Prilosec (omeprazole magnesium): Uses, Dosage, Side Effects & Warnings

Q: Who makes Prilosec?

Prilosec is listed by 1 labeler in the FDA NDC directory, including Covis Pharma US, Inc.

Q: Has Prilosec been recalled?

The FDA enforcement database lists 1 recall for Prilosec, most recently D-0466-2021 (class ii): CGMP Deviations: Intermittent exposure to temperature excursion during storage.

Uses

1 INDICATIONS AND USAGE PRILOSEC is a proton pump inhibitor (PPI) indicated for the:
• Treatment of active duodenal ulcer in adults ( 1.1 )
• Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults ( 1.2 )
• Treatment of active benign gastric ulcer in adults ( 1.3 )
• Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and older ( 1.4 )
• Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 1 month of age and older ( 1.5 )
• Maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older ( 1.6 )
• Pathologic hypersecretory conditions in adults ( 1.7 ) 1.1 Treatment of Active Duodenal Ulcer PRILOSEC is indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. 1.2 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Triple Therapy PRILOSEC in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults. Dual Therapy PRILOSEC in combination with clarithromycin is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults. Among patients who fail therapy, PRILOSEC with clarithromycin is more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see Clinical Pharmacology ( 12.4 ) and the clarithromycin prescribing information, Microbiology section ] . 1.3 Treatment of Active Benign Gastric Ulcer PRILOSEC is indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults. 1.4 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) PRILOSEC is indicated for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 1 year of age and older. 1.5 Treatment of Erosive Esophagitis (EE) Due to Acid-Mediated GERD Pediatric Patients 1 Year of Age to Adults PRILOSEC is indicated for the short-term treatment (4 to 8 weeks) of EE due to acid-mediated GERD that has been diagnosed by endoscopy in patients 1 year of age and older. The efficacy of PRILOSEC used for longer than 8 weeks in patients with EE has not been established. 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 EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of PRILOSEC may be considered. Pediatric Patients 1 Month to Less than 1 Year of Age PRILOSEC is indicated for the short-term treatment (up to 6 weeks) of EE due to acid-mediated GERD in pediatric patients 1 month to less than 1 year of age. 1.6 Maintenance of Healing of EE Due to Acid-Mediated GERD PRILOSEC is indicated for the maintenance healing of EE due to acid-mediated GERD in patients 1 year of age and older. Controlled studies do not extend beyond 12 months. 1.7 Pathological Hypersecretory Conditions PRILOSEC is indicated for the long-term treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.

