Omeprazole Delayed-Release Capsules

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Omeclamox®-Pak and other antibacterial drugs, Omeclamox®-Pak should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Eradication Of Helicobacter Pylori In Patients With Active Duodenal Ulcer Or History Of Duodenal Ulcer Disease

Omeprazole delayed-release capsules, clarithromycin tablets, and amoxicillin capsules taken together are indicated for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or one-year history) to eradicate H. pylori in adults. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [See Clinical Studies].

In patients who fail therapy with Omeclamox®-Pak, perform susceptibility testing. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, institute alternative antimicrobial therapy [See CLINICAL PHARMACOLOGY, Microbiology].

In case of an overdose, patients should contact a physician, poison control center, or emergency room. There is neither a pharmacologic basis nor data suggesting an increased toxicity of the combination compared to individual components.

As with the management of any overdose, the possibility of multiple drug ingestion should be considered. For current information on treatment of any drug overdose, contact your local Poison Control Center at 1-800-222-1222.

Omeprazole

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience [See ADVERSE REACTIONS]. Symptoms were transient, and no serious clinical outcome has been reported when omeprazole was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

Single oral doses of omeprazole at 1350, 1339, and 1200 mg/kg were lethal to mice, rats, and dogs, respectively. Animals given these doses showed sedation, ptosis, tremors, convulsions, and decreased activity, body temperature, and respiratory rate and increased depth of respiration.

Clarithromycin

Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea. Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.

Amoxicillin

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.1

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood concentrations may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin can be removed from circulation by hemodialysis.

Mechanism Of Action

Omeprazole is an antisecretory drug whereas clarithromycin and amoxicillin are antibacterial drugs [See Microbiology].

Pharmacokinetics

Pharmacokinetics when all three of the Omeclamox®-Pak components were coadministered has not been studied. Studies have shown the low risk of clinically significant interactions of omeprazole and amoxicillin or omeprazole and clarithromycin when administered together. There is no information about the gastric mucosal concentrations of omeprazole, clarithromycin and amoxicillin after administration of these drugs concomitantly. The systemic pharmacokinetic information presented below is based on studies in which each product was administered alone, or in combination of two components.

Omeprazole Delayed-Release Capsules, USP

Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acidlabile), so that absorption of omeprazole begins only after the granules leave the stomach. Absorption is rapid, with peak plasma concentrations of omeprazole occurring within 0.5 to 3.5 hours. Peak plasma concentrations of omeprazole and AUC are approximately proportional to doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in peak plasma concentration and AUC occurs with doses greater than 40 mg. Absolute bioavailability (compared with intravenous administration) is about 30-40% at doses of 20-40 mg, due in large part to presystemic metabolism. In healthy subjects the plasma half-life is 0.5 to 1 hour, and the total body clearance is 500-600 mL/min.

The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules.

Omeprazole delayed-release capsules 40 mg was bioequivalent when administered with and without applesauce. However, omeprazole delayed-release capsules 20 mg was not bioequivalent when administered with and without applesauce. When administered with applesauce, a mean 25% reduction in Cmax was observed without a significant change in AUC for omeprazole delayed-release capsules 20 mg. The clinical relevance of this finding is unknown. Protein binding is approximately 95%.

Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system. Following single dose oral administration of a buffered solution of omeprazole, little if any unchanged drug was excreted in urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recoverable in feces. This implies a significant biliary excretion of the metabolites of omeprazole. Three metabolites have been identified in plasma – the sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole. These metabolites have very little or no antisecretory activity.

The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was increased. Omeprazole was 76% bioavailable when a single 40 mg oral dose of omeprazole (buffered solution) was administered to healthy elderly volunteers, versus 58% in young volunteers given the same dose. Nearly 70% of the dose was recovered in urine as metabolites of omeprazole and no unchanged drug was detected. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers.

