Nexium I.V.

Dosage Forms And Strengths

NEXIUM I.V. for Injection is supplied as a freeze-dried white to off-white powder containing 20 mg or 40 mg of esomeprazole per single-use vial.

Storage And Handling

NEXIUM I.V. for Injection is supplied as a freeze-dried powder containing 20 mg or 40 mg of esomeprazole per single-use vial.

NDC 0186-6020-01 one carton containing 10 vials of NEXIUM I.V. for Injection (each vial contains 20 mg of esomeprazole).
NDC 0186-6040-01 one carton containing 10 vials of NEXIUM I.V. for Injection (each vial contains 40 mg of esomeprazole).

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°86°F). [See USP Controlled Room Temperature]. Protect from light. Store in carton until time of use.

Following reconstitution and administration, discard any unused portion of esomeprazole solution.

Manufactured for: AstraZeneca LP Wilmington, DE 19850. Revised: March 2014

Clinical Trials Experience With Intravenous NEXIUM

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

The safety of intravenous esomeprazole is based on results from clinical trials conducted in four different populations including patients having symptomatic GERD with or without a history of erosive esophagitis (n=199), patients with erosive esophagitis (n=160), healthy subjects (n=204) and patients with bleeding gastric or duodenal ulcers (n=375).

The data described below reflect exposure to NEXIUM I.V. for Injection in 359 patients. NEXIUM I.V. for Injection was studied only in actively-controlled trials. The population was 18 to 77 years of age; 45% Male, 52% Caucasian, 17% Black, 3% Asian, 28% Other, and had either erosive reflux esophagitis (44%) or GERD (56%). Most patients received doses of either 20 or 40 mg either as an infusion or an injection. Adverse reactions occurring in ≥ 1% of patients treated with intravenous esomeprazole (n=359) in clinical trials are listed below:

Table 2 : Adverse reactions occurring at an incidence ≥ 1% in the NEXIUM I.V. group

Intravenous treatment with esomeprazole 20 and 40 mg administered as an injection or as an infusion was found to have a safety profile similar to that of oral administration of esomeprazole.

Pediatric

A randomized, open-label, multi-national study to evaluate the pharmacokinetics of repeated intravenous doses of once daily esomeprazole in pediatric patients 1 month to 17 years old, inclusive was performed. The safety results are consistent with the known safety profile of esomeprazole and no unexpected safety signals were identified. [See CLINICAL PHARMACOLOGY]

The data described below reflect exposure to NEXIUM I.V. for Injection in 375 patients. NEXIUM I.V. for Injection was studied in a placebo-controlled trial. Patients were randomized to receive NEXIUM I.V. for Injection (n=375) or placebo (n=389). The population was 18 to 98 years old; 68% Male, 87% Caucasian, 1% Black, 7% Asian, 4% other, who presented with endoscopically confirmed gastric or duodenal ulcer bleeding. Following endoscopic hemostasis, patients received either 80 mg esomeprazole as an intravenous infusion over 30 minutes followed by a continuous infusion of 8 mg per hour or placebo for a total treatment duration of 72 hours. After the initial 72-hour period, all patients received oral proton pump inhibitor (PPI) for 27 days.

Table 3 : Incidence (%) of adverse reactions that occurred in greater than 1% of patients within 72 hours after start of treatment*

With the exception of injection site reactions described above, intravenous treatment with esomeprazole administered as an injection or as an infusion was found to have a safety profile similar to that of oral administration of esomeprazole.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of NEXIUM. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Postmarketing Reports - There have been spontaneous reports of adverse events with postmarketing use of esomeprazole. These reports occurred rarely and are listed below by body system:

Blood And Lymphatic System Disorders: agranulocytosis, pancytopenia;

Eye Disorders: blurred vision;

Gastrointestinal Disorders: pancreatitis; stomatitis; microscopic colitis;

Hepatobiliary Disorders: hepatic failure, hepatitis with or without jaundice;

Immune System Disorders: anaphylactic reaction/shock;

Infections and Infestations: GI candidiasis;

Metabolism and nutritional disorders: hypomagnesemia;

Musculoskeletal And Connective Tissue Disorders: muscular weakness, myalgia, bone fracture;

Nervous System Disorders: hepatic encephalopathy, taste disturbance;

Psychiatric Disorders: aggression, agitation, depression, hallucination;

Renal and Urinary Disorders: interstitial nephritis;

Reproductive System and Breast Disorders: gynecomastia;

Respiratory, Thoracic and Mediastinal Disorders: bronchospasm;

Skin and Subcutaneous Tissue Disorders: alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN, some fatal).

