OMEPRAZOLE

Omeprazole is a proton pump inhibitor (PPI) that has a long duration of action and is very potent, allowing for once-daily administration. It is indicated for short term therapy of gastroesophageal reflux disease, gastric and duodenal ulcers, and gastric hypersecretory conditions including Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenoma. It is also approved for use in combination with antibiotics in the eradication of Helicobacter pylori (H. pylori) infection for the reduction of the risk of duodenal ulcer recurrence . Clinicians should test for H. pylori infection in patients presenting with non-ulcer dyspepsia; patients found to be H. pylori positive should be started on combination eradication therapy. Eradication of H. pylori offers modest, but significant, symptom relief in non-ulcer dyspepsia and reduces the risk of developing peptic ulcer disease, atrophic gastritis, and gastric cancer. For populations with a low prevalence of H. pylori infection (< 10%), starting a 2 to 4 week empiric trial of a PPI is an alternate approach. On the basis of available research, no clear advantage has been demonstrated for the use of one PPI over another in the treatment of GERD. Instead, a key to optimizing effectiveness is tailoring dosage timing and considering twice daily dosing; traditional delayed release PPIs should be administered 30 to 60 min before a meal for maximal pH control. A one-time switch to a different PPI in a refractory patient may be useful. Due to concern regarding long-term use, omeprazole was originally approved by the FDA in September 1989 for acute treatment only; although precautions exist with the long-term use of PPIs, omeprazole has been approved for the maintenance of healing of erosive esophagitis. In July 2002, the FDA approved use for children aged >= 1 year of age for the treatment of acid-related gastrointestinal diseases, including symptomatic GERD and erosive esophagitis. In January 2009, a delayed-release oral suspension was FDA approved. A non-prescription omeprazole product was approved in June 2003; Prilosec OTC (delayed-release omeprazole 20 mg) is indicated for the short-term treatment of frequent heartburn (2 or more episodes per week). The OTC formulation is not considered bioequivalent to the prescription dosage formulations. In February 2016, the FDA approved use for infants aged >= 1 month for the treatment of erosive esophagitis due to acid-mediated GERD. NOTE: The information for omeprazole; sodium bicarbonate (Zegerid) capsules or powder packets for oral suspension is located in a separate monograph (omeprazole; sodium bicarbonate).

General Administration Information
For storage information, see the specific product information within the How Supplied section.

NOTE: The information for omeprazole; sodium bicarbonate (Zegerid) capsules or powder packets for oral suspension is located in a separate monograph.

Route-Specific Administration

Oral Administration
-Administer on an empty stomach, 60 minutes before meals. If given once daily, administer before the first meal of the day.
-May be taken concurrently with antacids.
Oral Solid Formulations
Non-prescription OTC tablets:
-Tablets should not be chewed, broken, or crushed into food. NOTE: Omeprazole tablets (OTC dosage form) and the omeprazole capsules (Rx-only dosage form) are not rated as bioequivalent.

Non-prescription OTC orally disintegrating tablets:
-Place tablet on the tongue; the tablet will disintegrate with or without water. Alternatively, the tablet may be swallowed whole with water. Do not chew or crush tablets.

Delayed-release capsules:
-Capsules contain enteric-coated, delayed-release granules. These granules should not be chewed or crushed. The capsules can be opened and the enteric-coated granules sprinkled on applesauce or yogurt, given with fruit juices, or swallowed immediately with water. Prepare just prior to administration. Administer entire dosage.
-Nasogastric tube administration: For administration via nasogastric (NG) tube, the capsules can be opened and the enteric-coated granules will remain intact when exposed to selected juices such as apple or cranberry juice for ease of administration.

Oral Liquid Formulations
-2.5 mg delayed-release suspension packet: When administering by mouth, empty the contents of the packet into a container with 5 mL of water. Stir gently, allowing 2 to 3 minutes for the suspension to thicken. Stir again, and then, administer. If any drug remains after drinking, add more water, stir, and administer immediately. When administering via an NG or gastric tube (French size 6 or larger), add 5 mL of water to a catheter tipped syringe; then, add the contents of a packet to the syringe. Shake immediately, allowing 2 to 3 minutes for the suspension to thicken. Shake once more and give through the NG or gastric tube. Refill the syringe with an equal amount of water. Shake and flush any remaining contents from the tube. In all cases, administer the suspension within 30 minutes of preparation.
-10 mg delayed-release suspension packet: When administering by mouth, empty the contents of the packet into a container with 15 mL of water. Stir gently, allowing 2 to 3 minutes for the suspension to thicken. Stir again, and then, administer. If any drug remains after drinking, add more water, stir, and administer immediately. When administering via an NG or gastric tube (French size 6 or larger), add 15 mL of water to a catheter tipped syringe; then, add the contents of a packet to the syringe. Shake immediately, allowing 2 to 3 minutes for the suspension to thicken. Shake once more and give through the NG or gastric tube. Refill the syringe with an equal amount of water. Shake and flush any remaining contents from the tube. In all cases, administer the suspension within 30 minutes of preparation.

Extemporaneous Compounding-Oral
Extemporaneous preparation of 2 mg/mL oral suspension ('simplified omeprazole suspension' or SOS):
NOTE: The extemporaneous preparation of omeprazole suspension is not approved by the FDA.
-Empty the contents of one or two 20-mg omeprazole capsules into an empty 10- or 20-mL syringe with needle in place (plunger removed). Then, replace the plunger and uncap the needle. Withdraw 10 or 20 mL of sodium bicarbonate 8.4% (1 mEq/mL) solution (for omeprazole 20 or 40 mg, respectively) from the bicarbonate vial. Allow preparation to stand for at least 30 minutes, with intermittent agitation, to allow the granules to suspend. The preparation forms a milky white suspension with a final concentration of 2 mg/mL. The suspension is stable for 14 days at 24 degrees C and for 30 days at 5 degrees C and -20 degrees C; at room temperature, greater than 90% potency is maintained for 7 days.

Animal and human data have demonstrated a proliferation of enterochromaffin-like cells due to hypergastrinemia, which may be associated with the development of malignant gastric carcinoma during long-term administration of omeprazole. Data suggest that omeprazole may be given for as long as 5 years without concern for the development of gastric neoplasia. Twenty-five patients with H2-receptor antagonist-resistant gastroesophageal reflux disease (GERD) were treated and then followed on long-term (at least 4 years) omeprazole therapy. Persistent increases in median gastrin concentrations were noted during treatment; concentrations did not significantly increase during maintenance therapy. A subgroup of patients with very high gastrin concentrations (more than 500 ng/L) had a higher incidence of enterochromaffin-like cell hyperplasia than did other patients. Neoplasia or dysplasia were not seen in biopsies, however. Gastro-duodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome receiving long-term omeprazole; however, this finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors. The overall risk of carcinoid tumors during therapy with proton pump inhibitors (PPIs) is low based on cumulative safety experience; monitoring of serum gastrin levels during PPI therapy is generally not necessary.

Common gastrointestinal (GI) related adverse events reported during double-blind and open-label studies of omeprazole include, abdominal pain (5.2%), nausea (4%), diarrhea (3.7%), vomiting (3.2%), flatulence (2.7%), acid regurgitation (1.9%), and constipation (1.5%). During postmarketing surveillance, the following GI adverse events were reported: abdominal swelling, anorexia, dysgeusia, esophageal candidiasis, irritable colon, mucosal atrophy of the tongue, pancreatitis (some fatal), stomatitis, stool discoloration, and xerostomia. PPI use is associated with an increased risk of gastric polyps/fundic gland polyps that increases with long-term use, especially beyond 1 year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. Gastroduodenal carcinoids have been reported in patients with Zollinger Ellison syndrome on long-term treatment with omeprazole; this finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hypersensitivity reactions including rash have been reported in 2% of patients receiving omeprazole during double-blind and open-label studies. In addition, postmarketing surveillance of omeprazole use has identified the following hypersensitivity and dermatological adverse reactions: alopecia, anaphylactic shock, anaphylactoid reactions, angioedema, bronchospasm, erythema multiforme, hyperhidrosis, petechiae, photosensitivity, purpura, pruritus, skin inflammation, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), urticaria, and xerosis.

During postmarketing surveillance, the following adverse events have been reported in association with omeprazole use: cholestasis, elevated hepatic enzymes (ALT, AST, GGT, alkaline phosphatase), hyperbilirubinemia, hepatic encephalopathy, hepatic failure (some fatal), hepatic necrosis (some fatal), hepatocellular disease, jaundice, and mixed hepatitis.

During postmarketing surveillance, hematologic adverse reactions have been reported with omeprazole use and include agranulocytosis (some fatal), anemia, hemolytic anemia, leukocytosis, leukopenia, neutropenia, pancytopenia, and thrombocytopenia. In addition, long-term (e.g., generally at least 2 to 3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). In a study of healthy volunteers, it was shown that omeprazole caused a significant reduction in cyanocobalamin absorption (vitamin B12 deficiency). One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively). A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy. Patients receiving at least 2 years of a proton pump inhibitor (PPI) (OR, 1.65 [95% CI, 1.58 to 1.73]) or at least 2 years of a H2-receptor antagonist (OR, 1.25 [95% CI, 1.17 to 1.34]) were associated with having an increased risk for vitamin B12 deficiency. A dose-dependant relationship was evident, as daily doses more than 1.5 PPI pills/day were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77 to 2.15]) compared to daily doses less than 0.75 pills/day (OR, 1.63 [95% CI, 1.48 to 1.78]; p = 0.007 for interaction). The possibility of cyanocobalamin deficiency and pernicious anemia should be considered if clinical symptoms are observed. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.

In double-blind and open-label studies of omeprazole, headache was among the most common adverse reactions reported (2.9% to 6.9%). Dizziness (1.5%) was also reported with omeprazole therapy at a greater frequency than placebo. Other nervous system and psychiatric adverse events identified during postmarketing surveillance of omeprazole therapy include aggression, agitation, anxiety, apathy, confusion, depression, dream abnormalities (abnormal dreams), drowsiness (somnolence), hallucinations, hemifacial dysesthesia, insomnia, nervousness, paresthesias, tremor, and vertigo.