Dosage and administration

Indication Recommended Adult ( 2.1 ) and Pediatric Dosage ( 2.2 ) Treatment of Active Duodenal Ulcer 20 mg once daily for 4 weeks; some patients may require an additional 4 weeks ( 2.1 ) H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: PRILOSEC Amoxicillin Clarithromycin 20 mg 1000 mg 500 mg Each drug twice daily for 10 days ( 2.1 )* Dual Therapy: PRILOSEC Clarithromycin 40 mg once daily for 14 days** 500 mg three times daily for 14 days ( 2.1 ) Active Benign Gastric Ulcer 40 mg once daily for 4 to 8 weeks ( 2.1 ) Symptomatic GERD 20 mg once daily for up to 4 weeks ( 2.1 ) See full prescribing information for weight based dosing in pediatric patients 1 year of age and older ( 2.2 ) EE due to Acid-Mediated GERD 20 mg once daily for 4 to 8 weeks ( 2.1 )*** See full prescribing information for weight based dosing in pediatric patients 1 month of age and older ( 2.2 ) Maintenance of Healing of EE due to Acid-Mediated GERD 20 mg once daily ( 2.1 )**** See full prescribing information for weight based dosing in pediatric patients 1 year of age and older ( 2.2 ) Pathological Hypersecretory Conditions Starting dose is 60 mg once daily (varies with individual patient, see full prescribing information) as long as clinically indicated ( 2.1 ) * if ulcer present, continue PRILOSEC 20 mg once daily for an additional 18 days. ** if ulcer present, continue PRILOSEC 20 mg once daily for an additional 14 days. *** an additional 4 weeks of treatment may be given if no response; if recurrence additional 4 to 8 week courses may be considered. **** studied for 12 months. Reduce the dosage to 10 mg once daily for patients with hepatic impairment (Child-Pugh Class A, B, or C) and Asian patients ( 8.6 , 8.7 ) 2.1 Recommended Adult Dosage Regimen by Indication Table 1 shows the recommended dosage of PRILOSEC in adult patients by indication. Table 1: Recommended Dosage Regimen of PRILOSEC in Adults by Indication Indication Dosage of PRILOSEC Treatment Duration Treatment of Active Duodenal Ulcer 20 mg once daily 4 weeks Most patients heal within 4 weeks; some patients may require an additional 4 weeks of therapy to achieve healing Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy PRILOSEC 20 mg Amoxicillin 1000 mg Clarithromycin 500 mg Take all three drugs twice daily 10 days In patients with an ulcer present at the time of initiation of therapy, continue PRILOSEC 20 mg once daily for an additional 18 days for ulcer healing and symptom relief. Dual Therapy PRILOSEC 40 mg once daily Clarithromycin 500 mg three times daily 14 days In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of PRILOSEC 20 mg once daily is recommended for ulcer healing and symptom relief. Active Benign Gastric Ulcer 40 mg once daily 4 to 8 weeks Treatment of Symptomatic GERD 20 mg once daily Up to 4 weeks Treatment of EE due to Acid-Mediated GERD 20 mg once daily 4 to 8 weeks The efficacy of PRILOSEC used for longer than 8 weeks in patients with EE has not been established. 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 EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of PRILOSEC may be considered. Maintenance of Healing of EE due to Acid-Mediated GERD 20 mg once daily Dosage reduction to 10 mg once daily is recommended for patients with hepatic impairment (Child-Pugh Class A, B or C) and Asian patients when used for the maintenance of healing of EE [see Use in Specific Populations ( 8.6 , 8.7 ) and Clinical Pharmacology ( 12.3 , 12.5 )]. Controlled studies do not extend beyond 12 months. Pathological Hypersecretory Conditions Starting dose is 60 mg once daily; adjust to patient needs Daily dosages of greater than 80 mg should be administered in divided doses. Dosages up to 120 mg three times daily have been administered. As long as clinically indicated. Some patients with Zollinger-Ellison syndrome have been treated continuously for more than 5 years. 2.2 Recommended Pediatric Dosage Regimen by Indication Table 2 shows the recommended dosage of PRILOSEC in pediatric patients by indication. Table 2: Recommended Dosage Regimen of PRILOSEC in Pediatric Patients by Indication Indication PRILOSEC Dosage Regimen and Duration Patient Age Weight-Based Dose (mg) Regimen and Duration Treatment of Symptomatic GERD 1 to 16 years 5 to less than 10 kg: 5 mg Once daily for up to 4 weeks 10 to less than 20 kg: 10 mg 20 kg and greater: 20 mg Treatment of EE due to Acid-Mediated GERD 1 to 16 years 5 to less than 10 kg: 5 mg Once daily for 4 to 8 weeks The efficacy of PRILOSEC used for longer than 8 weeks in patients with EE has not been established. 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 EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of PRILOSEC may be considered. 10 to less than 20 kg: 10 mg 20 kg and greater: 20 mg 1 month to less than 1 year 3 to less than 5 kg: 2.5 mg Once daily up to 6 weeks 5 to less than 10 kg: 5 mg 10 kg and greater: 10 mg Maintenance of Healing of EE due to Acid-Mediated GERD 1 to 16 years 5 to less than 10 kg: 5 mg Once daily. Controlled studies do not extend beyond 12 months 10 to less than 20 kg: 10 mg 20 kg and greater: 20 mg 2.3 Administration Instructions
• PRILOSEC is intended to be prepared in water and administered orally or via a nasogastric (NG) or gastric tube.
• Take PRILOSEC before meals.
• Antacids may be used concomitantly with PRILOSEC.
• Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose. Oral Administration in Water 1. Empty the contents of a 2.5 mg packet into a container containing 5 mL of water.

