PREVACID

The active ingredient in PREVACID Delayed-Release Capsules and PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets is lansoprazole, a substituted benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulfinyl] benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C 16 H 14 F 3 N 3 O 2 S with a molecular weight of 369.37. Lansoprazole has the following structure: Lansoprazole is a white to brownish-white odorless crystalline powder which melts with decomposition at approximately 166°C. Lansoprazole is freely soluble in dimethylformamide; soluble in methanol; sparingly soluble in ethanol; slightly soluble in ethyl acetate, dichloromethane and acetonitrile; very slightly soluble in ether; and practically insoluble in hexane and water. Lansoprazole is stable when exposed to light for up to two months. The rate of degradation of the compound in aqueous solution increases with decreasing pH. The degradation half-life of the drug substance in aqueous solution at 25°C is approximately 0.5 hour at pH 5.0 and approximately 18 hours at pH 7.0. PREVACID is supplied in delayed-release capsules and PREVACID SoluTab is supplied in delayed-release orally disintegrating tablets (SoluTab) for oral administration. PREVACID is available in one dosage strength: 30 mg of lansoprazole per capsule. Each delayed-release capsule contains enteric-coated granules consisting of 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: sugar sphere, sucrose, methacrylic acid copolymer, low substituted hydroxypropyl cellulose, starch, magnesium carbonate, talc, polyethylene glycol, titanium dioxide, polysorbate 80, hydroxypropyl cellulose, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, and FD&C Red No. 40. The 15 mg strength of PREVACID is not currently marketed by Takeda Pharmaceuticals America, Inc. PREVACID SoluTab is available in two dosage strengths: 15 and 30 mg of lansoprazole per tablet. Each delayed-release orally disintegrating tablet contains enteric-coated microgranules consisting of 15 or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: mannitol, methacrylic acid, hydroxypropyl cellulose, lactose monohydrate-microcrystalline cellulose sphere, triethyl citrate, crospovidone, polyacrylate, magnesium carbonate, aspartame Phenylketonurics: PREVACID SoluTab Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet. , glyceryl monostearate, hypromellose, magnesium stearate, citric acid, titanium dioxide, talc, artificial strawberry flavor, polyethylene glycol, polysorbate 80 and ferric oxide. Chemical Structure

PREVACID and PREVACID SoluTab are proton pump inhibitors (PPIs) indicated for the: Treatment of active duodenal ulcer in adults. ( 1.1 ) Eradication of H. pylori to reduce the risk of duodenal ulcer recurrence in adults. ( 1.2 ) Maintenance of healed duodenal ulcers in adults. ( 1.3 ) Treatment of active benign gastric ulcer in adults. ( 1.4 ) Healing of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults. ( 1.5 ) Risk reduction of NSAID-associated gastric ulcer in adults. ( 1.6 ) Treatment of symptomatic gastroesophageal reflux disease (GERD) in adults and pediatric patients 1 year of age and older. ( 1.7 ) Treatment of erosive esophagitis (EE) in adults and pediatric patients 1 year of age and older. ( 1.8 ) Maintenance of healing of EE in adults. ( 1.9 ) Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (ZES) in adults. ( 1.10 ) 1.1 Treatment of Active Duodenal Ulcer PREVACID and PREVACID SoluTab are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see Clinical Studies (14.1) ] . 1.2 Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: PREVACID or PREVACID SoluTab/amoxicillin/clarithromycin PREVACID or PREVACID SoluTab in combination with amoxicillin plus clarithromycin as triple therapy is indicated in adults for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.2) ] . Please refer to the full prescribing information for amoxicillin and clarithromycin. Dual Therapy: PREVACID or PREVACID SoluTab/amoxicillin PREVACID or PREVACID SoluTab in combination with amoxicillin as dual therapy is indicated in adults for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, Microbiology section). Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.2) ] . Please refer to the full prescribing information for amoxicillin. 1.3 Maintenance of Healed Duodenal Ulcers PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months [see Clinical Studies (14.3) ] . 1.4 Treatment of Active Benign Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see Clinical Studies (14.4) ] . 1.5 Healing of NSAID-Associated Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond eight weeks [see Clinical Studies (14.5) ] . 1.6 Risk Reduction of NSAID-Associated Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks [see Clinical Studies (14.6) ] . 1.7 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) PREVACID and PREVACID SoluTab are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with GERD [see Clinical Studies (14.7) ] . 1.8 Treatment of Erosive Esophagitis (EE) PREVACID and PREVACID SoluTab are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of EE. For adults who do not heal with PREVACID or PREVACID SoluTab for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. If there is a recurrence of erosive esophagitis an additional eight week course of PREVACID or PREVACID SoluTab may be considered [see Clinical Studies (14.8) ] . 1.9 Maintenance of Healing of EE PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of EE. Controlled studies did not extend beyond 12 months [see Clinical Studies (14.9) ] . 1.10 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (ZES) PREVACID and PREVACID SoluTab are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome [see Clinical Studies (14.10) ] .

