Controloc

CHARACTERISTICS OF THE MEDICINAL PRODUCT

1. NAME OF THE MEDICINAL PRODUCT

Controloc, 40 mg, powder for solution for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 40 mg of pantoprazole (as pantoprazole sodium).
A full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for solution for injection.
White or almost white substance.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

Controloc is indicated for use in adults in:

• Gastroesophageal reflux disease.
• Peptic ulcer disease and (or) duodenal ulcer.
• Zollinger-Ellison syndrome and other conditions associated with excessive gastric acid secretion.

4.2 Dosage and Administration

The medicinal product should be administered by medical personnel and under medical supervision.
Intravenous administration of Controloc is recommended only when oral administration of pantoprazole is not possible. Available data on intravenous use of the product are limited to 7 days.
If possible, oral therapy with 40 mg pantoprazole tablets should be initiated and intravenous treatment with Controloc discontinued.
Dosage
Gastric ulcer and (or) duodenal ulcer and gastroesophageal reflux disease
The recommended intravenous dose is one vial (40 mg pantoprazole) of Controloc per day.
Zollinger-Ellison syndrome and other conditions associated with excessive gastric acid secretion
Long-term treatment of Zollinger-Ellison syndrome and other conditions associated with excessive gastric acid secretion should be initiated at a daily dose of 80 mg of Controloc.
Subsequently, the dose may be increased or decreased as needed, based on the results of gastric acid secretion tests. Daily doses above 80 mg should be divided and administered twice daily. It is possible to temporarily increase the dose of pantoprazole above 160 mg per day, but it should not be used for longer than necessary to achieve the desired acid suppression.
In cases where rapid acid suppression is required, an initial dose of 2 x 80 mg of Controloc is sufficient in most patients to reduce acid secretion to the desired range (<10 meq h) within 1 hour.
Special patient populations
Patients with impaired liver function
The daily dose of pantoprazole should not exceed 20 mg (half a vial containing 40 mg of pantoprazole) in patients with severe liver impairment (see section 4.4).
Patients with impaired renal function
No dose adjustment is necessary in patients with impaired renal function (see section 5.2).
Elderly patients
No dose adjustment is necessary in elderly patients (see section 5.2).
Children and adolescents
The safety and efficacy of Controloc, powder for solution for injection, in children under 18 years of age have not been established. Therefore, Controloc, powder for solution for injection, is not recommended for use in individuals under 18 years of age.
Currently available data are presented in section 5.2, but there are no dosage recommendations.
Administration
The ready-to-use solution is prepared by dissolving the powder in 10 ml of 0.9% sodium chloride injection solution (concentration 9 mg/ml). Instructions for preparation, see section 6.6. The prepared solution may be administered directly or after mixing with 100 ml of 0.9% sodium chloride injection solution (concentration 9 mg/ml) or 100 ml of 5% glucose injection solution (concentration 55 mg/ml).
The prepared solution must be used within 12 hours.
The medicinal product should be administered intravenously over 2 to 15 minutes.

4.3 Contraindications

Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients listed in section 6.1.

4.4 Special Warnings and Precautions for Use

Gastric cancer
The symptomatic response to pantoprazole may mask the symptoms of gastric cancer and may delay its diagnosis. In the presence of alarm symptoms (such as significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, anemia, melena) and when gastric ulcer is suspected or confirmed, malignancy should be excluded.
Further investigations should be considered in patients with persistent symptoms despite adequate treatment.
Impaired liver function
In patients with severe liver impairment, liver enzymes should be monitored regularly. If liver enzymes increase, treatment should be discontinued (see section 4.2).
Concomitant use with HIV protease inhibitors
Concomitant use of pantoprazole with HIV protease inhibitors, whose absorption is dependent on acidic gastric pH, such as atazanavir, is not recommended, as it may significantly decrease their bioavailability (see section 4.5).
Gastrointestinal infections caused by bacteria
Treatment with Controloc may increase the risk of gastrointestinal infections caused by bacteria of the Salmonella and Campylobacter or Clostridium difficile families.
Hypomagnesemia
In patients treated with proton pump inhibitors (PPIs), including pantoprazole, for at least three months and in most cases for one year, rare cases of severe hypomagnesemia have been reported. Symptoms of severe hypomagnesemia, such as fatigue, tetany, delirium, seizures, dizziness, and cardiac arrhythmias, may develop insidiously and may not be recognized. Hypomagnesemia may lead to hypocalcemia and (or) hypokalemia (see section 4.8). In patients with the highest severity of hypomagnesemia (and hypomagnesemia-related hypocalcemia and (or) hypokalemia), discontinuation of PPIs and initiation of magnesium supplementation led to improvement.
In patients taking PPIs for a prolonged period and in patients taking PPIs with digoxin or other products that may cause hypomagnesemia (e.g., diuretics), healthcare professionals should consider measuring magnesium levels before starting PPI therapy and periodically during treatment.
Fractures
The use of proton pump inhibitors, especially at high doses and in long-term therapy (more than 1 year), may slightly increase the risk of fractures of the hip, wrist, or spine, particularly in elderly patients or patients with other risk factors. Observational studies suggest that PPIs may increase the overall risk of fractures by 10-40%. The increase in risk may also be due to other factors. Patients at risk of osteoporosis should be treated in accordance with clinical guidelines to ensure adequate intake of vitamin D and calcium.
Severe cutaneous adverse reactions (SCAR)
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of pantoprazole, with an unknown frequency. These reactions may be life-threatening or fatal (see section 4.8).
When prescribing the medicinal product, patients should be informed about the signs and symptoms and closely monitored for skin reactions.
In the event of signs and symptoms indicating these reactions, pantoprazole should be discontinued immediately and alternative treatment considered.
Subacute cutaneous lupus erythematosus (SCLE)
The use of proton pump inhibitors is associated with the rare occurrence of SCLE. If skin lesions occur, especially in sun-exposed areas, with joint pain, the patient should seek medical attention immediately, and the doctor should consider discontinuing Controloc.
The occurrence of SCLE due to previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Effect on laboratory tests
An increase in chromogranin A (CgA) levels may interfere with investigations for neuroendocrine tumors. To avoid this, treatment with Controloc should be discontinued at least 5 days before measuring CgA levels (see section 5.1). If CgA and gastrin levels are still elevated after initial measurement, measurements should be repeated after 14 days of discontinuation of PPI treatment.
Controloc contains sodium.
This medicinal product contains less than 1 mmol of sodium (23 mg) per vial, i.e., it is considered "sodium-free".

