Zegerid

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of omeprazole and sodium bicarbonate combination in children. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of omeprazole and sodium bicarbonate combination in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. 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 medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rilpivirine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amphetamine
• Atazanavir
• Bendamustine
• Benzphetamine
• Bosutinib
• Cilostazol
• Citalopram
• Clopidogrel
• Clorazepate
• Conivaptan
• Dasabuvir
• Dasatinib
• Delavirdine
• Dextroamphetamine
• Digoxin
• Elvitegravir
• Erlotinib
• Escitalopram
• Eslicarbazepine Acetate
• Gefitinib
• Indinavir
• Ketoconazole
• Ledipasvir
• Lisdexamfetamine
• Mefenamic Acid
• Memantine
• Methamphetamine
• Methotrexate
• Mycophenolate Mofetil
• Mycophenolic Acid
• Nelfinavir
• Netupitant
• Nilotinib
• Ombitasvir
• Paritaprevir
• Pazopanib
• Ritonavir
• Saquinavir
• Tacrolimus
• Velpatasvir
• Vismodegib
• Voriconazole

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Armodafinil
• Carbamazepine
• Dasatinib
• Digoxin
• Disulfiram
• Fluconazole
• Ginkgo Biloba
• Iron
• Levothyroxine
• Raltegravir
• St John's Wort
• Tipranavir
• Triazolam
• Warfarin

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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:

• Bartter's syndrome (rare kidney problem) or
• Diarrhea or
• Hypocalcemia (low calcium in the blood) or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood), history of or
• Osteoporosis (bone problem) or
• Respiratory alkalosis (low levels of carbon dioxide in the blood) or
• Seizures, history of or
• Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.

• Liver disease—You may need a dose adjustment. The effects may be increased because of slower removal of the medicine from the body.

Zegerid (omeprazole/sodium bicarbonate) is available as a capsule and as a powder for oral suspension in 20 mg and 40 mg strengths of omeprazole for adult use. Directions for use for each indication are summarized in Table 1. All recommended doses throughout the labeling are based upon omeprazole.

Since both the 20 mg and 40 mg oral suspension packets contain the same amount of sodium bicarbonate (1680 mg), two packets of 20 mg are not equivalent to one packet of Zegerid 40 mg; therefore, two 20 mg packets of Zegerid should not be substituted for one packet of Zegerid 40 mg.

Since both the 20 mg and 40 mg capsules contain the same amount of sodium bicarbonate (1100 mg), two capsules of 20 mg are not equivalent to one capsule of Zegerid 40 mg; therefore, two 20 mg capsules of Zegerid should not be substituted for one capsule of Zegerid 40 mg.

Zegerid should be taken on an empty stomach at least one hour before a meal.

For patients receiving continuous Nasogastric (NG)/Orogastric (OG) tube feeding, enteral feeding should be suspended approximately 3 hours before and 1 hour after administration of Zegerid Powder for Oral Suspension.

Special Populations

Hepatic Insufficiency

Consider dose reduction, particularly for maintenance of healing of erosive esophagitis. [See Clinical Pharmacology (12.3).]

Administration of Capsules

Zegerid Capsules should be swallowed intact with water. DO NOT USE OTHER LIQUIDS. DO NOT OPEN CAPSULE AND SPRINKLE CONTENTS INTO FOOD.

Preparation and Administration of Suspension

Directions for use: Empty packet contents into a small cup containing 1-2 tablespoons of water. DO NOT USE OTHER LIQUIDS OR FOODS. Stir well and drink immediately. Refill cup with water and drink.

If Zegerid is to be administered through a nasogastric (NG) or orogastric (OG) tube, the suspension should be constituted with approximately 20 mL of water. DO NOT USE OTHER LIQUIDS OR FOODS. Stir well and administer immediately. An appropriately-sized syringe should be used to instill the suspension in the tube. The suspension should be washed through the tube with 20 mL of water.

Zegerid 20 mg Capsules: Each opaque, hard gelatin, white capsule, imprinted with the Santarus logo and “20”, contains 20 mg omeprazole and 1100 mg sodium bicarbonate.

Zegerid 40 mg Capsules: Each opaque, hard gelatin, colored dark blue and white capsule, imprinted with the Santarus logo and “40”, contains 40 mg omeprazole and 1100 mg sodium bicarbonate.

