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  • CLASSES

    Bulk Agents for Compounding
    Compounding Kits Miscellaneous
    Proton Pump Inhibitors/PPIs

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Oral proton pump inhibitor (PPI), gastric antisecretory agent.
    Used for GERD, erosive esophagitis, and hypersecretory conditions; also used in antimicrobial combination regimens for H. pylori eradication.
    Available OTC for heartburn.

    COMMON BRAND NAMES

    First-Omeprazole, Prilosec, Prilosec OTC

    HOW SUPPLIED

    First-Omeprazole Oral Pwd F/Recon: 0.18g, 0.3g, 0.6g
    Omeprazole/Prilosec Oral Cap DR Pellets: 10mg, 20mg, 40mg
    Omeprazole/Prilosec OTC Oral Tab DR: 20mg
    Prilosec Oral Gran F/Recon: 2.8mg, 11.2mg

    DOSAGE & INDICATIONS

    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, 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, ranitidine, 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 up to 4 weeks. Per clinical practice guidelines, initiate empiric therapy based on a presumptive diagnosis of GERD in the setting of typical symptoms of heartburn and regurgitation. For patients with partial response to once daily therapy, consider an increase to omeprazole 20 mg PO twice daily or consider a one-time switch to a different PPI. Refer non-responders for further evaluation. Consider maintenance therapy for patients who continue to have symptoms after PPI discontinuation; the lowest effective dose, including on demand or intermittent therapy, should be used with regular assessment of the need for continued PPI therapy. Alternatively, step down maintenance therapy to an H2 blocker is acceptable.

    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†

    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 (% 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 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 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 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 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.

    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.

    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.

    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.

    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 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 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 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.

    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.

    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 stress gastritis prophylaxis† in critically-ill patients.
    NOTE: 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.
    Oral dosage
    Adults

    20—40 mg/day PO has been studied; doses up to 40 mg twice daily have been administered clinically. In a randomized trial comparing the efficacy of omeprazole to ranitidine, administration of omeprazole 40 mg/day PO/NG (n = 32) was associated with fewer cases of clinically important GI bleeding relative to ranitidine 150 mg/day IV (6% vs. 31%, respectively; p < 0.05). However, in this study, the risk factors for bleeding were not balanced between the 2 treatment groups, possibly overstating omeprazole's comparative efficacy. There is no clear evidence that PPI use is superior to H2 antagonists for SUP. Discontinue PPI use when risk factors for SUP are no longer present.

    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.

    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—8 hours later, then 10 mL (20 mg) daily thereafter. Administer SOS via tube and follow with 5—10 mL of water; clamp the tube for 1—2 hours after each administration. Efficacy, safety, and cost of SOS was 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 bleeding stopped in all patients within 36 hours.

    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 the treatment of proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) in the differential diagnosis of eosinophilic esophagitis (EoE)†.
    Oral dosage
    Adults

    PPI dosing in the range of 20—40 mg PO twice daily given 30—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. According to guidelines, a PPI trial is central to the differential diagnosis of EoE. If eosinophilia and symptoms persist on repeat endoscopy and biopsy following a PPI trial, then EoE can be formally diagnosed. If symptoms and eosinophilia resolve, then PPI-REE is diagnosed; PPI-REE patients may or may not have underlying GERD. More than one-third of all patients with esophageal eosinophilia on biopsy will respond to a PPI.

    †Indicates off-label use

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Consider dosage reduction in patients with hepatic impairment (see Contraindications).

    Renal Impairment

    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.

    ADMINISTRATION

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

    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.

    STORAGE

    Generic:
    - Protect from extreme heat
    - Protect from moisture
    - Store between 68 to 77 degrees F
    First-Omeprazole:
    - Protect from freezing
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    - Store reconstituted product in refrigerator (between 36 to 46 degrees F) for up to 30 days
    Prilosec:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Prilosec OTC:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Proton pump inhibitors (PPIs) hypersensitivity

    Omeprazole is contraindicated in patients with known proton pump inhibitors (PPIs) hypersensitivity. There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports. Although rare, occasionally such reactions can be serious (e.g., anaphylaxis, angioedema, or acute interstitial nephritis). Esomeprazole is the active isomer of racemic omeprazole; therefore the two drugs should not be taken together as this would constitute duplicative therapy.