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

Medicinal products whose pharmacokinetics is dependent on gastric pH
Due to the strong and long-lasting inhibition of gastric acid secretion by pantoprazole, it may interfere with the absorption of other medicinal products, for which gastric pH is an important factor influencing bioavailability, such as some azole antifungals, e.g., ketoconazole, itraconazole, posaconazole, and other drugs, such as erlotinib.
HIV protease inhibitors
Concomitant use of pantoprazole with HIV protease inhibitors, whose absorption is dependent on acidic gastric pH, such as atazanavir, is not recommended, as it may significantly decrease their bioavailability (see section 4.4).
If concomitant use of HIV protease inhibitors with a proton pump inhibitor is necessary, close monitoring of clinical status is recommended (e.g., viral load). A dose of more than 20 mg of pantoprazole per day should not be used. It may be necessary to adjust the dose of the HIV protease inhibitor.
Anticoagulants of the coumarin type (phenprocoumon or warfarin)
Concomitant use of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon, or the change in INR (International Normalized Ratio). However, increased INR and prothrombin time have been reported in patients taking PPIs and warfarin or phenprocoumon concomitantly. The increase in INR and prothrombin time may lead to abnormal bleeding and even death. In patients treated concomitantly with pantoprazole and warfarin or phenprocoumon, it may be necessary to monitor the increase in INR and prothrombin time.
Methotrexate
In some patients, concomitant use of high-dose methotrexate (e.g., 300 mg) with proton pump inhibitors has led to increased methotrexate levels. Therefore, in patients taking high-dose methotrexate, e.g., for malignancy or psoriasis, it is recommended to temporarily discontinue pantoprazole use.
Other interaction studies
Pantoprazole is extensively metabolized in the liver, mainly by the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19, and other metabolic pathways include oxidation by CYP3A4.
Interaction studies with other medicinal products, which are metabolized by the same enzyme system, such as carbamazepine, diazepam, glibenclamide, nifedipine, and oral contraceptives containing levonorgestrel and ethinylestradiol, did not reveal clinically significant interactions.
It cannot be excluded that pantoprazole interacts with other medicinal products or compounds, which are metabolized by the same enzyme system.
Results from interaction studies indicate that pantoprazole does not affect the metabolism of substances metabolized by CYP1A2 (e.g., caffeine, theophylline), CYP2C9 (e.g., piroxicam, diclofenac, naproxen), CYP2D6 (e.g., metoprolol), CYP2E1 (e.g., ethanol), and does not interfere with P-glycoprotein-mediated digoxin absorption.
No interactions were found with concomitantly used antacids.
Interaction studies were also conducted in which pantoprazole was administered concomitantly with the relevant antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically significant interactions were found.
Medicinal products that inhibit or induce CYP2C19
CYP2C19 inhibitors, such as fluvoxamine, may increase the systemic exposure to pantoprazole. It is recommended to consider a dose reduction in patients treated long-term with high doses of pantoprazole or in patients with impaired liver function.
CYP2C19 and CYP3A4 inducers, such as rifampicin or St. John's Wort (Hypericum perforatum), may decrease the plasma concentrations of proton pump inhibitors, metabolized by these enzyme systems.
Effect on laboratory tests
In some urine screening tests for tetrahydrocannabinol (THC), false-positive results have been reported in patients taking pantoprazole. Alternative testing methods should be considered to verify positive results.

