Omeprazole and sodium bicarbonate

Drugs for which gastric pH can affect bioavailability

Because of its inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts). In the clinical efficacy trials, antacids were used concomitantly with the administration of omeprazole.

Drugs metabolized by cytrochrom P450 (CYP)

Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin may need to be monitored for increases in INR and prothrombin time.

Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system (eg, cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with Omeprazole and Sodium Bicarbonate.

Concomitant administration of omeprazole and voriconazole (a combined inhibitor of CYP2C19 and CYP3A4) resulted in more than doubling of the omeprazole exposure. Dose adjustment of omeprazole is nto normally required. When voriconazole (400 mg every 12 hours for one day, then 200 mg for 6 days) was given with omeprazole (40 mg once daily for 7 days) to healthy subjects, it significantly increased the steady-state Cmax of AUC0-24 of omeprazole, an average of 2 times (90% CI: 1.8, 2.6) and 4 times (90% CI: 3.3, 4.4) respectively as compared to when omeprazole was given without voriconazole.

Drugs known to induce CYP2C19 or CYP3A4 (such as rifampin) may lead to decreased omperazole serum levels. In a cross-over study in 12 healthy male subjects, St, John's wort (300 mg three times daily for 14 days), an inducer of CYP3A4, decreased the systemic exposure of omeprazole in CYP2C19 poor metabolisers (Cmax and AUC decreased by 49.6% and 43.9%, respectively). Avoid concomitant use of St. John's Wort or rifampin with omeprazole.

Antiretroviral Agents

Concomitant administration of atazanavir and proton pump inhibitors is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.

Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19. For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole. Following multiple doses of nelfinavir (1250 mg, twice daily), and omeprazole (40 mg, daily), AUC was decreased by 36% and 92%, C max by 37% and 89% and Cmin by 39% and 75% respectively for nelfinavir and M8. Following multiple doses of atazanavir (400 mg, daily) and omeprazole (40 mg, daily, 2 hours before atazanavir), AUC was decreased by 94%, Cmax by 96%, and Cmin by 95%. Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is therefore not recommended.

Increased concentration of saquinavir

For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported with an increase in AUC by 82%, in Cmax by 75% and in Cmin by 106% following multiple dosing of saquinavir/ritonavir (1000/100 mg) twice daily for 15 days with omeprazole 40 mg daily co-administered days 11 to 15. Dose reduction of saquinavir should be considered from the safety perspective for individual patients. There are also some antiretroviral drugs of which unchanged serum levels have been reported when given with omeprazole.

Combination Therapy with Clarithromycin

Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interaction [see Warnings and Precautions in prescribing information for clarithromycin]. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs [see Contraindication in prescribing information for clarithromycin].

Clopidogrel

Omeprazole is an inhibitor of CYP2C19 enzyme. Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition Avoid concomitant administration of Omeprazole and Sodium Bicarbonate for oral suspension with clopidogrel. When using Omeprazole and Sodium Bicarbonate for oral suspension consider use of alternative anti-platelet therapy [see Pharmacokinetics (12.3)].

Tacrolimus

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

Interactions With Investigations of Neuroendocrine Tumors

Drug-induced decrease in gastric acidity results in enterochromaffin-like cell hyperplasia and increased Chromogranin A levels which may interfere with investigations for neuroendocrine tumors. [see Clinical Pharmacology (12)].

Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose, see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted. (See Warnings and Precautions ( 5.7).

Pregnancy

There are no adequate and well-controlled studies on the use of omeprazole in pregnant women. The vast majority of reported experience with omeprazole during human pregnancy is first trimester exposure and the duration of use is rarely specified, eg, intermittent vs. chronic. An expert review of published data on experiences with omeprazole use during pregnancy by TERIS – the Teratogen Information System – concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as fair). 1

Three epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy to the frequency of abnormalities among infants of women exposed to H2-receptor antagonists or other controls. A population-based prospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. 2 In utero exposure to omeprazole was not associated with increased risk of any malformation (odds ratio 0.82, 95% CI 0.50-1.34), low birth weight or low Apgar score. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole exposed infants than the expected number in the normal population. The author concluded that both effects may be random.

