Zegerid

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Zegerid

Classes

Proton Pump Inhibitors/PPIs

Administration
Oral Administration

Administer on an empty stomach, at least 60 minutes before meals. If given once daily, administer before the first meal of the day.

Oral Solid Formulations

Immediate-release capsules:
Swallow whole; do not open, crush, or chew. Administer with a glass of water at least 1 hour before eating.
Do not administer with any other liquid besides water
Do not open capsules and sprinkle the contents into food.
The 20 mg and 40 mg capsules each contain 1,100 mg sodium bicarbonate per capsule; thus two capsules of 20 mg are not equivalent to, and should not be substituted for, one 40 mg capsule.

Oral Liquid Formulations

Immediate-release oral suspension packets:
Prepare the suspension by emptying packet contents into a small cup containing 1 to 2 tablespoons (15 to 30 mL) of water; do not use other liquids or foods.
Stir the mixture well and administer immediately.
Refill the cup with water and have the patient drink.
The 20 mg and 40 mg suspension packets each contain 1,680 mg sodium bicarbonate; thus 2 packets of 20 mg are not equivalent to, and should not be substituted for, one 40 mg packet.
Administration to patients with a gastric tube: Use the oral suspension. For patients receiving continuous gastric tube feeding, suspend the enteral feeding approximately 3 hours before and 1 hour after administration. For administration via nasogastric (NG) or orogastric (OG) tube, prepare the oral suspension with approximately 20 mL of water only, do not use other liquids or foods. Stir the mixture well and administer immediately, using an appropriately-sized syringe to instill the suspension into the tube. After administration, flush the tube with an additional 20 mL of plain water.
Immediate-release oral suspension kit:
Prepare to reconstitute the suspension by holding the neck of the bottle containing the omeprazole powder, and tapping all four of the bottom edges on a hard surface to loosen the powder.
Shake the diluent bottle containing sodium bicarbonate for a few seconds. Open the diluent bottle and transfer about one-third of the contents into the bottle containing omeprazole powder, replace the omeprazole powder cap, and shake the bottle vertically for approximately 30 seconds.
Add a second one-third of the diluent into the omeprazole powder bottle and shake the bottle vigorously for approximately 30 seconds.
Add the remaining diluent into the omeprazole powder bottle. Allow diluent to drain into the omeprazole powder bottle for 10 seconds and shake the omeprazole bottle vigorously for approximately 30 seconds.
The reconstituted suspension contains 40 mg of omeprazole per 20 mL and should be pink to red and hazy.
Instruct the patient to shake the reconstituted suspension well before each use and to use an oral dosing device that measure the appropriate volume.
Administration to patients with a gastric tube: Use the oral suspension. For patients receiving continuous gastric tube feeding, suspend the enteral feeding approximately 3 hours before and 1 hour after administration. For administration via nasogastric (NG) or orogastric (OG) tube, prepare the oral suspension in the same process as above. Shake the mixture well and administer 20mL using an appropriately-sized syringe to instill the suspension into the tube. After administration, flush the tube with 20 mL of plain water.

Adverse Reactions
Severe

pancreatitis / Delayed / Incidence not known
hepatic encephalopathy / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
optic atrophy / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
renal failure / Delayed / Incidence not known

Moderate

constipation / Delayed / 1.5-4.5
elevated hepatic enzymes / Delayed / 1.7-1.7
candidiasis / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known
pernicious anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
confusion / Early / Incidence not known
hallucinations / Early / Incidence not known
depression / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
metabolic alkalosis / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
fluid retention / Delayed / Incidence not known
angina / Early / Incidence not known
palpitations / Early / Incidence not known
hypertension / Early / Incidence not known
colitis / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
glycosuria / Early / Incidence not known
hematuria / Delayed / Incidence not known
pyuria / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known

Mild

headache / Early / 2.9-6.9
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
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
xerostomia / Early / Incidence not known
stool discoloration / Delayed / Incidence not known
gastric polyps / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
leukocytosis / Delayed / Incidence not known
drowsiness / Early / Incidence not known
abnormal dreams / Early / Incidence not known
dysesthesia / Delayed / Incidence not known
tremor / Early / Incidence not known
agitation / Early / Incidence not known
paresthesias / Delayed / Incidence not known
insomnia / Early / Incidence not known
anxiety / Delayed / Incidence not known
vertigo / Early / Incidence not known
epistaxis / Delayed / Incidence not known
fever / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
diplopia / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
xerophthalmia / Early / Incidence not known
weight gain / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
increased urinary frequency / Early / Incidence not known
testicular pain / Early / Incidence not known
gynecomastia / Delayed / Incidence not known

Common Brand Names

KONVOMEP, OmePPi, Zegerid, Zegerid Powder

Dea Class

Rx, OTC

Description

Oral immediate-release proton pump inhibitor (PPI) combined with a sodium bicarbonate buffer
Prescription products used for GERD, erosive esophagitis, gastric and duodenal ulcer, and stress ulcer prophylaxis in critically ill patients
Nonprescription products used for short-term use (14 days) to treat frequent heartburn

Dosage And Indications
For the treatment of active duodenal ulcer. Oral dosage Adults

20 mg PO once daily for up to 4 weeks. Some patients may require an additional 4 weeks of therapy.

For the short-term treatment of active benign gastric ulcer. Oral dosage Adults

40 mg PO once a day 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 daily doses were observed.

For the treatment of gastroesophageal reflux disease (GERD). For symptomatic treatment of non-erosive GERD. Oral dosage Adults

20 mg PO once daily given 60 minutes before first meal of the day, for up to 4 weeks. Most patients respond within 4 weeks. Some patients may require an additional 4 weeks of therapy. Per treatment 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 increase to 20 mg PO twice daily or consider a switch to a different PPI. Refer nonresponders for further evaluation. Consider maintenance therapy for patients who continue to have symptoms after PPI discontinuation; use the lowest effective dose and consider on demand or intermittent therapy and regularly assess of the need for continued PPI therapy. Alternatively, step down maintenance therapy to an H2-blocker is acceptable.