Dosage forms and strengths

For Delayed-Release Oral Suspension: 2.5 mg and 10 mg omeprazole in unit dose packets containing a fine yellow powder, consisting of white to brownish omeprazole magnesium granules and pale yellow inactive granules. PRILOSEC for delayed-release oral suspension: 2.5 mg and 10 mg omeprazole in unit dose packets ( 3 )

Contraindications

• PRILOSEC is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6 )] .
• Proton pump inhibitors (PPIs), including PRILOSEC, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions ( 7 )].
• For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with PRILOSEC, refer to the CONTRAINDICATIONS section of their package inserts.
• Patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. ( 4 )
• Patients receiving rilpivirine-containing products. ( 4 , 7 )
• Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when administered in combination with PRILOSEC. ( 4 )

Warnings and precautions

• Gastric Malignancy : In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 )
• Acute Tubulointerstital Nephritis : Discontinue treatment and evaluate patients. ( 5.2 )
• Clostridium difficile -Associated Diarrhea : PPI therapy may be associated with increased risk. ( 5.3 )
• Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 )
• Severe Cutaneous Adverse Reactions : Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 )
• Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue PRILOSEC and refer to specialist for evaluation. ( 5.6 )
• Interaction with Clopidogrel : Avoid concomitant use of PRILOSEC. ( 5.7 , 7 )
• Cyanocobalamin (Vitamin B-12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.8 )
• Hypomagnesemia and Mineral Metabolism : Reported rarely with prolonged treatment with PPIs. ( 5.9 )
• Interaction with St. John’s Wort or Rifampin : Avoid concomitant use of PRILOSEC. ( 5.10 , 7 )
• Interactions with Diagnostic Investigations for Neuroendocrine Tumors : Increased Chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors; temporarily stop PRILOSEC at least 14 days before assessing CgA levels. ( 5.11 , 7 )
• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of PRILOSEC. ( 5.12 , 7 )
• Fundic Gland Polyps : Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.13 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with PRILOSEC does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) 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). 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 PRILOSEC and evaluate patients with suspected acute TIN [see Contraindications ( 4 )] . 5.3 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like PRILOSEC may be associated with an increased risk of Clostridium difficile -associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions ( 6.2 )] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with PRILOSEC, refer to Warnings and Precautions sections of the corresponding prescribing information. 5.4 Bone Fracture Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration ( 2.1 ) , Adverse Reactions ( 6.3 )] . 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) 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 [see Adverse Reactions ( 6.2 )] . Discontinue PRILOSEC at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly.