In double-blind and open-label studies, upper respiratory tract infection (1.9%) and cough (1.1%) were reported among omeprazole treated patients. In pediatric studies, adverse reactions of the respiratory system (not specified) were reported in 75% of patients 1 to younger than 2 years of age and in 18.5% of patients 2 to 16 years of age. Fever was reported in postmarketing reports of omeprazole use, and in 33% of patients 1 to 2 year of age. Epistaxis and pharyngeal pain have also been noted postmarketing. In addition, increasing evidence suggests a link between acid-suppression therapy and pneumonia (community- and hospital-acquired). Several mechanisms have been proposed to account for this association. One such mechanism states that gastric pH serves as a barrier against pathogenic colonization of the gastrointestinal tract. An increase in gastric pH allows for bacterial and viral invasion which, in theory, can precipitate respiratory infections. Another proposed mechanism accounts for the role that gastric acid may have on stimulating the cough reflex that allows for the clearing of infectious agents from the respiratory tract. Finally, the fact that acid-suppressive therapy may impair white blood cell function, which in turn may lead to a depressed immune response to an infection, is listed among possible mechanisms. Regardless of the mechanism, the use of H2-blockers and/or proton pump inhibitors (PPIs) has been associated with the development of pneumonia. Data from a large epidemiological trial, including 364,683 individuals who developed 5,551 first occurrences of community-acquired pneumonia (CAP), suggest an increased risk of developing CAP among users of acid-suppressive therapy compared to those who stopped therapy. After adjusting for confounders, the adjusted relative risk (RR) for CAP among PPI users compared to those who stopped therapy was 1.89 (95% CI, 1.36 to 2.62). Likewise, users of H2-blockers had an adjusted RR of 1.63 (95% CI, 1.07 to 2.48) compared to those who stopped therapy. In a second large cohort trial, including 63,878 hospital admissions, acid-suppressive therapy was ordered in 52% (83% PPI and 23% H2-blocker, with some patients exposed to both) of new admissions. Hospital-acquired pneumonia occurred in 2,219 admissions (3.5%) with a higher incidence recorded among acid-suppressive therapy exposed patients compared to non-exposed patients. A subset analysis found a statistically significant association between PPI use (OR, 1.3; 95% CI, 1.1 to 1.4) and pneumonia. A non-significant association was found with H2-blockers (OR, 1.2; 95% CI, 0.98 to 1.4); however, the lack of significance was attributed to the studies lack of power to detect significance for an OR of less than 1.3. Until more is known about the relationship between acid-suppression and pneumonia, clinicians are encouraged to carefully select patients before empirically initiating acid-suppressive therapy with H2-blockers or PPIs. A causal relationship between the use of omeprazole and pneumonia has not been established.

In double-blind and open-label studies, asthenia (1.3%) and back pain (1.1%) were reported in omeprazole treated patients. During postmarketing surveillance, arthralgia (joint pain), leg pain, muscle cramps, myalgia, and myasthenia (muscle weakness) were also reported. Proton pump inhibitors (PPIs) have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine. There have been 6 epidemiological studies that have reported an increased risk of fractures with the use of PPIs; the studies compared claims data of patients treated with PPIs versus individuals who were not using PPIs. Depending on the study, exposure to PPIs ranged between 1 and 12 years. The emergence of fractures varied among studies; 1 study reported an increase in fractures with use of PPIs in the previous year and another study found an increase after 5 to 7 years of PPI use. Increased risk was primarily observed in patients at least 50 years old, patients taking prescription PPIs for at least 1 year, and patients who had been taking high doses (doses greater than those recommended with OTC use). Alternatively, in another epidemiological study with similar study design, a relationship between PPI use and fractures was not established; the study population did not have major risk factors for fracture at study entry. It should be noted that randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; some limitations of these RCTs were the study durations (generally 6 months) and insufficient information on effects of higher than recommended doses. Until more data are available, when prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients at risk for or with osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.

Cutaneous lupus erythematosus (CLE), systemic lupus erythematosus (SLE), and lupus-like symptoms have occurred in patients taking proton pump inhibitors (PPIs), including omeprazole. Both exacerbation and new onset of existing autoimmune disease have be reported, with the majority of PPI-induced lupus erythematosus cases being CLE. Subacute CLE (SCLE) is the most common form of CLE reported in patients treated with PPIs, occurring within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Histological findings were usually observed without organ involvement. SLE is less commonly reported; PPI associated SLE is generally milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from infants to the elderly. Most patients presented with rash; however, arthralgia and cytopenia were also reported. Do not administer PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE occur, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks; serological testing (ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Omeprazole administration to pediatric patients is generally well tolerated, with an adverse event profile similar to that of adults. Side effects unique to the pediatric population, however, have been reported. For example, accidental injury occurs with a 3.8% frequency in the 2 to 16 year old age group; however, a causal relationship of these side effects to omeprazole has not been determined. Other miscellaneous adverse events reported during postmarketing surveillance of omeprazole in all patients include anterior ischemic optic neuropathy, blurred vision, diplopia, fatigue, malaise, ocular irritation, optic atrophy, optic neuritis, pain (unspecified), peripheral edema, tinnitus, and xerophthalmia.

Metabolic and nutritional adverse reactions reported during postmarketing surveillance of omeprazole use include hypoglycemia, hypomagnesemia with or without hypocalcemia and/or hypokalemia, hyponatremia, and weight gain. Cases of hypomagnesemia have been reported in association with prolonged (3 months to more than 1 year) proton pump inhibitor (PPI) use. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in patients at risk. Low serum magnesium may lead to serious adverse reactions such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Consider monitoring electrolyte concentrations and supplementing electrolytes when needed. Discontinuation of PPI therapy may be necessary.

Miscellaneous adverse events reported during postmarketing surveillance of omeprazole include angina, bradycardia, chest pain (unspecified), hypertension, palpitations, and sinus tachycardia. After completion of a comprehensive review, the FDA believes that the long-term use of omeprazole (or esomeprazole) is not likely to be associated with an increased risk of heart problems. Preliminary analysis of 2 small, long-term clinical studies raised concerns about a possible link between the long-term use of these drugs and cardiovascular events. In both studies, patients with severe gastroesophageal reflux disease (GERD) were randomized to receive drug therapy, with omeprazole or esomeprazole, or surgery to control GERD. Results from the studies appeared to show an increased risk of myocardial infarction, heart failure, and heart-related sudden death in patients who received drug therapy compared to those who received surgery. However, the results of these 2 studies along with results from other comparative studies of omeprazole, which did not show an increased risk of heart related adverse events, were analyzed by the FDA. The FDA did not find a correlation between the reported cardiovascular events and the use of either drug; thus, the FDA recommends that health care professionals and their patients continue to prescribe and use these products in accordance with their labeled uses.

During postmarketing surveillance of omeprazole, microscopic colitis has been reported. A link between the onset of microscopic colitis and proton pump inhibitor (PPI) therapy has been suggested in case reports and case series. Reports and subsequent histological confirmation of both collagenous colitis and lymphocytic colitis, 2 distinct forms of microscopic colitis, have been observed in patients treated with lansoprazole, another PPI. One case series included 6 patients who developed microscopic colitis after a formulary switch to lansoprazole from omeprazole; upon lansoprazole discontinuation, associated symptoms resolved. The mechanism of this rare adverse reaction is not clear; however, an idiosyncratic immune reaction is suspected. Because small changes in the structures of PPIs may elicit different immunological responses, it is difficult to predict if this adverse effect can be expected with other PPIs. Until more is known about the association between PPIs and microscopic colitis, clinicians should advise patients to report prolonged watery loose stools and PPI discontinuation or substitution should be considered in these patients.

C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with omeprazole. PPI therapy, such as omeprazole, may be associated with an increased risk of CDAD, especially in hospitalized patients. The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection or superinfection by encouraging the growth of gut microflora. If pseudomembranous colitis is suspected or confirmed, institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.

Acute tubulo-interstitial nephritis (AIN or TIN) has been observed in patients taking PPIs, including omeprazole, and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue omeprazole and evaluate patients with suspected acute AIN. Other urogenital adverse reactions reported during the use of omeprazole include hematuria, albuminuria (proteinuria), elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, increased urinary frequency, testicular pain, and gynecomastia. A few cases of renal failure have been described with omeprazole therapy in published literature case reports.

Omeprazole is contraindicated in patients with known hypersensitivity to omeprazole or other substituted benzimidazoles such as esomeprazole or lansoprazole (i.e., known proton pump inhibitors (PPIs) hypersensitivity). There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports, and some cases have been serious (e.g., angioedema or anaphylaxis). Serious rash and severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), erythema multiforme, and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs. Discontinue the PPI at the first signs or symptoms of severe cutaneous adverse reactions or other hypersensitivity and consider further evaluation. Acute tubulo-interstitial nephritis (TIN or AIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). There have been reports of patients who were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue omeprazole and evaluate patients with suspected acute TIN.

Omeprazole should be administered with caution to patients with hepatic disease since clearance of the drug can be prolonged. Dosage reduction is generally not necessary, but may be considered in patients with severe hepatic impairment (e.g., cirrhotic liver disease), especially those receiving long-term therapy. In addition, omeprazole has been associated with hepatitis and, in rare instances, hepatic failure.

Poor metabolizers of CYP2C19 are expected to have higher exposure to omeprazole than normal (extensive) metabolizers. Approximately 3% of White patients and 15% to 20% of Asian patients are CYP2C19 poor metabolizers. Asian patients exhibit a 4-fold increase in AUC of omeprazole compared to White patients. For adult patients, a dosage reduction of omeprazole to 10 mg once daily is recommended for Asian patients for maintenance of healing of erosive esophagitis (EE).

Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance. Patients are usually asymptomatic and fundic gland polyps are identified incidentally on endoscopy. The risk of fundic gland polyps increases with long term proton pump inhibitor (PPI) use, especially beyond one year. Use the shortest duration of PPI therapy appropriate to treat specific condition. Symptomatic response to therapy with omeprazole does not preclude the presence of gastric cancer or other malignancy. Omeprazole decreases intragastric acidity. Subsequently, the number of bacteria in gastric secretions and, correspondingly, the amount of carcinogenic N-nitroso compounds produced by these bacteria increase. Gastro-duodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome receiving long-term omeprazole; however, this finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors. The overall risk of carcinoid tumors during therapy with proton pump inhibitors (PPI) is low based on cumulative safety experience; monitoring of serum gastrin levels during PPI therapy is generally not necessary. One trial studied 25 patients with H2-receptor antagonist-resistant gastroesophageal reflux disease (GERD) who were treated and then followed on long-term (4 years or more) omeprazole therapy; neoplasia or dysplasia were not seen in biopsies.