4.6 Fertility, Pregnancy, and Lactation

Pregnancy
A moderate amount of data in pregnant women (between 300-1000 pregnant women) does not indicate that pantoprazole causes malformations or has other harmful effects on the fetus and newborn. In animal studies, adverse effects on reproduction have been observed (see section 5.3). As a precautionary measure, it is recommended to avoid the use of Controloc during pregnancy.
Breast-feeding
In animal studies, pantoprazole has been detected in breast milk. There are no sufficient data on the passage of pantoprazole into human milk, but there are reports of such passage. It cannot be excluded that adverse reactions may occur in the newborn/infant breastfed. Therefore, a decision should be made to either discontinue breast-feeding or to discontinue/avoid the use of Controloc, taking into account the benefits of breast-feeding for the child and the benefits of treatment for the mother.
Fertility
In animal studies, no impairment of fertility has been observed after administration of pantoprazole (see section 5.3).

4.7 Effects on Ability to Drive and Use Machines

Pantoprazole has no or negligible influence on the ability to drive and use machines.
Adverse reactions, such as dizziness and visual disturbances (see section 4.8), may occur. In such cases, patients should not drive vehicles or operate machinery.

4.8 Undesirable Effects

Undesirable effects may occur in approximately 5% of patients (ADRs - adverse drug reactions).
In the following table, undesirable effects are classified according to the following frequency:
Very common (≥1/10); common (≥1/100 to <1>For all undesirable effects reported after the medicinal product was placed on the market, it is not possible to apply a frequency classification, so their frequency is marked as "not known".
Within each frequency group, undesirable effects are listed in order of decreasing severity.
Table 1. Undesirable effects associated with the use of pantoprazole reported in clinical trials and after marketing authorization

Hypocalcemia and (or) hypokalemia may be associated with the occurrence of hypomagnesemia (see section 4.4)
Muscle spasms due to electrolyte disturbances
Reporting suspected adverse reactions
After the medicinal product has been placed on the market, it is important to report any suspected adverse reactions. This allows for the continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the Department of Adverse Reaction Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl .
Adverse reactions can also be reported to the marketing authorization holder.

4.9 Overdose

No symptoms of overdose are known in humans.
Doses of up to 240 mg administered intravenously over 2 minutes were well tolerated. Since pantoprazole is extensively bound to plasma proteins, it is not easily dialyzable.
In the event of overdose with clinical symptoms of poisoning, apart from symptomatic and supportive treatment, there are no specific therapeutic recommendations.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

Therapeutic group: proton pump inhibitors, ATC code: A02BC02
Mechanism of action
Pantoprazole is a substituted benzimidazole, which inhibits gastric acid secretion by specifically blocking the proton pump in parietal cells.
In the acidic environment of parietal cells, pantoprazole is converted to its active form and inhibits the activity of H+K+-ATPase, i.e., the final stage of gastric acid production. The degree of inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, symptom relief is achieved within 2 weeks. As with other proton pump inhibitors and H2 receptor antagonists, treatment with pantoprazole leads to a decrease in gastric acidity and a secondary increase in gastrin secretion in response to decreased acid secretion.
The increase in gastrin secretion is reversible. Since pantoprazole binds to the enzyme at the receptor level, it can affect acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the drug is administered orally or intravenously.
Pharmacodynamic effects
Fasting gastrin levels increase under the influence of pantoprazole. During short-term use, these values do not exceed the upper limit of normal in most cases. During long-term treatment, gastrin levels in most cases double. However, excessive increases in gastrin levels occur only in rare cases. As a result, in rare cases of long-term treatment, mild to moderate increases in the number of specific ECL cells in the stomach (simple to nodular hyperplasia) have been observed. However, according to the studies conducted so far, the development of preneoplastic changes (atypical hyperplasia) or gastric carcinoids, which have been observed in animal studies (see section 5.3), has not been observed in humans.
In the case of long-term therapy, when pantoprazole treatment lasts more than one year, according to animal studies, it cannot be entirely excluded that pantoprazole may have an effect on the parameters of thyroid function.
During treatment with anti-secretory medicinal products, gastrin levels in serum increase in response to decreased acid secretion. CgA levels also increase due to decreased intragastric acidity. The increase in CgA levels may interfere with investigations for neuroendocrine tumors.
Available published evidence suggests that treatment with proton pump inhibitors should be discontinued 5 to 2 weeks before measuring CgA levels. This is intended to allow CgA levels, which may be falsely elevated due to treatment with proton pump inhibitors, to return to reference values.

