Zipantola - instructions for use, dose, side effects, contraindications

Excipients: Mannitol 78.645 mg / 157.29 mg, crospovidone 2.20 mg / 4.40 mg, low-substituted giprolose 2.20 mg / 4.40 mg, sodium lauryl sulfate 1.10 mg / 2.20 mg, silicon dioxide colloid 0.55 mg / 1.10 mg, talc 1.65 mg / 3.30 mg, magnesium stearate 1.10 mg / 2.20 mg;

film sheath: Fell as AMB yellow 80W32009 8.80 mg / 17.60 mg (partially hydrolysed polyvinyl alcohol 4,006 mg / 8,012 mg, titanium dioxide 2,193 mg / 4,386 mg, talc 1,760 mg / 3,520 mg, iron oxide oxide yellow 0.382 mg / 0.764 mg, quinoline yellow aluminum varnish 0.241 mg / 0.482 mg, soy lecithin 0.176 mg / 0.352 mg, gum xanthanic 0.042 mg / 0.084 mg);shell intestinal: methacrylic acid and ethyl acrylate copolymer [1: 1] (Eudragit L 30D-55 *)13.45 mg / 25.28 mg, glyceryl monostearate 0.67 mg / 1.26 mg, triethyl citrate 1.34 mg / 2.53 mg, polysorbate-80 0.34 mg / 0.63 mg;

black ink Opacode S-1-17860, used for labeling on tablets: glaze pharmaceutical [shellac solution in ethanol] 55.0%, iron dye oxide black 25.0%, isopropanol 18.0%, ammonia water 1.0%, butanol 0.5%, propylene glycol 0.5%.

* - represents a 30% water dispersion of methacrylic acid and ethyl acrylate copolymer [1: 1] containing 0.7% sodium lauryl sulfate and 2.3% polysorbate-80.

Description:

Dosage of 20 mg:

Yellow, round, biconvex tablets, covered with enteric coating, with the inscription RA 783 black on one side.

Dosage of 40 mg:

Yellow, round, biconvex tablets, covered with enteric coating, with the inscription RA 784 black on one side.

Pharmacotherapeutic group:glands of the stomach secretion-lowering agent - proton pump inhibitor

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.02 Pantoprazole

Pharmacodynamics:

Pantoprazole is a proton pump inhibitor, selectively inhibits (forms, covalent bond) H⁺-TO⁺-ATPase parietal cells, violates the transfer of hydrogen ions in the lumen of the stomach, blocks the final stage of the secretion of hydrochloric acid, suppressing the basal and stimulated secretion, regardless of the type of stimulus - acetylcholine, histamine, gastrin. The maximum effect is manifested only in acidic medium with a pH of less than 3, at higher pH values it remains practically inactive. Does not affect the motility of the gastrointestinal tract (GIT). Secretory activity is normalized 3-4 days after the end of admission. Clinical improvement is achieved within 2 weeks. During 4-8 weeks of treatment, the level of gastrin in the plasma increases 1.5 times. With prolonged treatment in patients with peptic ulcer is accompanied by a slight increase in the number of enterochromafin-like (ECL) cells.

With duodenal ulcer associated with Helicobacter pylori, the normalization of secretion in the stomach helps to increase the anti-Helicobacter effect of antibiotics.

Pharmacokinetics:Quickly and completely absorbed from the digestive tract. Absolute bioavailability (about 77%), with food intake is not related. On average, the maximum concentration (C_max) - 1.5 μg / ml is achieved after 2.5 hours for a dose of 20 mg and 2.4 μg / ml - after 2.4 hours for a dose of 40 mg. The half-life period (T1 / 2) is about 1 hour, the apparent volume of distribution is about 11.0-23.6 liters, the clearance from plasma (C1) is about 0.1 l / h / kg, the area under the concentration-time curve " (AUC) 4.8 μg x h / ml. Binding to plasma proteins is about 98%, in mainly with albumins. Admission of antacids or food does not affect C_max, AUC and bioavailability.

Metabolised in the liver (oxidation, dealkylation, conjugation). It has low affinity for the cytochrome P450 system, metabolism is involved predominantly isoenzymes CYP3A4 and CYP2C19. The main metabolite in Plasma and urine is desmethylpentoprazole (T1/2 - about 1.5 hours), conjugated with sulphate. There is no data on the availability of pharmacological activity of metabolites. It is excreted mostly by the kidneys (about 71%) in the form of metabolites, in a small amount (about 18%) is found in the stool.

Do not cumulate. In some cases, the elimination is slow.Very weak permeates through the blood-brain barrier, withIt is secreted into breast milk.

In patients with cirrhosis of the liver (classes, A, B according to the Child-Pugh classification) increases to about 3-6 hours (for a dose of 20 mg) and up to 7-9 hours (for a dose of .40 mg).