Recommended Dosage : See full prescribing information for complete dosing information for PREVACID and PREVACID SoluTab by indication and age group and dosage adjustment in patients with severe hepatic impairment. ( 2.1 , 2.2 , 2.3 ) Administration Instructions ( 2.4 ) PREVACID capsules Should be swallowed whole. See full prescribing information for alternative administration options. PREVACID SoluTab Should not be broken or cut. Should not be chewed. Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed. See full prescribing information for alternative administration options. 2.1 Recommended Adult Dosage by Indication Indication Recommended Dose Frequency Duodenal Ulcers Short-Term Treatment 15 mg Once daily for 4 weeks Maintenance of Healed 15 mg Once daily Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence Please refer to the amoxicillin and clarithromycin full prescribing information, Contraindications and Warnings and Precautions sections, and for information regarding dosing in elderly and renally-impaired patients. Triple Therapy: PREVACID or PREVACID SoluTab 30 mg Twice daily for 10 or 14 days Amoxicillin 1 gram Twice daily for 10 or 14 days Clarithromycin 500 mg Twice daily for 10 or 14 days Dual Therapy: PREVACID or PREVACID SoluTab 30 mg Three times daily for 14 days Amoxicillin 1 gram Three times daily for 14 days Benign Gastric Ulcer Short-Term Treatment 30 mg Once daily for up to 8 weeks NSAID-Associated Gastric Ulcer Healing 30 mg Once daily for 8 weeks Controlled studies did not extend beyond indicated duration. Risk Reduction 15 mg Once daily for up to 12 weeks Gastroesophageal Reflux Disease (GERD) Short-Term Treatment of Symptomatic GERD 15 mg Once daily for up to 8 weeks Short-Term Treatment of Erosive Esophagitis 30 mg Once daily for up to 8 weeks For patients who do not heal with PREVACID or PREVACID SoluTab for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. If there is a recurrence of erosive esophagitis, an additional eight week course of PREVACID or PREVACID SoluTab may be considered. Maintenance of Healing of Erosive Esophagitis 15 mg Once daily Controlled studies did not extend beyond 12 months. Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome 60 mg Once daily Varies with individual patient. Recommended adult starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with PREVACID for more than four years. 2.2 Recommended Pediatric Dosage by Indication Pediatric Patients 1 to 11 Years of Age In clinical studies, PREVACID was not administered beyond 12 weeks in 1 to 11 year olds. It is not known if PREVACID is safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in pediatric patients as outlined below [see Use in Specific Populations (8.4) ] . Indication Recommended Dose Frequency Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis ≤30 kg 15 mg Once daily for up to 12 weeks >30 kg 30 mg Once daily for up to 12 weeks Pediatric Patients 12 to 17 Years of Age Indication Recommended Dose Frequency Short-Term Treatment of Symptomatic GERD Non-erosive GERD 15 mg Once daily for up to 8 weeks Erosive Esophagitis 30 mg Once daily for up to 8 weeks 2.3 Hepatic Impairment The recommended dosage is 15 mg orally daily in patients with severe liver impairment (Child-Pugh C) [see Use in Specific Populations (8.6) ] . 