Prevacid I.V. for injection

When patients are unable to take the oral formulations, PREVACID I.V. 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. for Injection as an initial treatment of erosive esophagitis have not been demonstrated. Refer to full prescribing information for the oral formulations of PREVACID.

PREVACID I.V. for Injection is contraindicated in patients with known hypersensitivity to any component of the formulation.

Clinical Safety Experience with PREVACID I.V. for Injection

More than 1,000 patients and subjects have participated in domestic and foreign clinical trials. Treatment with PREVACID I.V. for Injection was well tolerated.

In four U.S. trials involving 161 subjects exposed to PREVACID I.V. 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 <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 lansoprazole in Phase 2-3 clinical trials involving various dosages and durations of treatment. In general, lansoprazole 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:

Incidence of Possibly or Probably Treatment-Related Adverse Events in Short-Term, Placebo-Controlled 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 lansoprazole 15 mg and 30 mg, but higher in the patients who received lansoprazole 60 mg (2.9%, 1.4%, 4.2%, and 7.4%, respectively).

Additional adverse experiences occurring in <1% of patients or subjects in domestic trials are shown below. Refer to Postmarketing for adverse reactions occurring since the drug was marketed.

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

On-going Safety Surveillance: Additional adverse experiences have been reported since oral lansoprazole has been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole 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 - anaphylactoid-like reaction; Digestive System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Skin and Appendages - severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal); Special Senses - speech disorder; Urogenital System - urinary retention.

Laboratory Values

There were no clinically important changes identified in any laboratory parameter with PREVACID I.V. for Injection.

The following changes in laboratory parameters for oral lansoprazole 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) placebo patients and 0.4% (11/2677) lansoprazole patients had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these lansoprazole patients reported jaundice at any time during the study.

PREVACID I.V. for Injection MUST be reconstituted with 5 mL of Sterile Water for Injection, USP. Failure to reconstitute with Sterile Water may result in formation of precipitation/particulates. PREVACID I.V. 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 drug that is available for administration. (See instructions below).

1. Reconstitution in vial
   
   • 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).
   • 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 25[ordm ]C (77[ordm ]F) prior to further dilution.
2. 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 25[ordm ]C (77[ordm ]F) and should be administered within the designated time period as listed in the Table below. No refrigeration is required.
   
   

   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

   
   
3. 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.
   • It is recommended that this filter is changed at 24 hours.
   • Pumps should not be used downstream of filter.
4. Administration
   
   • IN-LINE FILTER MUST BE USED.
   • Administer intravenously over 30 minutes.
   • A dedicated line is not required; however, the intravenous line should be flushed before and after administration of PREVACID I.V. for Injection with either 0.9% Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or 5% Dextrose Injection, USP.
   • Do not administer with other drugs or diluents as this may cause incompatibilities.

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. 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 SUPPLIED0

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. 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.

U.S. Patent No. 4,628,098.

Distributed by

TAP Pharmaceuticals Inc.

Lake Forest, IL 60045, U.S.A.

(List 3954)

750035289R1, Rev. May, 2004

© 2004 TAP Pharmaceutical Products Inc.

PRODUCT PHOTO(S):

NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug's identity should be verified by chemical analysis.