Pantopraz IV

Pantoprazole.

Each vial contains: Pantoprazole (as sodium sesquihydrate) 40 mg.

Pharmacology: Pharmacodynamics: Mechanism of action: Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific blockade of the proton pumps of the parietal cells.
Pantoprazole is converted to its active form m the acidic environment in the parietal cells where it inhibits the H⁺, K⁺-ATPase enzyme, i.e. the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, freedom from symptoms is achieved within 2 weeks. As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole reduces acidity in the stomach and thereby increases gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible. Since pantoprazole binds to the enzyme distal to the cell receptor level, it can inhibit hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the product is given orally or intravenously.
The fasting gastrin values increase under pantoprazole. On short-term use, in most cases they do not exceed the upper limit of normal. During long-term treatment, gastrin levels double in most cases. An excessive increase, however, occurs only in isolated cases. As a result, a mild to moderate increase in the number of specific endocrine (ECL) cells in the stomach is observed in a minority cases during long-term treatment (simple to adenomatoid hyperplasia). However, according to the studies conducted so far, the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as were found in animal experiments have not been observed in humans.
An influence of a long term treatment with pantoprazole exceeding one year cannot be completely ruled out on endocrine parameters of the thyroid scatting to results in animal studies.
Pharmacokinetics: General pharmacokinetics: Pharmacokinetics does not vary after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are linear after both oral and intravenous administration.
Distribution: Pantoprazole's serum protein binding is about 98%. Volume of distribution is about 0.151/kg.
Elimination: The substance is almost exclusively metabolized in the liver. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulphate conjugation, another metabolic pathway includes oxidation by CYP3A4. Terminal half-life is about 1 hour and clearance is about 0.11/h/kg. There were a few cases of subjects with delayed elimination. Because of the specific binding of pantoprazole to the proton pumps at the parietal cell the elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion).
Renal elimination represents the major route of excretion (about 80%) for the metabolites of pantoprazole, the rest is excreted with feces. The main metabolite in both the serum and urine is desmethylpantoprazole which is conjugated with sulfate. The half-life of the main metabolite (about 1.5 hours) is not much longer than that or pantoprazole.
Characteristics in patients/special groups of subject: Approximately 3% of the European population lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals, the metabolism of pantoprazole is probably mainly catalyzed by CYP3A4.
After a single-dose administration of 40 mg pantoprazole, the mean area under the plasma concentration time curve was approximately 6 times higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). Mean peak plasma concentrations were increased by about 60%. These findings have no implications for the posology of pantoprazole.
No dose reduction is recommended when pantoprazole is administered to patients with impaired renal function (including dialysis patients). As with healthy subjects, pantoprazole's half-life is short. Only very small amounts of pantoprazole are dialyzed. Although the main metabolite has a moderately delayed half-life (2-3 h), excretion ts still rapid and thus accumulation does not occur. Although for patients with liver cirrhosis (classes A and B according to Child) the half-life values increased to between 7 and 9 h and the AUC values increased by a factor of 5-7, the maximum serum concentration only increased slightly by a factor of 1.5 compared with healthy subjects.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not clinically relevant.
Children: Following administration of single intravenous doses of 0.8 or 1.6 mg/kg pantoprazole to children aged 2-16 years there was no significant association between pantoprazole clearance and age or weight. AUC and volume of distribution were in accordance with data from adults.

For the treatment of: Short-term treatment (7 to 10 days) of Gastroesophageal Reflux Disease (GERD) associated with a history of Erosive Esophagitis.
Pathological hypersecretion conditions including Zollinger-Ellison syndrome.

Gastric and duodenal ulcer, reflux esophagitis: The recommended intravenous dose is one vial of Pantoprazole injection 40 mg once daily by IV infusion for 7 to 10 days.
Zollinger-Ellison Syndrome and other conditions producing too much acid in the stomach: It should start the treatment with a daily dose of 80 mg. Thereafter, the dose can be titrated up or down as needed using measurements of gastric acid secretion to guide.
With dose about 80 mg daily, the dose should be divided and given twice daily.
A temporary increase of the dose above 160 mg of Pantoprazole is possible but should not be applied longer than required for adequate acid control.
In case a rapid acid control is required, a starting dose of 2 x 80 mg is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.
A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver impairment.
A daily dose of 50 mg pantoprazole should not be exceeded in elderly and renal impairment patients.
Preparation of Dosage Form: The content of the vial should be reconstituted with 10 mL of 0.9% Sodium Chloride for Injection. The prepared solution should be administered intravenously either as a slow injection or it may be further diluted with 100 mL of 0.9% Sodium Chloride Injection or 5% Glucose Injection and administered as a short term infusion. The duration of administration should be 2 to 15 minutes. The reconstituted solution must be used within 12 hours of preparation.
Note: Intravenous administration of Pantoprazole is recommended only if oral administration is not appropriate. As soon as oral therapy is possible, treatment with Pantoprazole injection should be discontinue.

There are no known symptoms of overdose in man. Systemic exposure with up to 240 mg administered intravenously over 2 minutes were well tolerated. As Pantoprazole is extensively protein bound, it is not readily dialyzable. In the case of overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.