Consider pseudomembranous colitis in patients presenting with diarrhea after PPI use. PPI therapy, such as omeprazole, may be associated with an increased risk of C. difficile-associated diarrhea (CDAD), especially in hospitalized patients. CDAD may range in severity from mild to life-threatening. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Daily treatment with gastric acid-suppressing medication such as omeprazole over a long period of time (e.g., generally >= 2-3 years) may lead to malabsorption of cyanocobalamin and vitamin B12 deficiency. Cases of cyanocobalamin deficiency occurring with acid-suppression therapy have been reported in the literature. One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency. A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy of > 2 years duration [i.e., proton pump inhibitor (PPI), H2-receptor antagonist]. In addition, a dose-dependant relationship was evident, as larger daily PPI pill counts were more strongly associated with vitamin B12 deficiency. The possibility of cyanocobalamin deficiency should, therefore, be considered if clinical symptoms are observed.

Use proton pump inhibitors (PPIs) in patients with or who have risk factors for osteoporosis or osteopenia cautiously. PPIs have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine. Epidemiological studies have reported an increased risk of fractures with the use of PPIs; the studies compared claims data of patients treated with PPIs versus individuals who were not using PPIs. The risk of fracture was increased in patients who received high-dose (defined as multiple daily doses or doses greater than those recommended in non-prescription use), and long-term PPI therapy (a year or longer); fractures were primarily observed in adult patients 50 years of age and older. Pre-approval randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; however, these RCTs were of shorter study duration (generally 6 months or less). When prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients with or at risk for osteopenia or osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.

Use omeprazole with caution in patients with a pre-existing risk of hypocalcemia (e.g., hypoparathyroidism), hypokalemia, or hypomagnesemia; consider monitoring magnesium and calcium concentrations prior to initiating therapy and periodically while on treatment in these patients. Supplement with magnesium and/or calcium as needed and consider discontinuing proton pump inhibitor (PPI) therapy if hypomagnesemia or hypocalcemia is refractory to treatment. For patients expected to be on PPI therapy for a prolonged period of time or who take concomitant medications such as digoxin or those that may cause hypomagnesemia (e.g., diuretics), consider monitoring of serum magnesium prior to initiation and periodically during treatment. Daily treatment with a PPI over a long period of time (e.g., 3 months to more than 1 year) may lead to hypomagnesemia; cases have been reported in patients taking omeprazole. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in patients at risk. In most patients, the treatment of hypomagnesemia required magnesium replacement and PPI discontinuation. Low serum magnesium may lead to serious adverse reactions such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Use PPIs with caution and, if possible, avoid long term (greater than 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias.

Studies suggest that long-term PPI therapy is associated with a temporal increase in gastric acid secretion shortly following treatment discontinuation. A similar and well established response has been noted after withdrawal of H2 blockers. Profound gastric acid suppression during PPI therapy leads to a drug-induced reflex hypergastrinemia and subsequent rebound acid hypersecretion. In this hypersecretory state, enterochromaffin-like cell hypertrophy also results in a temporal increase in serum chromogranin A (CgA) levels. It is unclear, however, if this hypersecretory reflex results in clinically significant effects in patients on or attempting to discontinue PPI therapy. A clinically significant effect may lead to gastric acid-related symptoms upon PPI withdrawal and possible therapy dependence. Studies in healthy subjects (H. pylori negative) as well as GERD patients, present conflicting data regarding whether PPI therapy beyond 8-weeks is associated with rebound acid hypersecretion and associated dyspeptic symptoms shortly following PPI cessation. Until more consistent study results shed light on this possible effect, it is prudent to follow current treatment guidelines employing the lowest effective dose, for the shortest duration of time in symptomatic patients. For patients requiring maintenance therapy, consider on demand or intermittent PPI therapy, step down therapy to an H2 blocker, and regularly assess the need for continued gastric suppressive therapy.

There are no adequate and well-controlled studies of omeprazole in pregnant women. Available epidemiologic data fail to demonstrate an increased risk of major congential malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Animal reproductive studies have shown embryonic damage when omeprazole was given in high doses to rabbits and rats; however, more recent data have not shown an increase in congenital anomalies with omeprazole use versus controls, even in early pregnancy. In humans, omeprazole is known to cross the placenta to the fetus. Epidemiological evaluations have compared the rate of congenital abnormalities and stillbirths among those exposed to omeprazole in utero during pregnancy to similar findings for those exposed to H2-receptor antagonists or other controls. Overall, slightly higher rates of congenital malformations (e.g., ventricular septal defects) and number of stillborns have been reported for cases where exposure to omeprazole occurred in the first trimester of pregnancy and beyond. However, a large cohort study from Denmark did not show a significantly increased risk of birth defects in women who took proton pump inhibitors (PPIs), including omeprazole, during the first trimester. In a meta-analysis of 7 studies, there was no evidence linking PPI exposure in pregnancy to adverse outcomes such as congenital malformations, spontaneous abortions, or premature deliveries. When data was analyzed separately for omeprazole, there was no change in the results. Several studies have also reported no apparent adverse short-term effects on the infant when single dose omeprazole (PO or IV) was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, histamine type 2-receptor antagonists (H2RAs) can be used. Proton pump inhibitors should be reserved for pregnant patients who fail H2RA therapy. Self-medication with proton pump inhibitors (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.

Limited data suggest that omeprazole may be present in human milk. The clinical effects of proton pump inhibitor (PPI) exposure on the breastfed infant or on milk production have not been confirmed and PPI use is not recommended while breast-feeding; consider the developmental and health benefits of breast-feeding along with the clinical need for omeprazole and any potential adverse effects on the breastfed infant or from the underlying maternal condition. According to guidelines, if heartburn/gastroesophageal reflux (GERD) symptoms persist after delivery, antacids and sucralfate are safe to use because they are not concentrated in breast milk. Histamine type 2-receptor antagonists (H2RAs) are excreted in breast milk, but cimetidine and famotidine are considered safe for use during lactation and may be used if symptoms persist despite antacid use.

The package labeling for the non-prescription (OTC) omeprazole states that patients should not self-medicate with omeprazole if they have trouble swallowing (dysphagia), vomiting with blood, or bloody or black stools (GI bleeding). Also, a patient should speak with a health care provider prior to using omeprazole OTC if there is a history of any of the following: chest pain, heartburn for more than 3 months, heartburn with dizziness, lightheadedness or sweating, abdominal pain, unexplained weight loss, or wheezing. Such symptoms need medical evaluation and perhaps prescription therapy.

Use with caution in patients with a history of systemic lupus erythematosus (SLE) as omeprazole has been reported to activate or exacerbate SLE.

Administration of omeprazole may result in laboratory test interference, specifically serum chromogranin A (CgA) tests for neuroendocrine tumors, urine tests for tetrahydrocannabinol (THC), secretin stimulation tests, and diagnostic tests for Helicobacter pylori. Gastric acid suppression may increase serum CgA. Increased CgA concentrations may cause false positive results in diagnostic investigations for neuroendocrine tumors. To prevent this interference, temporarily stop omeprazole at least 14 days before assessing CgA concentrations and consider repeating the test if initial concentrations are high. If serial tests are performed, ensure the same commercial laboratory is used as reference ranges may vary. Reports have suggested use of proton pump inhibitors (PPIs) may cause false positive urine screening tests for THC. If a PPI-induced false positive urine screen is suspected, confirm the positive results using an alternative testing method. Omeprazole may cause a hyper-response in gastrin secretion to the secretin stimulation test, falsely suggesting gastrinoma. Health care providers are advised to temporarily stop omeprazole at least 14 days prior to performing a secretin stimulation test to allow gastrin concentrations to return to baseline. Preparations that combine PPIs with antimicrobials and bismuth are known to suppress H. pylori; thus, ingestion of these preparations within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of omeprazole in the 1 to 2 weeks prior to the test and the use of antimicrobials and bismuth preparations in the 4 weeks prior to the test.

According to the Beers Criteria, proton pump inhibitors (PPIs) are considered potentially inappropriate medications (PIMs) for use in geriatric patients due to the risk of Clostridium difficile infection and bone loss/fractures. Avoid use for more than 8 weeks except for high-risk patients (e.g., oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or need for maintenance treatment (e.g., due to failure of drug discontinuation trial or inadequate response to H-2 blockers). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); the indication for PPI use should be based on clinical symptoms and/or endoscopic findings. During the use of PPIs to treat or prevent NSAID-induced gastritis or esophagitis, there should be documentation that analgesics with less GI toxicity than NSAIDs have been tried or were not indicated. If a PPI is used for longer than 12 weeks, the clinical rationale and documentation for continued use should support an underlying chronic disease (e.g., GERD) or risk factors (e.g., chronic NSAID use). Monitor for adverse events, including an increased risk of Clostridium difficile colitis.

For the short-term, self-treatment of frequent dyspepsia or pyrosis (heartburn) that occurs 2 or more times per week:
Oral dosage (non-prescription omeprazole tablets and omeprazole magnesium tablets and capsules):
NOTE: Omeprazole magnesium 20.6 mg tablets and capsules contain 20 mg of omeprazole.
Adults: 20 mg PO once daily with a full glass of water 30 minutes before breakfast for 14 days. Full relief may take 1 to 4 days. If frequent heartburn returns soon after the initial 14-day treatment regimen, patients should contact their health care provider. Patients should not take a 14-day course of omeprazole OTC more often than once every 4 months, unless directed to do so by their provider.

