Pantoprazole

Pantoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Pantoprazole is a proton pump inhibitor used to treat erosive esophagitis, gastric acid hypersecretion, and to promote healing of tissue damage caused by gastric acid.

Pantoprazole rapidly absorbed and the peak plasma concentration approximately 2-2.5 hours (oral). The bioavailability is approximately 77%. The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in the extracellular fluid. The Plasma protein binding is approximately 98% (mainly to albumin). Pantoprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19 hepatic cytochrome enzyme, followed by sulfation; other metabolic pathways include oxidation by CYP3A4. Excreted Mainly via urine approximately 80%.

Pantoprazole shows side effects like Headache, nausea, vomiting, gas, joint pain, diarrhea, dizziness.

Pantoprazole is available in the form of Oral Tablet, Intravenous powder for injection.

Pantoprazole is available in India, US, Canada, Malaysia, Singapore, Japan, Spain, China, Germany, France, UK, and Australia.

Pantoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Proton pump inhibitors such as pantoprazole are substituted benzimidazole derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the canaliculi (small canal) of the gastric parietal cell, an acidic environment, to active sulfenamide derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the sulfhydryl group of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists.

The onset of action of Pantoprazole can be observed within an hour of its administration.

The duration of action of Pantoprazole lasts for an average duration of 24 hours.

Pantoprazole is available in the form of Oral Tablet, Intravenous powder for injection.

Pantoprazole tablet is taken orally, while powder for injection is given via intravenous route.

Pantoprazole is a medicine that helps to treat conditions that are caused by excess acid production in the stomach. Some of these conditions are peptic ulcer (sores in the stomach, small intestine, and food pipe), esophagitis (swelling of the food pipe), and gastroesophageal reflux disease (stomach acid flowing back into the food pipe). Pantoprazole works by reducing excess acid production in your stomach and relieving symptoms such as heartburn, difficulty in swallowing, stomach pain, and vomiting.

Pantoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Pantoprazole is proton pump inhibitor, suppresses gastric acid secretion by inhibiting the parietal cell H⁺/K⁺ ATP pump.

Pantoprazole is approved for use in the following clinical indications

Adult Dose

• Aspiration prophylaxis in patients undergoing anesthesia
• Barrett esophagus
• Dyspepsia, functional
• Eosinophilic esophagitis
• Gastroesophageal reflux disease, erosive or nonerosive
• Helicobacter pylori eradication
• Nonsteroidal anti-inflammatory drugs–induced ulcers, primary prevention
• Peptic ulcer disease, treatment, and secondary prevention
• Stress ulcer prophylaxis in select critically ill patients
• Zollinger-Ellison syndrome

Paediatric indication

• Gastroesophageal reflux disease, symptomatic
• Erosive esophagitis associated with GERD

Adult Dose

• Aspiration prophylaxis in patients undergoing anesthesia

Oral: 40 mg given the night before surgery and 40 mg given the morning of surgery.

IV: 40 mg as a single dose 1 hour prior to induction anesthesia.

• Barrett esophagus

Oral: 40 mg once daily; may increase the dose to 40 mg twice daily if needed to eliminate gastroesophageal reflux disease (GERD) symptoms or heal reflux esophagitis. Long-term maintenance therapy is recommended.

• Dyspepsia, functional

Oral: 20 to 40 mg once daily for a 4- to 8-week trial; can be continued for a longer duration in patients with symptom improvement. Some experts recommend attempting to discontinue every 6 to 12 months to minimize the long-term risk of therapy.

• Eosinophilic esophagitis

Oral: 40 mg twice daily for an 8-week trial. Once 8-week trial is complete and remission is achieved, the dose may be gradually lowered to an individualized maintenance level. Some experts initiate with once-daily dosing and increase to twice-daily dosing after 4 weeks if symptoms fail to improve.

• Gastroesophageal reflux disease, erosive or nonerosive

Oral: 20 mg once daily, can increase to 40 mg once daily after 4 to 8 weeks if necessary. Discontinue once asymptomatic for 8 weeks.

• Helicobacter pylori eradication

Oral: 40 mg or 80 mg twice daily as part of an appropriate combination regimen with antibiotics. Dose depends on the selected regimen.

• Nonsteroidal anti-inflammatory drugs–induced ulcers, primary prevention

Oral: 20 to 40 mg once daily for the duration of high-risk NSAID use.

• Peptic ulcer disease, treatment, and secondary prevention

Uncomplicated ulcer

Oral: 40 mg once daily. Duration depends on the size, location, and cause of ulcer and ranges from 4 to 8 weeks. In patients with refractory or recurrent disease, may increase the dose to 40 mg twice daily.

Complicated ulcer (perforation, penetration, or gastric outlet obstruction)

Oral, IV: 40 mg twice daily for 4 weeks, followed by 40 mg once daily. Duration depends on the location and etiology of ulcer.

• Stress ulcer prophylaxis in select critically ill patients

IV: 40 mg once daily. Discontinue prophylaxis once risk factors have resolved.

Oral or via nasogastric tube: 40 mg once daily.