2.4 Important Administration Information Take PREVACID or PREVACID SoluTab before meals. Do not crush or chew PREVACID capsule or PREVACID SoluTab. Take PREVACID or PREVACID SoluTab at least 30 minutes prior to sucralfate [see Drug Interactions (7) ] . Antacids may be used concomitantly with PREVACID or PREVACID SoluTab. Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose. PREVACID capsules Swallow whole; do not chew. For patients who have difficulty swallowing capsules, PREVACID capsules can be opened and administered orally or via a nasogastric tube in the soft foods or liquids specified below. Administration of PREVACID in foods or liquids other than those discussed below have not been studied clinically and therefore are not recommended. Administration in Soft Foods (applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears): Open capsule. Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears. Swallow immediately. Administration in Liquids (apple juice, orange juice or tomato juice): Open capsule. Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately two ounces). Mix briefly. Swallow immediately. To ensure complete delivery of the dose, rinse the glass with two or more volumes of juice and swallow the contents immediately. Administration with Apple Juice Through a Nasogastric Tube (≥16 French) Open capsule. Sprinkle intact granules into 40 mL of apple juice. Mix briefly. Using a catheter-tipped syringe, draw up the mixture. Inject through the nasogastric tube into the stomach. Flush with additional apple juice to clear the tube. PREVACID SoluTab Do not break or cut. Place the tablet on the tongue, allow it to disintegrate, with or without water, until the microgranules can be swallowed. Do not chew the microgranules. The tablet typically disintegrates in less than one minute. Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID SoluTab can be administered with water via oral syringe or NG tube as follows: Administration with Water in an Oral Syringe Place a 15 mg tablet in oral syringe and draw up 4 mL of water, or place a 30 mg tablet in oral syringe and draw up 10 mL of water. Shake gently to allow for a quick dispersal. After the tablet has dispersed, administer the contents within 15 minutes of mixing into the mouth. Do not save the water and microgranule mixture for later use. Refill the syringe with approximately 2 mL (5 mL for the 30 mg tablet) of water, shake gently, and administer any remaining contents. Administration with Water via a NG Tube (≥8 French) Place a 15 mg tablet in a catheter-tip syringe and draw up 4 mL of water, or place a 30 mg tablet in a catheter-tip syringe and draw up 10 mL of water. Shake gently to allow for a quick dispersal. After the tablet has dispersed, shake the catheter-tip syringe gently in order to keep the microgranules from settling, and immediately inject the mixture through the NG tube into the stomach within 15 minutes of mixing. Do not save the water and microgranule mixture for later use. Refill the catheter-tip syringe with approximately 5 mL of water, shake gently, and flush the tube.