5.2 Pharmacokinetic Properties

General pharmacokinetics
There are no differences in the pharmacokinetics of the product after single or repeated administration of the dose.
Within the dose range of 10 to 80 mg, the pharmacokinetics of pantoprazole in plasma is linear, both after oral and intravenous administration.
Distribution
Pantoprazole is bound to plasma proteins at approximately 98%. The volume of distribution is approximately 0.15 l/kg.
Metabolism
The substance is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19, and other metabolic pathways include oxidation by CYP3A4.
Elimination
The terminal half-life is approximately 1 hour, and clearance is approximately 0.1 l/h/kg.
A few cases of delayed elimination have been reported. Since pantoprazole specifically binds to the proton pump in parietal cells, the half-life for the elimination phase does not correlate with the longer duration of action (inhibition of acid secretion). The metabolites of pantoprazole are excreted mainly by the kidneys (approximately 80%), and the rest is excreted in the feces. The main metabolite in both serum and urine is demethylpantoprazole, which is conjugated with sulfate. The half-life of the main metabolite (approximately 1.5 hours) is not much longer than the half-life of pantoprazole.
Special patient populations
Poor metabolizers
In approximately 3% of the European population, defined as poor metabolizers, the functional enzyme CYP2C19 is not present. In these individuals, the metabolism of pantoprazole is probably catalyzed mainly by CYP3A4. After administration of a single dose of 40 mg of pantoprazole, the mean area under the plasma concentration-time curve was 6 times higher in poor metabolizers compared to individuals with a functional CYP2C19 enzyme (extensive metabolizers). The mean maximum plasma concentrations increased by approximately 60%. These data do not affect the dosing of pantoprazole.
Patients with impaired renal function
No dose reduction is necessary in patients with impaired renal function (including patients on dialysis). As in healthy individuals, the half-life of pantoprazole is short. Only small amounts of pantoprazole are removed during dialysis. Although the half-life of the main metabolite is moderately prolonged (2-3 hours), elimination is still rapid, and no accumulation of the product occurs.
Patients with impaired liver function
In patients with liver cirrhosis (Child A and B), the half-life is prolonged to 7-9 hours, and AUC values increase 5-7-fold. However, the maximum plasma concentration increases only slightly, 1.5-fold, compared to healthy individuals.
Elderly patients
A slight increase in AUC and maximum plasma concentration (C) in elderly volunteers compared to younger volunteers is not clinically significant.
Children and adolescents
After a single intravenous administration of pantoprazole to children aged 2-16 years at a dose of 0.8 or 1.6 mg/kg body weight, no significant relationship was found between the clearance of pantoprazole and age or body weight. The AUC and volume of distribution were consistent with the data obtained in adults.

5.3 Preclinical Safety Data

Non-clinical data from conventional pharmacological studies on safety, repeated dose toxicity, and genotoxicity do not indicate any special hazard for humans.
In two-year carcinogenicity studies in rats, the occurrence of neuroendocrine tumors was observed. Additionally, in rats, the occurrence of squamous cell papillomas in the forestomach was observed. The mechanism leading to the development of gastric carcinoids by substituted benzimidazoles has been extensively studied and allows us to conclude that it is a secondary reaction to significantly increased gastrin levels in the blood, which occur in rats during long-term treatment with high doses. In two-year studies, an increased number of cases of liver tumors was observed in rats and female mice, which was attributed to the high rate of pantoprazole metabolism in the liver.
In the case of rats receiving the highest doses of pantoprazole (200 mg/kg body weight), a slight increase in the frequency of thyroid tumors was observed. The occurrence of these tumors is associated with changes in the distribution of thyroxine in the liver of rats caused by pantoprazole. Since therapeutic doses in humans are low, no adverse effects on the thyroid gland are expected.
In a study on the effect on reproduction in rats during the postpartum period, aimed at assessing bone development, signs of toxicity were observed in the offspring (mortality, lower average body weight, lower average weight gain, and reduced bone growth) at exposure (C) corresponding to approximately 2 times the clinical exposure in humans. At the end of the recovery phase, bone parameters were similar in all groups, and body weights also showed a tendency to reversibility after the end of the recovery phase without drug administration. Increased mortality was observed only in young rats before the end of breastfeeding (up to 21 days), which is estimated to correspond to infants up to 2 years of age. The significance of this observation for the population of children and adolescents is unknown. An earlier study in rats during the perinatal period, with slightly lower doses, did not show any adverse effects at a dose of 3 mg/kg body weight compared to a low dose of 5 mg/kg body weight used in this study.
Studies have not shown any effect on fertility or teratogenic effects of the product.
Studies in rats on the passage through the placental barrier have shown increased passage into fetal circulation in late pregnancy. As a result, the concentration of pantoprazole in the fetus is increased shortly before birth.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

Disodium edetate
Sodium hydroxide (for pH adjustment)

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products, except for those mentioned in section 6.6.

6.3 Shelf Life

Product before opening: 2 years
Chemical and physical stability of the solution after reconstitution and after reconstitution and dilution for 12 hours at 25°C has been demonstrated.
Due to microbiological purity, the solution should be used immediately after preparation.
If the solution is not used immediately after preparation, the time and conditions of storage are the responsibility of the user.

6.4 Special Precautions for Storage

Do not store above 25°C.
Store the vial in the outer packaging to protect from light.
Storage conditions for the medicinal product after reconstitution and dilution, see section 6.3.

6.5 Nature and Contents of Container

Vial with a volume of 10 ml, made of colorless glass (type I) closed with a gray stopper and protected with an aluminum seal, containing 40 mg of powder for solution for injection.
Packaging: 1 vial or bulk packaging of 5 vials (5 packs of 1 vial) with powder for solution for injection.
Hospital packaging: 1 vial with powder for solution for injection.
Hospital bulk packaging: 5 vials (5 packs of 1 vial), 10 vials (10 packs of 1 vial), or 20 vials (20 packs of 1 vial) with powder for solution for injection.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal and Preparation of the Medicinal Product

for use
The ready-to-use solution is prepared by injecting 10 ml of 0.9% sodium chloride injection solution (concentration 9 mg/ml) into the vial containing the powder. After preparation, the product has the appearance of a clear yellow solution. The prepared solution may be administered directly or after mixing with 100 ml of 0.9% sodium chloride injection solution (concentration 9 mg/ml) or 100 ml of 5% glucose injection solution (concentration 55 mg/ml). For dilution, glass or plastic containers should be used.
Chemical and physical stability of the solution after reconstitution and after reconstitution and dilution for 12 hours at 25°C has been demonstrated.
Due to microbiological purity, the solution should be used immediately after preparation.
Controloc should not be reconstituted or mixed with solvents other than those specified above.
The medicinal product should be administered intravenously over 2 to 15 minutes.
The contents of the vial are intended for single use. Any amount of the product remaining in the vial or product whose appearance has changed (e.g., if the solution has become cloudy or precipitated) should be disposed of in accordance with local regulations.