For nocturnal acid breakthrough†. Oral dosage Adults

40 mg once daily at bedtime or 20 to 40 mg PO twice daily (breakfast and bedtime). After repeated once-daily dosing of omeprazole; sodium bicarbonate 40 mg suspension or pantoprazole 40 mg delayed-release tablets, significantly fewer patients experienced nocturnal acid breakthrough (NAB) with omeprazole taken at bedtime than after pantoprazole taken before dinner (53% vs. 78%, respectively). Additionally, the percentages of patients with NAB after twice daily dosing of omeprazole 20 mg, omeprazole 40 mg, and pantoprazole 40 mg were 46.7%, 11.8%, and 70.6%, respectively.

For the treatment of erosive esophagitis (erosive GERD). Oral dosage Adults

20 mg PO once daily (60 minutes before first meal of the day) for 4 to 8 weeks. The efficacy of omeprazole; sodium bicarbonate used for longer than 8 weeks in patients with erosive esophagitis (EE) has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of EE or GERD symptoms, an additional 4 to 8 week course may be considered. Maintenance of healing: 20 mg PO once daily; periodically reassess need for continued PPI therapy.

For stress gastritis prophylaxis in critically ill patients. Oral dosage Adults

Initially, 40 mg PO, followed by 40 mg PO in 6 to 8 hours on day 1, then 40 mg PO once daily for up to 14 days. Use beyond 14 days has not been evaluated in critically ill patients. An evaluation comparing omeprazole; sodium bicarbonate oral suspension and IV cimetidine infusion for the prevention of upper GI bleeding found favorable results in the omeprazole-treated group.  The 14-day study showed that omeprazole; sodium bicarbonate suspension administered via gastric tube, compared to IV cimetidine 50 mg/hour (after 300 mg IV loading dose), reduced the incidence of clinically significant bleeding (3.9% vs. 5.5%, respectively) and overt bleeding (19.1% vs. 32%, respectively). Additionally, inadequate pH control, defined as 2 consecutive gastric pH determinations of less than 4, were reported in 18% of omeprazole-treated patients compared to 58% of IV cimetidine-treated patients (p value less than 0.001).

For the non-prescription treatment of frequent pyrosis (heartburn) that occurs 2 or more days a week. Oral dosage (e.g., Zegerid OTC capsules; containing omeprazole 20 mg/sodium bicarbonate 1,100 mg per capsule) Adults

1 capsule PO once daily for 14 days, taken in the morning before eating. It may take 1 to 4 days for full effect, although some people get complete relief of symptoms within 24 hours. A 14-day course may be repeated every 4 months. Patients who have symptoms for more than 14 days, or, need more than one course every 4 months should see a health care provider for evaluation.

For the treatment of eosinophilic esophagitis (EoE)†. Oral dosage Adults

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

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Avoid use of omeprazole; sodium bicarbonate in patients with hepatic impairment for the maintenance of healing of erosive esophagitis. In patients with hepatic impairment (Child-Pugh Class A, B, or C) exposure to omeprazole substantially increased compared to healthy subjects.

Renal Impairment

No dosage adjustments are needed.