With renal failure T1 / 2, yis not significant, but T1 / 2 the main metabolite reaches 2-3 hours. Increase C_max and AUC are not clinically significant in elderly patients.

Indications:

- Gastroesophageal reflux disease (GERD): treatment of erosive reflux-esophagitis, symptomatic treatment of non-erosive reflux disease (NERD).

- Stomach ulcer and duodenal ulcer (in the phase of exacerbation), in including those associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs).

- Zollinger-Ellison Syndrome

- Eradication Helicobacter pylori in combination with antibacterial agents.

Contraindications:

- Hypersensitivity to the components of the drug, dyspepsia of the neurotic genesis.

- Simultaneous administration with atazanavir.

- The period of breastfeeding.

- Children's age to 12 years (insufficient data on the effectiveness and security).

- Children under 18 years of age with peptic ulcer of the stomach and duodenum (in the phase of exacerbation), including those associated with taking NSAIDs, Zollinger-Ellison syndrome and eradication Helicobacter pylori in combination with antibacterial agents (insufficient data on efficacy and safety).

Carefully:Liver failure, renal insufficiency, elderly patients (over 65 years), including those with a history of gastric ulcer or duodenal ulcer, as well as bleeding from the upper gastrointestinal tract, pregnancy.

Pregnancy and lactation:

Data on the use of the drug in pregnant women are limited. Use pantoprazole when pregnancy follows, provided that the expected benefit for the mother exceeds the possible risk to the fetus.

Dosing and Administration:

Inside, squeezed with liquid and swallowing whole (tablets can not be crushed or dissolved). Tablets can be taken regardless of food intake and antacids.

Adults and children over 12 years of age

GERD: treatment of erosive reflux esophagitis, symptomatic treatment of NERD

The recommended dose is 20-40 mg per day. Symptoms usually decrease within 2-4 weeks,for the treatment of concomitant esophagitis usually need 4 weeks. In case of insufficient clinical effect, take another 4 weeks. After eliminating the symptoms, you can take 20 mg once a day in on-demand mode. It is possible to switch to long-term therapy indose 20 mg 1 Once a day, if the "on-demand" Cures the symptoms of the disease.

Adults

Peptic ulcer of the stomach and duodenum (in the phase of exacerbation), including those associated with the intake of NSAIDs

The recommended dose is 40-80 mg per day. Duration of treatment 2 weeks with exacerbation of duodenal ulcer and 4-8 weeks with peptic ulcer exacerbation. Antrepid treatment of peptic ulcer of the stomach and duodenum - in a dose of 20 mg once a day.

Eradication Helicobacter pylori

The recommended dose is 40 mg 2 times a day in combination with one of the following combinations

- amoxicillin 1 g 2 times a day + clarithromycin 500 mg 2 times a day.

- clarithromycin 250-500 mg 2 times a day + metronidazole 400-500 mg 2 times in day.

-amoxicillin 1 g 2 times a day + metronidazole 400-500 mg 2 times a day.

The combined treatment should be followed for 7 days.After the end of treatment, the use of pantoprazole can be continued for the purpose of ulcer healing. If duodenal ulcer is taken, pantoprazole can be prolonged from 1 to 3 weeks.

Zollinger-Ellison Syndrome

The starting dose is 80 mg per day. Depending on the secretion of gastric juice, the dosage can be reduced or increased. The daily dose of 80 mg is divided into 2 parts and taken 2 times a day. Perhaps a short-term increase in the dose of pantoprazole above 160 mg. The duration of treatment, the Zipantol Zollinger-Ellison syndrome is not limited. The safety of long-term use of Zipantol is well studied. Long-term use of pantoprazole is also safe, as well as short-term, and well tolerated.

Elderly patient and patients with renal nedostatality

Correction of the dose is not required. However, it is not recommended to take more than 40 mg per day daily. The exception is eradication therapy Helicobacter pylori, when patients should take a dose of 40 mg 2 times a day in for 1 week.

Patients with severe hepatic insufficiency

The daily dose should not exceed 20 mg per day

Side effects:The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rare (including isolated cases) - less than 0.01%; frequency is unknown (can not be estimated from available data).

From the side of nutrition and metabolism: rarely - hyperlipidemia, increased triglycerides, cholesterol, changes in body weight; frequency is unknown - hyponatremia, hypomagnesemia.

From the immune system: rarely - hypersensitivity reaction (including, anaphylactic reaction, anaphylactic shock).

From the side of blood and lymphatic system: very rarely - thrombocytopenia, leukopenia.

From the central nervous system:

infrequently - headache, dizziness, sleep disturbance; rarely - depression; highly rarely - violation of orientation; frequency unknown - hallucinations, confusion consciousness (especially in predisposed patients).

From the gastrointestinal tract: infrequently - nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, discomfort, abdominal pain, bloating, flatulence.