7. MARKETING AUTHORIZATION HOLDER

RESPONSIBLE FOR BATCH RELEASE

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
Phone: +48 22 608 13 00
Fax: +48 22 608 13 03

8. MARKETING AUTHORIZATION NUMBER

8330

9. DATE OF FIRST MARKETING AUTHORIZATION

AND DATE OF LAST RENEWAL

Date of first marketing authorization: November 10, 2000
Date of last renewal: August 4, 2010

10. DATE OF REVISION OF THE TEXT

OF THE SUMMARY OF PRODUCT CHARACTERISTICS

April 26, 2023

LABELING OF OUTER PACKAGING

INFORMATION TO BE INCLUDED ON OUTER PACKAGING

UNIT CARTON OF SINGLE PACKAGING

1. NAME OF THE MEDICINAL PRODUCT

Controloc, 40 mg, powder for solution for injection
pantoprazolum

2. CONTENTS OF THE ACTIVE SUBSTANCE

Each vial contains 40 mg of pantoprazole (in the form of pantoprazole sodium).

3. LIST OF EXCIPIENTS

Excipients: disodium edetate, sodium hydroxide.
For further information, please refer to the package leaflet.

4. PHARMACEUTICAL FORM AND CONTENTS OF THE PACKAGING

Powder for solution for injection.
Packaging: 1 vial, code 5909990833016
Packaging: 5 vials (5 packs of 1 vial): code 5909990833023
Hospital packaging: 1 vial, code 5909990833016

5. METHOD AND ROUTE OF ADMINISTRATION

Intravenous administration.
For further information, please refer to the package leaflet before using the medicinal product.

6. SPECIAL WARNING ABOUT STORAGE OF THE MEDICINAL PRODUCT

OUT OF SIGHT AND REACH OF CHILDREN

Store the medicinal product out of sight and reach of children.

7. OTHER SPECIAL WARNINGS, IF NECESSARY

8. EXPIRY DATE

EXP:
Shelf life of the solution after preparation: 12 hours.

9. STORAGE CONDITIONS

Do not store above 25°C.
Store the vial in the outer packaging to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCT OR WASTE DERIVED FROM IT, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORIZATION HOLDER

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
((logo))

12. MARKETING AUTHORIZATION NUMBER

Marketing authorization number: 8330

13. BATCH NUMBER

Batch number (Lot):

14. GENERAL CATEGORY OF AVAILABILITY

Rp - Medicinal product subject to medical prescription.

15. INSTRUCTIONS FOR USE

16. INFORMATION PROVIDED IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

Includes a 2D barcode that is a carrier of a unique identifier.

18. UNIQUE IDENTIFIER – HUMAN-READABLE DATA

PC:
SN:
NN:

LABELING OF OUTER PACKAGING

LABEL ON HOSPITAL BULK PACKAGING (CELLOPHANE PACKAGING) WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Controloc, 40 mg, powder for solution for injection
pantoprazolum

2. CONTENTS OF THE ACTIVE SUBSTANCE

Each vial contains 40 mg of pantoprazole (in the form of pantoprazole sodium).

3. LIST OF EXCIPIENTS

Excipients: disodium edetate, sodium hydroxide.
For further information, please refer to the package leaflet.

4. PHARMACEUTICAL FORM AND CONTENTS OF THE PACKAGING

Powder for solution for injection.
Hospital bulk packaging: 5 vials (5 packs of 1 vial): code 5909990833023
Hospital bulk packaging: 10 vials (10 packs of 1 vial): code 5909990833030
Hospital bulk packaging: 20 vials (20 packs of 1 vial): code 5909990833047

5. METHOD AND ROUTE OF ADMINISTRATION

Intravenous administration.
For further information, please refer to the package leaflet before using the medicinal product.

6. SPECIAL WARNING ABOUT STORAGE OF THE MEDICINAL PRODUCT

OUT OF SIGHT AND REACH OF CHILDREN

Store the medicinal product out of sight and reach of children.

7. OTHER SPECIAL WARNINGS, IF NECESSARY

8. EXPIRY DATE

EXP:
Shelf life of the solution after preparation: 12 hours.

9. STORAGE CONDITIONS

Do not store above 25°C.
Store the vial in the outer packaging to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCT OR WASTE DERIVED FROM IT, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORIZATION HOLDER

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
((logo))

12. MARKETING AUTHORIZATION NUMBER

Authorization No. 8330

13. BATCH NUMBER

Batch Number (Lot):

14. GENERAL CATEGORY OF AVAILABILITY

Rp - Prescription-only medicine.

