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Prevacid I.V. (Lansoprazole) - Warnings and Precautions

 
 



PRECAUTIONS

General

Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.

Treatment with PREVACID I.V. for Injection should be discontinued as soon as the patient is able to resume treatment with PREVACID oral formulations.

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).

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) 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 body surface area) exceeded the low background incidence (range = 1.4 to 10%) for this strain of rat. Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/kg/day (13 times the recommended human dose based on body surface area) 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 body surface area. 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 body surface area) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times the recommended human dose based on body surface area) 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 body surface area).

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 body surface area) 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 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 body surface area). 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, this drug 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 the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of PREVACID I.V. 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 lansoprazole treated subjects, similar percentages of adverse events were reported in males and females.

Over 4,000 women were treated with oral lansoprazole. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events 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 adverse events and laboratory test abnormalities are also similar to those seen in younger patients. For elderly patients, dosage and administration of lansoprazole need not be altered for a particular indication.

Page last updated: 2006-09-19

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