A retrospective cohort study reported on 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester (134 exposed to omeprazole) .3 The overall malformation rate was 4.4% (95% CI 3.6-5.3) and the malformation rate for first trimester exposure to omeprazole was 3.6% (95% CI 1.5-8.1). The relative risk of malformations associated with first trimester exposure to omeprazole compared with nonexposed women was 0.9 (95% CI 0.3-2.2). The study could effectively rule out a relative risk greater than 2.5 for all malformations. Rates of preterm delivery or growth retardation did not differ between the groups.

A controlled prospective observational study followed 113 women exposed to omeprazole during pregnancy (89% first trimester exposures) 4. The reported rates of major congenital malformations was 4% for the omeprazole group, 2% for controls exposed to nonteratogens, and 2.8% in disease-paired controls (background incidence of major malformations 1-5%). Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight did not differ between the groups. The sample size in this study has 80% power to detect a 5-fold increase in the rate of major malformation.

Several studies have reported no apparent adverse short term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia.

Reproduction studies conducted with omeprazole in rats at oral doses up to 28 times the human dose of 40 mg/day (based on body surface area) and in rabbits at doses up to 28 times the human dose (based on body surface area) did not show any evidence of terogenicity. In pregnant rabbits, omeprazole at doses about 2.8 to 28 times the human dose of 40mg/day, (based on body surface area) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 2.8 to 28 times the human dose (based on body surface area), dose-related embryo/fetal toxicity and postnatal developmental toxicity occurred in offspring. [See Animal Toxicology and/or Pharmacology ( 13.2)].

There are no adequate and well-controlled studies in pregnant women. Because animal studies and studies in humans cannot rule out the possibility of harm, Omeprazole and Sodium Bicarbonate should be used during pregnancy only if the potential benefit to pregnant women justifies the potential risk to the fetus.

Nursing Mothers

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

Pediatric Use

Safety and effectiveness of Omeprazole and Sodium Bicarbonate have not been established in pediatric patients less than 18 years of age.

Geriatric Use

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

Pharmacokinetic studies with buffered omeprazole have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young subjects). The plasma half-life averaged one hour, about the same as that in nonelderly, healthy subjects taking Omeprazole and Sodium Bicarbonate. However, no dosage adjustment is necessary in the elderly. (See CLINICAL PHARMACOLOGY ( 12.3)]

Hepatic Impairment

Consider dose reduction, particularly for maintenance of healing erosive esophagitis. [See Clinical Pharmacology ( 12.3)]

Renal Impairment

No dose reduction is necessary. [See Clinical Pharmacology ( 12.3)]

Asian Population

Recommended dose reduction, particularly for maintenance of healing of erosive esophagitis. [See Clinical Pharmacology ( 12.3)]

Omeprazole and Sodium Bicarbonate for oral suspension is a combination of omeprazole, a proton-pump inhibitor, and sodium bicarbonate, an antacid. Omeprazole is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2‑pyridinyl)methyl]sulfinyl]-1 H-benzimidazole, a racemic mixture of two enantiomers that inhibits gastric acid secretion. Its structural formula is C17H19N3O3S, with a molecular weight of 345.42. The structural formula is:

Omeprazole is a white to off-white crystalline powder which melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.

Omeprazole and Sodium Bicarbonate is supplied as unit dose packets for oral suspension. Packets for oral suspension contain 40 mg or 20 mg of omeprazole and 1680 mg of sodium bicarbonate with the following excipients: xylitol, xanthan gum, sucralose powder, sodium bicarbonate, peach powder, sucrose and peppermint flavor.

Duodenal Ulcer Disease

Active Duodenal Ulcer – In a multicenter, double-blind, placebo controlled study of 147 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 2 and 4 weeks was significantly higher with omeprazole 20 mg once a day than with placebo (p ≤ 0.01). (See Table 7.)