In patients with chronic hepatic disease, the bioavailability of omeprazole increased to approximately 100% compared with an IV dose, reflecting decreased first-pass effect, and the plasma half-life of the drug increased to nearly 3 hours compared with the half-life in normals of 0.5-1 hour. Plasma clearance averaged 70 mL/min, compared with a value of 500-600 mL/min in normal subjects. It is recommended to avoid the use of Omeclamox®-Pak in patients with hepatic impairment.

In patients with chronic renal impairment, whose creatinine clearance ranged between 10 and 62 mL/min/1.73m,2 the disposition of omeprazole was very similar to that in healthy volunteers, although there was a slight increase in bioavailability. Because urinary excretion is a primary route of excretion of omeprazole metabolites, their elimination slowed in proportion to the decreased creatinine clearance. No dose reduction is necessary in patients with renal impairment.

In pharmacokinetic studies of single 20 mg omeprazole doses, an increase in AUC of approximately four-fold was noted in Asian subjects compared with Caucasians. It is recommended to avoid the use of Omeclamox®-Pak in Asian patients unless it is deemed that the benefits outweigh the risks.

Clarithromycin Tablets, USP

Clarithromycin is rapidly absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability of 250 mg clarithromycin tablets was approximately 50%. For a single 500 mg dose of clarithromycin, food slightly delays the onset of clarithromycin absorption, increasing the peak time from approximately 2 to 2.5 hours. Food also increases the clarithromycin peak plasma concentration by about 24%, but does not affect the extent of clarithromycin bioavailability. Food does not affect the onset of formation of the antimicrobially active metabolite, 14-OH clarithromycin or its peak plasma concentration but does slightly increase the extent of metabolite formation, indicated by an 11% decrease in area under the plasma concentration-time curve (AUC). Therefore, clarithromycin tablets may be given without regard to food.

In nonfasting healthy human subjects (males and females), peak plasma concentrations were attained within 2 to 3 hours after oral dosing. Steady-state peak plasma clarithromycin concentrations were attained within 3 days and were approximately 3 to 4 μg/mL with a 500 mg dose administered every 8 to 12 hours. The elimination half-life of clarithromycin was 5 to 7 hours with 500 mg administered every 8 to 12 hours. The nonlinearity of clarithromycin pharmacokinetics is slight at the recommended dose of 500 mg administered every 8 to 12 hours. With a 500 mg every 8 to 12 hours dosing, the peak steady-state concentration of 14-OH clarithromycin is up to 1 μg/mL, and its elimination half-life is about 7 to 9 hours. The steady-state concentration of this metabolite is generally attained within 3 to 4 days.

After a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is approximately 30%. The renal clearance of clarithromycin approximates the normal glomerular filtration rate. The major metabolite found in urine is 14-OH clarithromycin, which accounts for an additional 10% to 15% of the dose with a 500 mg tablet administered every 12 hours.

The steady-state concentrations of clarithromycin in subjects with impaired hepatic function did not differ from those in normal subjects; however, the 14-OH clarithromycin concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH clarithromycin was at least partially offset by an increase in renal clearance of clarithromycin in the subjects with impaired hepatic function when compared to healthy subjects.

The pharmacokinetics of clarithromycin was altered in subjects with impaired renal function. In the presence of severe renal impairment with or without coexisting hepatic impairment, prolonged dosing intervals for clarithromycin may be appropriate.

Amoxicillin Capsules, USP

Amoxicillin is stable in the presence of gastric acid and may be given without regard to meals. It is rapidly absorbed after oral administration. It diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxicillin is approximately 20% proteinbound.

Orally administered doses of 500 mg amoxicillin capsules result in average peak blood concentrations 1 to 2 hours after administration in the range of 5.5 μg /mL to 7.5 μg /mL. Detectable serum concentrations are observed up to 8 hours after an orally administered dose of amoxicillin. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.

Combination Therapy Of Omeprazole with Antimicrobials

Omeprazole 40 mg daily was given in combination with clarithromycin 500 mg every 8 hours to healthy adult male subjects. The steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24, and T½ increases of 30%, 89% and 34% respectively) by the concomitant administration of clarithromycin. The observed increases in omeprazole plasma concentration were associated with the following pharmacological effects. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with clarithromycin.