Zegerid Powder for Oral Suspension is a white, flavored powder packaged in unit-dose packets. Each packet contains either 20 mg or 40 mg omeprazole and 1680 mg sodium bicarbonate.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (approximately 0.4 to 34.2 times the human dose of 40 mg/day 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 (approximately 3.36 times the human dose of 40 mg/day on a body surface area basis) for one 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 one year (94% treated versus 10% controls). By the second year the difference between treated and control rats was much smaller (46% versus 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 two years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week toxicity study in Sprague Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4, 2, and 16 mg/kg/day (about 0.1 to 3.9 times the human dose of 40 mg/day on a body surface area basis). No astrocytomas were observed in female rats in this study. In a 2-year carcinogenicity study in Sprague Dawley rats, no astrocytomas were found in males and females at the high dose of 140.8 mg/kg/day (about 34 times the human dose of 40 mg/day on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive.

Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration assay. Omeprazole was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay and an in vivo rat liver DNA damage assay.

In a 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals [see Warnings and Precautions (5)]. Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Omeprazole at oral doses up to 138 mg/kg/day (about 33.6 times the human dose of 40 mg/day on a body surface area basis) was found to have no effect on the fertility and general reproductive performance in rats.

Animal Toxicology and/or Pharmacology

Reproductive Toxicology Studies

Reproduction studies conducted in pregnant rats with omeprazole at doses up to 138 mg/kg/day (about 33.6 times an oral human dose of 40 mg on a body surface area basis) and in pregnant rabbits at doses up to 69 mg/kg/day (about 33.6 times an oral human dose of 40 mg 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 mg/kg/day (about 3.3 to 33.6 times the human dose of 40 mg/day 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 3.3 to 33.6 times the human dose of 40 mg/day on a body surface area basis).

Juvenile Animal Study

A 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with esomeprazole magnesium at doses of 70 to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of 40 mg on a body surface area basis). An increase in the number of deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered esomeprazole magnesium from postnatal Day 7 through postnatal Day 35. In addition, doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg on a body surface area basis), produced treatment-related decreases in body weight (approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected overall growth. Comparable findings described above have also been observed in this study with another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole.

Zegerid is a combination medicine used to treat heartburn and other symptoms of gastroesophageal reflux disease (GERD). This medicine is also used to treat ulcers and other conditions involving excessive stomach acid production. Symptom relief does not mean that serious stomach problems (like cancer) do not exist. Talk to your doctor if old stomach symptoms return or new symptoms appear.

Zegerid contains sodium bicarbonate, a form of salt. Tell your doctor if you have Bartter's syndrome (a rare kidney disorder), or if you are on a low-salt diet.

Call your doctor at once if you have symptoms of a serious side effect: confusion, dizziness, tremors or muscle twitches, severe stomach pain, watery or bloody diarrhea, vomiting, and numbness or tingling in your face, arms, or legs.

Omeprazole may increase your risk of bone fracture in the hip, wrist, or spine, especially if you take this medicine long term or at high doses.

You should not take Zegerid if you are allergic to omeprazole or sodium bicarbonate.

Zegerid contains sodium bicarbonate, a form of salt. Each capsule contains the equivalent of 300 mg of sodium. Each packet of powder contains the equivalent of 460 mg of sodium. If you are on a low-salt or low-sodium diet, you may not be able to use Zegerid. Talk with your doctor.

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.

Ask a doctor or pharmacist if it is safe for you to use Zegerid if you have other medical conditions, especially:

• a rare kidney disorder called Bartter's syndrome;

• liver disease;

• any allergies;

• heart disease; or

• low levels of calcium, magnesium, or potassium levels in your blood.

Taking a proton pump inhibitor such as omeprazole may increase your risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people who have taken the medication long term or at high doses, and in those who are age 50 and older.

Some conditions are treated with a combination of antibiotics with Zegerid. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

It is not known whether Zegerid will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Omeprazole and sodium bicarbonate can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Zegerid is not approved for use by anyone younger than 18 years old.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Avoid taking this medicine with milk if you use Zegerid long-term.

