Merrem (Meropenem) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenesis studies have not been performed.

Mutagenesis

Genetic toxicity studies were performed with meropenem using the bacterial reverse mutation test, the Chinese hamster ovary HGPRT assay, cultured human lymphocytes cytogenic assay, and the mouse micronucleus test. There was no evidence of mutagenic potential found in any of these tests.

Impairment of fertility

Reproductive studies were performed with meropenem in rats at doses up to 1000 mg/kg/day, and cynomolgus monkeys at doses up to 360 mg/kg/day (on the basis of AUC comparisons, approximately 1.8 times and 3.7 times, respectively, to the human exposure at the usual dose of 1 g every 8 hours). There was no reproductive toxicity seen.

OVERDOSAGE

In mice and rats, large intravenous doses of meropenem (2200-4000 mg/kg) have been associated with ataxia, dyspnea, convulsions, and mortalities.

Intentional overdosing of MERREM I.V. is unlikely, although accidental overdosing might occur if large doses are given to patients with reduced renal function. The largest dose of meropenem administered in clinical trials has been 2 g given intravenously every 8 hours. At this dosage, no adverse pharmacological effects or increased safety risks have been observed.

Limited post-marketing experience indicates that if adverse events occur following overdosage, they are consistent with the adverse event profile described in the Adverse Reactions section and are generally mild in severity and resolve on withdrawal or dose reduction. Symptomatic treatments should be considered. In individuals with normal renal function, rapid renal elimination takes place. Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis; however, no information is available on the use of hemodialysis to treat overdosage.

CONTRAINDICATIONS

MERREM I.V. is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to β-lactams.

REFERENCES

1.NCCLS. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—Sixth Edition. NCCLS document M7-A6 (ISBN 1-56238-486-4). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, January, 2003.

2.NCCLS. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard -- Eighth Edition. NCCLS document M2-A8 (ISBN 1-56238-485-6). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, January, 2003.

3. Clinical and Laboratory Standards Institute (CLSI)/NCCLS. Performance Standards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement. CLSI/NCCLS document M100-S15 (ISBN 1-56238-556-9). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, January, 2005

4.NCCLS. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard Sixth Edition. NCCLS document M11-A6 (ISBN 1-56238-517-8). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA, January, 2004.

5.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16:31-41.

†NORMOSOL is a registered trademark of Hospira Inc.

All other trademarks are the property of the AstraZeneca group of companies.

© AstraZeneca 2006, 2007

Manufactured for:

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

By:

Dainippon Sumitomo Pharma Co., Ltd

6–8, Doshomachi 2–chrome, Chuo-ku, Osaka 541–8524, Japan

Made in Japan

SIC 30131-05

Rev 11/07