Drug Interactions

Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib capsules and omeprazole; decreased acalabrutinib exposure occurred in a drug interaction study. Consider using the acalabrutinib tablet formlation or use an antacid or H2-blocker if acid suppression therapy is needed. Separate the administration of acalabrutinib capsules and antacids by at least 2 hours; give acalabrutinib capsules 2 hours before a H2-blocker. Acalabrutinib capsuel solubility decreases with increasing pH values. The AUC of acalabrutinib was decreased by 43% when acalabrutinib capsules were coadministered with omeprazole 40 mg/day for 5 days. (Moderate) Separate the administration of acalabrutinib capsules and antacids by at least 2 hours if these agents are used together. Acalabrutinib capsule solubility decreases with increasing pH values; therefore, coadministration may result in decreased acalabrutinib exposure and effectiveness. In healthy subjects, the AUC of acalabrutinib was decreased by 53% when acalabrutinib capsules were coadministered with another antacid.
Acetaminophen: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Aspirin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Caffeine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Chlorpheniramine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Codeine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Dextromethorphan: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Diphenhydramine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Hydrocodone: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Ibuprofen: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Oxycodone: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Phenylephrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Acetaminophen; Pseudoephedrine: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetazolamide: (Minor) Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation via calcium phosphate supersaturation.
Acrivastine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Adagrasib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with adagrasib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Albuterol; Budesonide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other 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. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated 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.
Alendronate: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
Alendronate; Cholecalciferol: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Alprazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the CYP450 system, such as alprazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Amlodipine; Atorvastatin: (Moderate) Concomitant administration of atorvastatin with antacids reduced the plasma concentrations of atorvastatin by approximately 35 percent. However, LDL-cholesterol reduction was not altered.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Amobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Amphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine Salts: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamines: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
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) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Apalutamide: (Major) Avoid concomitant use of apalutamide with omeprazole as omeprazole plasma concentrations may be decreased, reducing its efficacy. Omeprazole is a CYP3A and CYP2C19 substrate. Apalutamide is a strong inducer of both CYP3A and CYP2C19. Coadministration with apalutamide has been observed to decrease the overall exposure of omeprazole by 85%.
Aprepitant, Fosaprepitant: (Minor) Use caution if omeprazole and aprepitant are used concurrently and monitor for an increase in omeprazole-related adverse effects for several days after administration of a multi-day aprepitant regimen. Omeprazole is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of omeprazole. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Moderate) In vitro data indicate that armodafinil is an inhibitor of CYP2C19. In theory, dosage reductions may be required for drugs that are largely eliminated via CYP2C19 metabolism such as omeprazole during coadministration with armodafinil. A 40% increase in exposure of omeprazole was observed during coadministration with armodafinil. The clinical significance of this interaction is unknown.
Ascorbic Acid, Vitamin C: (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
Aspirin, ASA: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
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. (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Carisoprodol: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (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: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (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; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Dipyridamole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Atazanavir: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
Atazanavir; Cobicistat: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Major) It is recommended that antacids not be given at the some time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.
Atenolol; Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Atorvastatin: (Moderate) Concomitant administration of atorvastatin with antacids reduced the plasma concentrations of atorvastatin by approximately 35 percent. However, LDL-cholesterol reduction was not altered.
Atorvastatin; Ezetimibe: (Moderate) Concomitant administration of atorvastatin with antacids reduced the plasma concentrations of atorvastatin by approximately 35 percent. However, LDL-cholesterol reduction was not altered. (Minor) Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Atropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Atropine; Difenoxin: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Avanafil: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Azilsartan; Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Barbiturates: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Belladonna; Opium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with a proton pump inhibitor (PPI). Concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Coadministration with other PPIs has decreased belumosudil exposure by 47% to 80% in healthy subjects.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of omeprazole with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and omeprazole is a CYP2C19 inhibitor.
Bempedoic Acid; Ezetimibe: (Minor) Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Benzhydrocodone; Acetaminophen: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Benztropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
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. (Minor) The concomitant use of bisacodyl tablets with antacids can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid antacids 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: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (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: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Bisphosphonates: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
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. (Moderate) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and antacids may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and antacids by more than 2 hours.
Brompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Budesonide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other 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. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated 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: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other 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. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated 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; Glycopyrrolate; Formoterol: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other 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. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Bumetanide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Butabarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Butalbital; Acetaminophen: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Butalbital; Aspirin; 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. (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Cabotegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Cannabidiol: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Capecitabine: (Moderate) Use caution if treatment with a proton pump inhibitor (PPI) is necessary in patients taking capecitabine, as progression-free survival (PFS) and overall survival (OS) may be adversely affected. The mechanism of this potential interaction is unknown and data are conflicting. In a posthoc, retrospective, subgroup analysis of a phase 3 clinical trial in patients with advanced or metastatic gastroesophageal cancer, administration of a PPI was associated with a significant decrease in PFS and OS in patients treated with capecitabine plus oxaliplatin (CapeOx) vs. patients who did not receive a PPI; a significant difference was not observed in the CapeOx plus lapatinib arm. Demographically, there were significantly more Asian patients in the PPI arm of this analysis; according to the manufacturer of capecitabine, Japanese patients have a 36% lower Cmax and 24% lower AUC for capecitabine compared with Caucasian patients. Additionally, there was not a significant increase in concentration dependent toxicities (e.g., hand-foot syndrome, rash, and diarrhea) or dose reductions in either arm. These observations are in line with a previous retrospective study in which patients with colorectal cancer receiving PPI treatment and adjuvant capecitabine also experienced poorer relapse-free survival compared with patients not receiving a PPI. Coadministration with antacids increased exposure to capecitabine and its metabolites, but this was not clinically significant or clinically relevant. Pharmacokinetic data on the impact of a PPI on capecitabine exposure are not available.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Carbamazepine: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as omeprazole, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Cefpodoxime: (Moderate) Because cefpodoxime proxetil requires a low gastric pH for dissolution, drugs which increase gastric pH, such as antacids, can decrease the bioavailability of 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.
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. (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
Cetirizine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlordiazepoxide: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as chlordiazepoxide. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Chlordiazepoxide; Amitriptyline: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as chlordiazepoxide. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Chlordiazepoxide; Clidinium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. (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.
Chloroquine: (Major) Chloroquine absorption may be reduced by antacids. Administer chloroquine and antacids at least 4 hours apart.
Chlorothiazide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpropamide: (Moderate) Urinary alkalinizing agents may increase the excretion of chlorpropamide by increasing renal clearance. Monitor for decreased efficacy of chlorpropamide (i.e., increased blood glucose) during coadministration.
Chlorthalidone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Chlorthalidone; Clonidine: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Choline Salicylate; Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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: (Moderate) Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin when possible. A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If sodium bicarbonate is used concomitantly, the solubility of ciprofloxacin might be decreased because of alkaline urine. Patients should be monitored for crystalluria, proper urination,and altered kidney function. Hydrate patients well to prevent the formation of highly concentrated urine. (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction.
Citalopram: (Moderate) Limit the dose of citalopram to 20 mg/day if coadministered with omeprazole. Concurrent use may increase citalopram exposure increasing the risk of QT prolongation. Citalopram is a sensitive CYP2C19 substrate; omeprazole is a weak inhibitor of CYP2C19.
Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of omeprazole. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and omeprazole is an inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
Clomipramine: (Minor) Coadministration may result in increased clomipramine exposure. Omeprazole is a CYP2C19 inhibitor and clomipramine is a CYP2C19 substrate.
Clopidogrel: (Major) Avoid concomitant use of clopidogrel and omeprazole as it significantly reduces the antiplatelet activity of clopidogrel. If necessary, consider using an alternative proton pump inhibitor, such as rabeprazole, pantoprazole, lansoprazole, or dexlansoprazole. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps. Omeprazole is an inhibitor of CYP2C19. In clinical studies, use of omeprazole significantly reduced the antiplatelet activity of clopidogrel when administered concomitantly or 12 hours apart.
Clorazepate: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as clorazepate. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Clozapine: (Moderate) The addition of omeprazole to clozapine therapy resulted in a roughly 40% reduction in clozapine plasma concentrations in at least 2 patients. Omeprazole is an inducer of CYP1A2, one of the isoenzymes reponsible for the metabolism of clozapine. According to the manufacturer of clozapine, patients receiving clozapine in combination with a weak to moderate CYP1A2 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary.
Cobicistat: (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.
Codeine; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Colchicine: (Moderate) The action of colchicine is potentiated by alkalinizing agents. The colchicine dose may need adjustment.
Cysteamine: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., sodium bicarbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. (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.
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.
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. (Moderate) Separate the administration of dasatinib and sodium bicarbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, 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. (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
Desloratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexbrompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextromethorphan; Quinidine: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with omeprazole is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP2C19 substrate and omeprazole is a CYP2C19 inhibitor. (Moderate) The coadministration of diazepam with antacids results in delayed diazepam absorption due to the fact that antacids delay gastric emptying. It may be prudent to separate dosing by 2 hours to limit any potential interaction.
Dicyclomine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Diflunisal: (Moderate) Concurrent use of diflunisal with