Other adverse events not observed with NEXIUM, but occurring with omeprazole can be found in the omeprazole package insert, ADVERSE REACTIONS section.

Read the entire FDA prescribing information for Nexium IV (Esomeprazole Sodium)

Esomeprazole injection is used to treat conditions where there is too much acid in the stomach. It is used for the short-term treatment (up to 10 days) of gastroesophageal reflux disease (GERD) with erosive esophagitis in adults and children 1 month of age and older. GERD is a condition where the acid in the stomach washes back up into the esophagus. This medicine is also used to lower risk of rebleeding in patients with acute gastric or duodenal ulcer after endoscopy.

Esomeprazole is a proton pump inhibitor (PPI). It works by decreasing the amount of acid that is produced by the stomach.

This medicine is available only with your doctor's prescription.

• 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 Nexium I.V..
• 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 Nexium I.V. 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.
• Lupus has happened with this medicine, 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.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Nexium I.V. while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

You should not use Nexium I.V. if you are allergic to esomeprazole or to any other benzimidazole medicine such as albendazole or mebendazole.

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

To make sure Nexium I.V. is safe for you, tell your doctor if you have:

• severe liver disease;

• low levels of magnesium in your blood;

• osteoporosis;

• low bone mineral density (osteopenia);

• if you are taking clopidogrel (Plavix); or

• if you take medicine to treat tuberculosis.

Tell your doctor if you have osteoporosis or osteopenia (low bone mineral density). Using a proton pump inhibitor such as esomeprazole may increase your risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people who have used the medicine long-term or at high doses, and in those who are age 50 and older. It is not clear whether esomeprazole is the actual cause of an increased risk of fracture.

It is not known whether Nexium I.V. will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

Esomeprazole can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Nexium I.V., especially:

• cilostazol;

• clopidogrel;

• digoxin;

• erlotinib;

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

• methotrexate;

• mycophenolate mofetil;

• rifampin;

• tacrolimus;

• antifungal medication - ketoconazole, voriconazole;

• a blood thinner - warfarin, Coumadin, Jantoven; or

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

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

Applies to esomeprazole: intravenous powder for injection, oral delayed release capsule, oral powder for reconstitution delayed release

General

The most frequently occurring adverse reactions were headache and diarrhea.
The most frequently reported adverse reactions for patients who received triple therapy for 10 days were diarrhea, taste perversion, and abdominal pain.[Ref]

Nervous system

Very Common (10% or more): Headache (up to 10.9%)
Common (1% to 10%): Dizziness, somnolence, vertigo
Uncommon (0.1% to 1%): Paresthesia
Rare (0.01% to 0.1%): Taste disturbance
Very rare (less than 0.01%): Hepatic encephalopathy
Frequency not reported: Hypertonia, hypoesthesia, migraine/aggravated migraine, parosmia, taste loss/perversion, tremor[Ref]

Gastrointestinal

Very common (10% or more): Flatulence (up to 10.3%)
Common (1% to 10%): Abdominal pain, benign fundic gland polyps, constipation, diarrhea, dry mouth, duodenal ulcer hemorrhage, epigastric pain/aggravated epigastric pain, gastritis/aggravated gastritis, nausea/aggravated nausea, regurgitation, tooth disorder, vomiting/aggravated vomiting
Rare (0.01% to 0.1%): GI candidiasis, stomatitis
Very rare (less than 0.01%): Microscopic colitis
Frequency not reported: Barrett's esophagus, benign polyps or nodules, bowel irregularity, constipation aggravated, duodenitis, dyspepsia, dysphagia, dysplasia gastrointestinal (GI), enlarged abdomen, eructation, esophagitis, esophageal disorder, esophageal stricture, esophageal ulceration, esophageal varices, frequent stools, gastric ulcer, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hernia, hiccup, melena, mouth disorder, mucosal discoloration, pharynx disorder, rectal disorder, tongue disorder, tongue edema, ulcerative stomatitis
Postmarketing reports: Clostridium difficile associated diarrhea, hemorrhagic necrotic gastritis, pancreatitis[Ref]