Patients who have hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients.
Patients who are using Atazanavir.

Implications of symptomatic response: Symptomatic response to therapy with Pantoprazole does not preclude the presence of gastric malignancy.
Injection site reaction: Thrombophlebitis was associated with the administration of Pantoprazole Injection.
Hypersensitivity and severe skin reactions: Anaphylaxis and other serious reactions such as erythema multiforme, Steven-Johnson's syndrome, and toxic epidermal necrolysis (TEN) have been reported with use of Pantoprazole injection. These may require emergency medical treatment.
Potential for exacerbation of zinc deficiency: Pantoprazole injection contains edetate disodium (the salt form of EDTA), a chelator of metal ions including zinc. Therefore, zinc supplementation should be considered in patients treated with Pantoprazole injection who are prone to zinc deficiency. Caution should be used when other EDTA containing products are also co-administered intravenously.
Acute interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs including Pantoprazole injection. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue Pantoprazole injection if acute interstitial nephritis develops.
Clostridium difficile associated diarrhea: Published observational studies suggest that PPI therapy like pantoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve.
Patient should use the lowest dose and shortest duration of PPI therapy appropriated to the condition being treated.
Bone fracture: Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk of osteoporosis-related fractures should be managed according to the established treatment guidelines.
Hepatic effects: Mild, transient transaminase elevations have been observed in clinical studies. The clinical significance of this finding in a large population of subjects administered intravenous pantoprazole is unknown.
Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Interference with urine screen for tetrahydrocannabinol may produce false-positive urine screen for THC (tetrahydrocannabinol).
Concomitant use with methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.
Use in Children: Safety and effectiveness in pediatric (under 18 years old) patients have not been established.
Use in Elderly: No age-related differences in the safety profile of intravenous pantoprazole were seen in international trials involving under 65 years old and over 65 years old patients with erosive esophagitis associated with GERD.

There are no adequate data from the use of Pantoprazole in pregnant women. The potential risk for human is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary.
Animal studies have shown excretion of Pantoprazole in breast milk. Excretion into human milk has been reported. Therefore, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Pantoprazole should be made taking into account the benefit of breast-feeding to the child and the benefit of Pantoprazole therapy to women.

Frequency of >2%: Headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, arthralgia.
Frequency of <2%: Body as a Whole: allergic reaction, fever, photosensitivity reaction, facial edema, thrombophlebitis (I.V. only).
Gastrointestinal: Constipation, dry mouth, hepatitis hematologic, leukopenia (reported in ex-US clinical trials only), thrombocytopenia.
Metabolic/Nutritional: Elevated CPK (creatinine phosphokinase), generalized edema, elevated triglycerides, liver function tests abnormal.
Musculoskeletal: Myalgia.
Nervous: Depression, vertigo.
Skin and Appendages: Urticarial, rash, pruritus.
Special Senses: Blurred vision.
Post Marketing Experience: General Disorders and Administration Conditions: asthenia, fatigue, malaise.
Immune System Disorders: anaphylaxis (including anaphylactic shock).
Investigations: weight changes.
Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme. Steven-Johnson syndrome, and toxic epidermal necrolysis (TEN), and angioedema (Quincke's edema).
Musculoskeletal Disorders: rhabdomyolysis, bone fracture.
Renal and Urinary Disorders: interstitial nephritis.
Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure.
Psychiatric Disorder: hallucinations, confusions, insomnia, somnolence.
Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia.
Infections and infestations: Clostridium difficile associated diarrhea.
Hematologic: pancytopenia, agranulocytosis.
Nervous: ageusia, dysgeusia.

Interference with Antiretroviral therapy: Concomitant use Atazanavir or Nelfinavir with proton pump inhibitors is not recommended. Co-administration of Atazanavir or Nelfinavir with proton pump inhibitors is expected to substantially decrease Atazanavir or Nelfinavir plasma concentrations and may result in a loss of therapeutic effect and development of drug resistance.
Coumarin Anticoagulants: There have been post marketing reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly should be monitored for increase in INR and prothrombin time.
Clopidogrel: Concomitant administration of pantoprazole and Clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of Clopidogrel or Clopidogrel-induced platelet inhibition. No dose adjustment of Clopidogrel is necessary when administered with an approved dose of pantoprazole sodium.
Drugs for which gastric pH can affect Bioavailability: Due to its effects on gastric acid secretion, pantoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, Atazanavir, iron salts, Eriotinib, and mycophenolate mofetil (MMF) can decrease.
False Positive urine tests for THC: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving proton pump inhibitors including pantoprazole. An alternative confirmatory method should be considered to verify positive results.
Methotrexate: Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose: see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.

Special Precautions: After reconstitution or dilution, chemical and physical in use stability has been demonstrated for 12 hours at 25°C. From a microbiological point of view, the product should be used immediately.
Pantoprazole powder for injection should not be prepared or mixed with solvent other than those stated.
The medicine should be administered intravenously over 2-15 minutes.
The contents of vial are for single use only.
Keep hermetic container for light protection before use.

Store at temperatures not exceeding 30°C. Protect from light.

Antacids, Antireflux Agents & Antiulcerants

A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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