antacids, such as sodium bicarbonate, may reduce plasma diflunisal concentrations. The effect may be clinically significant if antacids are used on a continuous schedule.
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.
Diphenhydramine; Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Diphenoxylate; Atropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Disulfiram: (Moderate) Monitor patients to determine if it is necessary to adjust the dose of disulfiram when taken concomitantly with omeprazole. In a single patient, the combined use of disulfiram and omeprazole caused disorientation, confusion, and nightmares. These reactions occurred on 2 separate challenges when omeprazole was added to disulfiram therapy.
Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Donepezil; Memantine: (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Omeprazole is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Efavirenz: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits and CYP2C19 and may inhibit the metabolism of omeprazole since it is a substrate for CYP2C19.
Elagolix: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., antacids) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as magaldrate. (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Minor) The plasma concentrations of omeprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while omeprazole is a CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Enzalutamide: (Major) Avoid concomitant use of enzalutamide, a strong CYP3A4 inducer and a moderate CYP2C19 inducer, and omeprazole, a CYP3A4 and CYP2C19 substrate, as omeprazole plasma exposure may be reduced. In a drug interaction trial in patients with castration-resistant prostate cancer, the AUC and Cmax of omeprazole was decreased following a single oral dose of omeprazole 20 mg administered after at least 55 days of oral enzalutamide 160 mg/day.
Ephedrine: (Moderate) Sodium bicarbonate-induced urinary alkalization can increase the half-life of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Sodium bicarbonate-induced urinary alkalization can increase the half-life of ephedrine.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Erlotinib: (Major) Avoid coadministration of erlotinib with omeprazole if possible due to decreases in erlotinib plasma concentrations. Erlotinib solubility is pH dependent and solubility decreases as pH increases. Coadministration of erlotinib with medications that increase the pH of the upper gastrointestinal tract may decrease the absorption of erlotinib. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period of time. Increasing the dose of erlotinib is also not likely to compensate for the loss of exposure. Coadministration with omeprazole decreased erlotinib exposure by 46% and the erlotinib Cmax by 61%. (Major) Separate administration by several hours if concomitant use of erlotinib with sodium bicarbonate is necessary. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from sodium bicarbonate therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. The effects of antacids on erlotinib pharmacokinetics has not been evaluated.
Escitalopram: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.
Eslicarbazepine: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Estazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as estazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Ethacrynic Acid: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Ethotoin: (Major) The oral absorption of ethotoin may be reduced by antacids. Separating the administration of ethotoin and antacids by at least 2 hours will help minimize the possibility of interaction.
Ezetimibe: (Minor) Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Ezetimibe; Simvastatin: (Minor) Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Fedratinib: (Moderate) Monitor for increased omeprazole adverse effects as coadministration of omeprazole and fedratinib increased omeprazole exposure by 3-fold in a drug interaction study. Although dose adjustments are not generally needed, patients with Zollinger-Ellison's syndrome who often require higher omeprazole doses may require an adjustment in omeprazole dose. Omeprazole is metabolized primarily by CYP2C19 and secondarily by CYP3A4; fedratinib is an inhibitor of CYP2C19 and CYP3A4.
Fenofibrate: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibric acid.
Ferric Maltol: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Fexofenadine: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Fexofenadine; Pseudoephedrine: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Flavoxate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Flecainide: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Flibanserin: (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Flurazepam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as flurazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Fluvastatin: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Fluvoxamine: (Moderate) Omeprazole is a primary substrate of CYP2C19 and CYP3A4. Reduced metabolism and resulting elevated plasma concentrations of omeprazole may occur if combined with fluvoxamine. Fluvoxamine is a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP3A4. Concomitant administration of omeprazole and a combined inhibitor of CYP2C19 and CYP3A4 resulted in more than doubling of the omeprazole exposure. No specific dose adjustments are recommended, unless the patient is receiving high doses of omeprazole, as for Zollinger-Ellison Syndrome; in such patients, omeprazole dose reduction might be necessary.
Food: (Moderate) Food or medicines containing a high sodium content (e.g., tomato juice) could increase the risk of complications of sodium excess when given with sodium bicarbonate. Patients and clinicians should be aware of the amount of sodium intake in medications and foods.
Fosamprenavir: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after oral sodium bicarbonate. Coadministration of antacids, such as sodium bicarbonate, may decrease the exposure of fosamprenavir and impair its efficacy.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Fosphenytoin: (Major) Avoid concomitant use of omeprazole and fosphenytoin as omeprazole exposure may be decreased, reducing its efficacy. Concomitant use may also increase phenytoin concentrations. Omeprazole is a CYP2C19 inhibitor and CYP3A substrate and fosphenytoin is a CYP2C19 substrate and strong CYP3A inducer.
Furosemide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Gabapentin: (Moderate) Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
Gastrointestinal Enzymes: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
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%. (Major) Avoid coadministration of sodium bicarbonate with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of sodium bicarbonate. Gefitinib exposure is affected by gastric pH. Coadministration with high doses of ranitidine with sodium bicarbonate to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
Glipizide: (Moderate) Monitor blood glucose concentrations closely during coadministration of glipizide and sodium bicarbonate. Antacids have been reported to increase the absorption of glipizide, enhancing its hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH.
Glipizide; Metformin: (Moderate) Monitor blood glucose concentrations closely during coadministration of glipizide and sodium bicarbonate. Antacids have been reported to increase the absorption of glipizide, enhancing its hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH.
Glyburide: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
Glyburide; Metformin: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
Glycopyrrolate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Glycopyrrolate; Formoterol: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Homatropine; Hydrocodone: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Hydrocodone; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Hydroxychloroquine: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
Hyoscyamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Ibuprofen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
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) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
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.
Indomethacin: (Moderate) Antacids may inhibit the oral absorption of indomethacin. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
Infigratinib: (Major) Avoid coadministration of infigratinib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease infigratinib exposure resulting in decreased efficacy. If necessary, infigratinib may be administered two hours before or ten hours after an H2-receptor antagonist or two hours before or after a locally acting antacid. Coadministration with a PPI decreased infigratinib exposure by 45%.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Iron Salts: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Iron: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with omeprazole may result in increased serum concentrations of omeprazole. Omeprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
Itraconazole: (Moderate) Administer antacids 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 antacids. (Moderate) When administering proton pump inhibitors with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when proton pump inhibitors are administered with the 65 mg itraconazole capsule. Administer proton pump inhibitors at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if proton pump inhibitors are administered with itraconazole 65 mg capsules.
Ketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption. (Major) Ketoconazole requires an acidic pH for absorption. Medications that increase gastric pH or decrease acid output can cause a notable decrease in the bioavailability of ketoconazole. Medications that have this effect are antacids, antimuscarinics, histamine H2-blockers, and proton pump inhibitors (PPIs). Except for antacids, these medications have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction; ketoconazole should be administered at least 2 hours before or 1 hour after antacids. 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.