Respiratory

Common (1% to 10%): Cough, respiratory infection, sinusitis, tachypnea (in pediatrics)
Uncommon (0.1% to 1%): Epistaxis
Rare (0.01% to 0.1%): Bronchospasm
Frequency not reported: Asthma aggravated, dyspnea, larynx edema, pharyngitis, rhinitis[Ref]

Other

Common (1% to 10%): Accident or injury, fever/pyrexia
Rare (0.01% to 0.1%): Malaise
Frequency not reported: Asthenia, earache, facial edema, fatigue, flu-like disorder, leg edema, otitis media, pain, rigors, thirst, tinnitus[Ref]

Dermatologic

Common (1% to 10%): Pruritus
Uncommon (0.1% to 1%): Dermatitis, rash, urticaria
Rare (0.01% to 0.1%): Alopecia, increased sweating, photosensitivity
Very rare (less than 0.01): Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)/ fatal TEN
Frequency not reported: Acne, pruritus ani, rash erythematous, rash maculopapular, skin inflammation, subacute cutaneous lupus erythematosus, sweating increased/hyperhidrosis
Postmarketing reports: Cutaneous lupus erythematosus, systemic lupus erythematosus[Ref]

Cardiovascular

Common (1% to 10%): Hypertension/aggravated hypertension
Uncommon (0.1% to 1%): Peripheral edema
Frequency not reported: Chest pain, flushing, generalized edema, hot flush, hypertension, irregular heartbeat, substernal chest pain, tachycardia[Ref]

Musculoskeletal

Common (1% to 10%): Back pain
Uncommon (0.1% to 1%): Fracture of the hip, wrist or spine
Rare (0.01% to 0.1%): Arthralgia, myalgia
Very rare (less than 0.01%): Muscular weakness
Frequency not reported: Arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, hyperuricemia/increased uric acid, increased alkaline phosphatase, polymyalgia rheumatic
Postmarketing reports: Bone fracture[Ref]

An increased risk of hip fracture has been reported in a cohort study. The risk was significantly increased among patients prescribed long-term high PPIs.[Ref]

Endocrine

Common (1% to 10%): Increased serum gastrin
Very rare (less than 0.01%): Gynecomastia
Frequency not reported: Decreased/increased thyroxine, goiter, increased thyroid stimulating hormone[Ref]

Local

Common (1% to 10%): Administration/injection site reactions
Postmarketing reports: Tissue inflammatory reaction[Ref]

Immunologic

Common (1% to 10%): Viral infection[Ref]

Hepatic

Uncommon (0.1% to 1%): Increased liver enzymes,
Rare (0.01% to 0.1%): Hepatitis with/without jaundice
Very rare (less than 0.01%): Hepatic failure
Frequency not reported: Abnormal hepatic function, ALT/AST increased, bilirubinemia, increased total bilirubin[Ref]

Ocular

Uncommon (0.1% to 1%): Blurred vision
Rare (0.01% to 0.1%): Visual accommodation disorder, visual field defect
Frequency not reported: Abnormal vision, conjunctivitis
Postmarketing reports: Irreversible visual impairment, loss of vision[Ref]

Psychiatric

Uncommon (0.1% to 1%): Insomnia
Rare (0.01% to 0.1%): Agitation, confusion, depression/aggravated depression
Very rare (less than 0.01%): Aggression, hallucinations
Frequency not reported: Apathy, irritability, nervousness, sleep disorder[Ref]

Hematologic

Rare (0.01% to 0.1%): Leukopenia, thrombocytopenia
Very rare (less than 0.01%): Agranulocytosis, pancytopenia
Frequency not reported: Anemia, anemia hypochromic, cervical lymphadenopathy, decreased/increased hemoglobin, decreased/increased platelets, decreased/increased white blood cell count, leukocytosis[Ref]