For the treatment of erosive esophagitis (erosive GERD):
Oral dosage (delayed-release capsules or delayed-release suspension):
Adults: 20 mg PO once daily for 4 to 8 weeks. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of erosive esophagitis, an additional 4 to 8-week courses of omeprazole may be considered. For maintenance of healing, 20 mg PO once daily; periodically reassess need for continued PPI therapy. Long-term maintenance treatment (up to 5 years) has been effective. A clinical study compared omeprazole 20 mg PO once daily with either cisapride, an H2-blocker, or a combination; no regimen was superior to omeprazole after 12 months of continuous administration.
Adolescents and Children weighing 20 kg or more: 20 mg PO once daily. Alternatively, a dose range of 0.7 to 3.3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Individualize dosage to attain clinical goals; typical doses range from 10 to 20 mg/day PO, although some studies have used higher dosages.
Children weighing 10 to 19 kg: 10 mg PO once daily. Alternatively, a dose range of 0.7 to 3.3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Individualize dosage to attain clinical goals; typical doses range from 10 to 20 mg/day PO, although some studies have used higher dosages.
Children weighing 5 to 9 kg: 5 mg PO once daily. Alternatively, a dose range of 0.7 to 3.3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Individualize dosage to attain clinical goals.
Infants weighing 10 kg and more: 10 mg PO once daily is the FDA-approved dose. Alternatively, 0.5 mg/kg/day PO once daily for 6 weeks has been studied and doses up to 1.5 mg/kg/day PO have been reported. In 12 infants (aged 2.9 +/- 0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine, 0.5 mg/kg/day resulted in a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity. In an 8-week trial of 115 patients (aged 0.7 to 21.8 months) receiving omeprazole 0.5 to 1.5 mg/kg/day, symptoms were reduced in all groups. A more rapid onset of symptomatic improvement was noted in patients receiving larger doses.
Infants weighing 5 to 9 kg: 5 mg PO once daily is the FDA-approved dose. Alternatively, 0.5 mg/kg/day PO once daily for 6 weeks has been studied and doses up to 1.5 mg/kg/day PO have been reported. In 12 infants (aged 2.9 +/- 0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine, 0.5 mg/kg/day resulted in a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity. In an 8-week trial of 115 patients (aged 0.7 to 21.8 months) receiving omeprazole 0.5 to 1.5 mg/kg/day, symptoms were reduced in all groups. A more rapid onset of symptomatic improvement was noted in patients receiving larger doses.
Infants weighing 3 to 4 kg: 2.5 mg PO once daily is the FDA-approved dose. Alternatively, 0.5 mg/kg/day PO once daily for 6 weeks has been studied and doses up to 1.5 mg/kg/day PO have been reported. In 12 infants (aged 2.9 +/- 0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine, 0.5 mg/kg/day resulted in a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity. In an 8-week trial of 115 patients (aged 0.7 to 21.8 months) receiving omeprazole 0.5 to 1.5 mg/kg/day, symptoms were reduced in all groups. A more rapid onset of symptomatic improvement was noted in patients receiving larger doses.
Neonates*: Limited data are available; 0.7 mg/kg/day PO once daily for 7 days has been studied. Single doses up to 1.5 mg/kg/day PO have been studied in a pharmacokinetic trial. In 10 preterm neonates (34 to 40 weeks postmenstrual age) with GERD, 0.7 mg/kg/day PO once daily was administered in a randomized, double blind, placebo-controlled trial. Compared to placebo, omeprazole significantly reduced gastric acidity (% time pH < 4, 54% vs. 14%, p < 0.0005) and number of acid GER episodes (119 vs. 60 episodes, p < 0.05). In a pharmacokinetic trial of 24 neonates and infants (aged 0 to 24 months), single doses of 1 to 1.5 mg/kg/dose were studied; increased omeprazole exposure was observed in a few patients younger than 5 months. Multiple doses of 1.5 mg/kg/day have not been studied in neonates.

For the treatment of non-erosive gastroesophageal reflux disease (GERD):
Oral dosage (delayed-release capsules or delayed-release suspension):
Adults: 20 mg PO once daily for 4 to 8 weeks. May increase dose up to 40 mg PO twice daily in persons with partial response to once daily therapy. Continue maintenance therapy at the lowest effective dose, including on demand or intermittent therapy, in persons who continue to have symptoms after discontinuation.
Adolescents and Children weighing 20 kg or more: 20 mg PO once daily. Alternatively, 0.7 to 3.3 mg/kg/day PO. Individualize dosage to attain clinical goals; typical doses range from 10 to 20 mg/day PO, although some studies have used higher dosages.
Children weighing 10 to 19 kg: 10 mg PO once daily. Alternatively, 0.7 to 3.3 mg/kg/day PO. Individualize dosage to attain clinical goals; typical doses range from 10 to 20 mg/day PO, although some studies have used higher dosages.
Children weighing 5 to 9 kg: 5 mg PO once daily. Alternatively, 0.7 to 3.3 mg/kg/day PO. Individualize dosage to attain clinical goals.
Infants*: Limited data are available; 0.5 mg/kg/day PO once daily for 6 weeks has been studied, however, doses up to 1.5 mg/kg/day PO have been reported. In 12 infants (aged 2.9 +/- 0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine, 0.5 mg/kg/day resulted in a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity. In an 8-week trial of 115 patients (aged 0.7 to 21.8 months) receiving omeprazole 0.5 to 1.5 mg/kg/day, symptoms were reduced in all groups. A more rapid onset of symptomatic improvement was noted in patients receiving larger doses. PPIs are not recommended as first line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).
Neonates*: Limited data are available; 0.7 mg/kg/day PO once daily for 7 days has been studied. Single doses up to 1.5 mg/kg/day PO have been studied in a pharmacokinetic trial. In 10 preterm neonates (34 to 40 weeks postmenstrual age) with GERD, 0.7 mg/kg/day PO once daily was administered in a randomized, double blind, placebo-controlled trial. Compared to placebo, omeprazole significantly reduced gastric acidity and number of acid GER episodes. In a pharmacokinetic trial of 24 neonates and infants (aged 0 to 24 months), single doses of 1 to 1.5 mg/kg/dose were studied; increased omeprazole exposure was observed in a few patients younger than 5 months. Multiple doses of 1.5 mg/kg/day have not been studied in neonates.

For the short-term treatment of active benign gastric ulcer:
Oral dosage (delayed-release capsules or delayed-release suspension):
Adults and Adolescents 17 years and older: 40 mg PO once daily for 4 to 8 weeks. For endoscopically diagnosed gastric ulcer larger than 1 cm, 40 mg once daily was significantly more effective than 20 mg once daily at 8 weeks. For ulcer size 1 cm or less, no difference in healing rates between 40 mg and 20 mg once daily doses were observed.

For the short-term treatment of active duodenal ulcer:
Oral dosage (delayed-release capsules or delayed-release suspension):
Adults and Adolescents 17 years and older: 20 mg PO once daily for 4 to 8 weeks. Most patients heal within 4 weeks; some patients may require 8 weeks of therapy.

For Helicobacter pylori (H. pylori) eradication:
-as part of initial dual therapy in adults:
Oral dosage:
Adults: Not recommended by guidelines. 40 mg PO once daily in combination with clarithromycin for 14 days is FDA-approved. FDA-labeling suggests an additional 14 days of omeprazole 20 mg PO once daily in patients with ulcers.
-as part of initial clarithromycin-based therapy in adults without previous macrolide exposure in regions where clarithromycin resistance is less than 15%:
Oral dosage:
Adults: 20 or 40 mg PO twice daily in combination with clarithromycin and either amoxicillin or metronidazole for 14 days. FDA-labeling suggests an additional 18 days of omeprazole 20 mg PO once daily in patients with ulcers.
-as part of initial clarithromycin-based therapy in adults with or without potential macrolide exposure or resistance*:
Oral dosage:
Adults: 20 mg PO twice daily as part of a combination therapy as a first-line treatment option. Quadruple therapy includes a proton pump inhibitor (PPI) in combination with clarithromycin, amoxicillin, and metronidazole for 10 to 14 days. Hybrid therapy includes amoxicillin plus PPI for 7 days followed by PPI in combination with clarithromycin, amoxicillin, and metronidazole for 7 days. Sequential therapy includes PPI and amoxicillin for 5 to 7 days followed by PPI in combination with clarithromycin and metronidazole for 5 to 7 days.
-as part of levofloxacin-based initial therapy in adults*:
Oral dosage:
Adults: 20 or 40 mg PO twice daily as part of combination therapy as a first-line treatment option. Triple therapy includes omeprazole 20 mg PO twice daily in combination with levofloxacin and amoxicillin for 10 to 14 days. Sequential therapy includes omeprazole 20 or 40 mg PO twice daily in combination with amoxicillin for 5 to 7 days followed by omeprazole 20 mg PO twice daily in combination with levofloxacin and a nitroimidazole for 5 to 7 days. Quadruple therapy includes omeprazole 40 mg PO once daily in combination with levofloxacin, nitazoxanide, and doxycycline for 7 to 10 days.
-as part of bismuth-based initial therapy in adults*:
Oral dosage:
Adults: 20 mg PO twice daily in combination with bismuth subcitrate or subsalicylate, metronidazole, and tetracycline for 10 to 14 days is recommended as a first-line treatment option, particularly in patients with any previous macrolide exposure or a penicillin allergy.
-as part of clarithromycin-based salvage therapy in adults who failed initial bismuth quadruple therapy*:
Oral dosage:
Adults: 20 mg PO twice daily in combination with clarithromycin, amoxicillin, and metronidazole for 10 to 14 days. For patients with a penicillin allergy, a PPI is recommended in combination with clarithromycin and metronidazole for 14 days.
-as part of levofloxacin-based salvage therapy in adults*:
Oral dosage:
Adults: 20 mg PO twice daily in combination with levofloxacin and amoxicillin for 14 days. Guidelines recommend this triple therapy in patients who have failed clarithromycin-triple or bismuth-quadruple initial therapies and without previous quinolone exposure. Levofloxacin in combination with metronidazole and a PPI for 14 days could be considered for patients with a penicillin allergy who have failed prior bismuth quadruple therapy.
-as part of bismuth-based quadruple salvage therapy in adults*:
Oral dosage:
Adults: 20 mg PO twice daily in combination with bismuth subcitrate or subsalicylate, tetracycline, and metronidazole for 14 days is recommended particularly in patients failing clarithromycin triple therapy. A subsequent repeat course of bismuth quadruple therapy may be considered after failed prior bismuth quadruple therapy.
-as part of rifabutin-based salvage therapy in adults*:
Oral dosage:
Adults: 20 mg PO twice daily in combination with rifabutin and amoxicillin for 10 days.
-as part of high-dose dual salvage therapy in adults*:
Oral dosage:
Adults: 20 mg or 40 mg PO 3 or 4 times daily in combination with high-dose amoxicillin for 14 days. A high-dose proton pump inhibitor in combination with metronidazole may be considered in patients with prior quinolone exposure and a penicillin allergy who have failed initial bismuth quadruple therapy.
-in combination with amoxicillin and clarithromycin in pediatric patients*:
Oral dosage:
Children and Adolescents weighing 35 kg or more: 40 mg PO twice daily in combination with amoxicillin and clarithromycin for 14 days. Triple therapy with standard-dose amoxicillin, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with fully susceptible H. pylori strains or strains susceptible to clarithromycin but resistant to metronidazole. In cases of penicillin allergy, use metronidazole in place of amoxicillin for patients infected with fully susceptible strains.
Children and Adolescents weighing 25 to 34 kg: 30 mg PO twice daily in combination with amoxicillin and clarithromycin for 14 days. Triple therapy with standard-dose amoxicillin, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with fully susceptible H. pylori strains or strains susceptible to clarithromycin but resistant to metronidazole. In cases of penicillin allergy, use metronidazole in place of amoxicillin for patients infected with fully susceptible strains.
Children weighing 15 to 24 kg: 20 mg PO twice daily in combination with amoxicillin and clarithromycin for 14 days. Triple therapy with standard-dose amoxicillin, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with fully susceptible H. pylori strains or strains susceptible to clarithromycin but resistant to metronidazole. In cases of penicillin allergy, use metronidazole in place of amoxicillin for patients infected with fully susceptible strains.
-in combination with amoxicillin and metronidazole in pediatric patients*:
Oral dosage:
Children and Adolescents weighing 35 kg or more: 40 mg PO twice daily in combination with amoxicillin and metronidazole for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a proton pump inhibitor (PPI) is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
Children and Adolescents weighing 25 to 34 kg: 30 mg PO twice daily in combination with amoxicillin and metronidazole for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a proton pump inhibitor (PPI) is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
Children weighing 15 to 24 kg: 20 mg PO twice daily in combination with amoxicillin and metronidazole for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a proton pump inhibitor (PPI) is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
-as part of a sequential therapy regimen in pediatric patients*:
Oral dosage:
Children and Adolescents weighing 35 kg or more: 40 mg PO twice daily for 10 days. Use in combination with amoxicillin for days 1 through 5, and then clarithromycin and metronidazole for days 6 through 10. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.
Children and Adolescents weighing 25 to 34 kg: 30 mg PO twice daily for 10 days. Use in combination with amoxicillin for days 1 through 5, and then clarithromycin and metronidazole for days 6 through 10. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.
Children weighing 15 to 24 kg: 20 mg PO twice daily for 10 days. Use in combination with amoxicillin for days 1 through 5, and then clarithromycin and metronidazole for days 6 through 10. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.
-as part of a quadruple therapy regimen in pediatric patients*:
Oral dosage:
Children and Adolescents weighing 35 kg or more: 40 mg PO twice daily in combination with amoxicillin, metronidazole, and clarithromycin for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
Children and Adolescents weighing 25 to 34 kg: 30 mg PO twice daily in combination with amoxicillin, metronidazole, and clarithromycin for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
Children weighing 15 to 24 kg: 20 mg PO twice daily in combination with amoxicillin, metronidazole, and clarithromycin for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