    Hepatic disease

    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.

    Asian patients

    Asian patients exhibit a four-fold increase in AUC of omeprazole compared to Caucasians. The manufacturer states that dosage reduction should be considered when administering omeprazole to Asian patients, particularly when maintenance of healing of erosive esophagitis is indicated. No specific dosage guidelines are available at this time.

    Gastric cancer

    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.

    Diarrhea, pseudomembranous colitis

    The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection by encouraging the growth of gut microflora and increasing susceptibility to organisms including Salmonella, Campylobacter jejuni, Escherichia coli, Clostridium difficile, Vibrio cholerae, and Listeria. A systematic review examined the relationship between PPI use and susceptibility to enteric infections and found enhanced susceptibility for Salmonella infections (adjusted RR range: 4.2—8.3 in 2 studies), Campylobacter (RR 3.5—11.7 in 4 studies) and C. difficile infections (RR 1.2—5.0 in 17 out of 27 studies). In particular, PPI use has been linked to an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve. Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. The PPIs, including omeprazole, are recommended for use in combination with certain antibiotics to eradicate Helicobacter pylori. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents in combination with PPIs.

    Vitamin B12 deficiency

    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.

    Bone fractures, geriatric, osteoporosis

    Use proton pump inhibitors (PPIs) in patients with or who have risk factors for osteoporosis 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 older adult and geriatric patients 50 years of age and older. It should be noted that 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. According to the Beers Criteria, PPIs are considered potentially inappropriate medications (PIMs) for use in geriatric patients due to the risk of Clostridium difficile and bone loss/fractures. Scheduled use for more than 8 weeks should be avoided except for high-risk patients (e.g., oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance treatment (e.g., due to failure of drug discontinuation trial or H-2 blockers). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, the indication for use of a proton pump inhibitor should be based on clinical symptoms and/or endoscopic findings. During use 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 used for longer than 12 weeks, clinical rationale for continued need and/or documentation should support an underlying chronic disease (e.g., GERD) or risk factors (e.g., chronic NSAID use). Adverse consequences of medication therapy include new or worsening headaches, nausea, emesis, flatulence, difficulty swallowing, abdomen pain, diarrhea, or other GI symptoms. In addition, PPIs may increase the risk of clostridium difficile colitis.

    Hypomagnesemia, long QT syndrome

    Daily treatment with a gastric acid-suppressing medication over a long period of time (e.g., 3 months to > 1 year) may lead to hypomagnesemia; cases have been reported in patients taking omeprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesemia is observed during PPI administration, discontinuation of the PPI may also be necessary. Low serum magnesium may lead to serious adverse events such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Use PPIs with caution and, if possible, avoid long-term (> 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias. In pediatric patients, irregular heartbeat may cause fatigue, upset stomach, dizziness, and lightheadedness. For patients expected to be on PPI therapy for a prolonged period of time, it is prudent for clinicians to obtain serum magnesium concentrations prior to initiating PPI therapy as well as throughout treatment. Patients on concomitant medications such as digoxin or diuretics (see Interactions) may also require periodic monitoring of serum magnesium.

    Rebound acid hypersecretion

    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.

    Pregnancy

    There are no adequate and well-controlled studies of omeprazole in pregnant women. Current data, including epidemiologic data and an expert review by TERIS (the Teratogen Information System), fail to demonstrate an increased risk of major congential malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Animal reproductive studies have been conducted with omeprazole and esomeprazole. Rats and rabbits dosed with omeprazole experienced 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 (BSA) for a 60 kg person. Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole in rats and rabbits during organogenesis with doses about 68 and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole, based on BSA for a 60 kg person. However, changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses >= 33.6 times an oral human dose of 40 mg. Although animal studies are not always predictive of human effects, because of the observed effect at high doses of esomeprazole magnesium on developing bone in rat studies, omeprazole use in pregnancy should be limited. 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. Use during pregnancy should be limited to cases where the benefit to the mother outweighs any potential risk to the fetus. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use. Self-medication with omeprazole (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.

