NEXIUM (Page 12 of 12)

14.7 Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome, in Adults

In a multicenter, open-label dose-escalation study of 21 adult patients (15 males and 6 females, 18 Caucasian and 3 Black, mean age of 56 years) with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, NEXIUM significantly inhibited gastric acid secretion. The initial dosage of NEXIUM delayed-release capsules was 40 mg twice daily in 19 patients and 80 mg twice daily in 2 patients. Total daily doses ranging from 80 mg to 240 mg for 12 months maintained gastric acid output below the target levels of 10 mEq/h in patients without prior gastric acid-reducing surgery and below 5 mEq/hr in patients with prior gastric acid-reducing surgery. At the Month 12 final visit, 18/20 (90%) patients had Basal Acid Output (BAO) under satisfactory control (median BAO = 0.17 mmol/hr). Of the 18 patients evaluated with a starting dose of NEXIUM 40 mg twice daily, 13 (72%) had their BAO controlled with the original dosing regimen at the final visit. See Table 15.

Table 15: Adequate Acid Suppression at Final Visit by Dosage Regimen in Adult Patients with Pathological Hypersecretory Conditions

* One patient was not evaluated.
NEXIUM dose at the Month 12 visit	BAO under adequate control at the Month 12 visit (N=20) *
40 mg twice daily	13/15
80 mg twice daily	4/4
80 mg three times daily	1/1

16 HOW SUPPLIED/STORAGE AND HANDLING

NEXIUM Delayed-Release Capsules, 40 mg esomeprazole, are opaque, hard gelatin, amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body. They are supplied as follows:

NDC: 70518-2038-00

PACKAGING: 20 in 1 BOTTLE PLASTIC

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Keep NEXIUM delayed-release capsules container tightly closed. Dispense in a tight container if the NEXIUM delayed-release capsules product package is subdivided.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Acute Tubulointerstitial Nephritis

Advise the patient or caregiver to call the patient’s healthcare provider immediately if they experience signs and/or symptoms associated with suspected acute TIN [see Warnings and Precautions (5.2)].

Clostridium difficile -Associated Diarrhea

Advise the patient or caregiver to immediately call the patient’s healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)].

Bone Fracture

Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient’s healthcare provider [see Warnings and Precautions (5.4)] .

Severe Cutaneous Adverse Reactions

Advise the patient or caregiver to discontinue NEXIUM and immediately call the patient’s healthcare provider for at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity signs or symptoms associated with Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5)] .

Cutaneous and Systemic Lupus Erythematosus

Advise the patient or caregiver to immediately call the patient’s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6)].

Cyanocobalamin (Vitamin B-12) Deficiency

Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient’s healthcare provider if they have been receiving NEXIUM for longer than 3 years [see Warnings and Precautions (5.8)].

Hypomagnesemia and Mineral Metabolism

Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to the patient’s healthcare provider, if they have been receiving NEXIUM for at least 3 months [see Warnings and Precautions (5.9) ].

Drug Interactions

Advise the patient or caregiver to report to their healthcare provider if starting treatment with rilpivirine-containing products, clopidogrel, St. John’s Wort or rifampin; or, if they take high-dose methotrexate [see Contraindications (4), Warnings and Precautions (5.7, 5.10, 5.12) ].

Administration

• Take NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension at least one hour before meals.
• Antacids may be used concomitantly with NEXIUM.
• Swallow NEXIUM delayed-release capsules whole; do not chew or crush the capsules.
• For patients who have difficulty swallowing capsules, NEXIUM delayed-release capsules can be opened, and the contents sprinkled on applesauce. Use with other foods is not recommended.
• Add one tablespoon of applesauce to an empty bowl. The applesauce used should not be hot and should be soft enough to be swallowed without chewing.
• Open the NEXIUM delayed-release capsule and carefully empty the granules inside the capsule onto the applesauce.
• Mix the granules with the applesauce.
• Administer the mixture immediately. Do not chew or crush the granules.
• Discard any remaining mixture. Do not store the mixture for future use.
• NEXIUM delayed-release capsules can also be administered via a nasogastric tube, as described in the Instructions for Use.
• Administer NEXIUM for delayed-release oral suspension orally or via a nasogastric or gastric tube, as described in the Instructions for Use.