Applies to omeprazole / sodium bicarbonate: oral capsule, oral packet

Along with its needed effects, omeprazole / sodium bicarbonate may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking omeprazole / sodium bicarbonate:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest pain
• confusion
• convulsions
• cough
• decreased urine
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• dry mouth
• fainting
• fast or irregular heartbeat
• fever or chills
• headache
• increased thirst
• lightheadedness
• loss of appetite
• muscle pain or cramps
• muscle spasms (tetany) or twitching
• nausea or vomiting
• nervousness
• numbness or tingling in the hands, feet, or lips
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• rapid, shallow breathing
• seizures
• slow heartbeat
• sneezing
• sore throat
• sweating
• tightness in the chest
• trembling
• troubled breathing
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach cramps or pain
• bladder pain
• blue lips, fingernails, or skin
• bone pain
• chest discomfort
• cloudy urine
• coma
• decreased urine output
• difficult or troubled breathing
• difficult, burning, or painful urination
• fast, pounding, or irregular heartbeat or pulse
• frequent urge to urinate
• headache
• irregular, fast or slow, or shallow breathing
• irritability
• lower back or side pain
• muscle cramps in the hands, arms, feet, legs, or face
• restlessness
• swelling
• swelling of the face, feet, lower legs, ankles, or hands
• weakness or heaviness of the legs

• Severe pain in the chest
• sudden onset of severe breathing difficulty

• Arm, back, or jaw pain
• blistering, peeling, or loosening of the skin
• bloating or swelling of the face, arms, hands, lower legs, or feet
• chest tightness or heaviness
• constipation
• cough or hoarseness
• dark-colored urine
• diarrhea
• difficulty with swallowing
• fever with or without chills
• general body swelling
• general feeling of tiredness or weakness
• greatly decreased frequency of urination or amount of urine
• high fever
• hives or skin rash
• indigestion
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• noisy breathing
• nosebleeds
• pain with swallowing
• pains in the stomach, side, or abdomen, possibly radiating to the back
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• red skin lesions, often with a purple center
• red, irritated eyes
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain, continuing
• sweating
• swollen glands
• unexplained bleeding or bruising
• unusual weight gain or loss
• weight gain
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking omeprazole / sodium bicarbonate:

• Feeling of warmth
• increased sweating
• redness of the face, neck, arms, and occasionally, upper chest

Some side effects of omeprazole / sodium bicarbonate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Agitation
• cold sweats
• cool, pale skin
• depression
• excess air or gas in the stomach or intestines
• flushed, dry skin
• fruit-like breath odor
• full feeling
• increased hunger
• increased thirst
• increased urination
• lack or loss of strength
• nightmares
• passing gas
• shakiness
• slurred speech
• white patches in the mouth or throat or on the tongue
• white patches with diaper rash

• Abnormal dreams
• attack, assault, or force
• bad, unusual, or unpleasant (after) taste
• blindness
• blue-yellow color blindness
• change in taste
• continuing ringing or buzzing or other unexplained noise in the ears
• decreased vision
• double vision
• dry eyes or skin
• eye pain
• feeling of constant movement of self or surroundings
• general feeling of discomfort or illness
• hair loss or thinning of the hair
• hearing loss
• hives or welts
• increased sensitivity of the skin to sunlight
• itching, redness, tearing, or other sign of eye irritation not present before use of this medicine or becoming worse during use
• lack of feeling or emotion
• pain in the testes
• pinpoint red or purple spots on the skin
• redness or other discoloration of the skin
• seeing, hearing, or feeling things that are not there
• sensation of spinning
• severe sunburn
• sleepiness or unusual drowsiness
• sugar in the urine
• swelling of the breasts or breast soreness in both females and males
• swelling or inflammation of the mouth
• trouble sleeping
• uncaring

Applies to omeprazole / sodium bicarbonate: oral capsule, oral powder for reconstitution

Other

Very common (10% or more): Pyrexia (Up to 20.2%)
Common (1% to 10%): Hyperpyrexia, candida infection NOS, sepsis NOS

Omeprazole:
Common (1% to 10%): Asthenia
Postmarketing reports: Fever, pain, fatigue, malaise, tinnitus[Ref]

Metabolic

Very common (10% or more): Hypokalemia (Up to 12.4%), hyperglycemia NOS (Up to 10.7%), hypomagnesemia (Up to 10.1%)
Common (1% to 10%): Fluid overload, hyperkalemia, hypernatremia, hypocalcemia, hyponatremia, hypoglycemia NOS, hypophosphatemia

Omeprazole:
Postmarketing reports: Anorexia, hyponatremia, hypoglycemia, hypomagnesemia, weight gain

Sodium Bicarbonate:
Postmarketing reports: Metabolic acidosis, tetany[Ref]