    Breast-feeding

     Limited data suggest that omeprazole may be present in human milk. The clinical effects of exposure to omeprazole on the breastfed infant or on milk production have not been confirmed. One study reported the use of omeprazole in late gestation and continued use through lactation. During breast feeding, the mother fed her infant prior to a dose of 20 mg of omeprazole. Samples of expressed milk were analyzed and a maximum daily exposure to the infant was calculated to be 4 mcg (based on the consumption of 200 ml of milk/day). Based on the above case, a maximum dose of 3 mcg/kg daily or about 0.9% of the maternal weight-adjusted dosage would be delivered to an exclusively breast fed infant based on a milk consumption of 150 ml/kg/day. For comparison, doses of 0.5 mg/kg PO once daily for 6 weeks have been studied in during infancy (age 2.9 +/- 0.9 months) for peptic esophagitis. Nevertheless, the methods of collection and calculations of the sampled milk were not clearly defined in this case report. Milk expressed early in feeding contains less lipid content as compared to milk expressed towards the end of feeding. Taking into account that omeprazole is a lipid soluble drug, milk expressed and analyzed early on in feeding may not accurately reveal the true exposure to a feeding infant. Potentially serious adverse reactions may occur with the use of omeprazole during breast-feeding, including suppression of gastric acid secretion in the nursing infant. Therefore, caution should exercised when omeprazole is used during breast feeding. Alternative therapies for consideration include antacids and H2 blockers.

    Abdominal pain, dysphagia, GI bleeding, vomiting

    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.

    Systemic lupus erythematosus (SLE)

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

    Laboratory test interference

    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.

    ADVERSE REACTIONS

    Severe

    pancreatitis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatic encephalopathy / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    optic atrophy / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    optic neuritis / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 1.5-1.5
    stomatitis / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    pernicious anemia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    pyuria / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    blurred vision / Early / Incidence not known
    palpitations / Early / Incidence not known
    angina / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypertension / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known

    Mild

    headache / Early / 6.9-6.9
    abdominal pain / Early / 5.2-5.2
    nausea / Early / 4.0-4.0
    diarrhea / Early / 3.7-3.7
    vomiting / Early / 3.2-3.2
    flatulence / Early / 2.7-2.7
    infection / Delayed / 1.9-1.9
    rash / Early / 1.5-1.5
    dizziness / Early / 1.5-1.5
    asthenia / Delayed / 1.3-1.3
    cough / Delayed / 1.1-1.1
    back pain / Delayed / 1.1-1.1
    dysgeusia / Early / Incidence not known
    xerostomia / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    stool discoloration / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    agitation / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    drowsiness / Early / Incidence not known
    tremor / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    fever / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    testicular pain / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known
    myalgia / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    ocular irritation / Rapid / Incidence not known
    gynecomastia / Delayed / Incidence not known
    malaise / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    diplopia / Early / Incidence not known