PREVACID and PREVACID SoluTab are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . Proton Pump Inhibitors (PPIs), including PREVACID and PREVACID SoluTab, are contraindicated with rilpivirine-containing products [see Drug Interactions (7) ] . For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Contraindications section of their prescribing information. Contraindicated in patients with known hypersensitivity to any component of the PREVACID or PREVACID SoluTab formulations. ( 4 ) Patients receiving rilpivirine-containing products. ( 4 , 7 )

The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.3) ] Bone Fracture [see Warnings and Precautions (5.4) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6) ] Cyanocobalamin (Vitamin B12) Deficiency [see Warnings and Precautions (5.7) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.8) ] Fundic Gland Polyps [see Warnings and Precautions (5.12) ] Most commonly reported adverse reactions (≥1%): diarrhea, abdominal pain, nausea and constipation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 clinical practice. Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials. The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients in Table 1 . Table 1. Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID Studies Body System/Adverse Reaction PREVACID (N=2768) % Placebo (N=1023) % Body as a Whole Abdominal Pain 2.1 1.2 Digestive System Constipation 1.0 0.4 Diarrhea 3.8 2.3 Nausea 1.3 1.2 Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 and 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9, 1.4, 4.2, and 7.4%, respectively). The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea. In the risk reduction study of PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with PREVACID, misoprostol, and placebo was 5, 22, and 3%, respectively. Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with PREVACID included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment. Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below: Body as a Whole – abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain Cardiovascular System – angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation Digestive System – abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis Endocrine System – diabetes mellitus, goiter, hypothyroidism Hemic and Lymphatic System – anemia, hemolysis, lymphadenopathy Metabolism and Nutritional Disorders – avitaminosis, gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss Musculoskeletal System – arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis Nervous System – abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo Respiratory System – asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor Skin and Appendages – acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria Special Senses – abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect Urogenital System – abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis 6.2 Postmarketing Experience Additional adverse experiences have been reported since PREVACID and PREVACID SoluTab have been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID or PREVACID SoluTab has not been established. Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below by COSTART body system. Body as a Whole – anaphylactic/anaphylactoid reactions, systemic lupus erythematosus; Digestive System – hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System – agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Infections and Infestations – Clostridium difficile -associated diarrhea; Metabolism and Nutritional Disorders – hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia; Musculoskeletal System – bone fracture, myositis; Skin and Appendages – severe dermatologic reactions including erythema multiforme, SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus; Special Senses – speech disorder; Urogenital System – interstitial nephritis, urinary retention. 6.3 Combination Therapy with Amoxicillin and Clarithromycin In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with PREVACID, amoxicillin, or clarithromycin. Triple Therapy: PREVACID/amoxicillin/clarithromycin The most frequently reported adverse reactions for patients who received triple therapy for 14 days were diarrhea (7%), headache (6%), and taste perversion (5%). There were no statistically significant differences in the frequency of reported adverse reactions between the 10 and 14 day triple therapy regimens. No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen. Dual Therapy: PREVACID/amoxicillin The most frequently reported adverse reactions for patients who received PREVACID three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with PREVACID three times daily plus amoxicillin three times daily dual therapy than with PREVACID alone. For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information. 6.4 Laboratory Values The following changes in laboratory parameters in patients who received PREVACID were reported as adverse reactions: Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported. In the placebo-controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and PREVACID, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received PREVACID reported jaundice at any time during the study. In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed. For information about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information.

Tables 2 and 3 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PREVACID or PREVACID SoluTab and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 2. Clinically Relevant Interactions Affecting Drugs Coadministered with PREVACID or PREVACID SoluTab and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with lansoprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with lansoprazole may increase toxicity of the antiretroviral drugs. There are other antiretroviral drugs which do not result in clinically relevant interactions with lansoprazole. Intervention: Rilpivirine-containing products : Concomitant use with PREVACID or PREVACID SoluTab is contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir : See prescribing information for atazanavir for dosing information. Nelfinavir : Avoid concomitant use with PREVACID or PREVACID SoluTab. See prescribing information for nelfinavir. Saquinavir : See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals : See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.10) ] . Intervention: A temporary withdrawal of PREVACID or PREVACID SoluTab may be considered in some patients receiving high-dose methotrexate. Digoxin Clinical Impact: Potential for increased exposure of digoxin. Intervention: Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. Theophylline Clinical Impact: Increased clearance of theophylline [see Clinical Pharmacology (12.3) ] . Intervention: Individual patients may require additional titration of their theophylline dosage when PREVACID or PREVACID SoluTab is started or stopped to ensure clinically effective blood concentrations. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Lansoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Coadministration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PREVACID and MMF. Use PREVACID and PREVACID SoluTab with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See Contraindications and Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Intervention: Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.9) , Clinical Pharmacology (12.2) ] . Intervention: Temporarily stop PREVACID or PREVACID SoluTab treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Intervention: Temporarily stop PREVACID or PREVACID SoluTab treatment at least 28 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2) ] . False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs. Intervention: An alternative confirmatory method should be considered to verify positive results. Table 3. Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Coadministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . Intervention: St John's Wort, rifampin : Avoid concomitant use with PREVACID or PREVACID SoluTab. Ritonavir-containing products : See prescribing information. CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . Intervention: Voriconazole : See prescribing information. Sucralfate Clinical Impact: Decreased and delayed absorption of lansoprazole [see Clinical Pharmacology (12.3) ] . Intervention: Take PREVACID or PREVACID SoluTab at least 30 minutes prior to sucralfate [see Dosage and Administration (2.4) ] . See full prescribing information for a list of clinically important drug interactions. ( 7 )

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].