Complete daytime and nighttime pain relief occurred significantly faster (p ≤ 0.01) in patients treated with omeprazole 20 mg than in patients treated with placebo. At the end of the study, significantly more patients who had received omeprazole had complete relief of daytime pain (p ≤ 0.05) and nighttime pain (p ≤ 0.01).

In a multicenter, double-blind study of 293 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 4 weeks was significantly higher with omeprazole 20 mg once a day than with ranitidine 150 mg b.i.d. (p < 0.01). (See Table 7)

Healing occurred significantly faster in patients treated with omeprazole than in those treated with ranitidine 150 mg b.i.d. (p < 0.01).

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically documented duodenal ulcer, 40 mg and 20 mg of omeprazole were compared to 150 mg b.i.d. of ranitidine at 2, 4 and 8 weeks.

At 2 and 4 weeks both doses of omeprazole were statistically superior (per protocol) to ranitidine, but 40 mg was not superior to 20 mg of omeprazole, and at 8 weeks there was no significant difference between any of the active drugs. (See Table 8)

Gastric Ulcer

In a U.S. multicenter, double-blind study of omeprazole 40 mg once a day, 20 mg once a day, and placebo in 520 patients with endoscopically diagnosed gastric ulcer, the following results were obtained. (See Table 9)

Table 9: Treatment of Gastric Ulcer % of Patients Healed (All Patients Treated)

For the stratified groups of patients with ulcer size less than or equal to 1 cm, no difference in healing rates between 40 mg and 20 mg was detected at either 4 or 8 weeks. For patients with ulcer size greater than 1 cm, 40 mg was significantly more effective than 20 mg at 8 weeks.

In a foreign, multinational, double-blind study of 602 patients with endoscopically diagnosed gastric ulcer, omeprazole 40 mg once a day, 20 mg once a day, and ranitidine 150 mg twice a day were evaluated. (See Table 10.)

Gastroesophageal Reflux Disease (GERD)

A placebo controlled study was conducted in Scandinavia to compare the efficacy of omeprazole 20 mg or 10 mg once daily for up to 4 weeks in the treatment of heartburn and other symptoms in GERD patients without erosive esophagitis. Results are shown in Table 11.

In a U.S. multicenter double-blind placebo controlled study of 40 mg or 20 mg of omeprazole in patients with symptoms of GERD and endoscopically diagnosed erosive esophagitis of grade 2 or above, the percentage healing rates (per protocol) were as shown in Table 12.

In this study, the 40 mg dose was not superior to the 20 mg dose of omeprazole in the percentage healing rate. Other controlled clinical trials have also shown that omeprazole is effective in severe GERD. In comparisons with histamine H2-receptor antagonists in patients with erosive esophagitis, grade 2 or above, omeprazole in a dose of 20 mg was significantly more effective than the active controls. Complete daytime and nighttime heartburn relief ocurred significantly faster (p < 0.01) in patients treated with omeprazole than in those taking placebo or histamine H2-receptor antagonists.

In this and five other controlled GERD studies, significantly more patients taking 20 mg omeprazole (84%) reported complete relief of GERD symptoms than patients receiving placebo (12%).

Long Term Maintenance Treatment of Erosive Esophagitis

In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of omeprazole were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of erosive esophagitis are shown in Table 13.

In an international multicenter double-blind study, omeprazole 20 mg daily and 10 mg daily were compared to ranitidine 150 mg twice daily in patients with endoscopically confirmed healed esophagitis. Table 15 provides the results of this study for maintenance of healing of erosive esophagitis.

In patients who initially had grades 3 or 4 erosive esophagitis, for maintenance after healing 20 mg daily of omeprazole was effective, while 10 mg did not demonstrate effectiveness.

Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients

A double-blind, multicenter, randomized, non-inferiority clinical trial was conducted to compare Omeprazole and Sodium Bicarbonate for oral suspension 40 mg/1680 mg and I.V. cimetidine for the reduction of risk of upper gastrointestinal (GI) bleeding in critically ill patients (mean APACHE II score = 23.7). The primary endpoint was significant upper GI bleeding defined as bright red blood which did not clear after adjustment of the nasogastric tube and a 5 to 10 minute lavage, or persistent Gastroccult® positive coffee grounds for 8 consecutive hours which did not clear with 100 cc lavage. Omeprazole/sodium bicarbonate oral suspension 40 mg/1680 mg (two doses administered 6 to 8 hours apart on the first day via orogastric or nasogastric tube, followed by 40 mg q.d. thereafter) was compared to continuous I.V. cimetidine (300 mg bolus, and 50 to 100 mg/hr continuously thereafter) for up to 14 days (mean = 6.8 days). A total of 359 patients were studied, age range 16 to 91 (mean = 56 yrs), 58.5% were males, and 64% were Caucasians. The results of the study showed that Omeprazole and Sodium Bicarbonate was non-inferior to I.V. cimetidine, 10/181(5.5%) patients in the cimetidine group vs. 7/178 (3.9%) patients in the Omeprazole and Sodium Bicarbonate group experienced clinically significant upper GI bleeding.

Note: Both strengths of Zegerid capsule and powder for oral suspension have identical sodium bicarbonate content, respectively. Do not substitute two 20 mg capsules/packets for one 40 mg dose.

Active duodenal ulcer: Oral: 20 mg once daily for 4 to 8 weeks

Gastric ulcers: Oral: 40 mg once daily for 4 to 8 weeks

Heartburn (OTC labeling): Oral: 20 mg once daily for 14 days. Do not take for >14 days or more often than every 4 months, unless instructed by healthcare provider.

Symptomatic GERD: Oral: 20 mg once daily for up to 4 weeks

Erosive esophagitis: Oral: 20 mg once daily for 4 to 8 weeks; maintenance of healing: 20 mg once daily for up to 12 months total therapy (including treatment period of 4 to 8 weeks)

Risk reduction of upper GI bleeding in critically ill patients (Zegerid powder for oral suspension): Oral:

Loading dose: Day 1: 40 mg every 6 to 8 hours for two doses

Maintenance dose: 40 mg daily for up to 14 days; therapy >14 days has not been evaluated

Refer to adult dosing.

No dosage adjustment necessary.

A 2 mg/mL oral suspension may be made with omeprazole-sodium bicarbonate powder and water. Pour the contents of six 20 mg omeprazole-sodium bicarbonate packets into a glass mortar. Add 30 mL water to the powder and mix to a uniform paste; mix while adding water in incremental proportions to almost 60 mL; transfer to a 60 mL bottle, rinse mortar with water, and add sufficient quantity of water to make 60 mL. Label "shake well" and "refrigerate". Stable for 45 days refrigerated.

Take 1 hour before a meal. Contains sodium; use with caution in patients on sodium-restricted diets.

AcetaZOLAMIDE: May enhance the adverse/toxic effect of Sodium Bicarbonate. Specifically, the risk of renal calculus formation may be increased. Monitor therapy

Alpha-/Beta-Agonists (Indirect-Acting): Alkalinizing Agents may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Amantadine: Alkalinizing Agents may increase the serum concentration of Amantadine. Monitor therapy

Amphetamines: Alkalinizing Agents may decrease the excretion of Amphetamines. Consider therapy modification

Antihepaciviral Combination Products: May decrease the serum concentration of Omeprazole. Monitor therapy

Antipsychotic Agents (Phenothiazines): Antacids may decrease the absorption of Antipsychotic Agents (Phenothiazines). Monitor therapy

Atazanavir: Antacids may decrease the absorption of Atazanavir. Consider therapy modification

Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: See full drug interaction monograph for details. Consider therapy modification

Bisacodyl: Antacids may diminish the therapeutic effect of Bisacodyl. Antacids may cause the delayed-release bisacodyl tablets to release drug prior to reaching the large intestine. Gastric irritation and/or cramps may occur. Consider therapy modification

