Omeprazole

Omeprazole is a Proton Pump Inhibitor of drug belonging to Gastrointestinal Agent.

Omeprazole is a proton pump inhibitor used to treat GERD associated conditions such as heartburn and gastric acid hypersecretion, and to promote healing of tissue damage and ulcers caused by gastric acid and H. pylori infection.

Rapid but variably absorbed from the gastrointestinal tract. Bioavailability is Approximately 30-40%. Time taken to reach peak plasma concentration is 0.5-3.5 hours. Volume of distribution is approximately 0.3L/kg, Protein binding is approximately 95%. Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system.

Omeprazole shows side effects like Constipation, gas, nausea, diarrhea, vomiting, headache.

Omeprazole is available in the form of Oral Tablet, Oral capsule, Oral suspension, and powder for reconstitution.

Omeprazole is available in India, Spain, Canada, US, Australia, China, and Italy.

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

Omeprazole is a member of a class of antisecretory compounds, the substituted benzimidazoles, that stop gastric acid secretion by selective inhibition of the H+/K+ ATPase enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the H+/K+ ATPase pump, inhibiting gastric acid secretion for up to 36 hours. This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus.

The Onset of action of Omeprazole is about 1 hour.

The Tmax of Omeprazole is approximately 2 hours.

Omeprazole is available in the form of Oral Tablet, Oral capsule, Oral suspension, and powder for reconstitution.

Omeprazole tablet, capsule, suspension and powder for reconstitution is taken orally.

Omeprazole is an anti-ulcer medicine used to treat conditions where the stomach produces too much acid. Stomach and duodenal ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome are certain problems caused by high levels of stomach acid. It relieves stress ulcers and acidity due to the intake of painkillers. Omeprazole is used in combination with antibiotics like amoxicillin and clarithromycin to prevent ulcers caused by Helicobacter pylori bacteria.

Omeprazole is a Proton Pump Inhibitor of drug belonging to Gastrointestinal Agent.

Omeprazole is proton pump inhibitor; suppresses gastric basal and stimulated acid secretion by inhibiting the parietal cell H+/K+ ATP pump.

Omeprazole is approved for use in the following clinical indications

Adult indication

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

Pediatric indication

• Erosive esophagitis
• Gastroesophageal reflux disease
• Helicobacter pylori eradication

Adult Dose

• Aspiration prophylaxis in patients undergoing anesthesia

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

• Barrett esophagus

Oral: 20 mg once daily; may increase the dose (eg, to 20 mg twice daily) if needed to eliminate gastroesophageal reflux disease symptoms or heal reflux esophagitis. Long-term maintenance therapy is recommended.

• Dyspepsia, functional

Oral: 20 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: 20 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 20 mg once daily and increase to twice daily dosing after 4 weeks if symptoms fail to improve.

• Gastroesophageal reflux disease, erosive or nonerosive

Oral: 10 mg once daily; can increase to 20 mg once daily after 4 to 8 weeks if necessary. Discontinue once asymptomatic for 8 week.

• Helicobacter pylori eradication

Oral: 20 mg or 40 mg twice daily as part of an appropriate combination regimen with antibiotics. Dose depends on the selected regimen.

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

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

• Peptic ulcer disease, treatment, and secondary prevention

Oral: 20 mg or 40mg once daily.

• Stress ulcer prophylaxis in select critically ill patients

Oral or via NG tube: 40 mg once daily or 40 mg initially, then another 40 mg dose given 6 to 8 hours later, followed by 40 mg once daily. Discontinue prophylaxis once risk factors have resolved.

• Zollinger-Ellison syndrome

Oral: Initial: 40 mg twice daily; if needed, may titrate upward early in therapy to a maximum of 180 mg/day; once acid output has been controlled, gradual dose reductions are usually possible; reported maintenance dosage range: 10 to 180 mg/day (mean: 60 to 70 mg/day); daily doses >80 mg are usually given in 2 divided doses; continue therapy as long as clinically indicated.

Paediatric Dose

• Erosive esophagitis

Infants, Children, and Adolescents: Oral:

3 to <5 kg: 2.5 mg once daily.

5 kg to <10 kg: 5 mg once daily.

10 kg to <20 kg: 10 mg once daily.

≥20 kg: 20 mg once daily.

• Gastroesophageal reflux disease

Children and Adolescents: Oral:

5 kg to <10 kg: 5 mg once daily.

