Prescription Drugs

PREVACID® I.V. (lansoprazole) for Injection 30 mg/vial DESCRIPTION The active ingredient in PREVACID I.V. (lansoprazole) for Injection is 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 C16H14F3N3O2S with a molecular weight of 369.37. PREVACID 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. PREVACID I.V. for Injection contains 30 mg of the active ingredient lansoprazole, 60 mg mannitol, 10 mg meglumine, and 3.45 mg sodium hydroxide and is supplied as a sterile, lyophilized powder for I.V. (intravenous) use. The solution of PREVACID I.V. (lansoprazole for injection) for Injection has a pH of approximately 11 following the first reconstitution with Sterile Water for Injection, USP, and approximately 10.2, 10.0, or 9.5 after further dilution with either 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or 5% Dextrose Injection, USP, respectively.

INDICATIONS When patients are unable to take the oral formulations, PREVACID I.V. (lansoprazole for injection) for Injection is indicated as an alternative for the short-term treatment (up to 7 days) of all grades of erosive esophagitis. Once the patient is able to take medications orally, therapy can be switched to an oral formulation of PREVACID for a total of 6 to 8 weeks. The safety and efficacy of PREVACID I.V. (lansoprazole for injection) for Injection as an initial treatment of erosive esophagitis have not been demonstrated. Refer to full prescribing information for the oral formulations of PREVACID. DOSAGE AND ADMINISTRATION PREVACID I.V. (lansoprazole for injection) for Injection admixtures should be administered intravenously using the in-line filter provided. The filter must be used to remove precipitate that may form when the reconstituted drug product is mixed with I.V. solutions. Studies have shown that filtration does not alter the amount of lansoprazole that is available for administration. Read the following instructions carefully. There are two methods for preparing PREVACID I.V. (lansoprazole for injection) for Injection: 1. Reconstitution in Vial and Preparation of Admixture. OR 2. Direct reconstitution with Baxter's MINI-BAG Plus Container. 1. Reconstitution in Vial and Preparation of Admixture There are two steps for preparing PREVACID I.V. (lansoprazole for injection) for Injection. STEP ONE - Reconstitution in Vial - First PREVACID I.V. (lansoprazole for injection) MUST be reconstituted with Sterile Water for Injection, USP. - Inject 5 mL of ONLY Sterile Water for Injection, USP into a 30 mg vial of PREVACID I.V. for Injection. The resulting solution will contain lansoprazole 6 mg/mL (30 mg/5 mL). - Failure to reconstitute with Sterile Water may result in formation of precipitation/particulates. - Mix gently until the powder is dissolved. The pH of this reconstituted solution is approximately 11. The reconstituted solution can be held for 1 hour when stored at 25ºC (77ºF) prior to further dilution. STEP TWO - Preparation of Admixture - Dilute the reconstituted solution in either 50 mL of 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or 5% Dextrose Injection, USP. - The admixture should be stored at 25ºC (77ºF) and should be administered within the designated time period as listed in Table 5. No refrigeration is required. Table 5 Diluent pH Administer within: 0.9% Sodium Chloride Injection, USP Approximately 10.2 24 hours Lactated Ringer's Injection, USP Approximately 10.0 24 hours 5% Dextrose Injection, USP Approximately 9.5 12 hours - Once the admixture is prepared, proceed to Instructions for Priming and Use of Filter. 