15. INSTRUCTIONS FOR USE

16. INFORMATION PROVIDED IN BRAILLE

17. UNIQUE IDENTIFIER - 2D CODE

Includes a 2D code that is a carrier of a unique identifier.

18. UNIQUE IDENTIFIER - HUMAN-READABLE DATA

PC:
SN:
NN:

INFORMATION TO BE INCLUDED ON THE INNER PACKAGING

INNER PACKAGING OF HOSPITAL PACKAGING (WITHOUT BLUE BOX)

1. NAME OF THE MEDICINAL PRODUCT

Controloc, 40 mg, powder for solution for injection
pantoprazolum

2. CONTENT OF ACTIVE SUBSTANCE

Each vial contains 40 mg of pantoprazole (in the form of pantoprazole sodium).

3. LIST OF EXCIPIENTS

Excipients: disodium edetate, sodium hydroxide.
You should read the leaflet to get more information.

4. PHARMACEUTICAL FORM AND CONTENT OF THE PACKAGING

Powder for solution for injection.
1 vial
Element of hospital collective packaging, cannot be sold separately.

5. METHOD AND ROUTE OF ADMINISTRATION

Intravenous administration.
You should read the leaflet before using the medicine.

6. WARNING ABOUT STORAGE OF THE MEDICINAL PRODUCT

IN A PLACE INVISIBLE AND INACCESSIBLE TO CHILDREN

Medicine should be stored in a place invisible and inaccessible to children.

7. OTHER SPECIAL WARNINGS, IF NECESSARY

8. EXPIRY DATE

EXP:
Storage time of the solution after preparation: 12 hours.

9. STORAGE CONDITIONS

Do not store above 25°C.
Store the vial in the outer packaging to protect it from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED

MEDICINAL PRODUCT OR WASTE DERIVED FROM IT, IF

APPLICABLE

11. NAME AND ADDRESS OF THE MARKETING AUTHORIZATION HOLDER

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
((logo))

12. MARKETING AUTHORIZATION NUMBER

Authorization No. 8330

13. BATCH NUMBER

Batch Number (Lot):

14. GENERAL CATEGORY OF AVAILABILITY

Rp - Prescription-only medicine.

15. INSTRUCTIONS FOR USE

16. INFORMATION PROVIDED IN BRAILLE

17. UNIQUE IDENTIFIER - 2D CODE

Not applicable

18. UNIQUE IDENTIFIER - HUMAN-READABLE DATA

Not applicable

MINIMUM INFORMATION TO BE INCLUDED ON SMALL PACKAGINGS

DIRECT

LABEL ON THE VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION

Controloc, 40 mg, powder for solution for injection
pantoprazolum
Intravenous administration.

2. METHOD OF ADMINISTRATION

You should read the leaflet before using the medicine.

3. EXPIRY DATE

EXP:
Storage time of the solution after preparation: 12 hours.

4. BATCH NUMBER

Lot:

5. CONTENT OF THE PACKAGING WITH ADMINISTRATION OF MASS, VOLUME OR NUMBER

OF UNITS

40 mg

6. OTHER

Do not store above 25°C.
Store the vial in the outer packaging to protect it from light.

PATIENT INFORMATION LEAFLET

Leaflet attached to the packaging: information for the patient

Controloc, 40 mg, powder for solution for injection

pantoprazolum

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Controloc and what is it used for
• 2. Important information before taking Controloc
• 3. How to take Controloc
• 4. Possible side effects
• 5. How to store Controloc
• 6. Contents of the packaging and other information

1. What is Controloc and what is it used for

Controloc contains the active substance pantoprazole. Controloc is a selective "proton pump inhibitor", a medicine that reduces the secretion of acid in the stomach. It is used to treat stomach and intestinal diseases related to the secretion of hydrochloric acid.
This medicine is given intravenously and is used only when, in the doctor's opinion, this route of administration is more beneficial for the patient than taking pantoprazole in tablet form. The intravenous medicine will be replaced with a tablet form as soon as the doctor considers it appropriate.

Controloc is used in adults for the treatment of

• Reflux esophagitis. Esophagitis (the section connecting the throat to the stomach) is accompanied by the reflux of hydrochloric acid from the stomach.
• Gastric and (or) duodenal ulcer disease.
• Zollinger-Ellison syndrome and other conditions associated with excessive secretion of hydrochloric acid in the stomach.

2. Important information before taking Controloc

When not to take Controloc

• If you are allergic to pantoprazole or any of the other ingredients of this medicine (listed in section 6).
• If you have been diagnosed with an allergy to medicines containing other proton pump inhibitors.

Warnings and precautions

Before starting to take Controloc, you should inform your doctor, pharmacist, or nurse.