    DRUG INTERACTIONS

    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and omeprazole; decreased acalabrutinib exposure occurred in a drug interaction study. Consider using an antacid or H2-blocker if acid suppression therapy is needed. Separate the administration of acalabrutinib and antacids by at least 2 hours; give acalabrutinib 2 hours before a H2-blocker. Acalabrutinib solubility decreases with increasing pH values. The AUC of acalabrutinib was decreased by 43% when acalabrutinib was coadministered with omeprazole 40 mg/day for 5 days.
    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; 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.
    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; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Alprazolam: (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 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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amitriptyline; 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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Amphetamine; Dextroamphetamine Salts: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Amphetamine; Dextroamphetamine: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    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.
    Anticholinergics: (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.
    Apalutamide: (Major) Avoid concomitant use of apalutamide with omeprazole, as omeprazole plasma concentrations may be reduced. Omeprazole is a CYP3A4 and CYP2C19 substrate. Apalutamide is a strong inhibitor of both CYP3A4 and CYP2C19. Coadministration with apalutamide decreased the single-dose AUC 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: (Severe) 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: (Severe) 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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Atropine: (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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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.
    Atropine; Difenoxin: (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.
    Atropine; Diphenoxylate: (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.
    Atropine; Edrophonium: (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.
    Atropine; Hyoscyamine; Phenobarbital; 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. (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.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    Belladonna Alkaloids; Ergotamine; 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. (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.
    Belladonna; Opium: (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.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Bendroflumethiazide; Nadolol: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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.
    Benztropine: (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.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Bortezomib: (Minor) Bortezomib may inhibit CYP2C19 activity at therapeutic concentrations and increase exposure to drugs that are substrates for this enzyme including proton pump inhibitors.
    Bosentan: (Moderate) Monitor for decreased efficacy of omeprazole if coadministration with bosentan is necessary. Omeprazole is metabolized by CYP2C19 and CYP3A4. Bosentan 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.
    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.
    Bumetanide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    Calcium Carbonate; Risedronate: (Major) 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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Cannabidiol: (Moderate) Consider a dose reduction of cannabidiol and/or omeprazole if coadministered. Coadministration may increase cannabidiol and/or omeprazole plasma concentrations increasing the risk of adverse reactions. Cannabidiol is metabolized by CYP2C19; in vitro data predicts inhibition of CYP2C19 by cannabidiol. Omeprazole is a sensitive substrate and moderate inhibitor of CYP2C19.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Carbamazepine: (Moderate) Omeprazole may increase the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation. Monitor carbamazepine serum concentrations when omeprazole is added to the drug regimen.
    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.
    Ceritinib: (Moderate) Use caution if coadministration of ceritinib with omeprazole is necessary, as the bioavailability of ceritinib may be reduced. Ceritinib displays pH-dependent solubility with decreased solubility at a higher pH, but data are conflicting regarding clinical significance. In healthy subjects, the AUC and Cmax of ceritinib decreased by 76% and 79%, respectively, when a single dose was administered with esomeprazole. However, in a subgroup of patients with NSCLC from a multicenter, open-label clinical trial, the AUC and Cmax of ceritinib decreased by 30% and 25%, respectively, after a single dose was administered with proton pump inhibitors; there was no clinically meaningful effect on ceritinib exposure at steady state.
    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; 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. (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.
    Chlorothiazide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Chlorthalidone: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Chlorthalidone; Clonidine: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    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.
    Clonazepam: (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 clonazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
    Clopidogrel: (Major) Avoid concomitant use of clopidogrel and omeprazole as it significantly reduces the antiplatelet activity of clopidogrel when given concomitantly or 12 hours apart. The American College of Cardiology Foundation (ACCF), American College of Gastroenterology (ACG) and American Heart Association (AHA) state that routine use of proton pump inhibitor (PPI) therapy is not recommended for patients at lower risk of gastrointestinal bleed but should be considered in those at high risk, such as those with a history of gastrointestinal bleed. Clinicians should carefully assess the risks and benefits of PPI use in patients on clopidogrel therapy and administration should be based on clinical need. If necessary, consider using a PPI medication with less pronounced effects on antiplatelet activity, 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. All PPIs are CYP219 substrates, and, to varying extents, are also inhibitors; thus, it is possible that any PPI may decrease the conversion of clopidogrel to its active metabolite, thereby reducing its effectiveness.
