Puloref^® (Tablets) Instructions for Use

Marketing Authorization Holder

Nobel Ilac Sanayii Ve Ticaret, A.S. (Turkey)

Manufactured By

Nobel Ilac Sanayii Ve Ticaret, A.S. (Turkey)

Or

Nobel Almaty Pharmaceutical Factory, JSC (Kazakhstan)

ATC Code

A02BC02 (Pantoprazole)

Active Substance

Pantoprazole (Rec.INN registered by WHO)

Dosage Form

Puloref®

Enteric-coated tablets, 40 mg: 14 or 28 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated tablets from yellow to light yellow in color, oval, biconvex, with a white or almost white core on the cross-section.

Excipients : sodium phosphate – 10 mg, isomalt LM-PF – 58.5 mg, croscarmellose sodium – 3 mg, crospovidone – 50 mg, sodium stearyl fumarate – 3.4 mg.

First coating composition hypromellose 2910 – 15.85 mg, povidone (PVP K25) – 0.32 mg, film coating material No.9 (Sepisperse AP 3232 Jaune Yellow) (30%) (purified water 45-55%, hypromellose (E464) 1-7%, propylene glycol 10-30%, titanium dioxide 20-30%, iron oxide yellow (E172) up to 5%) – 1.28 mg, propylene glycol – 3.446 mg.
Coating composition eudragit L30 D-55 30% (30% dispersion of methacrylic acid and ethyl acrylate copolymer [1:1], contains sodium lauryl sulfate and polysorbate 80) – 13.6 mg, triethyl citrate – 1.36 mg, simethicone emulsion 30% – 0.04 mg.

14 pcs. – blisters made of aluminum foil (1) – cardboard packages.
14 pcs. – blisters made of aluminum foil (2) – cardboard packages.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor. Antiulcer drug

Pharmacotherapeutic Group

Gastric secretion reducing agent – proton pump inhibitor

Pharmacological Action

H⁺-K⁺-ATPase inhibitor. It blocks the final stage of hydrochloric acid secretion, reducing the level of basal and stimulated (regardless of the type of stimulus) hydrochloric acid secretion in the stomach.

In duodenal ulcer associated with Helicobacter pylori, such a decrease in gastric secretion increases the sensitivity of the microorganism to antibiotics. Pantoprazole has its own antimicrobial activity against Helicobacter pylori.

Pharmacokinetics

Pantoprazole is rapidly absorbed after oral administration. The C_max after the first dose of 20 mg is about 1.0-1.5 µg/ml.

The pharmacokinetics of pantoprazole after single and multiple administration are the same. In the dose range of 10-80 mg, the pharmacokinetics of pantoprazole in plasma remain linear for both oral and intravenous administration.

The absolute bioavailability of pantoprazole when taken orally is about 77%. Plasma protein binding is 98%. The V_d is 0.15 l/kg.

It is metabolized mainly in the liver. The main metabolic pathway is demethylation via CYP2C19 followed by sulfate conjugation. Other metabolic pathways include oxidation via CYP3A4.

The terminal T_1/2 is approximately 1 hour, clearance is about 0.1 l/h/kg.

The main route of excretion is through the kidneys (about 80%) in the form of pantoprazole metabolites, the rest is excreted in the feces.

Indications

Gastric and duodenal ulcer in the acute phase, erosive gastritis (including that associated with NSAID use), stress ulcers and their complications (bleeding, perforation, penetration); Zollinger-Ellison syndrome; eradication of Helicobacter pylori (in combination with antibacterial therapy); gastroesophageal reflux disease; erosive reflux esophagitis.

ICD codes

Dosage Regimen

Administer the 40 mg enteric-coated tablet orally, swallowed whole with water, before a meal.

For erosive reflux esophagitis, use 40 mg once daily for 4 to 8 weeks. For maintenance therapy of reflux esophagitis, use 20 mg or 40 mg once daily.

For duodenal ulcer and gastric ulcer in the acute phase, use 40 mg once daily for 2 to 4 weeks.

For Helicobacter pylori eradication, use 40 mg twice daily in combination with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily for 7 to 14 days.

For Zollinger-Ellison syndrome, the initial dose is 80 mg once daily. Adjust the dose individually; daily doses above 160 mg should be divided.

For patients with severe hepatic impairment, do not exceed a daily dose of 20 mg.

For patients with renal impairment and elderly patients, do not exceed a daily dose of 40 mg.

The maximum recommended daily oral dose is 80 mg.