• If you have severe liver function disorders. You should inform your doctor if you have ever had liver function disorders in the past. Your doctor may order more frequent monitoring of liver enzyme activity. If liver enzyme activity increases, the use of the medicine should be discontinued.
• If you are taking HIV protease inhibitors such as atazanavir (used to treat HIV infection), you should ask your doctor for detailed advice.
• Taking a proton pump inhibitor like pantoprazole, especially for a period of more than 1 year, may slightly increase the risk of hip, wrist, or spine fractures. You should tell your doctor if you have osteoporosis (reduced bone density) or if your doctor has informed you that you are at risk of osteoporosis (e.g., if you are taking steroid medicines).
• If you take Controloc for a period longer than three months, you may experience a decrease in magnesium levels in the blood, which can cause fatigue, tetany, disorientation, seizures, dizziness, and ventricular arrhythmias. If you experience any of these symptoms, you should inform your doctor. Low magnesium levels in the blood can also cause a decrease in potassium and calcium levels in the blood. Your doctor may decide to periodically check your magnesium levels in the blood.
• If you have ever experienced a skin reaction after taking a medicine similar to Controloc, which reduces the secretion of hydrochloric acid in the stomach.
• If you have ever experienced a skin rash, especially in areas exposed to sunlight, you should tell your doctor as soon as possible, as it may be necessary to discontinue the use of Controloc. You should also tell your doctor about any other side effects, such as joint pain.
• Severe skin reactions have been reported with pantoprazole, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and erythema multiforme. You should discontinue taking pantoprazole and seek medical advice immediately if you notice any symptoms related to these severe skin reactions described in section 4.
• About a planned specific blood test (chromogranin A levels).

You should immediately inform your doctor,before starting or during the use of the medicine,
if you experience any of the following symptoms, which may be a sign of a more serious disease:

• unintentional weight loss;
• vomiting, especially if it is recurrent;
• bloody vomiting, which may look like dark coffee grounds;
• blood in the stool, black or tarry stool;
• difficulty swallowing or pain when swallowing;
• pallor and weakness (anemia);
• chest pain;
• abdominal pain;
• severe and (or) persistent diarrhea, as the use of this medicine is associated with a slight increase in the risk of infectious diarrhea.

Your doctor may decide to perform tests to rule out an underlying malignant disease, as treatment with pantoprazole may alleviate the symptoms of the malignant disease and delay its diagnosis. If the symptoms persist despite treatment, further tests should be considered.

Children and adolescents

Controloc is not recommended for use in children, as its effect has not been studied in children under the age of 18.

Controloc and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those that are available without a prescription.
Since Controloc may affect the effectiveness of other medicines, you should inform your doctor if you are taking:

• Medicines such as ketoconazole, itraconazole, and posaconazole (used to treat fungal infections) or erlotinib (used to treat certain types of cancer), as Controloc may inhibit the proper functioning of these and other medicines.
• Warfarin and phenprocoumon, which affect blood density and prevent blood clots. Further tests may be necessary.
• Medicines used to treat HIV infection, such as atazanavir.
• Methotrexate (used to treat rheumatoid arthritis, psoriasis, and cancer) - if you are taking methotrexate, your doctor may temporarily discontinue the use of Controloc, as pantoprazole may increase the levels of methotrexate in the blood.
• Fluvoxamine (used to treat depression and other mental disorders) - if you are taking fluvoxamine, your doctor may order a dose reduction.
• Rifampicin (used to treat infections).
• St. John's Wort (Hypericum perforatum) (used to treat mild depression).

Before starting to take pantoprazole, you should discuss it with your doctor if you are to undergo a specific urine test [for the presence of tetrahydrocannabinol (THC)].

Pregnancy and breastfeeding and fertility

Experience with the use of Controloc in pregnant women is limited. It has been found that the active substance of the medicine passes into human milk.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should ask your doctor or pharmacist for advice before taking this medicine.
The medicine may be used in pregnant women or women who are breastfeeding, or women who may become pregnant, only if the doctor considers that the benefit of its use is greater than the potential risk to the unborn child or infant.

Driving and using machines

Controloc has no effect or has a negligible effect on the ability to drive vehicles and operate machinery.
You should not drive vehicles or operate machinery if you experience side effects such as dizziness or vision disturbances.

Controloc contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which means that the medicine is considered "sodium-free".

3. How to take Controloc

The medicine is administered intravenously in a single daily dose over a period of 2-15 minutes by a nurse or doctor.
Recommended dose:

Adults

• -In the treatment of gastric and (or) duodenal ulcer disease and reflux esophagitisOne vial (40 mg of pantoprazole) per day.
• -In long-term treatment of Zollinger-Ellison syndrome and other diseases associated with excessive secretion of hydrochloric acid in the stomachTwo vials (80 mg of pantoprazole) per day. The dosage may be adjusted by the doctor, depending on the amount of acid secreted. Daily doses greater than 2 vials (80 mg) should be administered in two equal doses. It is possible to periodically increase the dose of pantoprazole to more than four vials (160 mg) per day. For rapid control of acid secretion, the initial dose of 160 mg (4 vials) should be sufficient to reduce acid secretion.

Patient with liver function disorders

In severe liver disease, the daily dose should be only 20 mg (½ vial).

Use in children and adolescents

Controloc is not recommended for use in children and adolescents under the age of 18.

Overdose of Controloc

The doctor or nurse will carefully check the dosage, so overdose of the medicine is unlikely. The symptoms of overdose are not known.
If you have any further questions about the use of this medicine, you should ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Controloc can cause side effects, although not everybody gets them.