For the long-term treatment of gastric hypersecretory conditions, including Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenoma syndrome:
Oral dosage (delayed-release capsules or delayed-release suspension):
Adults and Adolescents 17 years and older: 60 mg PO once daily initially, then titrated and given in single or multiple daily doses, with dosage titration up to 120 mg PO 3 times daily. Dosages greater than 80 mg/day should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously for more than 5 years.

For NSAID-induced ulcer prophylaxis*:
Oral dosage:
Adults and Adolescents 17 years and older: 20 mg PO once daily. Patients with a history of dyspepsia or uncomplicated peptic ulcer and who were to continue receiving a NSAID were randomized to either omeprazole or placebo. At 3 months, 4.7% (4 of 85) of subjects receiving omeprazole developed peptic ulcer compared with 16.7% (15 of 90) receiving placebo.

For stress gastritis prophylaxis* in critically-ill patients:
Oral dosage:
Adults: 20 to 40 mg/day PO has been studied; doses up to 40 mg twice daily have been administered clinically. There is no clear evidence that PPI use is superior to H2 antagonists for SUP. For those patients with risk factors qualifying them for stress ulcer prophylaxis (SUP), the H2 antagonists, cytoprotective agents, and some PPIs are adequate choices. Optimum duration is unclear, but it is reasonable to provide therapy while risk factors are present, the patient is in a critical care unit, or for a least 1 week after onset of critical illness. Discontinue PPI use when risk factors for SUP are no longer present.
Nasogastric dosage [extemporaneous preparation of 2 mg/mL oral suspension ('simplified omeprazole suspension' or SOS)]:
Adults: Initially, 20 mL (40 mg omeprazole) of SOS via nasogastric tube, followed by 20 mL (40 mg) 6 to 8 hours later, then 10 mL (20 mg) daily thereafter. Administer SOS via tube and follow with 5 to 10 mL of water; clamp the tube for 1 to 2 hours after each administration. Efficacy, safety, and cost of SOS were evaluated in a prospective, open-label study of mechanically ventilated, critically ill patients with at least 1 other risk factor for stress-related mucosal damage. In this study, none of the 65 patients receiving SOS developed new clinically significant upper GI bleeds, bleeding diminished in 4 of 5 patients (bleeding prior to study entry) within 18 hours, and the bleeding stopped in all patients within 36 hours.
Intravenous dosage* (intravenous omeprazole, not available in the US):
Adults: A variety of dosage regimens have been reported, from 40 mg IV once daily to 40 mg IV every 12 hours. Twice-daily regimens are often favored over once-daily for stress ulcer prophylaxis, for those patients with appropriate indications for stress ulcer prophylaxis (SUP). In addition, continuous infusion doses (i.e., 80 mg IV bolus, followed by 8 mg/hour IV continuous infusion) have also been employed, and are also favored over once-daily administration. Discontinue PPI use when risk factors for SUP are no longer present.

For the treatment of eosinophilic esophagitis (EoE)*:
Oral dosage:
Adults: A dosage range of 20 to 40 mg PO twice daily given 30 to 60 minutes before meals has been studied; treat for up to 8 weeks and continue until the time of the follow-up endoscopy and biopsy. The guidelines support the use of PPI therapy for EoE based on reports of reductions in histologic features of disease from 42% in observational studies.

Maximum Dosage Limits:
-Adults
40 mg/day PO for most indications; however, doses up to 160 mg/day have been used off-label for H. pylori eradication; up to 360 mg/day PO for Zollinger-Ellison syndrome.
-Geriatric
40 mg/day PO for most indications; however, doses up to 160 mg/day have been used off-label for H. pylori eradication; up to 360 mg/day PO for Zollinger-Ellison syndrome.
-Adolescents
40 mg/day PO is FDA-approved maximum; however, doses up to 80 mg/day have been used off-label.
-Children
20 kg or more: 20 mg/day PO is FDA-approved maximum; however, doses up to 80 mg/day have been used off-label.
10 to 19 kg: 10 mg/day PO is FDA-approved maximum; however, doses up to 3.3 mg/kg/day (Max: 40 mg/day) have been used off-label.
5 to 9 kg: 5 mg/day PO is FDA-approved maximum; however, doses up to 3.3 mg/kg/day have been used off-label.
-Infants
10 kg or more: 10 mg/day PO is FDA-approved maximum; however, doses up to 40 mg/day have been used off-label.
5 to 9 kg: 5 mg/day PO is FDA-approved maximum; however, doses up to 1.5 mg/kg/day have been used off-label.
3 to 4 kg: 2.5 mg/day PO is FDA-approved maximum; however, doses up to 1.5 mg/kg/day have been used off-label.
-Neonates
Safety and efficacy have not been established; however, 0.7 mg/kg/day PO has been used off-label for GERD. Single doses up to 1.5 mg/kg/day PO have been studied in a pharmacokinetic trial.

Patients with Hepatic Impairment Dosing
Consider dosage reduction in patients with hepatic impairment (see Contraindications).

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Intermittent hemodialysis
Since omeprazole is highly protein bound, it is not likely to be significantly removed by hemodialysis. No dosage adjustments are needed.

*non-FDA-approved indication

Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib capsules and omeprazole; decreased acalabrutinib exposure occurred in a drug interaction study. Consider using the acalabrutinib tablet formlation or use an antacid or H2-blocker if acid suppression therapy is needed. Separate the administration of acalabrutinib capsules and antacids by at least 2 hours; give acalabrutinib capsules 2 hours before a H2-blocker. Acalabrutinib capsuel solubility decreases with increasing pH values. The AUC of acalabrutinib was decreased by 43% when acalabrutinib capsules were coadministered with omeprazole 40 mg/day for 5 days.

Adagrasib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with adagrasib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.

Alendronate: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.

Alendronate; Cholecalciferol: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.

Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Alprazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the CYP450 system, such as alprazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Amobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Amphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.

Amphetamine; Dextroamphetamine Salts: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.

Amphetamine; Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.

Ampicillin: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.

Ampicillin; Sulbactam: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.

Apalutamide: (Major) Avoid concomitant use of apalutamide with omeprazole as omeprazole plasma concentrations may be decreased, reducing its efficacy. Omeprazole is a CYP3A and CYP2C19 substrate. Apalutamide is a strong inducer of both CYP3A and CYP2C19. Coadministration with apalutamide has been observed to decrease the overall exposure of omeprazole by 85%.

Aprepitant, Fosaprepitant: (Minor) Use caution if omeprazole and aprepitant are used concurrently and monitor for an increase in omeprazole-related adverse effects for several days after administration of a multi-day aprepitant regimen. Omeprazole is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of omeprazole. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.

Armodafinil: (Moderate) In vitro data indicate that armodafinil is an inhibitor of CYP2C19. In theory, dosage reductions may be required for drugs that are largely eliminated via CYP2C19 metabolism such as omeprazole during coadministration with armodafinil. A 40% increase in exposure of omeprazole was observed during coadministration with armodafinil. The clinical significance of this interaction is unknown.

Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Aspirin, ASA; Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as omeprazole, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.

Aspirin, ASA; Carisoprodol; Codeine: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as omeprazole, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.

Atazanavir: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.

Atazanavir; Cobicistat: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Atenolol; Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Avanafil: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.

Azilsartan; Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Barbiturates: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with a proton pump inhibitor (PPI). Concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Coadministration with other PPIs has decreased belumosudil exposure by 47% to 80% in healthy subjects.

Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of omeprazole with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and omeprazole is a CYP2C19 inhibitor.

Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Bendroflumethiazide; Nadolol: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Bisacodyl: (Minor) The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.

Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.

Bismuth Subsalicylate: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.

Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.

Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Bosutinib: (Major) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and proton-pump inhibitors, such as omeprazole, may result in decreased plasma exposure of bosutinib. Consider using a short-acting antacid or H2 blocker if acid suppression therapy is needed; separate the administration of bosutinib and antacids or H2-blockers by more than 2 hours.

Budesonide: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.

Budesonide; Formoterol: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.

Budesonide; Glycopyrrolate; Formoterol: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.

Bumetanide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.

Butabarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Butalbital; Acetaminophen: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Cabotegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.

Calcium Carbonate; Risedronate: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.

Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Cannabidiol: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.

Capecitabine: (Moderate) Use caution if treatment with a proton pump inhibitor (PPI) is necessary in patients taking capecitabine, as progression-free survival (PFS) and overall survival (OS) may be adversely affected. The mechanism of this potential interaction is unknown and data are conflicting. In a posthoc, retrospective, subgroup analysis of a phase 3 clinical trial in patients with advanced or metastatic gastroesophageal cancer, administration of a PPI was associated with a significant decrease in PFS and OS in patients treated with capecitabine plus oxaliplatin (CapeOx) vs. patients who did not receive a PPI; a significant difference was not observed in the CapeOx plus lapatinib arm. Demographically, there were significantly more Asian patients in the PPI arm of this analysis; according to the manufacturer of capecitabine, Japanese patients have a 36% lower Cmax and 24% lower AUC for capecitabine compared with Caucasian patients. Additionally, there was not a significant increase in concentration dependent toxicities (e.g., hand-foot syndrome, rash, and diarrhea) or dose reductions in either arm. These observations are in line with a previous retrospective study in which patients with colorectal cancer receiving PPI treatment and adjuvant capecitabine also experienced poorer relapse-free survival compared with patients not receiving a PPI. Coadministration with antacids increased exposure to capecitabine and its metabolites, but this was not clinically significant or clinically relevant. Pharmacokinetic data on the impact of a PPI on capecitabine exposure are not available.

Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Carbamazepine: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.

Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as omeprazole, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.

Cefpodoxime: (Moderate) Cefpodoxime proxetil requires a low gastric pH for dissolution; therefore, concurrent administration with medications that increase gastric pH, such as proton pump inhibitors (PPIs) may decrease the bioavailability of cefpodoxime. When cefpodoxime was administered with high doses of antacids and H2-blockers, peak plasma concentrations were reduced by 24% and 42% and the extent of absorption was reduced by 27% and 32%, respectively. The rate of absorption is not affected.

Ceftibuten: (Minor) Coadministration of 150 mg of ranitidine every 12 hours for 3 days increased the ceftibuten Cmax by 23 percent and ceftibuten AUC by 16 percent. Based on this information, increased gastric pH caused by PPIs may possibly affect the kinetics of ceftibuten.

Cefuroxime: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.

Chlordiazepoxide: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as chlordiazepoxide. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Chlordiazepoxide; Amitriptyline: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as chlordiazepoxide. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Chlordiazepoxide; Clidinium: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as chlordiazepoxide. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Chlorothiazide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Chlorthalidone; Clonidine: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Cilostazol: (Major) When significant CYP2C19 inhibitors, such as omeprazole, are administered concomitantly with cilostazol, the cilostazol dosage should be reduced by 50%. Cilostazol is metabolized by the CYP2C19 hepatic isoenzyme and appears to have pharmacokinetic interactions with many medications that are potent inhibitors of CYP2C19. When given concurrently with omeprazole, cilostazol AUC is increased by 26% and the Cmax is increased by 18%; the AUC of the active metabolite 3,4-dehydro-cilostazol is increased by 69% and the Cmax is increased by 29%.

Ciprofloxacin: (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction.

Citalopram: (Moderate) Limit the dose of citalopram to 20 mg/day if coadministered with omeprazole. Concurrent use may increase citalopram exposure increasing the risk of QT prolongation. Citalopram is a sensitive CYP2C19 substrate; omeprazole is a weak inhibitor of CYP2C19.

Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of omeprazole. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and omeprazole is an inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.

Clomipramine: (Minor) Coadministration may result in increased clomipramine exposure. Omeprazole is a CYP2C19 inhibitor and clomipramine is a CYP2C19 substrate.

Clopidogrel: (Major) Avoid concomitant use of clopidogrel and omeprazole as it significantly reduces the antiplatelet activity of clopidogrel. If necessary, consider using an alternative proton pump inhibitor, such as rabeprazole, pantoprazole, lansoprazole, or dexlansoprazole. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps. Omeprazole is an inhibitor of CYP2C19. In clinical studies, use of omeprazole significantly reduced the antiplatelet activity of clopidogrel when administered concomitantly or 12 hours apart.

Clorazepate: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as clorazepate. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Clozapine: (Moderate) The addition of omeprazole to clozapine therapy resulted in a roughly 40% reduction in clozapine plasma concentrations in at least 2 patients. Omeprazole is an inducer of CYP1A2, one of the isoenzymes reponsible for the metabolism of clozapine. According to the manufacturer of clozapine, patients receiving clozapine in combination with a weak to moderate CYP1A2 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary.

Cobicistat: (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Cysteamine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.

Dabrafenib: (Major) The concomitant use of dabrafenib and omeprazole may lead to decreased omeprazole concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of omeprazole efficacy. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Omeprazole is a sensitive CYP2C19 substrate.

Dacomitinib: (Major) Avoid coadministration of omeprazole with dacomitinib due to decreased plasma concentrations of dacomitinib which may impact efficacy. Coadministration with another proton pump inhibitor decreased the dacomitinib Cmax and AUC by 51% and 39%, respectively.

Darunavir: (Moderate) Coadministration of omeprazole and darunavir boosted with ritonavir may result in decreased omeprazole concentrations. Monitor patients receiving these drugs concurrently for reduced omeprazole efficacy and, if needed, consider increasing the dose of omeprazole up to a maximum of 40 mg per day.

Darunavir; Cobicistat: (Moderate) Coadministration of omeprazole and darunavir boosted with ritonavir may result in decreased omeprazole concentrations. Monitor patients receiving these drugs concurrently for reduced omeprazole efficacy and, if needed, consider increasing the dose of omeprazole up to a maximum of 40 mg per day. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of omeprazole and darunavir boosted with ritonavir may result in decreased omeprazole concentrations. Monitor patients receiving these drugs concurrently for reduced omeprazole efficacy and, if needed, consider increasing the dose of omeprazole up to a maximum of 40 mg per day. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Dosage adjustments of omeprazole may be required during concomitant administration with dasabuvir; ombitasvir; paritaprevir; ritonavir. Use of these drugs together results in decreased omeprazole serum concentrations. Monitor for decreasing efficacy and consider increasing the omeprazole dose if needed; however, adult doses should be limited to no more than 40 mg/day. The dose should be re-adjusted after completion of the 4-drug hepatitis C treatment regimen. (Moderate) Increased exposure to omeprazole may occur during concurrent administration of ritonavir. Although dosage adjustment of omeprazole is not normally required, dosage reduction may be considered in patients receiving higher omeprazole doses (e.g., those with Zollinger-Ellison syndrome). Ritonavir is a strong CYP3A4 inhibitor. Omeprazole is a CYP2C19 and CYP3A4 substrate. Coadministration of a dual CYP2C19/strong CYP3A4 inhibitor increased the omeprazole AUC by an average of 4-times.

Dasatinib: (Major) Do not administer proton pump inhibitors with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an proton pump inhibitor reduced the mean Cmax and AUC of dasatinib by 42% and 43%, respectively.

Delavirdine: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.

Dexamethasone: (Moderate) Monitor for decreased efficacy of omeprazole if coadministration with dexamethasone is necessary. Omeprazole is metabolized by CYP2C19 and CYP3A4. Dexamethasone is a moderate CYP3A4 inducer. The manufacturer of omeprazole recommends avoidance with strong inducers because decreased exposure of omeprazole can occur. Recommendations are not available for concomitant use with moderate inducers of CYP3A4.

Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.

Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with omeprazole is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP2C19 substrate and omeprazole is a CYP2C19 inhibitor.

Digoxin: (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.

Disulfiram: (Moderate) Monitor patients to determine if it is necessary to adjust the dose of disulfiram when taken concomitantly with omeprazole. In a single patient, the combined use of disulfiram and omeprazole caused disorientation, confusion, and nightmares. These reactions occurred on 2 separate challenges when omeprazole was added to disulfiram therapy.

Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.

Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.

Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Omeprazole is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.

Efavirenz: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.

Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.

Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.

Elagolix: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g. in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.

Elagolix; Estradiol; Norethindrone acetate: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g. in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.

Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.

Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.

Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.

Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Enzalutamide: (Major) Avoid concomitant use of enzalutamide, a strong CYP3A4 inducer and a moderate CYP2C19 inducer, and omeprazole, a CYP3A4 and CYP2C19 substrate, as omeprazole plasma exposure may be reduced. In a drug interaction trial in patients with castration-resistant prostate cancer, the AUC and Cmax of omeprazole was decreased following a single oral dose of omeprazole 20 mg administered after at least 55 days of oral enzalutamide 160 mg/day.

Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Erlotinib: (Major) Avoid coadministration of erlotinib with omeprazole if possible due to decreases in erlotinib plasma concentrations. Erlotinib solubility is pH dependent and solubility decreases as pH increases. Coadministration of erlotinib with medications that increase the pH of the upper gastrointestinal tract may decrease the absorption of erlotinib. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period of time. Increasing the dose of erlotinib is also not likely to compensate for the loss of exposure. Coadministration with omeprazole decreased erlotinib exposure by 46% and the erlotinib Cmax by 61%.

Escitalopram: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.

Eslicarbazepine: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.

Estazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as estazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Ethacrynic Acid: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.

Fedratinib: (Moderate) Monitor for increased omeprazole adverse effects as coadministration of omeprazole and fedratinib increased omeprazole exposure by 3-fold in a drug interaction study. Although dose adjustments are not generally needed, patients with Zollinger-Ellison's syndrome who often require higher omeprazole doses may require an adjustment in omeprazole dose. Omeprazole is metabolized primarily by CYP2C19 and secondarily by CYP3A4; fedratinib is an inhibitor of CYP2C19 and CYP3A4.

Fenofibrate: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.

Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.

Flibanserin: (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.

Flurazepam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as flurazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Fluvastatin: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.