Bismuth Subcitrate: Antacids may diminish the therapeutic effect of Bismuth Subcitrate. Management: Avoid administration of antacids within 30 minutes of bismuth subcitrate (tripotassium bismuth dicitrate) administration. Consider therapy modification

Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as antacids or H2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Consider therapy modification

Bosutinib: Antacids may decrease the serum concentration of Bosutinib. Management: Administer antacids more than 2 hours before or after bosutinib. Consider therapy modification

Calcium Polystyrene Sulfonate: Antacids may enhance the adverse/toxic effect of Calcium Polystyrene Sulfonate. The combined use of these two agents may result in metabolic alkalosis and/or loss of efficacy of the cation exchange resin. Management: To minimize this interaction, consider: a)separating doses by 2 or more hours; b)rectal administration of the exchange resin; or c)alternatives to antacids. Monitor for metabolic alkalosis and attenuation of CPS effects. Avoid magnesium hydroxide. Consider therapy modification

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. Monitor therapy

Captopril: Antacids may decrease the serum concentration of Captopril. Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cefditoren: Antacids may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy. If antacid therapy can not be avoided, separate dosing by several hours. Consider therapy modification

Cefditoren: Proton Pump Inhibitors may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Consider therapy modification

Cefpodoxime: Antacids may decrease the serum concentration of Cefpodoxime. Monitor therapy

Cefuroxime: Antacids may decrease the serum concentration of Cefuroxime. Management: Consider administering antacids and cefuroxime at least 2 hours apart. Consider therapy modification

Chloroquine: Antacids may decrease the serum concentration of Chloroquine. Management: Separate administration of antacids and chloroquine by at least 4 hours to minimize any potential negative impact of antacids on chloroquine bioavailability. Consider therapy modification

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

Citalopram: Omeprazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with omeprazole. Consider therapy modification

CloBAZam: Omeprazole may increase serum concentrations of the active metabolite(s) of CloBAZam. Monitor therapy

Clopidogrel: Omeprazole may diminish the antiplatelet effect of Clopidogrel. Omeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Clopidogrel labeling recommends avoiding concurrent omeprazole due to a possible decrease in clopidogrel effectiveness. Rabeprazole or pantoprazole may be lower-risk alternatives to omeprazole. Consider therapy modification

CloZAPine: Omeprazole may decrease the serum concentration of CloZAPine. Omeprazole may increase the serum concentration of CloZAPine. Monitor therapy

Corticosteroids (Oral): Antacids may decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Consider therapy modification

CycloSPORINE (Systemic): Omeprazole may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Cysteamine (Systemic): Antacids may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dabigatran Etexilate: Antacids may decrease the serum concentration of Dabigatran Etexilate. Management: Dabigatran etexilate Canadian product labeling recommends avoiding concomitant use with antacids for 24 hours after surgery. In other situations, administer dabigatran etexilate 2 hours prior to antacids. Monitor clinical response to dabigatran therapy. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates. Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: Proton Pump Inhibitors may decrease the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Proton Pump Inhibitors. Management: Seek alternatives to the proton pump inhibitor when possible. If concomitant therapy cannot be avoided, monitor for diminished effects of both drugs. Consider therapy modification

Darunavir: May decrease the serum concentration of Omeprazole. Monitor therapy

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Avoid combination

Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: Antacids may increase the absorption of Dexmethylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Elvitegravir: Antacids may decrease the serum concentration of Elvitegravir. Management: Separate administration of antacids and elvitegravir-containing products by at least 2 hours in order to minimize the risk for an interaction. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates. Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Avoid combination

Escitalopram: Omeprazole may increase the serum concentration of Escitalopram. Management: Monitor for increased escitalopram toxicity with concomitant use of omeprazole. Recommendations for management of this interaction found in product labeling may differ by country. Consult appropriate labeling. Consider therapy modification

Flecainide: Sodium Bicarbonate may diminish the arrhythmogenic effect of Flecainide. Sodium Bicarbonate may increase the serum concentration of Flecainide. Monitor therapy

Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Monitor therapy

Fosinopril: Antacids may decrease the serum concentration of Fosinopril. Management: The US and Canadian fosinopril manufacturer labels recommend separating the doses of antacids and fosinopril by 2 hours. Consider therapy modification

Fosphenytoin: Omeprazole may increase the serum concentration of Fosphenytoin. Fosphenytoin may decrease the serum concentration of Omeprazole. Monitor therapy

Gabapentin: Antacids may decrease the serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after antacid administration. Monitor patients closely for evidence of reduced response to gabapentin therapy when both of these drugs are being used. Consider therapy modification

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Consider therapy modification

Gefitinib: Antacids may decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of an antacid, and closely monitor clinical response to gefitinib. Consider therapy modification

HMG-CoA Reductase Inhibitors: Antacids may decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Hyoscyamine: Antacids may decrease the serum concentration of Hyoscyamine. Management: Administer immediate release hyoscyamine before meals and antacids after meals when these agents are given in combination. Consider therapy modification

Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Monitor therapy

Iron Salts: Antacids may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Isoniazid: Antacids may decrease the absorption of Isoniazid. Consider therapy modification

Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Consider therapy modification

Itraconazole: Antacids may decrease the serum concentration of Itraconazole. Management: Administer itraconazole at least 1 hour after and 2 hours before administration of any antacids. Itraconazole oral suspension may be less sensitive to the effects of decreased gastric acidity. Consider therapy modification

Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Proton Pump Inhibitors. Consider therapy modification

Ketoconazole (Systemic): Antacids may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any antacid product. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Consider therapy modification

Lanthanum: Antacids may diminish the therapeutic effect of Lanthanum. Consider therapy modification

Ledipasvir: Antacids may decrease the serum concentration of Ledipasvir. Management: Separate the administration of ledipasvir and antacids by 4 hours. Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: PPI doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Administration with higher doses of PPIs, 2 hours after a PPI, or in combination with food and PPIs may reduce ledipasvir bioavailability. Consider therapy modification

Lithium: Sodium Bicarbonate may increase the excretion of Lithium. Monitor therapy

Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. Monitor therapy

Mecamylamine: Alkalinizing Agents may increase the serum concentration of Mecamylamine. Monitor therapy

Memantine: Alkalinizing Agents may increase the serum concentration of Memantine. Monitor therapy

Mesalamine: Antacids may diminish the therapeutic effect of Mesalamine. Antacid-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Avoid concurrent administration of antacids with sustained-release mesalamine products. Separating antacid and mesalamine administration, and/or using lower antacid doses may be adequate means of avoiding this interaction. Consider therapy modification

Mesalamine: Proton Pump Inhibitors may diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Consider therapy modification

Methenamine: Antacids may diminish the therapeutic effect of Methenamine. Consider therapy modification

Methotrexate: Proton Pump Inhibitors may increase the serum concentration of Methotrexate. Monitor therapy

Methylphenidate: Antacids may increase the absorption of Methylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Antacids may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, antacids may decrease the absorption of orally administered iron. Management: Separate dosing of oral iron-containing multivitamin preparations and antacids by as much time as possible in order to minimize impact on therapeutic efficacy of the iron preparation. Consider therapy modification

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Monitor therapy

Nalmefene: Omeprazole may decrease the serum concentration of Nalmefene. Monitor therapy

Nelfinavir: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Proton Pump Inhibitors may decrease the serum concentration of Nelfinavir. Avoid combination

Neratinib: Proton Pump Inhibitors may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Avoid combination

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Consider therapy modification

Nilotinib: Antacids may decrease the serum concentration of Nilotinib. Management: Separate the administration of nilotinib and any antacid by at least 2 hours whenever possible in order to minimize the risk of a significant interaction. Consider therapy modification

PAZOPanib: Proton Pump Inhibitors may decrease the serum concentration of PAZOPanib. Avoid combination

PenicillAMINE: Antacids may decrease the serum concentration of PenicillAMINE. Consider therapy modification