Metabolic

Rare (0.01% to 0.1%): Hyponatremia
Very rare (less than 0.01%): Hypomagnesemia with or without hypocalcemia and/or hypokalemia, severe hypomagnesemia
Frequency not reported: Anorexia, decreased/increased potassium, decreased/increased sodium, increased appetite, vitamin B12 deficiency, weight decrease/increase[Ref]

Hypersensitivity

Rare (0.01% to 0.1%): Anaphylactic reaction/shock, angioedema, hypersensitivity reactions
Frequency not reported: Allergic reaction[Ref]

Renal

Very rare (less than 0.01%): Interstitial nephritis with/without renal failure
Frequency not reported: Glycosuria
Postmarketing reports: Impaired renal function, increased creatinine, nephrosis[Ref]

Genitourinary

Frequency not reported: Abnormal urine, albuminuria, cystitis, dysmenorrhea, dysuria, fungal infection, genital moniliasis, hematuria, menstrual disorder, micturition frequency, moniliasis, polyuria, vaginitis
Postmarketing reports: Impotence[Ref]

Some side effects of Nexium IV may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Acid Suppression in Gastroesophageal Reflux Disease (GERD)

Four multicenter, open-label, two-period crossover studies were conducted to compare the pharmacodynamic efficacy of the intravenous formulation of esomeprazole (20 mg and 40 mg) to that of NEXIUM delayed-release capsules at corresponding doses in patients with symptoms of GERD, with or without erosive esophagitis. The patients (n=206, 18 to 72 years old; 112 female; 110 Caucasian, 50 Black, 10 Oriental, and 36 Other Race) were randomized to receive either 20 or 40 mg of intravenous or oral esomeprazole once daily for 10 days (Period 1), and then were switched in Period 2 to the other formulation for 10 days, matching their respective dose level from Period 1. The intravenous formulation was administered as a 3-minute injection in two of the studies, and as a 15-minute infusion in the other two studies. Basal acid output (BAO) and maximal acid output (MAO) were determined 22-24 hours post-dose on Period 1, Day 11; on Period 2, Day 3; and on Period 2, Day 11. BAO and MAO were estimated from 1-hour continuous collections of gastric contents prior to and following (respectively) subcutaneous injection of 6.0 µg/kg of pentagastrin.

In these studies, after 10 days of once daily administration, the intravenous dosage forms of NEXIUM 20 mg and 40 mg were similar to the corresponding oral dosage forms in their ability to suppress BAO and MAO in these GERD patients (see table below).

There were no major changes in acid suppression when switching between intravenous and oral dosage forms.

General

Symptomatic response to therapy with NEXIUM does not preclude the presence of gastric malignancy.

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole, of which NEXIUM is an enantiomer.

Treatment with NEXIUM I.V. for Injection should be discontinued as soon as the patient is able to resume treatment with NEXIUM Delayed-Release Capsules.

Drug Interactions

Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4.

In vitro and in vivo studies have shown that esomeprazole is not likely to inhibit CYPs 1A2, 2A6, 2C9, 2D6, 2E1 and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes would be expected. Drug interaction studies have shown that esomeprazole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin. Post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

Esomeprazole may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme. Coadministration of esomeprazole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time, the plasma levels of diazepam were below the therapeutic in-terval, and thus this interaction is unlikely to be of clinical relevance.

Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did not seem to change the pharmacokinetic profile of esomeprazole.

Studies evaluating concomitant administration of esomeprazole and either naproxen (non-selective NSAID) or rofecoxib (COX-2 selective NSAID) did not identify any clinically relevant changes in the pharmacokinetic profiles of esomeprazole or these NSAIDs.

Esomeprazole inhibits gastric acid secretion. Therefore, esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and digoxin).

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of esomeprazole was assessed using omeprazole studies. In two 24-month oral carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (about 0.7 to 57 times the human dose of 20 mg/day expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 5.6 times the human dose on a body surface area basis) for 1 year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of 1 year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for 2 years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. A 78-week oral mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive.