Side effects

The following serious adverse reactions are described below and elsewhere in labeling:
• Acute Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.2 )]
• Clostridium difficile -Associated Diarrhea [see Warnings and Precautions ( 5.3 )]
• Bone Fracture [see Warnings and Precautions ( 5.4 )]
• Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )]
• Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions ( 5.6 )]
• Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions ( 5.8 )]
• Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions ( 5.9 )]
• Fundic Gland Polyps [see Warnings and Precautions ( 5.13 )] Adults: Most common adverse reactions in adults (incidence ≥2%) are
• Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. ( 6 ) Pediatric patients (1 to 16 years of age):
• Safety profile similar to that in adults, except that respiratory system events and fever were the most frequently reported reactions in pediatric studies. ( 8.4 ) To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience with PRILOSEC Monotherapy Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure to omeprazole magnesium delayed-release capsules in 3096 patients from worldwide clinical trials (465 patients from US studies and 2631 patients from international studies). Indications clinically studied in US trials included duodenal ulcer, resistant ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥2%) from PRILOSEC-treated patients enrolled in these studies included headache (7%), abdominal pain (5%), nausea (4%), diarrhea (4%), vomiting (3%), and flatulence (3%). Additional adverse reactions that were reported with an incidence ≥1% included acid regurgitation (2%), upper respiratory infection (2%), constipation (2%), dizziness (2%), rash (2%), asthenia (1%), back pain (1%), and cough (1%). The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less. The clinical trial safety profile in pediatric patients who received omeprazole magnesium delayed-release capsules was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of the respiratory system were frequently reported in the 1 month to <1 year age group, the 1 to <2 year age group, and the 2 to 16 year age group (42%, 75%, and 19%, respectively). In addition, otitis media was frequently reported in the 1 month to <1 year age group (22%), fever was frequently reported in the 1 to <2 year age group (33% ), and accidental injuries were frequently reported in the 2 to 16 year age group (4%) [see Use in Specific Populations ( 8.4 )] . 6.2 Clinical Trials Experience with PRILOSEC in Combination Therapy for H. pylori Eradication In clinical trials using either dual therapy with omeprazole magnesium delayed-release capsules and clarithromycin, or triple therapy with omeprazole magnesium delayed-release capsules, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone. Dual Therapy (omeprazole magnesium delayed-release capsules/clarithromycin) Adverse reactions observed in controlled clinical trials using combination therapy with omeprazole magnesium delayed-release capsules and clarithromycin (n = 346) that differed from those previously described for omeprazole magnesium delayed-release capsules alone were taste perversion (15%), tongue discoloration (2%), rhinitis (2%), pharyngitis (1%), and flu-syndrome (1%). (For more information on clarithromycin, refer to the clarithromycin prescribing information, Adverse Reactions section.) Triple Therapy (omeprazole magnesium delayed-release capsules/clarithromycin/amoxicillin) The most frequent adverse reactions observed in clinical trials using combination therapy with omeprazole magnesium delayed-release capsules, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%), taste perversion (10%), and headache (7%). None of these occurred at a higher frequency than that reported by patients taking antimicrobial agents alone. (For more information on clarithromycin or amoxicillin, refer to the respective prescribing information, Adverse Reactions sections.) 6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of omeprazole. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure. Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; systemic lupus erythematosus Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema Endocrine: Gynecomastia Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis, fundic gland polyps. Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with omeprazole.

Drug interactions

Table 3 and Table 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with omeprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Omeprazole and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.
• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )].
• Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with omeprazole may increase toxicity [see Clinical Pharmacology ( 12.3 )].
• There are other antiretroviral drugs which do not result in clinically relevant interactions with omeprazole. Intervention: Rilpivirine-containing products : Concomitant use with PRILOSEC is contraindicated [see Contraindications ( 4 )] . Atazanavir : Avoid concomitant use with PRILOSEC. See prescribing information for atazanavir for dosing information. Nelfinavir : Avoid concomitant use with PRILOSEC. See prescribing information for nelfinavir. Saquinavir : See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities. Other antiretrovirals : See prescribing information for specific antiretroviral drugs. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain target INR range. Methotrexate Clinical Impact: Concomitant use of omeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions ( 5.11 )]. Intervention: A temporary withdrawal of PRILOSEC may be considered in some patients receiving high-dose methotrexate. CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam) Clopidogrel Clinical Impact: Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Clinical Pharmacology ( 12.3 )]. There are no adequate combination studies of a lower dose of omeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel. Intervention: Avoid concomitant use with PRILOSEC. Consider use of alternative anti-platelet therapy [see Warnings and Precautions ( 5.6 )] . Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology ( 12.3 )] . Intervention: Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram. Cilostazol Clinical Impact: Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-cilostazol) [see Clinical Pharmacology ( 12.3 )] . Intervention: Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol. Phenytoin Clinical Impact: Potential for increased exposure of phenytoin. Intervention: Monitor phenytoin serum concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for phenytoin. Diazepam Clinical Impact: Increased exposure of diazepam [see Clinical Pharmacology ( 12.3 )] . Intervention: Monitor patients for increased sedation and reduce the dose of diazepam as needed. Digoxin Clinical Impact: Potential for increased exposure of digoxin [see Clinical Pharmacology ( 12.3 )] . Intervention: Monitor digoxin concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See digoxin prescribing information. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Co-administration of omeprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PRILOSEC and MMF. Use PRILOSEC with caution in transplant patients receiving MMF [see Clinical Pharmacology ( 12.3 )] . See the prescribing information for other drugs dependent on gastric pH for absorption. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See Contraindications , Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. Tacrolimus Clinical Impact: Potential for increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Intervention: Monitor tacrolimus whole blood concentrations.