The plasma concentrations of clarithromycin and 14-hydroxy-clarithromycin were increased by the concomitant administration of omeprazole. For clarithromycin, the mean Cmax was 10% greater, the mean Cmin was 27% greater, and the mean AUC0-8 was 15% greater when clarithromycin was administered with omeprazole than when clarithromycin was administered alone. Similar results were seen for 14-hydroxy-clarithromycin, the mean Cmax was 45% greater, the mean Cmin was 57% greater, and the mean AUC0-8 was 45% greater. Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.

Table 1 : Mean ± SD Clarithromycin Tissue Concentrations 2 hours after Dose

Drug Interactions

The clinical importance and the mechanisms behind interactions between omeprazole and antiretroviral drugs are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via inhibition of CYP2C19.

Following multiple doses of nelfinavir (1250 mg twice daily) and omeprazole (40 mg once daily), AUC of nelfinavir and the M8 metabolite was decreased by 36% and 92%, Cmax by 37% and 89% and Cmin by 39% and 75%.

Following multiple doses of atazanavir (400 mg once daily) and omeprazole (40 mg once daily 2 hours before atazanavir), AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. Concomitant administration with omeprazole and atazanavir is not recommended.

Saquinavir serum AUC, Cmax and Cmin increased by 82%, 75% and 106%, respectively, following multiple dosing of saquinavir/ritonavir (1000/100 mg) twice daily for 15 days with omeprazole 40 mg once daily coadministered days 11 to 15 [See DRUG INTERACTIONS].

Omeprazole acts as an inhibitor of CYP2C19. Omeprazole, given in doses of 40 mg daily for one week to 20 healthy subjects in crossover study, increased Cmax and AUC of cilostazol by 18% and 26% respectively. Cmax and AUC of one of its active metabolites, 3,4-dihydro-cilostazol, which has 4-7 times the activity of cilostazol, were increased by 29% and 69% respectively. Co-administration of cilostazol with omeprazole is expected to increase concentrations of cilostazol and its above mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg b.i.d. to 50 mg b.i.d. should be considered [See DRUG INTERACTIONS].

Theophylline is metabolized by CYP1A2 and CYP3A4. Clarithromycin will increase theophylline plasma concentrations when it is administered concomitantly. In two studies in which theophylline was administered with clarithromycin (theophylline sustainedrelease formulation dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg every 12 hours clarithromycin), the steadystate Cmax, Cmin, and AUC of theophylline increased about 20%. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range [See DRUG INTERACTIONS].

Voriconazole is an inhibitor of CYP2C19, CYP2C9, and CYP3A4. Coadministration of voriconazole and omeprazole will increase omeprazole plasma exposure. When voriconazole (400 mg every 12 hours x 1 day, then 200 mg x 6 days) was given with omeprazole (40 mg once daily x 7 days) to healthy subjects, it significantly increased the steady-state Cmax and AUC0-24 of omeprazole, an average of 2 times (90% CI: 1.8, 2.6) and 4 times (90% CI: 3.3, 4.4) respectively as compared to when omeprazole was given without voriconazole. Dose adjustment of omeprazole is not normally required.

Administration of omeprazole 20 mg twice daily for 4 days and a single 1000 mg dose of mycophenolate mofetil approximately one hour after the last dose of omeprazole to 12 healthy subjects in a cross-over study resulted in a 52% reduction in the Cmax and 23% reduction in the AUC of mycophenolic acid.

Microbiology

Omeprazole, an antisecretory drug with the substituted benzimidazoles, suppresses gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-dependent and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Omeprazole can also exhibit anti-bacterial activity depending on the culture conditions. Animal studies indicate that after rapid disappearance from plasma, omeprazole can be found within the gastric mucosa for a day or more.

Clarithromycin exerts its antibacterial activity by binding to the 50S ribosomal subunit of susceptible microorganisms resulting in inhibition of protein synthesis.

Amoxicillin acts through the inhibition of biosynthesis of cell wall mucopeptide.

Triple therapy with omeprazole, clarithromycin and amoxicillin has been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections as indicated [See INDICATIONS AND USAGE].