Esomeprazole was negative in the Ames mutation test, in the in vivo rat bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test. Esomeprazole, however, was positive in the in vitro human lymphocyte chromosome aberration test. Omeprazole was positive in the in vitro human lymphocyte chromosome aberration test, the in vivo mouse bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test.

The potential effects of esomeprazole on fertility and reproductive performance were assessed using omeprazole studies. Omeprazole at oral doses up to 138 mg/kg/day in rats (about 56 times the human dose on a body surface area basis) was found to have no effect on reproductive performance of parental animals.

Pregnancy

Teratogenic Effects. Pregnancy Category B

Teratology studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Teratology studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 56 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 5.5 to 56 times the human dose on a body surface area basis) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis). There are no adequate and well-controlled studies in pregnant women. Sporadic reports have been received of congenital abnormalities occurring in infants born to women who have received omeprazole during pregnancy.

Nursing Mothers

The excretion of esomeprazole in milk has not been studied. However, omeprazole concentrations have been measured in breast milk of a woman following oral administration of 20 mg. Because esomeprazole is likely to be excreted in human milk, because of the potential for serious adverse reactions in nursing infants from esomeprazole, and because of the potential for tumorigenicity shown for omeprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the total number of patients who received oral NEXIUM in clinical trials, 1,459 were 65 to 74 years of age and 354 patients were >/=75 years of age.

No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

GERD with a history of Erosive Esophagitis

The recommended adult dose is either 20 or 40 mg esomeprazole given once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 to 30 minutes).

NEXIUM I.V. for Injection should not be administered concomitantly with any other medications through the same intravenous site and or tubing. The intravenous line should always be flushed with either 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP or 5% Dextrose Injection, USP both prior to and after administration of NEXIUM I.V. for Injection.

Treatment with NEXIUM I.V. for Injection should be discontinued as soon as the patient is able to resume treatment with NEXIUM Delayed-Release Capsules.

Safety and efficacy of NEXIUM I.V. for Injection as a treatment of GERD patients with a history of erosive esophagitis for more than 10 days have not been demonstrated (see INDICATIONS AND USAGE ).

Special Populations

Geriatric:   No dosage adjustment is necessary. (See CLINICAL PHARMACOLOGY , Pharmacokinetics. )

Renal Insufficiency:   No dosage adjustment is necessary. (See CLINICAL PHARMACOLOGY , Pharmacokinetics. )

Hepatic Insufficiency:   No dosage adjustment is necessary in patients with mild to moderate liver impairment (Child Pugh Classes A and B). For patients with severe liver impairment (Child Pugh Class C), a dose of 20 mg of NEXIUM should not be exceeded (See CLINICAL PHARMACOLOGY , Pharmacokinetics. )

Gender:   No dosage adjustment is necessary. (See CLINICAL PHARMACOLOGY , Pharmacokinetics. )

Preparations for use:

Intravenous Injection (20 or 40 mg) over no less than 3 minutes

The freeze-dried powder should be reconstituted with 5 mL of 0.9% Sodium Chloride Injection, USP. Withdraw 5 mL of the reconstituted solution and administer as an intravenous injection over no less than 3 minutes.

The reconstituted solution should be stored at room temperature up to 30°C (86°F) and administered within 12 hours after reconstitution. No refrigeration is required.

Intravenous Infusion (20 or 40 mg) over 10 to 30 minutes

A solution for intravenous infusion is prepared by first reconstituting the contents of one vial with 5 mL of 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP or 5% Dextrose Injection, USP and further diluting the resulting solution to a final volume of 50 mL. The solution (admixture) should be administered as an intravenous infusion over a period of 10 to 30 minutes.

The admixture should be stored at room temperature up to 30°C (86°F) and should be administered within the designated time period as listed in the Table below. No refrigeration is required.

NEXIUM I.V. for Injection should not be administered concomitantly with any other medications through the same intravenous site and or tubing. The intravenous line should always be flushed with either 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP or 5% Dextrose Injection, USP both prior to and after administration of NEXIUM I.V. for Injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.