Fluvoxamine: (Moderate) Omeprazole is a primary substrate of CYP2C19 and CYP3A4. Reduced metabolism and resulting elevated plasma concentrations of omeprazole may occur if combined with fluvoxamine. Fluvoxamine is a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP3A4. Concomitant administration of omeprazole and a combined inhibitor of CYP2C19 and CYP3A4 resulted in more than doubling of the omeprazole exposure. No specific dose adjustments are recommended, unless the patient is receiving high doses of omeprazole, as for Zollinger-Ellison Syndrome; in such patients, omeprazole dose reduction might be necessary.

Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Fosphenytoin: (Major) Avoid concomitant use of omeprazole and fosphenytoin as omeprazole exposure may be decreased, reducing its efficacy. Concomitant use may also increase phenytoin concentrations. Omeprazole is a CYP2C19 inhibitor and CYP3A substrate and fosphenytoin is a CYP2C19 substrate and strong CYP3A inducer.

Furosemide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.

Gefitinib: (Major) Avoid coadministration of omeprazole with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 12 hours after the last dose or 12 hours before the next dose of omeprazole. Gefitinib exposure is affected by gastric pH. Coadministration with another drug to maintain gastric pH above 5 decreased gefitinib exposure by 47%.

Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.

Indinavir: (Major) Omeprazole has been reported to decrease the oral bioavailability of indinavir. In one study, indinavir plasma levels fell to below 95% of normal in roughly half of the patients receiving omeprazole concurrently. An increase in indinavir dosage resolved the interaction. It is unclear if other gastric acid-pump inhibitors would interact with indinavir in this manner.

Infigratinib: (Major) Avoid coadministration of infigratinib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease infigratinib exposure resulting in decreased efficacy. If necessary, infigratinib may be administered two hours before or ten hours after an H2-receptor antagonist or two hours before or after a locally acting antacid. Coadministration with a PPI decreased infigratinib exposure by 45%.

Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Iron: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.

Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.

Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.

Isoniazid, INH; Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.

Itraconazole: (Moderate) When administering proton pump inhibitors with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when proton pump inhibitors are administered with the 65 mg itraconazole capsule. Administer proton pump inhibitors at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if proton pump inhibitors are administered with itraconazole 65 mg capsules.

Ketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption.

Ledipasvir; Sofosbuvir: (Major) Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with proton pump inhibitors (PPIs) may result in lower ledipasvir plasma concentrations. Ledipasvir can be administered with PPIs if given simultaneously under fasting conditions. The PPI dose should not exceed a dose that is comparable to omeprazole 20 mg/day.

Letermovir: (Moderate) Monitor for reduced omeprazole efficacy and adjust the dose of omeprazole if needed during concurrent use of letermovir. Coadministration may result in a clinically relevant decrease in the plasma concentration of omeprazole. Omeprazole is a sensitive substrate of CYP2C19. Letermovir is a CYP2C19 inducer.

Levoketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption.

Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Lonafarnib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with lonafarnib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.

Loop diuretics: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.

Lopinavir; Ritonavir: (Moderate) Increased exposure to omeprazole may occur during concurrent administration of ritonavir. Although dosage adjustment of omeprazole is not normally required, dosage reduction may be considered in patients receiving higher omeprazole doses (e.g., those with Zollinger-Ellison syndrome). Ritonavir is a strong CYP3A4 inhibitor. Omeprazole is a CYP2C19 and CYP3A4 substrate. Coadministration of a dual CYP2C19/strong CYP3A4 inhibitor increased the omeprazole AUC by an average of 4-times.

Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Luliconazole: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.

Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of omeprazole by substantially decreasing its systemic exposure. If used together, an omeprazole dosage adjustment may be necessary to obtain the desired therapeutic effect. Omeprazole is a CYP3A4 and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A; in vitro data suggests is also has the potential to induce CYP2C19.

Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.

Mefloquine: (Moderate) Proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.

Methohexital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Methotrexate: (Major) Avoid concomitant use of methotrexate and proton pump inhibitors (PPIs) due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions; consider temporary withdrawal of the PPI in some patients receiving high-dose methotrexate. Concomitant use of methotrexate, primarily at high dose, and PPIs may increase and prolong serum concentrations of methotrexate, possibly leading to methotrexate toxicities.

Methyclothiazide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Metolazone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Midazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as midazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Mitotane: (Moderate) Use caution if mitotane and omeprazole are used concomitantly, and monitor for decreased efficacy of omeprazole and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and omeprazole is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of omeprazole.

Mycophenolate: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).

Nelfinavir: (Major) Use of proton pump inhibitors with nelfinavir is not recommended. Coadministration may result in decreased nelfinavir exposure, subtherapeutic antiretroviral activity, and possibility resistant HIV mutations. In one study, concurrent use of nelfinavir with omeprazole resulted in decreased nelfinavir AUC, Cmax, and Cmin by 36%, 37%, and 39%, respectively.

Neratinib: (Major) Avoid concomitant use of neratinib with proton pump inhibitors due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. Concomitant use with lansoprazole decreased neratinib exposure by 65%.

Nilotinib: (Major) Avoid the concomitant use of nilotinib and proton pump inhibitors (PPIs), as PPIs may cause a reduction in nilotinib bioavailability. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. PPIs inhibit gastric acid secretion and elevate the gastric pH. Administration of a single 400-mg nilotinib dose with multiple oral doses of esomeprazole 40 mg/day reduced the nilotinib AUC by 34% in a study in healthy subjects. Increasing the dose is unlikely to compensate for the loss of nilotinib exposure; additionally, separating the administration of these agents may not eliminate the interaction as PPIs affect the pH of the upper GI tract for an extended period of time.

Nirmatrelvir; Ritonavir: (Moderate) Increased exposure to omeprazole may occur during concurrent administration of ritonavir. Although dosage adjustment of omeprazole is not normally required, dosage reduction may be considered in patients receiving higher omeprazole doses (e.g., those with Zollinger-Ellison syndrome). Ritonavir is a strong CYP3A4 inhibitor. Omeprazole is a CYP2C19 and CYP3A4 substrate. Coadministration of a dual CYP2C19/strong CYP3A4 inhibitor increased the omeprazole AUC by an average of 4-times.

Obeticholic Acid: (Minor) Concurrent administration of 20 mg omeprazole as a single dose with obeticholic acid 10 mg once daily resulted in a 32% increase in omeprazole AUC and a 33% increase in omeprazole Cmax. The clinical significance of this interaction is unknown. Even though omeprazole is a CYPC19 substrate, obeticholic acid is not expected to inhibit the CYPC19 isoenzyme. The mechanism of this interaction has not been described.

Octreotide: (Moderate) Coadministration of oral octreotide with proton pump inhibitors (PPIs) may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including PPIs, may alter the absorption of octreotide and lead to a reduction in bioavailability. This interaction has been documented with esomeprazole and can occur with the other PPIs.

Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Dosage adjustments of omeprazole may be required during concomitant administration with dasabuvir; ombitasvir; paritaprevir; ritonavir. Use of these drugs together results in decreased omeprazole serum concentrations. Monitor for decreasing efficacy and consider increasing the omeprazole dose if needed; however, adult doses should be limited to no more than 40 mg/day. The dose should be re-adjusted after completion of the 4-drug hepatitis C treatment regimen. (Moderate) Increased exposure to omeprazole may occur during concurrent administration of ritonavir. Although dosage adjustment of omeprazole is not normally required, dosage reduction may be considered in patients receiving higher omeprazole doses (e.g., those with Zollinger-Ellison syndrome). Ritonavir is a strong CYP3A4 inhibitor. Omeprazole is a CYP2C19 and CYP3A4 substrate. Coadministration of a dual CYP2C19/strong CYP3A4 inhibitor increased the omeprazole AUC by an average of 4-times.

Oritavancin: (Moderate) Administration of oritavancin, a weak inhibitor of CYP2C19, with omeprazole resulted in a 15% increase in the ratio of omeprazole to 5-OH-omeprazole concentrations in the plasma. Monitor patients for omeprazole toxicities, such as headache or gastrointestinal distress, if these drugs are administered concurrently.

Pazopanib: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.

Pentobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Pexidartinib: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.

Phenobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Phenytoin: (Major) Avoid concomitant use of omeprazole and phenytoin as omeprazole exposure may be decreased, reducing its efficacy. Concomitant use may also increase phenytoin concentrations. Omeprazole is a CYP2C19 inhibitor and CYP3A substrate and phenytoin is a CYP2C19 substrate and strong CYP3A inducer.

Polyethylene Glycol; Electrolytes; Bisacodyl: (Minor) The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.

Posaconazole: (Major) The concurrent use of posaconazole immediate-release oral suspension and proton pump inhibitors (PPIs) should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. PPIs increase gastric pH, resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with esomeprazole (40 mg PO daily), the mean reductions in Cmax were 46% and the mean reductions in AUC were 32% for posaconazole. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by PPIs. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of many PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole). Coadministration may result in increased plasma concentration of the PPIs.

Primidone: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Quazepam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as quazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.

Rifapentine: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.

Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.

Riluzole: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.

Risedronate: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.

Ritonavir: (Moderate) Increased exposure to omeprazole may occur during concurrent administration of ritonavir. Although dosage adjustment of omeprazole is not normally required, dosage reduction may be considered in patients receiving higher omeprazole doses (e.g., those with Zollinger-Ellison syndrome). Ritonavir is a strong CYP3A4 inhibitor. Omeprazole is a CYP2C19 and CYP3A4 substrate. Coadministration of a dual CYP2C19/strong CYP3A4 inhibitor increased the omeprazole AUC by an average of 4-times.

Saquinavir: (Major) Coadministration with omeprazole results in significantly increased saquinavir concentrations. A similar interaction is expected with all proton pump inhibitors (PPIs). If saquinavir must be administered with PPIs, the patient should be closely monitored for saquinavir-related toxicities, including gastrointestinal symptoms, increased triglycerides, and deep vein thrombosis (DVT). Coadministration with omeprazole results in significantly increased saquinavir concentrations. In a small study, 18 healthy individuals received saquinavir 1000 mg (with ritonavir 100 mg) twice daily for 15 days; on days 11 through 15 omeprazole 40 mg was given once daily, which resulted in an 82% increase in the saquinavir AUC. A similar interaction is expected with all PPIs.

Secobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.

Secretin: (Major) Discontinue use of proton pump inhibitors before administering secretin. Patients who are receiving proton pump inhibitors at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma. The time required for serum gastrin concentrations to return to baseline after discontinuation of a proton pump inhibitor is specific to the individual drug.