Repackaged By / Distributed By: RemedyRepack Inc.

625 Kolter Drive, Indiana, PA 15701

(724) 465-8762

MEDICATION GUIDE

NEXIUM ^® (nex-e-um) NEXIUM ^® (nex-e-um)

(esomeprazole magnesium) (esomeprazole magnesium)

delayed-release capsules, for oral use for delayed-release oral suspension

What is the most important information I should know about NEXIUM?

NEXIUM may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

NEXIUM can cause serious side effects, including:

• A type of kidney problem (acute tubulointerstitial nephritis). Some people who take proton pump inhibitor (PPI) medicines, including NEXIUM, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with NEXIUM. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine.
• Diarrhea caused by an infection ( Clostridium difficile) in your intestines. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever.
• Bone fractures (hip, wrist, or spine). Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine.
• Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including NEXIUM, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Talk to your doctor about your risk of these serious side effects.

NEXIUM can have other serious side effects. See “ What are the possible side effects of NEXIUM? ”

What is NEXIUM?

A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach.

NEXIUM is used in adults for:

• 4 to 8 weeks for the healing and symptom relief of acid-related damage to the esophagus (erosive esophagitis or EE). Your doctor may prescribe another 4-8 weeks of NEXIUM in patients whose EE does not heal.
• maintaining healing of EE.
• 4-8 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD).
• up to 6 months to reduce the risk of stomach ulcers in some people taking pain medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
• treating patients with a stomach infection ( Helicobacter pylori) and a stomach ulcer, along with the antibiotics amoxicillin and clarithromycin.
• the long-term treatment of conditions where your stomach makes too much acid, including Zollinger-Ellison Syndrome. Zollinger-Ellison Syndrome is a rare condition in which the stomach produces a more than normal amount of acid.

NEXIUM is used in children and adolescents 12 to 17 years of age for:

• 4 to 8 weeks to heal EE.
• 4 weeks to treat heartburn and other symptoms that happen with GERD.

NEXIUM is used in children 1 to 11 years of age for:

• 8 weeks to heal EE.
• up to 8 weeks to treat heartburn and other symptoms that happen with GERD.

NEXIUM is used in children 1 month to less than 1 year of age to treat GERD with EE for up to 6 weeks.

It is not known if NEXIUM is safe and effective in children under 1 month of age for the treatment of GERD with EE.

It is not known if NEXIUM is safe and effective in children less than 1 year of age for the treatment of GERD symptoms.

It is not known if NEXIUM is safe and effective in children to reduce the risk of stomach ulcers in children who take medicines called NSAIDs, to treat Helicobacter pylori stomach infection to lower the risk of a stomach ulcer returning, and to treat conditions where your stomach makes too much acid.

Do not take NEXIUM if you are:

• allergic to esomeprazole magnesium, any other PPI medicine, or any of the ingredients in NEXIUM. See the end of this Medication Guide for a complete list of ingredients in NEXIUM.

Tell your doctor right away or get emergency medical help if you get any of the following symptoms of an allergic reaction with NEXIUM:

• • rash
  • face swelling
  • throat tightness
  • difficulty breathing
• taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY) used to treat HIV-1 (Human Immunodeficiency Virus).

Before taking NEXIUM, tell your doctor about all of your medical conditions, including if you:

• have low magnesium levels, low calcium levels and low potassium levels in your blood.
• have liver problems.
• are pregnant or plan to become pregnant. It is not known if NEXIUM will harm your unborn baby.
• are breastfeeding or planning to breastfeed. NEXIUM may pass into your breast milk. Talk to your doctor about the best way to feed your baby if you take NEXIUM.

Tell your doctor about all of the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take: clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), rilpivirine (EDURANT), St. John’s Wort (Hypericum perforatum), or rifampin (Rimactane, Rifater, Rifamate).

How should I take NEXIUM?