In vitro studies show that chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with bactericidal effects of penicillin; however, the clinical significance of this interaction is not well documented.

Helicobacter pylori Pretreatment Resistance

Clarithromycin pretreatment resistance rates were 9.3% (41/439) in omeprazole/clarithromycin/amoxicillin triple therapy studies [See Clinical Studies].

Amoxicillin pretreatment susceptible isolates ( ≤ 0.25 μg/mL) were found in 99.3% (436/439) of the patients in the omeprazole/clarithromycin/amoxicillin triple therapy studies (1, 2, and 3). Amoxicillin pretreatment minimum inhibitory concentrations (MICs) > 0.25 μg/mL occurred in 0.7% (3/439) of the patients, all of whom were in the clarithromycin and amoxicillin study arm. One patient had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of > 256 μg/mL by Etest.®

Table 2: Pre-treatment and post-treatment clarithromycin susceptibility test results and clinical/bacteriological outcomes in patients treated with triple therapy*

In the triple therapy clinical trials, 84.9% (157/185) of the patients in the omeprazole/clarithromycin/amoxicillin treatment group who had pretreatment amoxicillin susceptible MICs ( ≤ 0.25 μg/mL) were eradicated of H. pylori and 15.1% (28/185) failed therapy. Of the 28 patients who failed triple therapy, 11 had no post-treatment susceptibility test results and 17 had post-treatment H. pylori isolates with amoxicillin susceptible MICs. Eleven of the patients who failed triple therapy also had post-treatment H. pylori isolates with clarithromycin resistant MICs.

The reference methodology for susceptibility testing of H. pylori is agar dilution MICs [See REFERENCES]. One to three microliters of an inoculum equivalent to a No. 2 McFarland standard (1 x 107 – 1 x 108 CFU/mL for H. pylori) are inoculated directly onto freshly prepared antimicrobial containing Mueller-Hinton agar plates with 5% aged defibrinated sheep blood ( ≥ 2 weeks old). The agar dilution plates are incubated at 35°C in a microaerobic environment produced by a gas generating system suitable for campylobacters.

After 3 days of incubation, the MICs are recorded as the lowest concentration of antimicrobial agent required to inhibit growth of the organism. The clarithromycin and amoxicillin MIC values should be interpreted according to the following criteria:

Table 3 : In vitro Susceptibility Interpretive Criteria for Clarithromycin and Amoxicillin

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard clarithromycin and amoxicillin powders should provide the following MIC values:

Table 4 : Quality Control for Susceptibility Testing

Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

Clinical Studies

H. pylori Associated Duodenal Ulcer Disease

Three U.S., randomized, double-blind clinical studies in patients with H. pylori infection and duodenal ulcer disease (n = 558) compared omeprazole plus clarithromycin plus amoxicillin with clarithromycin plus amoxicillin. Two studies (1 and 2) were conducted in patients with an active duodenal ulcer, and the other study (3) was conducted in patients with a history of a duodenal ulcer in the past 5 years but without an ulcer present at the time of enrollment. The dose regimen in the studies was omeprazole 20 mg twice daily plus clarithromycin 500 mg twice daily plus amoxicillin 1 g twice daily for 10 days; or clarithromycin 500 mg twice daily plus amoxicillin 1 g twice daily for 10 days. In studies 1 and 2, patients who took the omeprazole regimen also received an additional 18 days of omeprazole 20 mg once daily. Endpoints studied were eradication of H. pylori and duodenal ulcer healing (studies 1 and 2 only). H. pylori status was determined by CLOtest,® histology and culture in all three studies. For a given patient, H. pylori was considered eradicated if at least two of these tests were negative and none was positive.

The combination of omeprazole plus clarithromycin plus amoxicillin, was effective in eradicating H. pylori.

Table 5: Per-Protocol and Intent-to-Treat H. pylori Eradication Rates % of Patients Cured [95% Confidence Interval]

REFERENCES

1. Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin ingestions in children less than six years of age. Vet Hum Toxicol. 1988;30:66-67.