Selpercatinib: (Major) Avoid coadministration of selpercatinib with omeprazole due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, selpercatinib must be taken with food. Coadministration under fasting conditions with omeprazole decreased selpercatinib exposure by 69%; however, concomitant use increased selpercatinib exposure by 2% or less when it was administered with a meal.

Sibutramine: (Moderate) According to the manufacturer, data from a pharmacokinetic study indicate that omeprazole decreases the metabolism of sibutramine and its active metabolites (M1 and M2). Increases in the serum concentration of sibutramine and its metabolites may lead to an increased risk of sibutramine-related adverse reactions.

Sofosbuvir; Velpatasvir: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.

Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.

Solifenacin: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.

Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with a PPI decreased sotorasib exposure by 57% under fed conditions and 42% under fasted conditions.

Sparsentan: (Major) Avoid concurrent use of sparsentan and proton pump inhibitors (PPIs) due to the risk for decreased sparsentan exposure which may reduce its efficacy. Medications that affect gastric pH may reduce sparsentan absorption.

Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of St. John's wort with the proton pump inhibitors (PPIs) as PPI exposure may be decreased, reducing their efficacy. PPIs are CYP3A4 and CYP2C19 substrates and St. John's wort is a strong CYP3A4 and CYP2C19 inducer. For example, coadministration of omeprazole with St. John's wort decreased omeprazole plasma concentrations by approximately 40%.

Stiripentol: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.

Sucralfate: (Minor) Proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. Sucralfate has been shown to delay absorption and reduce the bioavailability of omeprazole by about 16%.

Tacrolimus: (Moderate) Concomitant administration of omeprazole and tacrolimus may increase tacrolimus serum concentrations possibly leading to increased risk of serious adverse reactions (e.g., neurotoxicity, infection, QT prolongation), especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Monitor tacrolimus whole blood concentrations; reduce tacrolimus dose if needed to maintain therapeutic concentrations.

Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Thiazide diuretics: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Thyroid hormones: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.

Tipranavir: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Tipranavir markedly induces the hepatic cytochrome P-450 enzyme CYP2C19, an enzyme responsible for the metabolism of PPIs. However, since tipranavir is not given unless it is co-prescribed with ritonavir, a known marked enzyme inhibitor, a reduction in PPI metabolism may be unlikely to occur. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If tipranavir and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.

Tirofiban: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.

Tocilizumab: (Minor) Concomitant use of tocilizumab and omeprazole may lead to a decrease in the efficacy of omeprazole. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 12 to 28% decrease in omeprazole exposure occurred 1 week after a single tocilizumab dose. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Omeprazole is a substrate of both CYP2C19 and CYP3A4.

Tolterodine: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.

Torsemide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.

Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Triazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as triazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.

Trospium: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.

Tucatinib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with tucatinib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.

Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.

Voriconazole: (Moderate) Reduce the omeprazole dose by one-half when initiating voriconazole therapy in patients who are currently receiving omeprazole at doses of 40 mg/day or greater. Levels of omeprazole may increase by up to 2-fold due to CYP2C19 and CYP3A4 inhibition by voriconazole.

Warfarin: (Moderate) Monitor the INR in patients receiving warfarin with proton pump inhibitors. Increases in INR may lead to abnormal bleeding. Adjust the warfarin dose to maintain the target INR.

Omeprazole belongs to the class of GI antisecretory agents, the substituted benzimidazoles, which suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of parietal cells. Following activation in an acidic pH, omeprazole binds irreversibly to the H+/K+ ATPase pump on the secretory surface of the parietal cell membrane. Subsequently, the secretion of hydrogen ions into the gastric lumen is inhibited. Omeprazole is characterized as a gastric acid pump inhibitor because it blocks the final step of gastric acid production. It inhibits both basal and stimulus-induced acid secretion. Omeprazole is an extremely potent drug. Intragastric pH of patients receiving omeprazole is often higher and affected longer than during therapy with H2-antagonists. Omeprazole is also more effective than either H2-antagonists or sucralfate in the treatment of gastroesophageal reflux disease (GERD).

Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated for omeprazole. Omeprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without antimicrobial therapy.

Serum gastrin levels increase during the initial 1-2 weeks of therapy, and median increases in gastrin are greater than the increases produced by H2-receptor antagonists. Gastrin levels return to baseline within 1-2 weeks following discontinuance of therapy. Gastrin concentrations in patients with Zollinger-Ellison syndrome are not affected. Although prolonged hypergastrinemia has been associated with gastric tumors, long-term studies of proton pump inhibitors have not revealed an increased development of tumors, which was an initial concern in animal models.

Omeprazole is administered orally. It is not known if it crosses the placenta, but it is excreted into breast milk. Omeprazole is 95% bound to plasma proteins. Extensive hepatic metabolism occurs, and the metabolites have minimal antisecretory activity. Plasma clearance averages 500 to 600 mL/minute in normal subjects. The plasma half-life in healthy patients is 0.5 to 1 hour. Secretory activity returns to normal 3 to 5 days after therapy is discontinued. Approximately 72 to 80% of a dose is excreted renally, and 18 to 23% is excreted in the feces.

Serum gastrin levels increase during the initial 1 to 2 weeks of therapy, and median increases in gastrin are greater than the increases produced by H2-receptor antagonists. Gastrin levels return to baseline within 1 to 2 weeks following discontinuance of therapy. Gastrin concentrations in patients with Zollinger-Ellison syndrome are not affected.

Affected cytochrome P450 isoenzymes and drug transporters: CYP2C19, CYP3A4, CYP2C9
Omeprazole is metabolized by CYP2C19 (primary) and by CYP3A4 (secondary). It inhibits CYP2C19 in vitro and in vivo and CYP2C9 in vitro. Omeprazole is a time-dependent inhibitor of CYP2C19 and can increase the systemic exposure of co-administered drugs that are CYP2C19 substrates. In addition, administration of omeprazole increases intragastric pH and can alter the systemic exposure of certain drugs that exhibit pH-dependent solubility. Omeprazole does not appear to inhibit CYP3A4. In vitro, omeprazole induces CYP1A2.


-Route-Specific Pharmacokinetics
Oral Route
Omeprazole should be taken prior to meals, preferably in the morning. Due to a significant first-pass effect, bioavailability following oral doses of 20 to 40 mg of the delayed-release omeprazole capsules is 30 to 40%, but may approach 100% in patients with hepatic impairment. Upon repeated administration, the bioavailability increases slightly. The AUC and Cmax for delayed-release oral suspension are 87% and 88% of those for delayed-release oral capsules, respectively. Omeprazole is rapidly absorbed following oral administration and distributes throughout the body tissues, concentrating in the gastric parietal cells. The drug's onset of action is 1 hour, and the duration of inhibition is greater than 72 hours.


-Special Populations
Hepatic Impairment
In patients with chronic hepatic disease, the bioavailability of buffered omeprazole solution increases to approximately 100%, reflecting decreased first-pass effect. Additionally, the half-life increases to nearly 3 hours in chronic hepatic impairment as compared to the mean half-life of 1 hour in normal subjects. Plasma clearance averages 70 mL/minute, compared to a value of 500 to 600 mL/minute in normal subjects. Although the impact of hepatic disease has not been studied in pediatric patients, similar findings are expected. In a 5-year-old child with impaired hepatic function, the elimination was delayed, clearance was slower (0.16 L/hour/kg) and the half-life was longer (2.76 hours) than that of healthy children.

Renal Impairment
In renal impairment, the bioavailability of omeprazole is slightly increased. Because omeprazole inactive metabolites are primarily excreted in the urine, elimination of these metabolites slows in proportion to decreased CrCl. In a study that included 4 children with impaired renal function, the pharmacokinetic parameters of omeprazole in 3 of the children were in the range of those seen for the 9 children with normal renal function. The fourth child also had concomitant hepatic impairment, so the pharmacokinetic parameters were outside of the normal range in this child.

Pediatrics
Neonates
In neonates, omeprazole clearance is slower than that of older children and adults (0.12 to 0.20 L/hour/kg vs. 0.45 L/hour/kg) and the half-life is longer (1.6 to 2.1 hours vs. 0.75 to 1.2 hours).

Infants and Children
The bioavailability of omeprazole increases by 16 to 64% with repeated dosing in children, compared to values obtained after a single dose. This is thought to occur due to both decreased first-pass elimination and reduced systemic clearance due to inhibition of CYP2C19 by omeprazole. The mean volume of distribution is approximately 0.4 L/kg in pediatric patients, which is similar to that of an adult (0.31 to 0.34 L/kg). The half-life of omeprazole is approximately 1 hour in pediatric patients and the clearance of omeprazole appears to be faster for pediatric patients than for adults. Following comparable mg per kg doses of omeprazole, younger children (2 to 5 years) have a lower mean AUC, half-life, and Cmax than older children (6 to 16 years) or adults; the mean AUC of the latter two groups do not differ. Since omeprazole is metabolized by CYP2C19 and CYP3A4, some of the differences in pharmacokinetic parameters may be explained by the maturation changes in these enzyme systems. These hepatic enzymes have reduced activity at birth, but reach adult levels of activity in early infancy. Hepatic P450 enzyme activity levels then exceed adult enzymatic activity levels throughout childhood and revert back to adult levels some time during adolescence. The pharmacokinetics of omeprazole are dose dependant, with nonlinear increases in plasma concentration with increasing doses.

Geriatric
In elderly subjects, the elimination rate of omeprazole is somewhat decreased and the bioavailability is increased; however, no dosage adjustment is needed.

Ethnic Differences
Asian patients exhibit a 4-fold increase in AUC of omeprazole compared to White patients.

Other
CYP2C19 Poor Metabolizers
CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole. The CYP2C19*1 allele is fully functional while the CYP2C19*2 and *3 alleles are nonfunctional. There are other alleles associated with no or reduced enzymatic function. Patients carrying 2 fully functional alleles are extensive metabolizers and those carrying 2 loss-of-function alleles are poor metabolizers. In extensive metabolizers, omeprazole is primarily metabolized by CYP2C19. The systemic exposure to omeprazole varies with a patient's metabolism status, with poor metabolizers having the greatest exposure and extensive metabolizers having the least exposure. Approximately 3% of White patients and 15 to 20% of Asian patients are CYP2C19 poor metabolizers. In pharmacokinetic studies of single 20 mg omeprazole dose, the AUC of omeprazole in Asian subjects was approximately 4-fold of that in White subjects.