomeprazole should be preceded by acid suppression therapy, which consists of the use of esomeprazole as a solution for infusion.
Treatment of Zollinger-Ellison syndrome: 40 mg 2 times a day. The dosage should be selected individually, the duration of treatment is determined by clinical indications. According to the obtained clinical data, in most patients the disease can be controlled by taking 80 to 160 mg of esomeprazole per day. If the dose exceeds 80 mg/day, it should be divided into two doses.
Patients with impaired renal function.
There is no need to adjust the dosage regimen. Due to the lack of experience with the use of esomeprazole in patients with severe renal insufficiency, the drug should be prescribed with caution.
Liver dysfunction
There is no need to adjust the dosage regimen in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, the maximum dose of esomeprazole should not exceed 20 mg.
Elderly patients
There is no need to adjust the dosage regimen.
Children aged 12 and over
Gastroesophageal reflux disease (GERD)
- Treatment of erosive reflux esophagitis:
40 mg once daily for 4 weeks.
Patients with untreated esophagitis or persistent symptoms are recommended to use the drug for an additional 4 weeks.
Children under 12 years old
Isomer should not be used in children under 12 years of age, as there is no data on such use.
Method of application
The tablet should be swallowed whole with liquid. The tablets should not be chewed or crushed.
For patients who cannot swallow, the tablets should be dissolved in still water and administered via a gastric tube. It is important to carefully check the suitability of the selected syringe and tube. Instructions for preparation and administration via a tube are given below.
Administration of the drug through a gastric tube
1. Place the tablet in a suitable syringe and draw approximately 25 ml of water and approximately 5 ml of air into the syringe. Some probes may require dilution of the drug in 50 ml of water to avoid clogging of the probe with tablet granules.
2. Immediately shake the syringe for approximately 2 minutes to dissolve the tablet.
3. Hold the syringe with the tip pointing up and make sure the tip is not clogged.
4. Connect the syringe to the probe, continuing to hold the syringe pointing upwards.
5. Shake the syringe and turn it upside down. Immediately inject 5–10 ml of the dissolved drug into the tube. After injection, return the syringe to its previous position and shake (the syringe should be held with the tip up to avoid clogging the tip).
6. Turn the syringe tip down and inject another 5–10 ml of the drug into the tube. Repeat this procedure until the syringe is completely empty.
7. Draw 25 ml of water and 5 ml of air into the syringe and repeat step 5 if necessary to flush out any sediment remaining in the syringe. For some probes, draw 50 ml of water if necessary.
Children.
Isomer should not be used in children under 12 years of age, as there is no data on such use.
It is used in children over 12 years of age for the following indications:
Gastroesophageal reflux disease (GERD)
- treatment of erosive reflux esophagitis.
Overdose
Data on overdose are limited. Gastrointestinal symptoms and weakness have been described after taking 280 mg of esomeprazole. A single dose of 80 mg of esomeprazole does not cause serious side effects. No specific antidote is known. Esomeprazole is highly bound to plasma proteins and is therefore not dialysable.
Treatment: symptomatic and supportive therapy.
Adverse reactions
The following adverse reactions have been reported during clinical trials and after the introduction of esomeprazole into widespread medical practice. No dose-related effects were observed. Adverse reactions are classified according to frequency: common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000) and very rare (<1/10000).
Blood and lymphatic system disorders:
rarely: leukopenia, thrombocytopenia;
very rare: agranulocytosis, pancytopenia.
On the part of the immune system:
Rare: hypersensitivity reactions including fever, angioedema, anaphylactic reactions/shock.
From the side of metabolism and nutrition:
uncommon: peripheral edema;
rarely: hyponatremia;
Very rare: hypomagnesemia; severe hypomagnesemia may lead to hypocalcemia.
Mental disorders:
uncommon: insomnia;
Rare: agitation, depression, confusion;
very rare: aggression, hallucinations.
From the nervous system:
common: headache;
infrequently: dizziness, weakness, paresthesia, drowsiness;
Rare: taste disturbance.
On the part of the organs of vision:
Rare: blurred vision.
Hearing and labyrinth disorders:
uncommon: vertigo.
From the respiratory system, chest organs and mediastinum:
Rare: bronchospasm.
From the digestive tract:
often: abdominal pain, constipation, diarrhea, bloating, nausea, vomiting;
uncommon: dry mouth;
rarely: stomatitis, gastrointestinal candidiasis;
very rare: microscopic colitis.
From the hepatobiliary system:
uncommon: increased liver enzymes;
Rare: hepatitis with or without jaundice;
very rare: hepatic failure, encephalopathy in patients with liver disease.
Skin and subcutaneous tissue disorders:
infrequently: dermatitis, itching, urticaria, rash;
Rare: alopecia, photosensitivity;
very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders:
uncommon: fracture of the hip, wrist or spine (see section "Special warnings and precautions for use");
Rare: arthralgia, myalgia;
very rare: muscle weakness.
From the kidneys and urinary system:
very rare: interstitial nephritis (in some patients - simultaneously with renal failure).
From the reproductive system and mammary glands:
very rare: gynecomastia.
General disorders:
Rare: weakness, increased sweating.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging
7 tablets in a blister. 2 or 4 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
LAMP SAN PROSPERO S.P.A./LAMP SAN PROSPERO SPA
Location of the manufacturer and its business address
Via Della Pace, 25/A, 41030 San Prospero (MO), Italy.
Applicant
PERRERY FARMACEUTICI SRL/PERRERY FARMACEUTICI SRL.
Applicant's location
Corso San Lorenzo, 1, 37026 Pescantina (VR), Italy/Corso San Lorenzo, 1, 37026 Pescantina (VR), Italy.