Phenytoin: May decrease the serum concentration of Omeprazole. Omeprazole may increase the serum concentration of Phenytoin. Monitor therapy

Phosphate Supplements: Antacids may decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate administration. Separating administer of oral phosphate supplements from antacid administration by as long as possible may minimize the interaction. Exceptions: Sodium Glycerophosphate Pentahydrate. Consider therapy modification

Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Consider therapy modification

Potassium Phosphate: Antacids may decrease the serum concentration of Potassium Phosphate. Management: Consider separating administration of antacids and oral potassium phosphate by at least 2 hours to decrease risk of a significant interaction. Consider therapy modification

QuiNIDine: Antacids may decrease the excretion of QuiNIDine. Monitor therapy

QuiNINE: Alkalinizing Agents may increase the serum concentration of QuiNINE. Monitor therapy

Raltegravir: Proton Pump Inhibitors may increase the serum concentration of Raltegravir. Monitor therapy

RifAMPin: May decrease the serum concentration of Omeprazole. Avoid combination

Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Avoid combination

Riociguat: Antacids may decrease the serum concentration of Riociguat. Management: Separate the administration of antacids and riociguat by at least 1 hour in order to minimize any potential interaction. Consider therapy modification

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Avoid combination

Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Secretin: Proton Pump Inhibitors may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of proton pump inhibitors (PPIs) and secretin, and discontinue PPIs several weeks prior to secretin administration, with the duration of separation determined by the specific PPI. See full monograph for details. Consider therapy modification

Sotalol: Antacids may decrease the serum concentration of Sotalol. Management: Avoid simultaneous administration of sotalol and antacids. Administer antacids 2 hours after sotalol. Consider therapy modification

St John's Wort: May decrease the serum concentration of Omeprazole. Avoid combination

Sulpiride: Antacids may decrease the serum concentration of Sulpiride. Management: Separate administration of antacids and sulpiride by at least 2 hours in order to minimize the impact of antacids on sulpiride absorption. Consider therapy modification

Tacrolimus (Systemic): Proton Pump Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose adjustment may be required. Rabeprazole, pantoprazole, or selected H2-receptor antagonists (i.e., ranitidine or famotidine) may be less likely to interact. Genetic testing may predict patients at highest risk. Consider therapy modification

Tetracycline Derivatives: Antacids may decrease the absorption of Tetracycline Derivatives. Consider therapy modification

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Monitor therapy

Trientine: Antacids may decrease the absorption of Trientine. Management: Separate trientine dosing from other oral drugs (eg, antacids) by at least 1 hour. Monitor for decreased therapeutic effects of trientine if an antacid is initiated/dose increased, or increased effects if an antacid is discontinued/dose decreased. Consider therapy modification

Velpatasvir: Proton Pump Inhibitors may decrease the serum concentration of Velpatasvir. Avoid combination

Vitamin K Antagonists (eg, warfarin): Omeprazole may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Management: In patients receiving omeprazole 40 mg/day or greater, reduce omeprazole dose by half when initiating voriconazole. Monitor therapy

Omeprazole 20 mg orally once a day
-Duration of therapy: Up to 14 days (Over-the-Counter [OTC] formulations) and up to 4 weeks (prescription formulations)

Comments:
-The OTC formulation course of treatment may be repeated every 4 months as necessary.
-The full effect of treatment may not be reached for up to 4 days.

Uses:
-Treatment of symptomatic gastroesophageal reflux disease (GERD) without esophageal erosions
-Treatment of frequent heartburn occurring at least 2 days a week

Data not available

Following an oral dose of 20 mg, the peak concentration of omeprazole in breast milk was less than 7% of the mother's peak serum concentration, or a dose of approximately 0.004 mg of omeprazole in 200 mL of milk.

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes (omeprazole); Data not available (sodium bicarbonate) Excreted into animal milk: Data not available (sodium bicarbonate) Comment: This drug may cause serious adverse events and/or tumorigenicity in breastfed neonates and infants.