    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.
    Cobicistat; Elvitegravir; 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.
    Cobicistat; Elvitegravir; 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.
    Conivaptan: (Moderate) Increased exposure to omeprazole may occur during concurrent administration of conivaptan. 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). Conivaptan 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.
    Cyanocobalamin, Vitamin B12: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency.
    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.
    Dexmethylphenidate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release dexmethylphenidate (Focalin XR) have not been studied. Per the manufacturer of extended-release dexmethylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release dexmethylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release dexmethylphenidate.
    Dextroamphetamine: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Diazepam: (Moderate) Omeprazole inhibits the CYP2C19 metabolic pathway for diazepam. Omeprazole can increase the plasma concentrations and the elimination half-life of diazepam. It is recommended that patients receiving omeprazole and diazepam concomitantly should be monitored for enhanced diazepam response. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
    Diclofenac: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as omeprazole; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Diclofenac; Misoprostol: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as omeprazole; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Dicyclomine: (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.
    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: (Minor) In one patient, the combined use of disulfiram and omeprazole caused disorientation, confusion, and nightmares. These reactions occurred on two separate challenges when omeprazole was added to disulfiram therapy. Caution is advised when using disulfiram and omeprazole together.
    Dolutegravir; Rilpivirine: (Severe) 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.
    Doxepin: (Moderate) Doxepin is primarily metabolized by CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Omeprazole inhibits the CYP2C19 isoenzyme in vitro and in vivo and the CYP2C9 isoenzyme in vitro. In vitro, omeprazole induces the CYP1A2 isoenzyme. The clinical significance of this potential interaction is not known; monitor patients receiving doxepin and omeprazole concurrently for both doxepin efficacy and potential adverse effects.
    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.
    Dronabinol: (Major) Use caution if coadministration of dronabinol with omeprazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; omeprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    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 CYP2C9 and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C9 or CYP2C19.
    Efavirenz; Emtricitabine; Tenofovir: (Minor) Efavirenz inhibits CYP2C9 and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C9 or CYP2C19.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits CYP2C9 and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C9 or CYP2C19.
    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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Severe) 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: (Severe) 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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    Flavoxate: (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.
    Flibanserin: (Major) The concomitant use of flibanserin and strong CYP2C19 inhibitors, such as proton pump inhibitors (PPIs), may increase flibanserin concentrations, resulting in severe hypotension, syncope, and/or CNS depression. Therefore, patients should be monitored for flibanserin-induced adverse reactions, and the risks of combination therapy should be discussed with the patient. In addition, the concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including pantoprazole, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Fosphenytoin: (Moderate) Omeprazole can exhibit a dose-dependent inhibition of the hepatic cytochrome P-450 enzyme system, specifically CYP2C19. Because of this, omeprazole can interfere with the clearance of drugs metabolized via this pathway, such as phenytoin or fosphenytoin, resulting in increased phenytoin plasma concentrations. Clinical data do not exist, but an interaction is possible based on the known pathways of elimination. Patients should be monitored carefully for signs of increased drug effect if omeprazole is used with these drugs. In addition, some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Phenytoin induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If phenytoin 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.
    Furosemide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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%.
    Glycopyrrolate: (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.
    Glycopyrrolate; Formoterol: (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.
    Homatropine; Hydrocodone: (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.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hyoscyamine: (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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (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.
    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.
    Indacaterol; Glycopyrrolate: (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.
    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.
    Iron: (Major) 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) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Isoniazid, INH; Rifampin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Itraconazole: (Moderate) Administer proton pump inhibitors at least 2 hours before or 2 hours after oral itraconazole to minimize the potential for an interaction. Because itraconazole oral bioavailability requires an acidic environment for solubility, its absorption may be decreased with concomitant administration of proton pump inhibitors.