10 kg to <20 kg: 10 mg once daily.

≥20 kg: 20 mg once daily.

• Helicobacter pylori eradication

15 to <25 kg: 20 mg twice daily.

25 to 34 kg: 30 mg twice daily.

>34 kg: 40 mg twice daily.

Omeprazole is available in the form of Oral Tablet, Oral capsule, Oral suspension, and powder for reconstitution.

• Dosage Adjustment in Kidney Patient.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary.

Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary.

Peritoneal dialysis: No dosage adjustment necessary.

CRRT: No dosage adjustment necessary.

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary.

• Dosage Adjustment in Hepatic impairment Patient

Mild to severe impairment (Child-Pugh class A, B, or C): 10 mg once daily when used for maintenance of healing of erosive esophagitis. There are no dosage adjustments provided for the other indications. Alternatively, a maximum dose of 20 mg/day regardless of indication, has been recommended. In a very small study, omeprazole systemic exposure and half-life increased ~2- and ~3-fold respectively, in patients with mild to severe hepatic impairment.

Omeprazole is contraindicated in patients with

• Omeprazole is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria.
• Proton pump inhibitors (PPIs), including omeprazole, are contraindicated in patients receiving rilpivirine-containing products.

• Concomitant Gastric Malignancy

Symptomatic response to therapy with omeprazole 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 omeprazole.

• Clostridium difficile associated diarrhea

Published observational studies suggest that PPI therapy like PRILOSEC 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. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium diffficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents.

• 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.

• Diminished Anti-platelet Activity of clopidogrel due to Impaired CYP2C19 Function by Omeprazole

Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that interfere with CYP2C19 activity. Avoid concomitant use of clopidogrel and omeprazole. Co-administration of clopidogrel with 80 mg omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12 hours apart.

• 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.

• Concomitant use of omeprazole with St John’s Wort or rifampin

Drugs which induce CYP2C19 or CYP3A4 (such as St John’s Wort or rifampin) can substantially decrease omeprazole concentrations. Avoid concomitant use of omeprazole with St John’s Wort or rifampin.

• Interactions with Diagnostic Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Providers should temporarily stop omeprazole treatment before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

• Concomitant use of omeprazole 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.

Omeprazole concentrations have been measured in breast milk of a woman following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was less than 7% of the peak serum concentration. This concentration would correspond to 0.004 mg of omeprazole in 200 mL of milk. Because omeprazole is excreted in human milk, because of the potential for serious adverse reactions in nursing infants from omeprazole, and because of the potential for tumorigenicity shown for omeprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy category C

Reproductive studies in rats and rabbits with omeprazole and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are no adequate and well-controlled studies on the use of omeprazole 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.

Common Adverse effects

• Respiratory system disorder, Skin rash, Abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting, Dizziness, headache, Asthenia, back pain, Cough, upper respiratory infection.

Rare Adverse effects

• Acute coronary syndrome, angina pectoris, bradycardia, chest pain, increased blood pressure, palpitations, peripheral edema, tachycardia, Acute generalized exanthematous pustulosis, alopecia, cutaneous lupus erythematosus, dermatitis, hyperhidrosis, hypertrichosis, maculopapular rash, pruritus, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, xeroderma, Glycosuria, gynecomastia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, vitamin B12 deficiency, weight gain, Abdominal swelling, anorexia, Clostridioides difficile associated diarrhea, colitis (microscopic), dysgeusia, esophageal candidiasis, fecal discoloration, gastric polyp, gastroenteritis, irritable bowel syndrome, pancreatitis, sore throat, stomatitis, tongue mucosa atrophy, xerostomia, Hematuria, microscopic pyuria, proteinuria, testicular pain, urinary frequency, urinary tract infection, Agranulocytosis, anemia, benign polyp of the stomach, hemolytic anemia, leukocytosis, leukopenia, neutropenia, pancytopenia, petechia, thrombocytopenia , Cholestatic hepatitis, hepatic encephalopathy, hepatic failure, hepatic necrosis, hepatocellular hepatitis, hepatotoxicity, Anaphylactic shock, anaphylaxis, angioedema, Drug reaction with eosinophilia and systemic symptoms, Abnormal dreams, aggressive behavior, agitation, anterior ischemic optic neuropathy, anxiety, apathy, confusion, dementia, depression, drowsiness, fatigue, hallucination, insomnia, myasthenia, nervousness, pain, paresthesia, sleep disturbance, vertigo, Arthralgia, bone fracture, lower leg pain, muscle cramps, myalgia, systemic lupus erythematosus, tremor, Blurred vision, diplopia, dry eye syndrome, eye irritation, optic atrophy, optic neuritis, Tinnitus, Acute interstitial nephritis, renal disease, Bronchospasm, epistaxis, pneumonia, Fever.