In case of experiencing any of the following side effects, you should immediately inform your doctor or contact the nearest hospital where emergency services are provided:

• Severe allergic reactions (rare: less frequent than 1 in 1000 people):swelling of the tongue and (or) throat, difficulty swallowing, hives (rash like nettle burn), difficulty breathing, allergic swelling of the face (Quincke's edema/angioedema), severe dizziness with rapid heartbeat and profuse sweating.
• Severe skin reactions (frequency unknown: frequency cannot be determined based on available data):the patient may notice one or more of the following symptoms
• blistering of the skin and rapid deterioration of the general condition, erosion (with slight bleeding) of the eyes, nose, mouth/ lips or genitals, or rash, especially in areas of the skin exposed to sunlight. Joint pain or flu-like symptoms, fever, swelling of the lymph nodes (e.g., in the armpits), and changes in white blood cells or liver enzymes may also occur.
• red, non-raised spots or round patches on the torso, often with blisters in the center, peeling of the skin, ulceration of the mouth, throat, nose, genitals, and eyes. The appearance of such a severe skin rash may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• widespread rash, high fever, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
• Other severe reactions (frequency unknown: frequency cannot be determined based on available data):yellowing of the skin and eyes (severe liver cell damage, jaundice) or fever, rash, and kidney problems manifested by their enlargement, sometimes with pain when urinating and pain in the lower back (severe kidney inflammation), which can lead to kidney failure.

Other known side effects that occur:

• Frequent(less frequent than 1 in 10 people) Inflammation of blood vessel walls and blood clots (thrombophlebitis) at the injection site; mild gastric polyps.
• Uncommon(less frequent than 1 in 100 people) Headache; dizziness; diarrhea; nausea, vomiting; feeling of fullness in the abdominal cavity and bloating with gas (gas); constipation; dry mouth; abdominal pain and discomfort; skin rash, redness, skin eruptions; itching; weakness, fatigue, or general malaise; sleep disturbances; fractures of the hip, wrist, or spine.
• Rare(less frequent than 1 in 1000 people) Disturbances or complete loss of taste; vision disturbances, such as blurred vision; hives; joint pain; muscle pain; changes in body weight; elevated body temperature; high fever; swelling of the limbs (peripheral edema); allergic reactions; depression; breast enlargement in men.
• Very rare(less frequent than 1 in 10,000 people) Disorientation.
• Frequency unknown(frequency cannot be determined based on available data) Hallucinations, confusion (especially in patients who have experienced such symptoms before); feeling of tingling, prickling, tingling, burning, or numbness, rash that may be accompanied by joint pain, colitis (inflammation of the large intestine) causing persistent watery diarrhea.

Side effects detected by blood tests that occur:

• Uncommon(less frequent than 1 in 100 people) Increased liver enzyme activity.
• Rare(less frequent than 1 in 1000 people) Increased bilirubin levels; increased fat levels in the blood; associated with high fever, sudden decrease in the number of circulating granulocytes - white blood cells.
• Very rare(less frequent than 1 in 10,000 people) Decreased platelet count, which can cause more frequent bleeding and bruising; decreased white blood cell count, which can contribute to more frequent infections; concurrent, abnormal decrease in the number of red and white blood cells, as well as platelets.
• Frequency unknown(frequency cannot be determined based on available data) Decreased levels of sodium, magnesium, calcium, or potassium in the blood (see section 2).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Controloc

Store in a place invisible and inaccessible to children.
Do not use this medicine after the expiry date stated on the box and vial after the expiry date.
Do not store above 25°C.
Store the vial in the outer packaging to protect it from light.
The solution after reconstitution should be used within 12 hours.
The reconstituted and diluted solution should be used within 12 hours.
Due to the maintenance of microbiological purity, the solution should be used immediately after preparation. If the solution is not used immediately after preparation, the user is responsible for the time and conditions of storage before use. It is not recommended to store the solution for more than 12 hours at a temperature not exceeding 25°C.
Do not use Controloc if its appearance has changed (e.g., the solution has become cloudy or precipitate has formed).
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Controloc contains

• The active substance of the medicine is pantoprazole. Each vial contains 40 mg of pantoprazole (in the form of pantoprazole sodium).
• Other ingredients are: disodium edetate, sodium hydroxide (for pH adjustment).

What Controloc looks like and what the packaging contains

Controloc is a white or almost white powder for solution for injection.
A 10 ml vial made of colorless glass, closed with a gray rubber stopper and protected with an aluminum cap, containing 40 mg of powder for solution for injection.
Controloc is available in the following packaging:
Packaging with 1 vial.
Collective packaging with 5 vials (5 packages of 1 vial).
Hospital packaging with 1 vial.
Hospital collective packaging with 5 vials (5 packages of 1 vial).
Hospital collective packaging with 10 vials (10 packages of 1 vial).
Hospital collective packaging with 20 vials (20 packages of 1 vial).
Not all packaging sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
medinfoEMEA@takeda.com

Manufacturer

Takeda GmbH
Manufacturing site Singen
Robert-Bosch-Strasse 8
78224 Singen
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of the leaflet: 04/2023