Esomeprazole

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Esomeprazole falls into category B. There are no well-done studies that have been done in humans with esomeprazole. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• cilostazol;

• clopidogrel;

• diazepam;

• digoxin;

• erlotinib;

• iron-containing medicines (ferrous fumarate, ferrous gluconate, ferrous sulfate, and others);

• methotrexate;

• mycophenolate mofetil;

• rifampin;

• St. John's wort;

• tacrolimus;

• warfarin (Coumadin, Jantoven);

• antifungal medication--ketoconazole, voriconazole; or

• HIV/AIDS medication--atazanavir, nelfinavir, saquinavir.

This list is not complete. Other drugs may interact with esomeprazole, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and other laboratory tests may be needed to check for unwanted effects. If your condition does not improve, or if it becomes worse, check with your doctor.

esomeprazole is sometimes given together with amoxicillin (Amoxil®) and clarithromycin (Biaxin®) to treat ulcers. Be sure you understand the risks and proper use of any other medicines your doctor prescribes.

Atrophic gastritis (inflammation in the stomach) may occur, especially if you take esomeprazole for a long time. Talk with your doctor if you have concerns about this.

Check with your doctor right away if you have a fever, joint pain, skin rash, swelling of the body, feet, or ankles, or unusual weight gain after taking esomeprazole. These could be symptoms of acute interstitial nephritis.

Taking esomeprazole for a long time may make it harder for your body to absorb vitamin B12. Tell your doctor if you have concerns about vitamin B12 deficiency.

Check with your doctor right away if you have a watery stool that does not go away, stomach pain, and fever with esomeprazole.

esomeprazole may increase your risk of having fractures of the hip, wrist, and spine. This is more likely if you are 50 years of age and older, use high doses, or use it for one year or more.

esomeprazole may cause hypomagnesemia (low magnesium in the blood). This is more likely to occur if you are taking esomeprazole for more than one year, or if you are taking esomeprazole together with digoxin (Lanoxin®) or certain diuretics (water pills). Check with your doctor right away if you have convulsions (seizures), a fast, racing, or uneven heartbeat, muscle spasms (tetany), tremors, or unusual tiredness or weakness.

Do not stop using esomeprazole without first checking with your doctor.

Make sure any doctor or dentist who treats you knows that you are using esomeprazole. esomeprazole may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription (eg, clopidogrel, atazanavir, nelfinavir, Plavix®, Reyataz®, Viracept®) or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Delayed Release, Oral, as magnesium [strength expressed as base]:

NexIUM: 20 mg, 40 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]

NexIUM 24HR: 20 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

NexIUM 24HR Clear Minis: 20 mg [contains corn starch, fd&c blue #2 (indigotine), fd&c blue #2 aluminum lake, fd&c red #40]

Generic: 20 mg, 40 mg

Capsule Delayed Release, Oral, as strontium:

Generic: 24.65 mg, 49.3 mg

Packet, Oral, as magnesium [strength expressed as base]:

NexIUM: 2.5 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 20 mg (30 ea); 40 mg (30 ea)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

NexIUM I.V.: 20 mg (1 ea [DSC]); 40 mg (1 ea)

Generic: 20 mg (1 ea); 40 mg (1 ea)

Tablet Delayed Release, Oral, as magnesium [strength expressed as base]:

NexIUM 24HR: 20 mg [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake]

Note: All dosing is expressed in terms of esomeprazole base, regardless of the salt associated with the dosing information. Esomeprazole strontium 24.65 mg is equivalent to 20 mg of esomeprazole base; esomeprazole strontium 49.3 mg is equivalent to 40 mg of esomeprazole base.

Erosive esophagitis (healing): Oral: Esomeprazole magnesium, esomeprazole strontium: Initial: 20 to 40 mg once daily for 4 to 8 weeks; if incomplete healing, may continue for an additional 4 to 8 weeks; maintenance: 20 mg once daily (controlled studies did not extend beyond 6 months)

Heartburn (OTC labeling): 20 mg once daily for 14 days (maximum: 20 mg/day); treatment may be repeated after 4 months if needed

Nonerosive reflux disease (NERD) (Canadian labeling): Oral: Esomeprazole magnesium: Initial: 20 mg once daily for 2 to 4 weeks; lack of symptom control after 4 weeks warrants further evaluation; maintenance (in patients with successful initial therapy): 20 mg once daily as needed

Symptomatic gastroesophageal reflux: Oral: Esomeprazole magnesium, esomeprazole strontium: 20 mg once daily for 4 weeks; may consider an additional 4 weeks of treatment if symptoms do not resolve

Treatment of GERD (short-term): IV: 20 mg or 40 mg once daily. Note: Indicated only in cases where oral therapy is inappropriate or not possible; safety/efficacy ≥10 days has not been established.

Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopy: IV: 80 mg over 30 minutes, followed by 8 mg/hour continuous infusion for a total of 72 hours, then 40 mg orally once daily for 27 additional days (Sung, 2009) or may follow continuous infusion with any single daily-dose oral proton pump inhibitor (PPI) for a duration dictated by the underlying etiology (Barkun, 2010). Note: The use of intermittent PPIs was found to be comparable with the use of continuous infusion PPIs in patients with high-risk endoscopic findings and may be preferred (Sachar, 2014).

Helicobacter pylori eradication: Oral:

Manufacturer labeling: Esomeprazole magnesium, esomeprazole strontium: 40 mg once daily administered with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 10 days

American College of Gastroenterology guidelines (Chey, 2007):

Nonpenicillin allergy: 40 mg once daily administered with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 10 to 14 days

Penicillin allergy: 40 mg once daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10 to 14 days or 40 mg once daily administered with bismuth subsalicylate 525 mg and metronidazole 250 mg plus tetracycline 500 mg 4 times daily for 10 to 14 days

Canadian labeling: Esomeprazole magnesium: 20 mg twice daily for 7 days; requires combination therapy

Prevention of NSAID-induced gastric ulcers: Oral:

US labeling: Esomeprazole magnesium, esomeprazole strontium: 20 to 40 mg once daily for up to 6 months

Canadian labeling: Esomeprazole magnesium: 20 mg once daily for up to 6 months

Note: 40 mg daily did not show additional benefit over 20 mg daily in clinical trials.

Treatment of NSAID-induced gastric ulcers (Canadian labeling; off-label in US): Oral: Esomeprazole magnesium: 20 mg once daily for 4 to 8 weeks (Goldstein, 2007)

Pathological hypersecretory conditions (Zollinger-Ellison syndrome): Oral: Esomeprazole magnesium, esomeprazole strontium: 40 mg twice daily; adjust regimen to individual patient needs; doses up to 240 mg daily have been administered

Oral:

Esomeprazole magnesium: Mild-to-severe impairment: No dosage adjustment necessary.

Esomeprazole strontium:

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is not recommended (has not been studied).

IV: Mild-to-severe impairment: No dosage adjustment necessary.

Oral:

Safety and efficacy not established in children with hepatic impairment.

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Maximum: 20 mg daily.

IV:

Treatment of GERD (short-term):

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Dose should not exceed 20 mg daily

Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopy:

Mild to moderate impairment (Child-Pugh class A or B): 80 mg over 30 minutes, followed by a maximum continuous infusion of 6 mg/hour for a total of 72 hours

Severe impairment (Child-Pugh class C): 80 mg over 30 minutes, followed by a maximum continuous infusion of 4 mg/hour for a total of 72 hour

Granules for oral administration: Empty the 2.5 mg or 5 mg packet into a container with 5 mL of water or empty the 10 mg, 20 mg, or 40 mg packet into a container with 15 mL of water and stir; leave 2-3 minutes to thicken.

Powder for injection:

For IV injection (≥3 minutes): Adults: Reconstitute powder with 5 mL NS.

For IV infusion (10 to 30 minutes):

Children: Initially reconstitute powder (20 mg or 40 mg) with 5 mL of NS, LR, or D5W, then further dilute to a final volume of 50 mL; withdraw the appropriate amount of the final solution to administer the intended dose.

Adults: Initially reconstitute powder with 5 mL of NS, LR, or D5W, then further dilute to a final volume of 50 mL.

For IV infusion (loading dose and continuous infusion): Prepare the 80 mg loading dose by reconstituting two 40 mg vials with NS (5 mL each); the contents of the two vials should then be further diluted in NS 100 mL. To prepare the continuous infusion, also reconstitute two 40 mg vials with NS (5 mL each); the contents of the two vials should then be further diluted in NS 100 mL.

Oral:

Capsule: Swallow whole and take at least 1 hour before eating (best if taken before breakfast). Capsule can be opened and contents mixed with 1 tablespoon of applesauce. Swallow immediately; mixture should not be chewed or warmed. For patients with difficulty swallowing, use of granules may be more appropriate.

