METRONIDAZOLE- metronidazole_tablet

Absorption Plasma concentrations of metronidazole are proportional to the administered dose. Oral administration of 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of 6 mcg/mL, 12 mcg/mL, and 40 mcg/mL, respectively. Studies reveal no significant bioavailability differences between males and females; however, because of weight differences, the resulting plasma levels in males are generally lower. Distribution Metabolism/Excretion in vitro Renal clearance of metronidazole is approximately 10 mL/min/1. 73 m 2 Renal Impairment Subjects with end-stage renal disease (ESRD; CL CR max max CR PRECAUTIONS Effect of Dialysis DOSAGE AND ADMINISTRATION Hepatic Impairment 24 24 DOSAGE AND ADMINISTRATION PRECAUTIONS DOSAGE AND ADMINISTRATION Geriatric Patients PRECAUTIONS Pediatric Patients Microbiology Mechanism of Action Metronidazole, USP is active against most obligate anaerobes, but does not possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Activity In Vitro In Vivo Metronidazole has been shown to be active against most isolates of the following bacteria both in vitro INDICATIONS AND USAGE Gram-positive anaerobes Clostridium Eubacterium Peptococcus Peptostreptococcus Gram-negative anaerobes Bacteroides fragilis B. fragilis, B. distasonis, B. thetaiotaomicron, B. vulgatus Fusobacterium Protozoal parasites Entamoeba histolytica Trichomonas vaginalis The following in vitro but their clinical significance is unknown: Metronidazole exhibits in vitro Gram-negative anaerobes Bacteroides fragilis B. uniformis Prevotella P. disiens Susceptibility Test Methods in vitro Anaerobic Techniques 1,2 Susceptibility Test Interpretive Criteria for Metronidazole MIC (mcg/mL) Interpretation <= 8 Susceptible (S) 16 Intermediate (I) >= 32 Resistant (R) For protozoal parasites: A report of "Susceptible" indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of the drug product is physiologically concentrated or in situations where a high dosage of the drug product can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected. Quality Control 1,2 Agar and Broth Acceptable Quality Control Ranges for Metronidazole Acceptable Quality Control Ranges for Metronidazole QC Strain Minimum Inhibitory Agar Broth Bacteroides fragilis 0. 0 Bacteroides thetaiotaomicron 0.

Symptomatic Trichomoniasis. T. vaginalis Asymptomatic Trichomoniasis. T. vaginalis Treatment of Asymptomatic Sexual Partners. T. vaginalis Amebiasis. In amebic liver abscess, METRONIDAZOLE, USP therapy does not obviate the need for aspiration or drainage of pus. Anaerobic Bacterial Infections. INTRA-ABDOMINAL INFECTIONS, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides B. fragilis B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus Clostridium Eubacterium Peptococcus Peptostreptococcus SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides B. fragilis Clostridium Peptococcus Peptostreptococcus Fusobacterium GYNECOLOGIC INFECTIONS, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused by Bacteroides B. fragilis Clostridium Peptococcus Peptostreptococcus Fusobacterium BACTERIAL SEPTICEMIA caused by Bacteroides B. fragilis Clostridium BONE AND JOINT INFECTIONS, (as adjunctive therapy), caused by Bacteroides B. fragilis CENTRAL NERVOUS SYSTEM (CNS) INFECTIONS, including meningitis and brain abscess, caused by Bacteroides B. fragilis LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, empyema, and lung abscess, caused by Bacteroides B. fragilis ENDOCARDITIS caused by Bacteroides B. fragilis To reduce the development of drug-resistant bacteria and maintain the effectiveness of METRONIDAZOLE, USP and other antibacterial drugs, METRONIDAZOLE, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Trichomoniasis: One-day treatment Seven-day course of treatment The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen. A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other. Pregnant patients should not be treated during the first trimester (see CONTRAINDICATIONS PRECAUTIONS, Pregnancy When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatment. In the Male: Treatment should be individualized as it is for the female. Amebiasis For acute intestinal amebiasis (acute amebic dysentery): For amebic liver abscess: Pediatric patients: Anaerobic Bacterial Infections The usual adult oral dosage is 7. 5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period. The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment. Dosage Adjustments Patients with Severe Hepatic Impairment CLINICAL PHARMACOLOGY PRECAUTIONS Patients Undergoing Hemodialysis: CLINICAL PHARMACOLOGY.

The following reactions have been reported during treatment with metronidazole: Central Nervous System: WARNINGS Gastrointestinal: Mouth: Candida Dermatologic: Hematopoietic: Cardiovascular: Hypersensitivity: Renal: Other: Candida Patients with Crohn’s disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn’s disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn’s disease is not an approved indication for METRONIDAZOLE tablets, USP. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at 1-866-562-4597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Hypersensitivity In patients with trichomoniasis, METRONIDAZOLE Tablets, USP is contraindicated during the first trimester of pregnancy (see PRECAUTIONS Psychotic Reaction with Disulfiram PRECAUTIONS, Drug Interactions Interaction with Alcohol PRECAUTIONS, Drug Interactions.

Disulfiram CONTRAINDICATIONS Alcoholic Beverages CONTRAINDICATIONS Warfarin and other Oral Anticoagulants Lithium Busulfan Drugs that Inhibit CYP450 Enzymes Drugs that Induce CYP450 Enzymes Drug/Laboratory Test Interactions +

WARNINGS
Central and Peripheral Nervous System Effects Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole. CNS lesions seen on MRI have also been described as reversible. Peripheral neuropathy, mainly of sensory type has been reported and is characterized by numbness or paresthesia of an extremity. Convulsive seizures have been reported in patients treated with metronidazole. Aseptic meningitis: Cases of aseptic meningitis have been reported with metronidazole. Symptoms can occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued. The appearance of abnormal neurologic signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy (see ADVERSE REACTIONS
OVERDOSAGE
Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia. Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day. Treatment of Overdosage:
REFERENCES
Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - Eighth Edition. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement,

Rising Pharma Holdings, Inc.

METRONIDAZOLE- metronidazole_tablet Product manual source documgent