Lactulose: (Minor) Oral, nonabsorbable antacids may interfere with the decrease in colon pH necessary for lactulose's action.
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. (Moderate) Separate administration of ledipasvir and antacids by at least 4 hours. Solubility of ledipasvir decreases as gastric pH increases; thus, simultaneous administration of these drugs may result in lower ledipasvir plasma concentrations.
Letermovir: (Moderate) Monitor for reduced omeprazole efficacy and adjust the dose of omeprazole if needed during concurrent use of letermovir. Coadministration may result in a clinically relevant decrease in the plasma concentration of omeprazole. Omeprazole is a sensitive substrate of CYP2C19. Letermovir is a CYP2C19 inducer.
Levoketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption. (Major) Ketoconazole requires an acidic pH for absorption. Medications that increase gastric pH or decrease acid output can cause a notable decrease in the bioavailability of ketoconazole. Medications that have this effect are antacids, antimuscarinics, histamine H2-blockers, and proton pump inhibitors (PPIs). Except for antacids, these medications have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction; ketoconazole should be administered at least 2 hours before or 1 hour after antacids. 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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Lithium: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with lithium, especially patients who are stabilized on lithium, as urinary alkalinization increases the renal clearance of lithium. If coadministration can not be avoided, monitor lithium serum concentrations and patient clinical response very closely. Also of note, lithium clearance is increased if hypernatremia occurs.
Lonafarnib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with lonafarnib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of tipranavir and ritonavir with antacids results in decreased tipranavir concentrations. Administer tipranavir and ritonavir 2 hours before or 1 hour after antacids. (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.
Loratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Luliconazole: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of omeprazole by substantially decreasing its systemic exposure. If used together, an omeprazole dosage adjustment may be necessary to obtain the desired therapeutic effect. Omeprazole is a CYP3A4 and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A; in vitro data suggests is also has the potential to induce CYP2C19.
Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Mefenamic Acid: (Moderate) Ingestion of mefenamic acid with antacids is not recommended. Administration with an antacid containing 1.7 grams of magnesium hydroxide resulted in a 36 percent increase in the area under the time versus concentration curve of mefenamic acid.
Mefloquine: (Moderate) Antacids 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. (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.
Memantine: (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Mesalamine, 5-ASA: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Methenamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Methenamine; Sodium Acid Phosphate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Methenamine; Sodium Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.
Methohexital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Methotrexate: (Major) Avoid concomitant use of methotrexate and proton pump inhibitors (PPIs) due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions; consider temporary withdrawal of the PPI in some patients receiving high-dose methotrexate. Concomitant use of methotrexate, primarily at high dose, and PPIs may increase and prolong serum concentrations of methotrexate, possibly leading to methotrexate toxicities.
Methscopolamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Methyclothiazide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Metolazone: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Mexiletine: (Major) If alkalinizing agents, such as sodium bicarbonate, are administered concomitantly with mexiletine, urinary excretion and plasma half-life of the antiarrhythmic can be altered. Elimination of mexiletine is decreased when the urine is alkaline and increased when it is acidic. Dosage adjustments should be made as necessary.
Midazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as midazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Mitotane: (Moderate) Use caution if mitotane and omeprazole are used concomitantly, and monitor for decreased efficacy of omeprazole and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and omeprazole is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of omeprazole.
Mycophenolate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption. (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).
Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Naproxen; Esomeprazole: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Naproxen; Pseudoephedrine: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
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.
Neostigmine; Glycopyrrolate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Neratinib: (Major) Administer neratinib at least 3 hours after administration of sodium bicarbonate if concomitant use is necessary due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. (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. (Moderate) If concomitant use of these agents is necessary, administer the antacid approximately 2 hours before or approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH; therefore, concomitant use of nilotinib and antacids may result in decreased bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) was administered approximately 2 hours before or approximately 2 hours after a single 400-mg nilotinib dose.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of tipranavir and ritonavir with antacids results in decreased tipranavir concentrations. Administer tipranavir and ritonavir 2 hours before or 1 hour after antacids. (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.
Nitrofurantoin: (Major) Antacids can delay both the rate and the extent of GI absorption of nitrofurantoin. This interaction may be due to surface absorption of the antibacterial onto the antacid. Separate administration by at least 1 hour.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Octreotide: (Moderate) Coadministration of oral octreotide with antacids may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including antacids, may alter the absorption of octreotide and lead to a reduction in bioavailability. (Moderate) Coadministration of oral octreotide with proton pump inhibitors (PPIs) may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including PPIs, may alter the absorption of octreotide and lead to a reduction in bioavailability. This interaction has been documented with esomeprazole and can occur with the other PPIs.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
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) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Pancrelipase: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
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. (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
Penicillamine: (Moderate) Because penicillamine chelates heavy metals, it is possible that antacids could reduce penicillamine bioavailability, which can decrease the therapeutic effects of penicillamine. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
Pentobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Pexidartinib: (Major) Avoid coadministration of pexidartinib with omeprazole as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. As an alternative to a proton pump inhibitor (PPI), use locally-acting antacids or H2-receptor antagonists. Coadministration of another PPI decreased pexidartinib exposure by 50%.
Phenobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Phenytoin: (Major) Avoid concomitant use of omeprazole and phenytoin as omeprazole exposure may be decreased, reducing its efficacy. Concomitant use may also increase phenytoin concentrations. Omeprazole is a CYP2C19 inhibitor and CYP3A substrate and phenytoin is a CYP2C19 substrate and strong CYP3A inducer. (Moderate) Because the absorption of phenytoin suspension can be reduced by antacids containing magnesium, aluminum, or calcium, administration at the same time of day should be avoided when possible. Ingestion times of phenytoin capsules and calcium antacids should be staggered in patients with low serum phenytoin levels to prevent absorption difficulties. Studies evaluating the effects of magnesium-aluminium antacids on the absorption of phenytoin capsules or tablets have yielded conflicting results. Nevertheless, serum phenytoin levels and clinical response should be closely monitored if these agents are co-administered. The mechanisms by which antacids reduce phenytoin absorption may involve increased gastric transit time, chelation, adsorption, and/or altered solubility. The oral absorption of phenytoin may be reduced by calcium carbonate (e.g., as found in antacids) or other calcium salts. Calcium products may form complexes with phenytoin that are nonabsorbable. Although the magnitude of the interaction is not great, an occasional patient may be affected and the interaction may lead to subtherapeutic phenytoin concentrations. Separating the administration of phenytoin and antacids or calcium salts by at least 2 hours will help minimize the possibility of interaction.
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. (Minor) The concomitant use of bisacodyl tablets with antacids can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid antacids within 1 hour before or after the bisacodyl dosage.