Granules: Empty the 2.5 mg or 5 mg packet into a container with 5 mL of water or the 10 mg, 20 mg, or 40 mg packet into a container with 15 mL of water and stir; leave 2 to 3 minutes to thicken. Stir and drink within 30 minutes. If any medicine remains after drinking, add more water, stir and drink immediately.

Tablet: Swallow whole; do not crush or chew; administer with a full glass of water before breakfast in the morning.

Tablet (Canadian formulation): Swallow whole with water or may be dispersed in a half a glass of noncarbonated water. Stir until tablets disintegrate, and drink the liquid with pellets immediately or within 30 minutes. Do not chew or crush pellets. After drinking, rinse glass with water and drink.

IV: Flush line prior to and after administration with NS, LR, or D5W.

Children: Administer by intermittent infusion (10 to 30 minutes); the manufacturer recommends that children receive intravenous esomeprazole by intermittent infusion only.

Adults:

Treatment of GERD: May be administered by injection (≥3 minutes), or intermittent infusion (10 to 30 minutes)

Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopy: Administer the loading dose over 30 minutes, followed by the continuous infusion at a rate of 8 mg/hour over 71.5 hours (adjust rate of continuous infusion in patients with hepatic dysfunction)

Nasogastric tube:

Capsule: Open capsule and place intact granules into a 60 mL catheter-tip syringe; mix with 50 mL of water. Replace plunger and shake vigorously for 15 seconds. Ensure that no granules remain in syringe tip. Do not administer if pellets dissolve or disintegrate. Use immediately after preparation. After administration, flush nasogastric tube with additional water.

Granules: Delayed release oral suspension granules can also be given by nasogastric or gastric tube. If using a 2.5 mg or 5 mg packet, first add 5 mL of water to a catheter-tipped syringe, then add granules from packet. If using a 10 mg, 20 mg, or 40 mg packet, first add 15 mL of water to a catheter-tipped syringe, then add granules from packet. Shake the syringe, leave 2 to 3 minutes to thicken. Shake the syringe and administer through nasogastric or gastric tube (size 6 French or greater) within 30 minutes. Refill the syringe with equal amount (5 mL or 15 mL) of water, shake and flush nasogastric/gastric tube.

Tablet (Canadian formulation): Dispersed tablets can also be given by nasogastric tube (size 8 to 20 French) using a 25 to 60 mL disposable syringe. Disperse tablet in 50 mL of water. After administration, flush with additional 25 to 50 mL of water to clear the syringe and tube. In larger nasogastric feeding tubes (ie, size 14 French or greater), the dispersion volume may be reduced to 25 mL.

Take at least 1 hour before meals; best if taken before breakfast.

Concerns related to adverse effects:

• Carcinoma: No reports of enterochromaffin-like (ECL) cell carcinoids, dysplasia, or neoplasia have occurred.

• Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of esomeprazole.

• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose or long-term therapy (≥1 year) should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of proton pump inhibitors may increase risk of these infections.

• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of esomeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Hepatic impairment: Patients with severe hepatic impairment may require dosage reductions.

• Renal impairment: Pharmacokinetics of esomeprazole are not expected to be altered in renal impairment; dosage adjustments are not necessary for any degree of renal impairment when using esomeprazole magnesium or esomeprazole sodium. However, since pharmacokinetics of the strontium may be reduced in mild to moderate renal impairment, esomeprazole strontium is not recommended for use in severe impairment (has not been studied).

Concurrent drug therapy issues:

• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham 2010; Levine 2011).

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Bioavailability may be increased in elderly patients.

• Pediatric: Esomeprazole strontium: Strontium competes with calcium for intestinal absorption and is incorporated into bone; use of esomeprazole strontium in pediatric patients is not recommended.

Dosage form specific issues:

• Intravenous: Safety and efficacy of IV treatment for GERD beyond 10 days have not been established; transition from IV to oral therapy as soon possible.

Other warnings/precautions:

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2007).

• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop esomeprazole treatment ≥14 days before CgA test; if CgA level high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider before use if any of the following are present: heartburn for >3 months; frequent wheezing, particularly with heartburn; unexplained weight loss; nausea or vomiting; or stomach pain. Discontinue use and notify health care provider if heartburn continues or worsens; diarrhea occurs; if >14 days of therapy is needed; or if >1 course of therapy is needed every 4 months.