Use in specific populations

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see Data ] . The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H 2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H 2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Animal Data Omeprazole Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human doses of 40 mg on a body surface area basis), administered prior to mating through the lactation period. Esomeprazole The data described below was generated from studies using esomeprazole, an enantiomer of omeprazole. The animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis.

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see Data ] . The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H 2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H 2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Animal Data Omeprazole Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human doses of 40 mg on a body surface area basis), administered prior to mating through the lactation period. Esomeprazole The data described below was generated from studies using esomeprazole, an enantiomer of omeprazole. The animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of PRILOSEC have been established in pediatric patients 1 to 16 years for the treatment of symptomatic GERD, treatment of EE due to acid-mediated GERD, and maintenance of healing of EE due to acid-mediated GERD. Use of PRILOSEC in this age group is supported by adequate and well-controlled studies in adults and uncontrolled safety, efficacy, and pharmacokinetic studies performed in pediatric and adolescent patients [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.8 )] . The safety and effectiveness of PRILOSEC have been established in pediatric patients 1 month to less than 1 year of age for the treatment of EE due to acid-mediated GERD and is supported by adequate and well-controlled studies in adults and safety, pharmacokinetic, and pharmacodynamic studies performed in pediatric patients [see Clinical Pharmacology ( 12.3 )] . In the pediatric population, adverse reactions of the respiratory system were frequently reported in the entire (1 month to 16 year) age group. Otitis media was frequently reported in the 1 month to <1 year age group, fever was frequently reported in the 1 to <2 year age group, and accidental injuries were frequently reported in the 2 to 16 year age group [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of PRILOSEC have not been established in:
• patients less than 1 year of age for: o Treatment of symptomatic GERD o Maintenance of healing of EE due to acid-mediated GERD
• pediatric patients for: o Treatment of active duodenal ulcer o H. pylori eradication to reduce the risk of duodenal ulcer recurrence o Treatment of active benign gastric ulcer o Pathological hypersecretory conditions
• patients less than 1 month of age for any indication. Juvenile Animal Data Esomeprazole, an enantiomer of omeprazole, was shown to decrease body weight, body weight gain, femur weight, femur length, and overall growth at oral doses about 34 to 68 times a daily human dose of 40 mg esomeprazole or 40 mg omeprazole based on body surface area in a juvenile rat toxicity study. The animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. A 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with esomeprazole magnesium at doses of 70 to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). An increase in the number of deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered esomeprazole magnesium from postnatal day 7 through postnatal day 35. In addition, doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis), produced treatment-related decreases in body weight (approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected overall growth. Comparable findings described above have also been observed in this study with another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole.

Geriatric use

8.5 Geriatric Use Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly [see Clinical Pharmacology ( 12.3 )] .

Overdosage

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience [see Adverse Reactions ( 6 )] . Symptoms were transient, and no serious clinical outcome has been reported when PRILOSEC was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

Description

The active ingredient in PRILOSEC (omeprazole magnesium) for delayed-release oral suspension, is 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole, magnesium salt (2:1). Omeprazole magnesium is a white to off white powder with a melting point with degradation at 200°C. The salt is slightly soluble (0.25 mg/mL) in water at 25°C, and it is soluble in methanol. The half-life is highly pH dependent. The empirical formula for omeprazole magnesium is (C 17 H 18 N 3 O 3 S) 2 Mg, the molecular weight is 713.12 and the structural formula is: Each packet of PRILOSEC for delayed-release oral suspension contains either 2.5 mg or 10 mg of omeprazole (equivalent to 2.8 mg or 11.2 mg of omeprazole magnesium trihydrate), in the form of enteric-coated granules with the following inactive ingredients: glyceryl monostearate, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer C, polysorbate, sugar spheres, talc, and triethyl citrate, and also inactive granules. The inactive granules are composed of the following ingredients: citric acid, crospovidone, dextrose, hydroxypropyl cellulose, iron oxide and xanthan gum. The omeprazole granules and inactive granules are constituted with water to form a suspension and are given by oral, nasogastric, or direct gastric administration. omeprazole magnesium structural formula