Polysaccharide-Iron Complex: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Posaconazole: (Major) The concurrent use of posaconazole immediate-release oral suspension and proton pump inhibitors (PPIs) should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. PPIs increase gastric pH, resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with esomeprazole (40 mg PO daily), the mean reductions in Cmax were 46% and the mean reductions in AUC were 32% for posaconazole. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by PPIs. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of many PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole). Coadministration may result in increased plasma concentration of the PPIs.
Primidone: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Probenecid; Colchicine: (Moderate) The action of colchicine is potentiated by alkalinizing agents. The colchicine dose may need adjustment.
Propantheline: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Propranolol: (Major) Antacids may reduce the absorption of propranolol. The need to stagger doses of propranolol has not been established, but may be prudent. Monitor clinical response, and adjust propranolol dosage if needed to attain therapeutic goals.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Antacids may reduce the absorption of propranolol. The need to stagger doses of propranolol has not been established, but may be prudent. Monitor clinical response, and adjust propranolol dosage if needed to attain therapeutic goals. (Moderate) Monitor magnesium concentration before and periodically during concomitan t omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Pseudoephedrine; Triprolidine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Quazepam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as quazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Quinidine: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Quinine: (Moderate) Use caution if using sodium bicarbonate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Rifampin: (Major) Avoid coadministration of omeprazole with rifampin due to the risk of decreased omeprazole plasma concentrations which may decrease efficacy. Omeprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. (Moderate) Concomitant use of sodium bicarbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of sodium bicarbonate.
Rifapentine: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Riluzole: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Risedronate: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Ritonavir: (Moderate) Concurrent administration of tipranavir and ritonavir with antacids results in decreased tipranavir concentrations. Administer tipranavir and ritonavir 2 hours before or 1 hour after antacids. (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.
Rosuvastatin: (Major) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Rosuvastatin; Ezetimibe: (Major) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed. (Minor) Antacids may decrease the peak plasma concentration (Cmax) of total ezetimibe by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Salsalate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Secobarbital: (Major) Avoid coadministration of omeprazole with barbiturates because it can result in decreased efficacy of omeprazole. Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
Secretin: (Major) Discontinue use of proton pump inhibitors before administering secretin. Patients who are receiving proton pump inhibitors at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma. The time required for serum gastrin concentrations to return to baseline after discontinuation of a proton pump inhibitor is specific to the individual drug.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with omeprazole due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, selpercatinib must be taken with food. Coadministration under fasting conditions with omeprazole decreased selpercatinib exposure by 69%; however, concomitant use increased selpercatinib exposure by 2% or less when it was administered with a meal.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids.
Sodium Polystyrene Sulfonate: (Moderate) Sodium polystyrene sulfonate should be used cautiously with other agents that can induce hypokalemia such as loop diuretics, insulins, or intravenous sodium bicarbonate. Because of differences in onset of action, sodium polystyrene sulfonate is often used with these agents. With appropriate monitoring, hypokalemia can be avoided.
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.
Sotalol: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer magnesium hydroxide two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with a PPI decreased sotorasib exposure by 57% under fed conditions and 42% under fasted conditions.
Sparsentan: (Major) Avoid concurrent use of sparsentan and proton pump inhibitors (PPIs) due to the risk for decreased sparsentan exposure which may reduce its efficacy. Medications that affect gastric pH may reduce sparsentan absorption. (Moderate) Administer sparsentan 2 hours before or after antacids. Simultaneous coadministration may decrease sparsentan exposure and efficacy. Medications that affect gastric pH may reduce sparsentan absorption.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of St. John's wort with the proton pump inhibitors (PPIs) as PPI exposure may be decreased, reducing their efficacy. PPIs are CYP3A4 and CYP2C19 substrates and St. John's wort is a strong CYP3A4 and CYP2C19 inducer. For example, coadministration of omeprazole with St. John's wort decreased omeprazole plasma concentrations by approximately 40%.
Stiripentol: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Sucralfate: (Major) Antacids can interfere with the binding capacity of sucralfate to the GI mucosa, decreasing its effectiveness. Antacids should not be administered within 30 minutes of 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%.
Sumatriptan; Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
Tacrolimus: (Moderate) Administration of oral tacrolimus at the same time as sodium bicarbonate may result in pH-dependent degradation of tacrolimus. Administer oral Tacrolimus 1 hour before or 2 hours after the Sodium Bicarbonate dose to help limit an interaction. Separation of the oral tacrolimus and sodium bicarbonate doses by at least 2 hours may not be necessary, but more data are needed. Tacrolimus concentrations can be maintained with appropriate monitoring and dosage adjustment. Intravenous and topical forms of tacrolimus do not interact. (Moderate) Concomitant administration of omeprazole and tacrolimus may increase tacrolimus serum concentrations possibly leading to increased risk of serious adverse reactions (e.g., neurotoxicity, infection, QT prolongation), especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Monitor tacrolimus whole blood concentrations; reduce tacrolimus dose if needed to maintain therapeutic concentrations.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Tetracyclines: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
Thiazide diuretics: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Thiothixene: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
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.
Ticlopidine: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Tipranavir: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Tipranavir markedly induces the hepatic cytochrome P-450 enzyme CYP2C19, an enzyme responsible for the metabolism of PPIs. However, since tipranavir is not given unless it is co-prescribed with ritonavir, a known marked enzyme inhibitor, a reduction in PPI metabolism may be unlikely to occur. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If tipranavir and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Tirofiban: (Minor) Patients who receive omeprazole concomitantly with tirofiban may have a higher rate of tirofiban clearance than patients who do not receive omeprazole. The clinical significance of this is unknown.
Tocilizumab: (Minor) Concomitant use of tocilizumab and omeprazole may lead to a decrease in the efficacy of omeprazole. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 12 to 28% decrease in omeprazole exposure occurred 1 week after a single tocilizumab dose. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Omeprazole is a substrate of both CYP2C19 and CYP3A4.
Tolmetin: (Major) The bioavailability of tolmetin is decreased by sodium bicarbonate. Do not use a sodium bicarbonate containing antacid concurrently with tolmetin.
Tolterodine: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
Torsemide: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Tramadol; Acetaminophen: (Minor) Antacids can delay the oral absorption of acetaminophen, but the interactions are not likely to be clinically significant as the extent of acetaminophen absorption is not appreciably affected.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Triazolam: (Moderate) Omeprazole inhibits CYP2C19. There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P450 system, such as triazolam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole.
Trihexyphenidyl: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Trospium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
Tucatinib: (Moderate) Monitor for omeprazole-related adverse effects during coadministration with tucatinib. Concurrent use may increase omeprazole exposure. Omeprazole is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valproic Acid, Divalproex Sodium: (Minor) Sodium bicarbonate may increase valproic acid AUC. Patients should be monitored for adverse effects in this situation.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Voriconazole: (Moderate) Reduce the omeprazole dose by one-half when initiating voriconazole therapy in patients who are currently receiving omeprazole at doses of 40 mg/day or greater. Levels of omeprazole may increase by up to 2-fold due to CYP2C19 and CYP3A4 inhibition by voriconazole.
Warfarin: (Moderate) Monitor the INR in patients receiving warfarin with proton pump inhibitors. Increases in INR may lead to abnormal bleeding. Adjust the warfarin dose to maintain the target INR.