2. Clinical Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard- Eighth Edition. CLSI document M07-A8. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.

Administration

Inform patients that each dose of Omeclamox®-Pak contains four pills: one opaque lavender/grey capsule (omeprazole), one white tablet (clarithromycin) and two opaque, peach/orange capsules (amoxicillin).

Take each dose of four pills in the morning and four pills in the evening before eating a meal, for 10 days. Capsules and tablets should not be crushed or chewed, and should be swallowed whole [See DOSAGE AND ADMINISTRATION].

Drug Interactions

Patients should be advised to report to their doctor the use of any other medications while taking Omeclamox®-Pak [See DRUG INTERACTIONS].

The simultaneous administration of any of the following drugs with Omeclamox®-Pak may result in clinically significant adverse reactions or even death:

• Colchicine
• Ergotamine/dihydroergotamine
• Pimozide
• Antiarrhythmic drugs (e.g., quinidine, disopyramide)
• Digoxin
• Anticoagulants (e.g., warfarin)
• Atazanavir
• Nelfinavir
• Saquinavir
• Cilostazol
• Tacrolimus
• Theophylline
• Carbamazepine
• Sildenafil
• HMG-CoA reductase inhibitors (also known as statins)
• Triazolobenziodidiazepines (e.g., triazolam and alprazolam) and related benzodiazepines (e.g., midazolam)
• Probenecid
• Drugs for which gastric pH can affect bioavailability

Clostridium Difficile-Associated Diarrhea

Advise patients that diarrhea is a common problem caused by omeprazole and antibiotics that usually ends when the drug is discontinued. Sometimes after starting treatment, patients can develop severe diarrhea with watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the drug. If this occurs, patients should contact a physician as soon as possible [See WARNINGS AND PRECAUTIONS].

Antibacterial Resistance

Counsel patients that antibacterial drugs including Omeclamox®-Pak should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Omeclamox®-Pak is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Omeclamox®-Pak or other antibacterial drugs in the future.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Use care if you have risks for soft, brittle bones (osteoporosis). Some of these risks include drinking alcohol, smoking, taking steroids, taking drugs to treat seizures, or having family members with osteoporosis. Talk with your doctor about your risks of osteoporosis.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine (omeprazole delayed-release capsules).
• Call your doctor if you have throat pain, chest pain, very bad belly pain, trouble swallowing, or signs of a bleeding ulcer like black, tarry, or bloody stools, throwing up blood, or throw up that looks like coffee grounds. These may be signs of a worse health problem.
• Take calcium and vitamin D as you were told by your doctor.
• This medicine may raise the chance of hip, spine, and wrist fractures in people with weak bones (osteoporosis). The chance may be higher if you take this medicine in high doses or for longer than a year, or if you are older than 50 years old. Talk with your doctor.
• Low magnesium levels have rarely happened in people taking drugs like this one for at least 3 months. Most of the time, this has happened after 1 year of care. You will need to have your blood work checked if you will be taking this medicine (omeprazole delayed-release capsules) for a long time or if you take certain other drugs like digoxin or water pills. Talk with your doctor.
• Long-term treatment (for instance longer than 3 years) with drugs like this one has rarely caused low vitamin B-12 levels. Talk with the doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• Lupus has happened with this medicine (omeprazole delayed-release capsules), as well as lupus that has gotten worse in people who already have it. Tell your doctor if you have lupus. Call your doctor right away if you have signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
• Very bad pancreas, liver, and white blood cell problems have happened in people who were taking this medicine. Rarely, these have been fatal. Talk with the doctor if you have questions.
• If you are of Asian descent, use this medicine (omeprazole delayed-release capsules) with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine (omeprazole delayed-release capsules) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take this medicine before meals.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine (omeprazole delayed-release capsules) as you have been told by your doctor or other health care provider, even if you feel well.
• Swallow whole. Do not chew or crush.
• You may sprinkle contents of capsule on applesauce. Do not chew. Swallow right away and follow with water or juice.
• After mixing, take your dose right away. Do not store for future use.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.