• Take NEXIUM exactly as prescribed by your doctor.
• Do not change your dose or stop NEXIUM without talking to your doctor.
• Take NEXIUM at least 1 hour before a meal.
• Antacids may be taken with NEXIUM.
• Swallow NEXIUM capsules whole. Never chew or crush NEXIUM.
• If you have difficulty swallowing NEXIUM capsules, you may open the capsule and empty the granules into 1 tablespoon of applesauce. The applesauce used should not be hot and should be soft enough to swallow without chewing. Do not mix the NEXIUM granules with any other food.
• Do not crush or chew the granules. Be sure to swallow the applesauce right away. Throw away any remaining mixture. Do not store it for later use.
• If you forget to take a dose of NEXIUM, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose on time. Do not take a double dose to make up for a missed dose.
• If you take too much NEXIUM, call your doctor or local poison control center right away at 1-800-222-1222, or go to the nearest hospital emergency room.
• See the Instructions for Use at the end of this Medication Guide for instructions how to take NEXIUM for delayed-release oral suspension, and how to mix and give NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension through a nasogastric tube or gastric tube.

What are the possible side effects of NEXIUM?

NEXIUM can cause serious side effects, including:

• See “What is the most important information I should know about NEXIUM?”
• Low vitamin B-12 levels in your body can happen in people who have taken NEXIUM for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs.
• Low magnesium levels in your body can happen in people who have taken NEXIUM for at least 3 months.
• Tell your doctor right away if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice.
• Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.
• Severe skin reactions. NEXIUM can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:
  • Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).
  • You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.

Stop taking NEXIUM and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.

The most common side effects of NEXIUM may include:

headache diarrhea nausea gas

These are not all the possible side effects of NEXIUM. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store NEXIUM? Keep NEXIUM and all medicines out of the reach of children. General information about the safe and effective use of NEXIUM. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NEXIUM for a condition for which it was not prescribed. Do not give NEXIUM to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about NEXIUM that is written for health professionals. What are the ingredients in NEXIUM? Active ingredient: esomeprazole magnesium trihydrate Inactive ingredients in NEXIUM delayed-release capsules (including the capsule shells): glyceryl monostearate 40-55, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, triethyl citrate, gelatin, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, shellac, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, sodium hydroxide, polyvinyl pyrrolidone, and D&C Yellow #10. Inactive granules in NEXIUM for delayed-release oral suspension: dextrose, xanthan gum, crospovidone, citric acid, iron oxide, and hydroxypropyl cellulose. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: March 2022 Instructions for Use NEXIUM ® (nex-e-um) (esomeprazole magnesium) for delayed-release oral suspension Taking NEXIUM in water: Giving NEXIUM with water through a nasogastric tube (NG tube) or gastric tube NEXIUM delayed-release capsules: NEXIUM for delayed-release oral suspension: This Instructions for Use has been approved by the U.S. Food and Drug Administration. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762 stomach (abdominal) pain constipation dry mouth Store NEXIUM at room temperature between 68°F to 77°F (20°C to 25°C). Keep the container of NEXIUM closed tightly. NEXIUM for delayed-release oral suspension comes in foil packets containing 2.5 mg, 5 mg, 10 mg, 20 mg, or 40 mg of NEXIUM. Use an oral syringe to measure the amount of water needed to mix your dose. Ask your pharmacist for an oral syringe. If your prescribed dose is 2.5 mg or 5 mg, add 5 mL of water to a container. Add the contents of a foil packet containing the dose prescribed by your doctor. If your prescribed dose is 10 mg, 20 mg, or 40 mg, add 15 mL of water to a container. Add the contents of a foil packet containing the dose prescribed by your doctor. If you or your child are instructed to use more than one foil packet for the prescribed dose, follow the mixing instructions provided by your pharmacist or doctor. Stir. Leave the mixture for 2 to 3 minutes to thicken. Stir and drink the mixture within 30 minutes. If not used within 30 minutes, throw away this dose and mix a new dose. If any medicine remains in the container after drinking, add more water, stir, and drink right away. For young children, you can give the dose with an oral syringe. Rinse the oral syringe with water after each use. Open the capsule and empty the granules into a 60 mL catheter tipped syringe. Mix with 50 mL of water. Use only a catheter tipped syringe to give NEXIUM through a NG tube. Replace the plunger and shake the syringe well for 15 seconds. Hold the syringe with the tip up and check for granules in the tip. Do not give the granules if they have dissolved or have broken into pieces. Attach the syringe to the NG tube. Give the medicine right away in the syringe through the NG tube into the stomach. After giving the granules, flush the NG tube with more water. NEXIUM for delayed-release oral suspension comes in foil packets containing 2.5 mg, 5 mg, 10 mg, 20 mg, or 40 mg of NEXIUM. Use only a catheter tipped syringe to give NEXIUM through a NG tube or gastric tube. If your prescribed dose is 2.5 mg or 5 mg, add 5 mL of water to a catheter tipped syringe. Add the contents of a foil packet containing the dose prescribed by your doctor. If your prescribed dose is 10 mg, 20 mg, or 40 mg, add 15 mL of water to a catheter tipped syringe. Add the contents of a foil packet containing the dose prescribed by your doctor. Shake the syringe well for 15 seconds and then leave it for 2 to 3 minutes to thicken. Shake the syringe and give the medicine through the NG or gastric tube (French size 6 or larger) into the stomach within 30 minutes. Refill the syringe with the same amount of water (either 5 mL or 15 mL of water depending on your dose). Shake the syringe and flush any remaining medicine from the NG tube or gastric tube into the stomach.