Respiratory

Very common (10% or more): Nosocomial pneumonia (Up to 11.2%)
Common (1% to 10%): Acute respiratory distress syndrome, respiratory failure
Uncommon (0.1% to 1%): Pneumothorax NOS

Omeprazole:
Common (1% to 10%): Upper respiratory infection, cough
Postmarketing reports: Bronchospasm, epistaxis, pharyngeal pain[Ref]

Hematologic

Very common (10% or more): Thrombocytopenia (Up to 10.1%)
Common (1% to 10%): Anemia NOS, anemia NOS aggravated

Omeprazole:
Postmarketing reports: Pancytopenia, agranulocytosis/fatal agranulocytosis, thrombocytopenia, neutropenia, leukopenia, anemia, leukocytosis, hemolytic anemia[Ref]

Cardiovascular

Common (1% to 10%): Atrial fibrillation, bradycardia not otherwise specified (NOS), supraventricular tachycardia, tachycardia NOS, ventricular tachycardia, edema NOS, hypertension NOS, hypotension NOS

Omeprazole:
Postmarketing reports: Chest pain/angina, tachycardia, bradycardia, palpitation, elevated blood pressure, peripheral edema[Ref]

Gastrointestinal

Common (1% to 10%): Constipation, diarrhea NOS, gastric hypomobility, oral candidiasis
Frequency not reported: Upper gastrointestinal bleeding

Omeprazole:
Common (1% to 10%): Diarrhea, abdominal pain, nausea, vomiting, constipation, flatulence, acid regurgitation
Postmarketing reports: Pancreatitis/fatal pancreatitis, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, dry mouth, stomatitis, abdominal swelling, gastric fundic gland polyps, Clostridium difficile associated diarrhea[Ref]

Benign gastric fundic gland polyps occurred rarely and appeared to be reversible when omeprazole was discontinued.[Ref]

Dermatologic

Common (1% to 10%): Decubitus ulcer, rash NOS

Omeprazole:
Common (1% to 10%): Rash
Postmarketing reports: Urticaria, severe generalized skin reactions, toxic epidermal necrolysis (TEN)/fatal TEN, Steven-Johnson syndrome, erythema multiforme/severe erythema multiforme, purpura and/or petechia with/without rechallenge, skin inflammation, urticaria, pruritus, photosensitivity, alopecia, dry skin, hyperhidrosis, systemic lupus erythematosus, cutaneous lupus erythematosus[Ref]

Hepatic

Common (1% to 10%): Abnormal liver function tests NOS

Omeprazole:
Postmarketing reports: Mild to marked elevation of liver function tests (ALT, AST, gamma-glutamyl transpeptidase, alkaline phosphatase), overt liver disease, jaundice, hepatocellular/cholestatic/mixed hepatitis, liver necrosis/fatal liver necrosis, hepatic failure/fatal hepatic failure[Ref]

Psychiatric

Common (1% to 10%): Agitation

Omeprazole:
Postmarketing reports: Psychiatric disturbances, depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, anxiety, abnormal dreams[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection NOS

Omeprazole:
Postmarketing reports: Urinary tract infection, microscopic pyuria, urinary frequency, proteinuria, hematuria, testicular pain[Ref]

Nervous system

Omeprazole:
Common (1% to 10%): Headache, dizziness
Postmarketing reports: Hepatic encephalopathy, tremors, somnolence, vertigo, paresthesia, hemifacial dysesthesia, taste perversion

Sodium Bicarbonate:
Postmarketing reports: Seizures[Ref]

Musculoskeletal

Omeprazole:
Common (1% to 10%): Back pain
Postmarketing reports: Muscle cramps, myalgia, muscle weakness, joint pain, bone fracture, leg pain[Ref]

Ocular

Omeprazole:
Postmarketing reports: Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis, double vision[Ref]

Hypersensitivity

Omeprazole:
Postmarketing reports: Hypersensitivity reactions, anaphylaxis, anaphylactic shock, angioedema[Ref]

Renal

Omeprazole:
Postmarketing reports: Interstitial nephritis with/without positive rechallenge, elevated serum creatinine, glycosuria[Ref]

Oncologic

Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term therapy. This condition may be a manifestation of the underlying condition, which is known to be associated with these tumors.[Ref]

Omeprazole:
Postmarketing reports: Gastroduodenal carcinoids[Ref]

Endocrine

Omeprazole:
Postmarketing reports: Gynecomastia[Ref]

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