Intravenous administration is only indicated when oral therapy is not possible.

Adverse Reactions

From the hematopoietic system: rarely – agranulocytosis; very rarely – thrombocytopenia, leukopenia, pancytopenia.

From the nervous system: infrequently – headache, dizziness; rarely – taste disturbances; frequency unknown – paresthesia.

From the psyche: infrequently – sleep disorders; rarely – depression (including exacerbation of existing disorders); very rarely – disorientation (including exacerbation of existing disorders); frequency unknown – hallucinations, confusion (especially in predisposed patients), as well as possible exacerbation of symptoms if they existed before the start of therapy.

From the organ of vision: rarely – blurred vision.

From the digestive system: frequently – gastric fundic gland polyps (benign); infrequently – diarrhea, nausea, vomiting, abdominal bloating, flatulence, constipation, dry mouth, abdominal discomfort and pain.

From the liver and biliary tract: infrequently – increased activity of liver enzymes (transaminases, γ-glutamyltransferase); rarely – increased bilirubin level; frequency unknown – hepatocellular damage, jaundice, hepatocellular failure.

From the urinary system: frequency unknown – interstitial nephritis.

From the musculoskeletal system: infrequently – wrist, hip, spine fractures; rarely – arthralgia, myalgia.

From metabolism: rarely – hyperlipidemia, change in body weight; frequency unknown – hyponatremia, hypomagnesemia.

From the immune system: rarely – hypersensitivity reactions (including anaphylactic reactions and anaphylactic shock), angioedema.

From the reproductive system: rarely – gynecomastia.

From the skin and subcutaneous tissues: infrequently – exanthema/rash, itching, dermatitis; rarely – urticaria; frequency unknown – malignant exudative erythema (Stevens-Johnson syndrome), exudative multiforme erythema, toxic epidermal necrolysis, photosensitivity, subacute cutaneous lupus erythematosus.

General reactions: infrequently – weakness, fatigue, general malaise; rarely – increased body temperature, peripheral edema.

Contraindications

Hypersensitivity to pantoprazole; neurogenic dyspepsia, malignant diseases of the gastrointestinal tract, severe hepatic insufficiency; pregnancy, lactation (breastfeeding) period; childhood; use of HIV protease inhibitors such as atazanavir and nelfinavir, the absorption of which depends on the pH of gastric juice (for oral administration).

With caution hepatic insufficiency.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during the lactation (breastfeeding) period.

If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated for use in severe hepatic insufficiency. When used in patients with impaired liver function, the activity of liver enzymes in the blood plasma should be regularly monitored and Pantoprazole should be discontinued if it increases.

Use in Renal Impairment

In case of impaired renal function, it is not recommended to exceed the dose of 40 mg/day.

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

Proton pump inhibitors, especially when used in high doses and for a long time (more than 1 year), may moderately increase the risk of fractures of the femur, wrist, and spine, mainly in the elderly. In elderly patients, it is not recommended to exceed the dose of 40 mg/day.

Special Precautions

Intravenous use of pantoprazole is recommended only if its oral administration is not possible.

Before starting therapy, the possibility of a malignant neoplasm in the stomach and esophagus should be excluded, because the use of pantoprazole reduces the severity of symptoms and may delay the establishment of the correct diagnosis. The diagnosis of reflux esophagitis requires mandatory endoscopic confirmation.

In elderly patients and in case of impaired renal function, it is not recommended to exceed the dose of 40 mg/day.

When used in patients with impaired liver function, the activity of liver enzymes in the blood plasma should be regularly monitored and Pantoprazole should be discontinued if it increases.

Proton pump inhibitors, especially when used in high doses and for a long time (more than 1 year), may moderately increase the risk of fractures of the femur, wrist, and spine, mainly in the elderly or in the presence of other risk factors.

Effect on the ability to drive vehicles and mechanisms

During the use of pantoprazole, patients should be cautious when driving vehicles and mechanisms, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Pantoprazole may change the absorption of drugs whose absorption depends on the pH of the gastric contents (for example, ketoconazole, itraconazole, posaconazole and other drugs such as erlotinib).

Concomitant use of pantoprazole and HIV protease inhibitors, the absorption of which depends on the acidity (pH) of gastric juice, such as atazanavir, nelfinavir, significantly reduces their bioavailability.

Since Pantoprazole is metabolized in the liver by the cytochrome P450 enzyme system, the possibility of drug interaction with drugs metabolized by the same enzyme system cannot be excluded.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.