Mechanism of action

12.1 Mechanism of Action Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H + /K + ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

How supplied

(omeprazole magnesium) for delayed-release oral suspension, 2.5 mg or 10 mg omeprazole, is supplied as a unit dose packet containing a fine yellow powder, consisting of white to brownish omeprazole magnesium granules and pale yellow inactive granules. PRILOSEC unit dose packets are supplied as follows: NDC 70515-625-01 unit dose packages of 30: 2.5 mg packets NDC 70515-610-01 unit dose packages of 30: 10 mg packets Storage Store PRILOSEC for delayed-release oral suspension at 25°C (77°F); excursions permitted to 15 – 30°C (59 – 86°F). [See USP Controlled Room Temperature.]

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Acute Tubulointerstitial Nephritis Advise the patient or caregiver to call the patient’s healthcare provider immediately if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Warnings and Precautions ( 5.2 )] . Clostridium difficile -Associated Diarrhea Advise the patient or caregiver to immediately call the patient’s healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions ( 5.3 )] . Bone Fracture Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient’s healthcare provider [see Warnings and Precautions ( 5.4 )] . Severe Cutaneous Adverse Reactions Advise the patient or caregiver to discontinue PRILOSEC and report to their healthcare provider at the first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity [see Warnings and Precautions ( 5.5 )]. Cutaneous and Systemic Lupus Erythematosus Advise the patient or caregiver to immediately call the patient’s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions ( 5.6 )] Cyanocobalamin (Vitamin B-12) Deficiency Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient’s healthcare provider if they have been receiving PRILOSEC for longer than 3 years [see Warnings and Precautions ( 5.8 )] . Hypomagnesemia and Mineral Metabolism Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to the patient’s healthcare provider, if they have been receiving PRILOSEC for at least 3 months [see Warnings and Precautions ( 5.9 )] . Drug Interactions Advise patients to report to their healthcare provider if they start treatment with rilpivirine-containing products, clopidogrel, St. John’s Wort or rifampin; or, if they take high-dose methotrexate [see Contraindications ( 4 ), Warnings and Precautions ( 5.7 , 5.10 , 5.12 )] . Administration
• PRILOSEC is intended to be prepared in water and administered orally or via a nasogastric (NG) or gastric tube, as described in the Medication Guide.
• Take PRILOSEC before meals.
• Antacids may be used concomitantly with PRILOSEC.
• Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose.

Active ingredients

Omeprazole Magnesium in 2 products

Prilosec NDC products (2)

NDC	Strength & form	Labeler	Type
70515-610	Omeprazole Magnesium 10 mg/1 Granule, Delayed Release	Covis Pharma US, Inc	NDA
70515-625	Omeprazole Magnesium 2.5 mg/1 Granule, Delayed Release	Covis Pharma US, Inc	NDA

Prilosec recalls

D-0466-2021 Jun 2, 2021 · Class II · Terminated
CGMP Deviations: Intermittent exposure to temperature excursion during storage.

Frequently asked questions

What is Prilosec used for?

1 INDICATIONS AND USAGE PRILOSEC is a proton pump inhibitor (PPI) indicated for the: • Treatment of active duodenal ulcer in adults ( 1.1 ) • Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults ( 1.2 ) • Treatment of active benign gastric ulcer in adults ( 1.3 ) • Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and…

What are the side effects of Prilosec?

The following serious adverse reactions are described below and elsewhere in labeling: • Acute Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.2 )] • Clostridium difficile -Associated Diarrhea [see Warnings and Precautions ( 5.3 )] • Bone Fracture [see Warnings and Precautions ( 5.4 )] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )] • Cutaneous and… See the full label for the complete list.

Who makes Prilosec?

Prilosec is listed by 1 labeler in the FDA NDC directory, including Covis Pharma US, Inc.

Has Prilosec been recalled?

The FDA enforcement database lists 1 recall for Prilosec, most recently D-0466-2021 (class ii): CGMP Deviations: Intermittent exposure to temperature excursion during storage.