DRUG: NEXIUM

GENERIC: Esomeprazole magnesium

DOSAGE: CAPSULE, DELAYED RELEASE

ADMINSTRATION: ORAL

NDC: 70518-2038-0

COLOR: purple

SHAPE: CAPSULE

SCORE: No score

SIZE: 14 mm

IMPRINT: NEXIUM40mg

PACKAGING: 20 in 1 BOTTLE, PLASTIC

ACTIVE INGREDIENT(S):

• ESOMEPRAZOLE MAGNESIUM 40mg in 1

INACTIVE INGREDIENT(S):

• GLYCERYL MONOSTEARATE
• SODIUM HYDROXIDE
• POLYETHYLENE GLYCOL, UNSPECIFIED
• BUTYL ALCOHOL
• ISOPROPYL ALCOHOL
• ALCOHOL
• TITANIUM DIOXIDE
• D&C RED NO. 28
• FD&C RED NO. 40
• FD&C BLUE NO. 1
• GELATIN, UNSPECIFIED
• POLYSORBATE 80
• TRIETHYL CITRATE
• TALC
• METHACRYLIC ACID
• MAGNESIUM STEARATE
• HYPROMELLOSE, UNSPECIFIED
• HYDROXYPROPYL CELLULOSE (1600000 WAMW)
• POVIDONE, UNSPECIFIED
• D&C YELLOW NO. 10

NEXIUM esomeprazole magnesium capsule, delayed release

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70518-2038(NDC:0186-5040) Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ESOMEPRAZOLE MAGNESIUM (ESOMEPRAZOLE) ESOMEPRAZOLE 40 mg

Inactive Ingredients Ingredient Name Strength GLYCERYL MONOSTEARATE HYDROXYPROPYL CELLULOSE (1600000 WAMW) HYPROMELLOSE, UNSPECIFIED MAGNESIUM STEARATE METHACRYLIC ACID TALC TRIETHYL CITRATE POLYSORBATE 80 GELATIN, UNSPECIFIED FD&C BLUE NO. 1 FD&C RED NO. 40 D&C RED NO. 28 TITANIUM DIOXIDE ALCOHOL ISOPROPYL ALCOHOL BUTYL ALCOHOL POLYETHYLENE GLYCOL, UNSPECIFIED SODIUM HYDROXIDE POVIDONE, UNSPECIFIED D&C YELLOW NO. 10

Product Characteristics Color purple (Amethyst) Score no score Shape CAPSULE Size 14mm Flavor Imprint Code NEXIUM40mg Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:70518-2038-0 20 CAPSULE, DELAYED RELEASE in 1 BOTTLE, PLASTIC None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021153 04/26/2019

Labeler — REMEDYREPACK INC. (829572556)

Revised: 03/2022 REMEDYREPACK INC.