• Zollinger-Ellison syndrome

Oral: Initial: 80 mg twice daily; if needed, may titrate upward early in therapy to a maximum of 240 mg/day (as either 80 mg three times daily or 120 mg twice daily); once acid output has been controlled, gradual dose reductions are usually possible; reported maintenance dosage range: 40 to 200 mg/day (mean: 116 mg/day); daily doses ≥80 mg are usually given in 2 to 3 divided doses; continue therapy as long as clinically indicated.

IV (when oral administration is not possible): Initial: 80 mg every 8 to 12 hours; doses up to 240 mg/day (given as 120 mg every 12 hours or 80 mg every 8 hours) have been used for a limited period (up to 6 days); switch to oral administration when possible.

Paediatric Dose

• Gastroesophageal reflux disease, symptomatic

Infants, Children, and Adolescents: Oral: 1 to 2 mg/kg/day once daily; maximum daily dose: 40 mg/day.

• Erosive esophagitis associated with GERD

Children ≥5 years and Adolescents: Oral:

≥15 to <40 kg: 20 mg once daily for up to 8 weeks.

≥40 kg: 40 mg once daily for up to 8 weeks.

Pantoprazole is available in the form of Oral Tablet, Intravenous powder for injection.

• Dosage Adjustment in Kidney Patient

IV, Oral: Mild to severe impairment: No dosage adjustment necessary.

Pantoprazole is contraindicated in patients with

• Pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation.

• Concurrent Gastric Malignancy

Symptomatic response to therapy with Pantoprazole does not preclude the presence of gastric malignancy.

• Atrophic Gastritis

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with Pantoprazole, particularly in patients who were H. pylori positive.

• Cyanocobalamin (Vitamin B-12) Deficiency

Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

• 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 for osteoporosis-related fractures should be managed according to established treatment guidelines.

• Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, 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 the 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.

• Tumorigenicity

Due to the chronic nature of GERD, there may be a potential for prolonged administration of Pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown.

• Concomitant use of Pantoprazole 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.

Pantoprazole may pass into breast milk. An alternate medicine may be preferred, especially while you are nursing a newborn or preterm infant.

Pantoprazole is usually not recommended to pregnant women as there is not enough proof of its safety during pregnancy. Prescribe this medicine only if the benefit outweighs the risk.

Common

• Acute coronary syndrome, Acute generalized exanthematous pustulosis, cutaneous lupus erythematosus (subacute), maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, Hypocalcemia, hypokalemia, hypomagnesemia, Agranulocytosis, neutropenia, pancytopenia, Anaphylaxis, angioedema, asthenia, confusion, dementia, drowsiness, fatigue, hallucination, insomnia, bone fracture, rhabdomyolysis.

• Interference with Antiretroviral Therapy

Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Coadministration 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 postmarketing 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 increases 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 clopidogrelinduced platelet inhibition No dose adjustment of clopidogrel is necessary when administered with an approved dose of Pantoprazole.

• Drugs for Which Gastric pH Can Affect Bioavailability

Pantoprazole causes long-lasting inhibition of gastric acid secretion. Therefore, pantoprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts).

• 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. 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.

The common side effects of Pantoprazole include the following

Common side effects

• Headache, nausea, vomiting, gas, joint pain, diarrhea, dizziness.

Rare side effects

• Blistering, peeling, or bleeding skin; sores on the lips, nose, mouth, or genitals; swollen glands; shortness of breath; fever; or flu-like symptoms, Rash hives; itching; swelling of the eyes, face, lips, mouth, throat, or tongue, difficulty breathing or swallowing; or hoarseness, irregular, fast, or pounding heartbeat muscle spasms; uncontrollable shaking of a part of the body, excessive tiredness, lightheadedness, dizziness, or seizures, severe diarrhea with watery stools, stomach pain, or fever that does not go away, new or worsening joint pain; rash on cheeks or arms that is sensitive to sunlight, increased or decreased urination, blood in urine, fatigue, nausea, loss of appetite, fever, rash, or joint pain.

• Pregnancy

Pregnancy Category B

Reproduction studies have been performed in rats at oral doses up to 88 times the recommended human dose and in rabbits at oral doses up to 16 times the recommended human dose and have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

Pantoprazole and its metabolites are excreted in the milk of rats. Pantoprazole excretion in human milk has been detected in a study of a single nursing mother after a single 40 mg oral dose. The clinical relevance of this finding is not known. Many drugs which are excreted in human milk have a potential for serious adverse reactions in nursing infants. Based on the potential for tumorigenicity shown for pantoprazole in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

• Pediatric Use

The safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis (EE) associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole for pediatric uses other than EE have not been established.

• Geriatric Use

In short-term US clinical trials, erosive esophagitis healing rates in the 107 elderly patients (≥ 65 years old) treated with pantoprazole were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

Experience in patients taking very high doses of pantoprazole (> 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole. Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

Pharmacodynamic

This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion.

• General Effects

Pantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction.

Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal C. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.

Pharmacokinetics

• Absorption

Pantoprazole rapidly absorbed and the peak plasma concentration approximately 2-2.5 hours (oral). The bioavailability is approximately 77%.

• Distribution

The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in the extracellular fluid. The Plasma protein binding is approximately 98% (mainly to albumin).

• Metabolism and Excretion

Pantoprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19 hepatic cytochrome enzyme, followed by sulfation; other metabolic pathways include oxidation by CYP3A4.

Excreted Mainly via urine approximately 80%.

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