PROXIUMTM (injection solution)

APPROVED

by Order of the Ministry of Health

of Ukraine

as of 13.05.09 No. 331

Registration Certificate

No. UA/9651/01/01

INSTRUCTION

For medical application of drug

PROXIUMTM

 

 

Drug Formulation:

active substance: pantoprazole;

1 vial contains pantoprazole 40 mg;

adjuvant: mannitol (E421).

 

Dosage Form. Powder for preparation of injection solution.

Pharmacotherapeutic Group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. Pantoprazole.

ATC Code A02B C02.

Clinical Characteristics.

Indications. Exacerbated stage of stomach or duodenal ulcer, moderate and severe reflux-esophagitis, Zollinger-Ellison syndrome and other pathologic hypersecretory conditions.

Contraindications.

Hypersensitivity to pantoprazole or any other component of the drug. The drug should not be taken with atazanavir.

 

Method of Application and Dosage.

Intravenous introduction of pantoprazole is recommended only in case when its oral application is impossible.

Recommended doses.

Peptic ulcer of stomach and duodenum, reflux-esophagitis of moderate and severe degree. 1 vial (40 mg of pantoprazole) per day intravenously. Peptic ulcers complicated by gastrointestinal bleedings with the purpose of prevention of repeated bleeding – 80 mg of pantoprazole intravenously painfully, then in the form of dropping infusion 8 mg/hour within 9 days.

Long-term treatment of Zollinger-Ellison syndrome and other pathologic hypersecretory conditions.

The initial daily dose is 80 mg of pantoprazole. If necessary the dose may be titrated by increasing or reducing it depending on the gastric acid secretion indices. Doses that exceed 80 mg/day should be divided for 2 introductions. Temporary increase in pantoprazole dose over 160 mg is possible, but the duration of application should be limited to the period required for adequate control of acid secretion.

When the rapid acidity reduction is required, the initial dose of 80 mg twice a day is enough in most patients in order to achieve the desired level (<10 mEquiv/hour) within 1 hour.

 

General instructions for application of the drug. The powder is dissolved in 10 ml of sodium chloride solution by adding it into the vial. This solution may be introduced directly after mixing with 100 ml of sodium chloride solution or 5-10% glucose solution.

The drug shall not be prepared or mixed with solvents other than those indicated above.

Intravenous introduction should last for 1-15 min.

The prepared solution may be used within 12 hours.

In case there is a possibility of oral application of pantoprazole, it is necessary to refuse of intravenous introduction of the drug. In case of duodenal ulcer treatment the duration of pantoprazole application is usually 2 weeks. In some case the treatment with pantoprazole should be prolonged for another 2 weeks.

The duration of gastric ulcer and reflux-esophagitis treatment with pantoprazole is usually 4 weeks. If necessary the course of treatment may be prolonged up to 8 weeks.

In case of patients with impaired liver function of moderate and severe degree the daily dose should be reduced to 20 mg of pantoprazole. In case of such patients it is necessary to control the level of liver enzymes, and if they are increased the treatment shall be stopped.

Side effects.

According to the frequency of occurrence the side effects are classified into the following categories: often (less than 1/100 and less than 1/10), sometimes (more than 1/1000 and less than 1/100), rarely (more than 1/10000 and less than 1/1000), very rarely (less than 1/10000, including isolated cases).

On digestive system: often – pain in epigastric area, diarrhoea, constipation, meteorism;

On nervous system: often – headache; sometimes – dizziness, visual impairment (blurred vision); very rarely – depression.

On skin and musculoskeletal system: sometimes – allergic reactions (itching, rash); rarely – arthralgia; very rarely – myalgia, urticaria, angioedema, erythema multiforme, Lyell’s syndrome, Stevens-Johnson syndrome, photosensitisation.

On immune system: very rarely – anaphylactic reactions including anaphylactic shock.

On blood system and lymphatic system: Very rarely – leukopenia, thrombocytopenia.

On liver: very rarely – increase in level of liver enzymes (transaminases, GGT), triglycerides, increased body temperature, hepatocellular disorder which leads to jaundice with/without liver impairment.

On kidneys and urinary system: very rarely – interstitial nephritis.

General disorders: very rarely – peripheral oedemas, thrombophlebitis at point of introduction.

Overdosage.

Symptoms of overdosage in people are unknown. Doses up to 240 mg when slowly introduced intravenously (more than 2 minutes) are well-tolerated.

In case of overdosage with symptoms of intoxication it is necessary to take general disintoxication measures.