    Ketoconazole: (Major) Because ketoconazole requires an acidic pH for absorption, coadministration of a proton pump inhibitor (PPI) with ketoconazole can cause a notable decrease in the bioavailability of ketoconazole. PPIs have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction. An alternative imidazole antifungal should be chosen if any of these gastrointestinal medications are required. If these drugs must be coadministered, administer ketoconazole tablets with an acidic beverage and closely monitor for breakthrough infection.
    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.
    Lesinurad: (Moderate) Use lesinurad and omeprazole together with caution; omeprazole may increase the systemic exposure of lesinurad. Omeprazole is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    Lesinurad; Allopurinol: (Moderate) Use lesinurad and omeprazole together with caution; omeprazole may increase the systemic exposure of lesinurad. Omeprazole is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    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.
    Loop diuretics: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    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.
    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.
    Mepenzolate: (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.
    Mephobarbital: (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.
    Mesalamine, 5-ASA: (Major) The dissolution of the coating on mesalamine extended-release capsules (Apriso) and the delayed-release tablets (Lialda) is dependent on pH. Avoid coadministration with drugs that raise gastric pH like proton pump inhibitors.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (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.
    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) Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitors (PPIs); a temporary withdrawal of the PPI should be considered in some patients receiving high-dose methotrexate. Case reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs such as omeprazole, pantoprazole, or esomeprazole with methotrexate primarily at high dose may elevate and prolong serum methotrexate concentrations and/or its metabolite hydroxymethotrexate, which may lead to methotrexate toxicities. In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was coadministered with PPIs but was not observed when methotrexate was coadministered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted. Among adults who received high-dose methotrexate (median dose of 3500 mg/m2, range of 1000-5000 mg/m2), coadministration of PPIs such as omeprazole, lansoprazole, or rabeprazole was identified as a risk factor for delayed methotrexate elimination with an OR of 2.65 (95% confidence interval 1.036.82). The interaction may be partially explained by the inhibitory effects of PPIs on breast cancer resistance protein (BCRP, ABCG2) -mediated methotrexate transport. Altered methotrexate elimination may not be present or problematic among patients who receive lower methotrexate doses. For example, coadministration of lansoprazole 30 mg daily and naproxen 500 mg twice daily for 7 days to recipients of stable oral methotrexate doses (7.515 mg/week) for a minimum of 3 months did not alter the pharmacokinetic profile of either methotrexate or 7-hydroxymethotrexate. Specifically, the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries.
    Methscopolamine: (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.
    Methyclothiazide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Methylphenidate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
    Metolazone: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    Modafinil: (Minor) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Modafinil induces hepatic cytochrome P-450 enzyme CYP3A4 but significantly inhibits CYP2C19; both of these enzymes are responsible for the metabolism of PPIs. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. If modafinil 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, or for signs of PPI side effects.
    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.
    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: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    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.
    Oxybutynin: (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.
    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.
    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.
    Phenytoin: (Moderate) Omeprazole can exhibit a dose-dependent inhibition of the hepatic cytochrome P-450 enzyme system, specifically CYP2C19. Because of this, omeprazole can interfere with the clearance of drugs metabolized via this pathway, such as phenytoin or fosphenytoin, resulting in increased phenytoin plasma concentrations. Clinical data do not exist, but an interaction is possible based on the known pathways of elimination. Patients should be monitored carefully for signs of increased drug effect if omeprazole is used with these drugs. In addition, some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Phenytoin induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If phenytoin 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.
    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.
    Ponatinib: (Major) Avoid concomitant use of ponatinib with omeprazole unless the benefit outweighs the possible risk of ponatinib underexposure. Ponatinib displays pH-dependent aqueous solubility; therefore, concomitant use of ponatinib and omeprazole may result in decreased bioavailability and plasma exposure of ponatinib. If the use of both agents is necessary, monitor patients for signs of reduced efficacy.
    Posaconazole: (Major) The concurrent use of posaconazole 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 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.
    Propantheline: (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.
    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.
    Rifabutin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Rifampin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Rifamycins: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Rifapentine: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin 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.
    Rilpivirine: (Severe) 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: (Major) 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.
    Scopolamine: (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.
    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.
    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.