2. Reconstitution with Baxter's MINI-BAG Plus Container - PREVACID I.V. (lansoprazole for injection) for Injection can be reconstituted directly into 50 mL of 0.9% Sodium Chloride for Injection, USP or 5% Dextrose Injection, USP utilizing Baxter's MINI-BAG Plus Container. - Refer to separate instructions that are provided with Baxter's MINI-BAG Plus Container. - Once the admixture is prepared, proceed to Instructions for Priming and Use of Filter. The admixture should be stored at 25ºC (77ºF) and should be administered within the designated time period as listed in Table 6. No refrigeration is required. Table 6 Diluent pH Administer within: 0.9% Sodium Chloride Injection, USP Approximately 10.2 24 hours 5% Dextrose Injection, USP Approximately 9.5 8 hours Instructions for Priming and Use of Filter TO PRIME FILTER - Prime administration set in usual manner and close administration set clamp. - Connect luer adapter of administration set to filter inlet using a twisting motion. Over-tightening should be avoided. - Hold filter below the level of solution container. - Open administration set clamp and slowly prime filter. - Close administration set clamp. Verify no air bubbles are present on patient side of filter. - If air bubbles are observed, open set clamp slightly to re-establish flow then gently tap filter housing. Observe that no air bubbles are present and close clamp. - Connect to patient and regulate flow. Filter may be primed using a syringe and saline. - The administration set can then be connected to inlet of filter. PRECAUTIONS WITH USE OF FILTER Follow instructions carefully: - Use Aseptic technique. For single use only. Do not resterilize or reuse. Do not use if package is damaged. - If repositioning of filter is required, loosen luer locking collar, reposition, then retighten locking collar firmly. - Maximum working pressure is 1500 mmHg (30 psi, 2 bar). When the working limits of the filter are exceeded, causes of the added resistance should be investigated and corrected. - The internal volume of the filter is approx. 0.7 mL. - The administration set clamp should be closed during solution container change. - Pumps should not be used downstream of filter. Administration Do not administer with other drugs or diluents as this may cause incompatibilities. IN-LINE FILTER THAT IS PROVIDED MUST BE USED when administering PREVACID I.V. (lansoprazole for injection) for Injection via an administration set. Follow these steps: Flush the PREVACID I.V. (lansoprazole for injection) for Injection administration port before administration of PREVACID I.V. (lansoprazole for injection) for Injection with at least 5 cc of either: 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or 5% Dextrose Injection, USP. Attach the filter and administration set. Administer PREVACID I.V. (lansoprazole for injection) for Injection over 30 minutes. Remove and discard the administration set, including the filter, used for PREVACID I.V. (lansoprazole for injection) for Injection. Flush the administration port with at least 5 cc of above mentioned solutions. If the administration port is not flushed and the administration set is not removed, lansoprazole degradation may occur with time, and black or brown particulate may be observed in the tubing or on the filter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Treatment of Erosive Esophagitis The recommended adult dose (when patients are unable to take the oral therapy) is 30 mg of lansoprazole (1 vial of PREVACID I.V. (lansoprazole for injection) for Injection) per day administered by I.V. infusion over 30 minutes for up to 7 days. Once the patient is able to take medications orally, therapy can be switched to an oral PREVACID formulation for a total of 6 to 8 weeks. Refer to full prescribing information for the oral formulations of PREVACID. No dosage adjustment is necessary in patients with renal insufficiency or the elderly. For patients with severe liver disease, dosage adjustment should be considered. HOW SUPPLIED PREVACID I.V. for Injection contains 30 mg of lansoprazole as white to pale yellow friable masses and powder in a vial and is available as follows: NDC 0300-3954-25 Tray containing 10 single dose vial packs: Each pack containing one 30-mg single dose vial of PREVACID I.V. for Injection and 1 required in-line filter (1.2 µm pore size). Store PREVACID I.V. (lansoprazole for injection) for Injection at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from light. Use carton to protect contents from light. Distributed by: TAP Pharmaceuticals Inc.,Lake Forest, IL 60045, U.S.A. MINI-BAG is a trademark of Baxter International Inc. Rev. December 2006 FDA rev date: 5/16/2007