• Interference with Antiretroviral Therapy

Concomitant use of atazanavir and nelfinavir with proton pump inhibitors is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and may result in a loss of therapeutic effect and the development of drug resistance. Co-administration of saquinavir with proton pump inhibitors is expected to increase saquinavir concentrations, which may increase toxicity and require dose reduction. Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP 2C19. There are also some antiretroviral drugs of which unchanged serum levels have been reported when given with omeprazole.

• Drugs for Which Gastric pH Can Affect Bioavailability

Because of its profound and long lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with 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, iron salts and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with omeprazole. Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (30% in two subjects). Therefore, patients may need to be monitored when digoxin is taken concomitantly with omeprazole. In the clinical trials, antacids were used concomitantly with the administration of omeprazole.

• Effects on Hepatic Metabolism/Cytochrome P-450 Pathways

Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including omeprazole, 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 may need to be monitored for increases in INR and prothrombin time. Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P450 system (e.g., cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with omeprazole.

• Tacrolimus

Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.

• Interactions With Investigations of Neuroendocrine Tumors

Drug-induced decrease in gastric acidity results in enterochromaffin like cell hyperplasia and increased Chromogranin A levels which may interfere with investigations for neuroendocrine tumors.

• Combination Therapy with Clarithromycin

Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs.

• 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 effect of Omeprazole includes the following

Common

• Constipation, gas, nausea, diarrhea, vomiting, headache.

Rare

• Blisters, 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, 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 C

Reproductive studies in rats and rabbits with omeprazole and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are no adequate and well-controlled studies on the use of omeprazole 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

Omeprazole concentrations have been measured in breast milk of a woman following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was less than 7% of the peak serum concentration. This concentration would correspond to 0.004 mg of omeprazole in 200 mL of milk. Because omeprazole is excreted in human milk, because of the potential for serious adverse reactions in nursing infants from omeprazole, and because of the potential for tumorigenicity shown for omeprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

Use of omeprazole in pediatric and adolescent patients 1 to 16 years of age for the treatment of GERD is supported by extrapolation of results, already included in the currently approved labeling, from adequate and well-controlled studies that supported the approval of Omeprazole for adults, and safety and pharmacokinetic studies performed in pediatric and adolescent patients. The safety and effectiveness of omeprazole for the treatment of GERD in patients <1 year of age have not been established. The safety and effectiveness of omeprazole for other pediatric uses have not been established.

• Geriatric Use

Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Symptoms: Nausea, vomiting, dizziness, abdominal pain, diarrhoea, headache apathy, depression, and confusion.

Management: Symptomatic and supportive treatment.

Pharmacodynamic

• Effects on gastric acid secretion

This drug decreases gastric acid secretion. After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days.

· Effects on serum gastrin

In studies of 200 or more patients, serum gastrin levels increased during the first 1-2 weeks of daily administration of therapeutic doses of omeprazole. This occurred in a parallel fashion with the inhibition of acid secretion. No further increase in serum gastrin occurred with continued omeprazole administration. Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may lead to false positive results in diagnostic studies for neuroendocrine tumors.

· Enterochromaffin-like (ECL) cell effects

Human gastric biopsy samples have been obtained from more than 3000 pediatric and adult patients treated with omeprazole in long-term clinical studies. The incidence of enterochromaffin-like cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia have been identified in these patients. These studies, however, are of insufficient in power and duration to draw conclusions on the possible influence of long-term administration of omeprazole in the development of any premalignant or malignant conditions.

Pharmacokinetics

• Absorption

Rapid but variably absorbed from the gastrointestinal tract. Bioavailability is Approximately 30-40%. Time taken to reach peak plasma concentration is 0.5-3.5 hours.

• Distribution

Volume of distribution is approximately 0.3L/kg, Protein binding is approximately 95%.

• Metabolism and Excretion

Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system.

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