How Supplied

KONVOMEP Oral Sol: 1mL, 2-84mg
KONVOMEP Oral Susp: 1mL, 2-84mg
OmePPi/Omeprazole, Sodium Bicarbonate/Zegerid Oral Cap: 20-1100mg, 40-1100mg
Omeprazole, Sodium Bicarbonate/Zegerid/Zegerid Powder Nasogastric Pwd F/Recon: 20-1680mg, 40-1680mg
Omeprazole, Sodium Bicarbonate/Zegerid/Zegerid Powder Oral Pwd F/Recon: 20-1680mg, 40-1680mg

Maximum Dosage
Adults

40 mg/day PO (omeprazole 40 mg; 1100 mg sodium bicarbonate) for oral capsules and 40 mg/day PO (omeprazole 40 mg; 1680 mg sodium bicarbonate) for packets for oral suspension are recommended by the manufacturer; however, doses up to 80 mg/day have been studied for nocturnal acid breakthrough.

Elderly

40 mg/day PO (omeprazole 40 mg; 1100 mg sodium bicarbonate) for oral capsules and 40 mg/day PO (omeprazole 40 mg; 1680 mg sodium bicarbonate) for packets for oral suspension are recommended by the manufacturer; however, doses up to 80 mg/day have been studied for nocturnal acid breakthrough.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Omeprazole is a GI antisecretory agent that belongs to the substituted benzimidazoles class, also known as proton pump inhibitors (PPIs). PPIs suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of parietal cells. Omeprazole is a lipophilic weak base (pKa 4) and is transformed into an active acidic sulfonamide form when exposed to acidic conditions. Following activation, omeprazole binds selectively and 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. Therefore, PPIs block the final step of gastric acid production. This effect is dose-dependent and leads to the inhibition of both basal and stimulus-induced acid secretion. As with all PPIs, omeprazole is acid-labile and is rapidly degraded by gastric acid. Conventional PPIs are enteric-coated to avoid degradation, while omeprazole; sodium bicarbonate products contain non-enteric coated omeprazole powder. By administering omeprazole with sodium bicarbonate, omeprazole is protected against acid degradation until it can be absorbed. Furthermore, the concomitant administration of omeprazole with sodium bicarbonate may also provide a temporary stimulus to gastrin release which may stimulate the parietal cell mass and promote omeprazole entry into and inhibition of the H+/K+ ATPase pumps. Sodium bicarbonate may be responsible for the rapid rise in intragastric pH seen after administration, while prolonged antisecretory effects are due to omeprazole absorption.
 