    Sorafenib: (Minor) Sorafenib displays pH-dependent aqueous solubility; therefore, concomitant use of sorafenib and agents that increase the gastric pH, such as proton pump inhibitors (PPIs), may result in decreased plasma exposure of sorafenib. However, there was no clinically significant change in sorafenib exposure following a single oral dose of sorafenib administered after 5 days of omeprazole 40 mg/day. No sorafenib dosage adjustment is necessary.
    St. John's Wort, Hypericum perforatum: (Major) Coadministration of St. John's Wort, Hypericum perforatum (300 mg three times daily) for 14 days with a one time dose of omeprazole (20 mg) on day 15 resulted in decreased omeprazole plasma concentrations in healthy subjects. Omeprazole AUC was reduced by approximately 40% in both poor and extensive metabolizers of CYP2C19. The clinical significance of this interaction is not clear; however, due to variations in the amounts of active ingredient in herbal products, the magnitude of this interaction and the resultant clinical effect may vary. St. John's Wort induces both CYP3A4 and CYP2C19 dependent metabolism of omeprazole. Since, proton pump inhibitors (PPIs) are primary substrates of the CYP2C19 enzyme, patients taking St. John's Wort concomitantly with a PPI should be monitored for PPI efficacy.
    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 the serum concentrations of tacrolimus.
    Telithromycin: (Minor) Concentrations of omeprazole may be increased with concomitant use of telithromycin. Omeprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Thiazide diuretics: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Thiopental: (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.
    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) In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. It is expected that the formation of CYP450 enzymes could be normalized during tocilizumab receipt. In clinical trials of patients taking both omeprazole and tocilizumab, a decrease in omeprazole exposure (AUC) was noted. One week after a single tocilizumab dose, a 12 to 28% decrease in omeprazole exposure occurred. Use caution when using tocilizumab in combination with CYP-metabolized drugs where a decrease in effectiveness is undesirable.
    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) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    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.
    Trihexyphenidyl: (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.
    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.
    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) Omeprazole (CYP2C19 inhibitor) can prolong the elimination of warfarin, particularly R-warfarin which is partially metabolized by CYP2C19. The combined use of omeprazole and warfarin has been associated with reports of increased INR and prothrombin time (PT). In addition, post-marketing reports of the combination of esomeprazole and warfarin have indicated elevations in PT. There have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving other proton pump inhibitors (PPIs) (including esomeprazole, lansoprazole, rabeprazole, and pantoprazole and warfarin concomitantly. It is prudent to monitor the INR more closely if these agents are combined with warfarin.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of omeprazole in pregnant women. Current data, including epidemiologic data and an expert review by TERIS (the Teratogen Information System), fail to demonstrate an increased risk of major congential malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Animal reproductive studies have been conducted with omeprazole and esomeprazole. Rats and rabbits dosed with omeprazole experienced 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 (BSA) for a 60 kg person. Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole in rats and rabbits during organogenesis with doses about 68 and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole, based on BSA for a 60 kg person. However, changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses >= 33.6 times an oral human dose of 40 mg. Although animal studies are not always predictive of human effects, because of the observed effect at high doses of esomeprazole magnesium on developing bone in rat studies, omeprazole use in pregnancy should be limited. 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. Use during pregnancy should be limited to cases where the benefit to the mother outweighs any potential risk to the fetus. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use. Self-medication with omeprazole (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 exposure to omeprazole on the breastfed infant or on milk production have not been confirmed. One study reported the use of omeprazole in late gestation and continued use through lactation. During breast feeding, the mother fed her infant prior to a dose of 20 mg of omeprazole. Samples of expressed milk were analyzed and a maximum daily exposure to the infant was calculated to be 4 mcg (based on the consumption of 200 ml of milk/day). Based on the above case, a maximum dose of 3 mcg/kg daily or about 0.9% of the maternal weight-adjusted dosage would be delivered to an exclusively breast fed infant based on a milk consumption of 150 ml/kg/day. For comparison, doses of 0.5 mg/kg PO once daily for 6 weeks have been studied in during infancy (age 2.9 +/- 0.9 months) for peptic esophagitis. Nevertheless, the methods of collection and calculations of the sampled milk were not clearly defined in this case report. Milk expressed early in feeding contains less lipid content as compared to milk expressed towards the end of feeding. Taking into account that omeprazole is a lipid soluble drug, milk expressed and analyzed early on in feeding may not accurately reveal the true exposure to a feeding infant. Potentially serious adverse reactions may occur with the use of omeprazole during breast-feeding, including suppression of gastric acid secretion in the nursing infant. Therefore, caution should exercised when omeprazole is used during breast feeding. Alternative therapies for consideration include antacids and H2 blockers.

    MECHANISM OF ACTION

    Mechanism of Action: 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.

    PHARMACOKINETICS

    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.
     
    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 does not appear to inhibit CYP3A4 (evaluated via erythromycin breath test). In vitro, it induces CYP1A2. 

    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.