From the liver and bile ducts: infrequently - increased activity "hepatic" transaminases, gamma glutamyl transferase; rarely increased bilirubin concentration; frequency unknown - cell damage liver, jaundice, liver failure.

From the side of the organ of vision: rarely - decrease visual acuity, blurred vision.

From the skin and subcutaneous tissues: infrequently - skin rash, exanthema, itching of the skin; rarely - hives, angioedema;

frequency is unknown - Stevens-Johnson, multiform erythema, syndrome Lyell, the reaction of photosensitization.

From the side of the musculoskeletal and connective tissue: infrequently - a fracture of the femur, bones of the wrist, vertebrae; rarely - myalgia, arthralgia (see section "Special instructions").

From the side of the kidneys and urinary tract: frequency unknown - interstitial nephritis.

On the part of the reproductive system and mammary glands: rarely - gynecomastia.

Other: infrequently - asthenia, weakness, lethargy; rarely - fever, peripheral edema.

Overdose:

Symptoms of overdose are unknown.Doses in excess of 240 mg intravenously were administered within 2 minutes and were well tolerated.

Treatment: symptomatic therapy. Hemodialysis is not effective.

Interaction:

Pantoprazole, like other proton pump inhibitors, can reduce or increase the absorption of drugs whose bioavailability depends on the pH of the stomach (ketoconazole, itraconazole, atazanavir).

Despite the fact that there is no interaction of pantoprazole with fenprocumone or warfarin, as confirmed by pharmacokinetic studies, there are few data on the change in the international normalized relationship (INR). Patients taking this combination of drugs require regular monitoring of prothrombin time / INR at the beginning of therapy, when it is completed, as well as the irregular use of pantoprazole.

There were no significant interactions between pantoprazole and other drugs, such as diazepam, diclofenac, digoxin, glibenclamide, nifedipine, carbamazepine caffeine, phenytoin, naproxen, piroxicam, theophylline, metoprolol, ethanol, oral contraceptives.

Nevertheless, since pantoprazole metabolized with the participation of the CYP2C19 isoenzyme, as well as other cytochrome P450 isoenzymes, the possibility of interacting with other drugs that are metabolized using these enzymes can not be completely ruled out.

There is no interaction of pantoprazole with concomitant antacids.

Special instructions:

In patients taking inhibitors proton pump, including pantoprazole, at high doses, as well as duration of treatment more than 1 year, increased risk of fracture of the femur, bones of the wrist and vertebrae. Patients with risk of osteoporosis provide assistance in accordance with current recommendations on prevention of osteoporosis, and Ensure sufficient intake of calcium and vitamin C in the body D.

In patients taking proton pump inhibitors from 3 months to 1 year or more, was noted expressed hypomagnesemia. Patients on long-term therapy or taking medications that cause hypomagnesemia (cardiac glycosides, diuretics) require regular monitoring of the magnesium content in the blood plasma.

It should be regularly monitored the activity of "liver" transaminases in the blood plasma when pantoprazole is prescribed to patients with severe hepatic insufficiency, especially with prolonged use. When the activity of "hepatic" transaminases increases in the blood, the drug treatment should be stopped.

In patients who have an increased risk of developing complications from the gastrointestinal tract and long-term receiving NSAIDs, pantoprazole in a dose of 20 mg for the prevention of peptic ulcer of the stomach and duodenum should be used with caution. It is necessary to use caution pantoprazole in elderly patients (over 65 years of age) who have a history of gastric ulcer or duodenal ulcer, as well as bleeding from the upper sections of the gastrointestinal tract.

Before and after treatment, endoscopic control is necessary to exclude the possibility of having malignant diseases of the stomach or esophagus.treatment can mask symptomatology and make it difficult to properly diagnose. Reduction of the acidity of gastric juice by means of reducing the secretion of the glands of the stomach, including proton pump inhibitors, can promote the reproduction of the natural microflora of the gastrointestinal tract,which may slightly increase the risk of developing gastrointestinal infections caused by Salmonella and Campylobacter.

Pantoprazole, like all drugs that block the production of hydrochloric acid in the stomach glands, can reduce the absorption of vitamin B12 as a result of hypo- and achlorhydria. This should be considered with prolonged therapy in patients with low body weight or with an increased risk of reducing absorption of vitamin B12.

Patients who have symptoms of the disease after 4 weeks of treatment, or long-term pantoprazole (more than 1 year), require an additional examination.

Form release / dosage:Tablets coated with enteric-coated 20 mg and 40 mg.

Packaging:For 14 tablets per blister, from OPA / aluminum foil / PVC / aluminum foil.

2 blisters with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001361/08

Date of registration:29.02.2008

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp08.09.2015

Illustrated instructions

Instructions

Zipantola (Zipantola)