Application during Pregnancy and Breast-Feeding Periods. The experience of pantoprazole application in pregnant is limited. In course of animal study of reproductive function the slight embryotoxicity of doses over 5 mg/kg was observed. Data concerning pantoprazole penetration into breast milk is absent.

The drug may be applied only when the use of such application is greater than the potential risk for the foetus.

 

Children. Safety and effectiveness of drug application in children under 18 have not been established, therefore the drug is not applied in patients of this age.

 

Peculiarities of Application. Intravenous introduction of pantoprazole is recommended only if its oral application is impossible.

Before and after the treatment it is necessary to perform endoscopic examination in order to exclude malignant neoplasms, since pantoprazole may mask the symptoms and delay the correct diagnostics. Diagnosed reflux-esophagitis requires obligatory endoscopic confirmation.

If the drug is applied in patients with impaired liver function the daily dose should be reduced to 20 mg of pantoprazole.  It is necessary to control the activity of liver enzymes in course of treatment. If it is increased, the application of drug shall be stopped.

The daily dose for patients with impaired renal function and elderly patients should not exceed 40 mg.

It is not recommended to apply the drug in case of insignificant gastrointestinal abnormalities, such as nervous dyspepsia for instance.

Ability to Affect Rate of Reactions when Driving or Operating Other
Mechanisms.
Has no effect.

Interaction with Other Drugs and Other Types of Interaction.

If You take any other drugs, please consult a doctor concerning the possibility of application of this drug.

Pantoprazole may inhibit absorption of drugs bioavailability of which depends on pH (e.g., ketoconazole). Pantoprazole should not be taken with atazanavir.

It is compatible with drugs that are metabolised with the help of cytochrome enzyme system P450. Any clinically significant interaction of pantoprazole with carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamid, metoprolol, nifedipine, phenytoin, teofilin, warfarin, and oral contraceptives has not been detected.

In case of simultaneous taking with coumarin anticoagulants, phenprocoumon, warfarin, it is recommended to monitor the prothrombin time.

No interaction was observed in case of simultaneous application with antacids.

Pharmacological Properties.

Pharmacodynamics. Antisecretory, antiulcer agent. Blocks the final stage of hydrochloric acid formation by means of irreversible inhibition of H+/K+-ATPase (“proton pump”) in parietal cells of stomach. Activity of H+/K+-ATPase is restored by de novo enzyme synthesis. Reduces the basal and stimulated (food, pentagastrin, insulin) gastric secretion. Inhibits growth of Helicobacter pylori, favours formation of IgA specific to these bacteria in mucous membrane, and intensifies anti-helicobacter activity of antimicrobial agents.

The therapeutic effect after single-time taking is rapidly developed and preserved within 24 hours.

Pharmacokinetics. Pantoprazole is not acid-resistant, is almost completely absorbed only in alkaline environment of small intestine, and enters the system blood flow. Bioavailability is 70-80%. Food and simultaneous taking of antacids does not influence the drug bioavailability. Pantoprazole easily penetrates into the tissues, including parietal cells of stomach. Binding with plasma enzymes is 98%.  Distribution volume is 0.16 l/kg, period of half-excretion is 0.9-1.9 hours, general clearance is 0.1 l/kg/hour/kg. The drug is metabolized in liver with the help of cytochrome enzyme system P450 by means of oxidation, dealkylation, and conjugation. Main metabolites are desmethyl pantoprazole and two sulphated conjugates. The drug is excreted by kidneys (71%) and intestine (18%). It is not cumulated in body, hardly penetrates through blood-brain barrier, is hardly excreted into breast milk.

In elderly patients the bioavailability and maximum concentration of pantoprazole is slightly increased. In case of patients with liver cirrhosis the half-excretion period increases up to 7.9 hours; in case of impaired renal function these indices are slightly increased.

Pharmaceutical Characteristics.

Main Physicochemical Properties: crystalline powder of white or almost white colour.

Incompatibility. Sodium pantoprazole is incompatible with acid solutions.

Effective Period. 2 years. When diluted the efficiency period of ready-made solution is 12 hours.

Storage Conditions.

Store in original packaging under the temperature below 25°C.

Packaging. 1 vial and 1 ampule with solvent in polymeric insert enclosed into the carton box.

Category of Selling. On prescription.

Manufacturer. Alpa Laboratories Ltd.

Location. 33/2 Pigdamber, A.B. Road, Indore 453446, India

Date of Last Revision.