PATIENT INFORMATION No information provided. Please refer to the PRECAUTIONS section

OVERDOSE Single intravenous doses of PREVACID at 218 mg/kg in mice (approximately 30 times the recommended human dose based on BSA) and 167 mg/kg in rats (approximately 46 times the recommended human dose based on BSA) were lethal. The symptoms of acute toxicity were decreased locomotor response, ataxia, ptosis and tonic convulsions. PREVACID is not removed from the circulation by hemodialysis. CONTRAINDICATIONS PREVACID I.V. (lansoprazole for injection) for Injection is contraindicated in patients with known severe hypersensitivity to any component of the formulation.

SIDE EFFECTS Clinical Safety Experience with PREVACID I.V. (lansoprazole for injection) for Injection More than 1,000 patients and subjects have participated in domestic and foreign clinical trials. Treatment with PREVACID I.V. (lansoprazole for injection) for Injection was well-tolerated. In four U.S. trials involving 161 subjects exposed to PREVACID I.V. (lansoprazole for injection) for Injection, the following treatment-related adverse events were reported in ≥ 1% of subjects: headache (1.0%), injection site pain (1.0%), injection site reaction (1.0%) and nausea (1.3%). Treatment-related adverse events occurring in less than 1% of subjects included abdominal pain, vasodilatation, diarrhea, dyspepsia, vomiting, dizziness, paresthesia, rash, and taste perversion. No additional adverse drug reactions were reported with the intravenous formulation that had not been reported previously with the oral formulations. Clinical Safety Experience with Oral Formulations of PREVACID Worldwide, over 10,000 patients have been treated with oral 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 events 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 4. Table 4: Incidence of Possibly or Probably Treatment-Related Adverse Events in Short-Term, Placebo-Controlled PREVACID Studies Body System/Adverse Event PREVACID Oral (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 mg 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). 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, oral 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; Metabolic and Nutritional Disorders - gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss; Musculoskeletal System - arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, synovitis; Nervous System - abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, 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, 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, blurred vision, conjunctivitis, deafness, dry eyes, ear disorder, eye pain, otitis media, parosmia, photophobia, retinal degeneration, 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 tract infection, urinary urgency, urination impaired, vaginitis. Postmarketing Additional adverse experiences have been reported since oral PREVACID has been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID has not been established. Because these events 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; Digestive System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Musculoskeletal System - myositis; Skin and Appendages - severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal); Special Senses - speech disorder; Urogenital System - interstitial nephritis, urinary retention. Laboratory Values There were no clinically important changes identified in any laboratory parameter with PREVACID I.V. (lansoprazole for injection) for Injection. The following changes in laboratory parameters in patients who received PREVACID were reported as adverse events: 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, eosinophilia, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, and increased gastrin levels. 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. DRUG INTERACTIONS Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels. In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. 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. Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, ampicillin esters, iron salts, digoxin).

WARNINGS No information provided. PRECAUTIONS General Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy. Treatment with PREVACID I.V. (lansoprazole for injection) for Injection should be discontinued as soon as the patient is able to resume treatment with PREVACID oral formulations. Carcinogenesis, Mutagenesis, Impairment of Fertility In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with doses of 5 to 150 mg/kg/day-about 1 to 40 times the exposure on a body surface (mg/m2) basis of a 50-kg person of average height [1.46 m2 body surface area (BSA)] given the recommended human dose of 30 mg/day (22.2 mg/m2). Lansoprazole produced dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, lansoprazole produced a dose-related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/kg/day (4 to 40 times the recommended human dose based on BSA) exceeded the low background incidence (range = 1.4 to 10%) for this strain of rat. Testicular interstitial cell adenoma occurred in 1 of 30 rats treated with 50 mg/kg/day (13 times the recommended human dose based on BSA) in a 1-year toxicity study. In a 24-month carcinogenicity study, CD-1 mice were treated orally with doses of 15 to 600 mg/kg/day, 2 to 80 times the recommended human dose based on BSA. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/kg/day (40 to 80 times the recommended human dose based on BSA) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times the recommended human dose based on BSA) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/kg/day (10 to 80 times the recommended human dose based on BSA). Lansoprazole was not genotoxic in the Ames test, the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone marrow cell chromosomal aberration test. It was positive in in vitro human lymphocyte chromosomal aberration assays. Lansoprazole at intravenous doses of up to 30 mg/kg/day (approximately 8 times the recommended human dose based on BSA) was found to have no effect on fertility and reproductive performance in male and female rats. Pregnancy: Teratogenic Effects Pregnancy Category B Teratology studies have been conducted in rats and rabbits using intravenous lansoprazole doses of up to 30 mg/kg/day (approximately 8 times in rats and 16 times in rabbits of the recommended human dose based on BSA). Treatment with lansoprazole did not result in any impairment of fertility or harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women using the intravenous route. Because animal reproduction studies are not always predicative of human response, PREVACID I.V. (lansoprazole for injection) for Injection should be used during pregnancy only if clearly needed. Nursing Mothers Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue PREVACID I.V. (lansoprazole for injection) for Injection, taking into account the importance of PREVACID I.V. (lansoprazole for injection) for Injection to the mother. Pediatric Use The safety and effectiveness of PREVACID I.V. (lansoprazole for injection) for Injection have not been established for pediatric patients. For further information, please see the PREVACID package insert for the oral formulations. Use in Women Among intravenous PREVACID treated subjects, similar percentages of adverse events were reported in males and females. Over 4,000 women were treated with oral PREVACID. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events in females were also similar to those seen in males. Use in Geriatric Patients Data in elderly patients administered intravenous lansoprazole is limited; however, with oral lansoprazole, ulcer healing rates in elderly patients are similar to those in a younger age group. The incidence rates of PREVACID-associated adverse events and laboratory test abnormalities are similar to those seen in younger patients. For geriatric patients, dosage and administration of PREVACID need not be altered for a particular indication.