Treatment with omeprazole; sodium bicarbonate products is highly effective at reducing the production of gastric acid, measured by the percent decrease from baseline in 24 hour integrated gastric acidity. Following administration of a repeated once daily dose of 40 mg and 20 mg omeprazole; sodium bicarbonate in healthy subjects, the 24-hour integrated gastric acidity (mmol x hour/L) is 84% and 82%, respectively. During a 14 day trial, the majority of critically ill patients have documented gastric pH values 4 and higher while receiving 40 mg Zegerid oral suspension administered once daily via gastric tube. Approximately 99% and 92% of patients have gastric pH values 4 and higher measured at 1 to 2.5 and 6 hours after the first dose, respectively. The antisecretory effects last longer than would be expected from the very short plasma half-life, apparently due to irreversible binding to the parietal H+/K+ ATPase enzyme.
 
Serum gastrin concentrations increase during the initial 1 to 2 weeks of therapy, and median increases in gastrin are greater than the increases produced by H2-receptor antagonists. Gastrin levels return to baseline within 1 to 2 weeks following discontinuation of therapy. 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; sodium bicarbonate products are administered orally.
Omeprazole: Omeprazole is approximately 95% bound to plasma proteins. Extensive hepatic metabolism occurs, and the metabolites have minimal antisecretory activity. Omeprazole is extensively metabolized. Omeprazole metabolism is primarily dependent on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on CYP3A4, responsible for the formation of omeprazole sulphone. In healthy subjects, the mean plasma half-life is 1 hour and the total body clearance is 500 to 600 mL/minute. Approximately 77% of a dose is eliminated in the urine as metabolites, and the remainder of the dose is excreted in the feces.
Sodium bicarbonate: Sodium bicarbonate is not metabolized, and bicarbonate ions are filtered and reabsorbed by the kidneys.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C19, CYP3A4, CYP2C9
Omeprazole is metabolized by CYP2C19 (primary) and by CYP3A4 (secondary). It inhibits CYP2C19 in vitro and in vivo and CYP2C9 in vitro. Omeprazole is a time-dependent inhibitor of CYP2C19 and can increase the systemic exposure of co-administered drugs that are CYP2C19 substrates. In addition, administration of omeprazole increases intragastric pH and can alter the systemic exposure of certain drugs that exhibit pH-dependent solubility. In vitro, ompeprazole induces CYP1A2. Omeprazole does not appear to inhibit CYP3A4.

Oral Route

Following single or repeated once-daily oral dosing of omeprazole; sodium bicarbonate, the maximumm concentration (Cmax) of omeprazole was approximately proportional from 20 mg to 40 mg doses. A greater than dose proportional increase in mean steady-state exposure (AUC) (more than 3-fold increase on Day 7) was observed when doubling the dose to 40 mg. The bioavailability of omeprazole increases upon repeated administration. The percent changes in Cmax and AUC between steady-state (Day 7) and single dose (Day 1) indicate omeprazole is a time-dependent autoinhibitor of CYP2C19. When omeprazole; sodium bicarbonate 40 mg oral suspension was administered in a 2-dose loading regimen, the omeprazole AUC (ng x hour/mL) was 1,665 after Dose 1 and 3,356 after Dose 2, while the Tmax was approximately 30 minutes for both Dose 1 and Dose 2. When omeprazole; sodium bicarbonate 40 mg oral suspension or omeprazole; sodium bicarbonate 40 mg oral capsule is administered 1 hour after a meal, the omeprazole AUC is reduced by approximately 27% and 22%, respectively, relative to administration 1 hour prior to a meal. Omeprazole; sodium bicarbonate should be taken on an empty stomach.

Pregnancy And Lactation
Pregnancy

There are no adequate and well-controlled studies of omeprazole; sodium bicarbonate products during pregnancy. Available epidemiologic data fail to demonstrate an increased risk of major congential malformations or other adverse pregnancy outcomes with first trimester omeprazole use. In humans, omeprazole is known to cross the placenta to the fetus. Epidemiological evaluations have compared the rate of congenital abnormalities and stillbirths among those exposed to omeprazole in utero during pregnancy to similar findings for those exposed to H2-receptor antagonists or other controls. Overall, slightly higher rates of congenital malformations (e.g., ventricular septal defects) and number of stillborns have been reported for cases where exposure to omeprazole occurred in the first trimester of pregnancy and beyond. However, a large cohort study from Denmark did not show a significantly increased risk of birth defects in women who took proton pump inhibitors (PPIs), including omeprazole, during the first trimester. In a meta-analysis of 7 studies, there was no evidence linking PPI exposure in pregnancy to adverse outcomes such as congenital malformations, spontaneous abortions, or premature deliveries. When data was analyzed separately for omeprazole, there was no change in the results. Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, histamine type 2-receptor antagonists (H2RAs) can be used. Proton pump inhibitors should be reserved for pregnant patients who fail H2RA therapy. The sodium bicarbonate in the omeprazole; sodium bicarbonate products is present to buffer the dosage formulations; however, it is prudent to choose a product containing the PPI alone and avoid use of sodium bicarbonate altogether since metabolic alkalosis and fluid retention may occur in the pregnant individual and the fetus with chronic use. Self-medication with proton pump inhibitors (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.

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