Nexium

Esomeprazole comes as a delayed-release (releases the medication in the intestine to prevent break-down of the medication by stomach acids) capsule to take by mouth or to open, mix with water, and give through a feeding tube, and as granules to mix with water and take by mouth or give through a feeding tube. Esomeprazole is usually taken once a day at least 1 hour before a meal. When esomeprazole is used to treat certain conditions in which the stomach makes too much acid, it is taken twice a day. Take esomeprazole at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take esomeprazole exactly as directed. Do not take more or less of it or take it more often than or for a longer period of time than prescribed by your doctor or stated on the package.

Swallow the capsules whole; do not split, chew, or crush them. If you cannot swallow the capsule, put 1 tablespoon of cool, soft applesauce in an empty bowl. Open one esomeprazole capsule and carefully sprinkle the pellets onto the applesauce. Mix the pellets with the applesauce and swallow the entire tablespoonful of the applesauce and pellet mixture immediately. Do not chew the pellets in the applesauce. Do not save the pellets and applesauce for later use.

To mix the granules, follow these steps:

1. Place 1 tablespoon (15 mL) of water into a cup.
2. Open the esomeprazole packet and empty the granules into the cup containing the water.
3. Stir the granules into the water and leave the mixture alone for 2 to 3 minutes so that it will thicken.
4. Stir the mixture again, and drink all of the mixture within 30 minutes.
5. If any material remains in the cup after drinking, add some more water and stir. Drink all of the mixture immediately.

The granules and the contents of the capsules can both be given through a feeding tube. If you have a feeding tube, ask your doctor or pharmacist how you should take the medication. Follow those directions carefully.

It may take several weeks or longer for you to feel the full benefit of esomeprazole. Call your doctor if your symptoms worsen or do not improve during this time. Continue to take esomeprazole even if you feel well. Do not stop taking esomeprazole without talking to your doctor.

If your condition does not improve or gets worse, call your doctor.

Mechanism of Action

S-isomer of omeprazole; PPI; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in blockage of acid secretion

Absorption

Bioavailability: PO: 89-90%; food decreases AUC by 33-53%; take 1 hr before meal

Onset: 1-2 hr (gastric acid inhibition); within 4 wk (GERD)

Duration (multiple dose): Gastric acid inhibition; PO: 17 hr

Peak plasma time: PO: 1-1.6 hr

Distribution

Protein bound: 97%

Vd: 16 L

Metabolism

Liver; extensively metabolized by hepatic P450 enzyme; major metabolic pathway is via CYP2C19; the rest is via CYP3A4

Metabolites: 5-hydroxyesomeprazole (inactive), esomeprazole sulfone (inactive), desmethyl-esomeprazole (activity unknown)

Enzymes inhibited: CYP2C19

Slow metabolizers (3% of Caucasians and African-Americans) are deficient in CPY2C19 enzyme system; plasma concentration can be higher than in persons who have the enzyme

Elimination

Half-life: 1.2-1.5 hr

Total body clearance: 9-16 L/hr

Excretion: Urine (80%); feces (20%)

Pharmacogenomics

Metabolites of esomeprazole lack antisecretory activity

The major part of esomeprazole’s metabolism is dependent on the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites

CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15-20% of Asians lack CYP2C19 and are termed poor metabolizers

At steady state, the ratio of AUC in poor metabolizers to AUC in the rest of the population (extensive metabolizers) is approximately 2

1. NexIUM

Esomeprazole, like other PPIs, is well-tolerated. The most common side effects are

• diarrhea,
• nausea,
• vomiting,
• headaches,
• rash and
• dizziness.

Nervousness, abnormal heartbeat, muscle pain, weakness, leg cramps, and water retention occur infrequently.

Proton pump inhibitors may increase the risk of Clostridium difficile infection. High doses and long-term use (1 year or longer) may increase the risk of osteoporosis-related fractures of the hip, wrist, or spine. Prolonged use also reduces absorption of vitamin B12 (cyanocobalamin).

Long-term use of PPIs has also been associated with low levels of magnesium (hypomagnesemia). Analysis of patients taking PPIs for long periods of time showed an increased risk of heart attacks.

Therefore, it is important to use the lowest doses and shortest duration of treatment necessary for the condition being treated.

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Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Cranberry

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diarrhea or
• Hypomagnesemia (low magnesium in the blood), history of or
• Osteoporosis (thinning of the bones) or
• Seizures, history of—Use with caution. May make these conditions worse.

• Liver disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Store Nexium capsules and packets at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep the container of Nexium closed tightly.
• Keep Nexium and all medicines out of the reach of children.

Nexium I.V. is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6)].

The active ingredient in Nexium® I.V. (esomeprazole sodium) for Injection is (S)-5-methoxy-2[[(4-methoxy-3,5- dimethyl-2-pyridinyl)-methyl]sulfinyl]-1 H-benzimidazole sodium, a proton pump inhibitor that inhibits gastric acid secretion. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. Its empirical formula is C17H18N3O3SNa with molecular weight of 367.4 g/mol (sodium salt) and 345.4 g/mol (parent compound). Esomeprazole sodium is very soluble in water and freely soluble in ethanol (95%). The structural formula is:

Nexium I.V. for Injection is supplied as a sterile, freeze-dried, white to off-white, porous cake or powder in a 5 mL vial, intended for intravenous administration after reconstitution with 0.9% Sodium Chloride Injection, USP; Lactated Ringer’s Injection, USP or 5% Dextrose Injection, USP. Nexium I.V. for Injection contains esomeprazole sodium 21.3 mg or 42.5 mg equivalent to esomeprazole 20 mg or 40 mg, edetate disodium 1.5 mg and sodium hydroxide q.s. for pH adjustment. The pH of reconstituted solution of Nexium I.V. for Injection depends on the reconstitution volume and is in the pH range of 9 to 11. The stability of esomeprazole sodium in aqueous solution is strongly pH dependent. The rate of degradation increases with decreasing pH.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;

• seizure (convulsions);

• joint pain or swelling with fever, swollen glands, and skin rash on your cheeks or arms (worsens in sunlight);

• kidney problems--urinating more or less than usual, blood in your urine, swelling, rapid weight gain; or

• symptoms of low magnesium--dizziness, confusion; fast or uneven heart rate; tremors (shaking) or jerking muscle movements; feeling jittery; muscle cramps, muscle spasms in your hands and feet; cough or choking feeling.

Common side effects may include:

• headache, drowsiness;

• mild diarrhea;

• nausea, stomach pain, gas, constipation; or

• dry mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.