Other Definitions
metronidazole (dict)
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MetronidazoleMetronidazole is an antibiotic and antiparasitic drug classified as a nitroimidazole. It inhibits nucleic acid synthesis and is used for the treatment of infections involving anaerobic bacteria as well as protozoal infections. Conditions it is useful in include: giardiasis, amoebiasis, Trichomonas vaginalis infections, bacterial vaginosis, pseudomembranous colitis, Helicobacter pylori infections, and acne rosacea. Brand names for metronidazole include Flagyl, Metryl, Protostat, Satric, and Neo-Tric. DESCRIPTION WARNING Metronidazole has been shown to be carcinogenic in mice and rats (see PRECAUTIONS.) Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS AND USAGE section below. This monograph contains full prescribing information for metronidazole tablets and gel. Information for metronidazole intravenous injection is provided in the following sections: DESCRIPTION , INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION. Oral Metronidazole is an oral synthetic antiprotozoal and antibacterial agent, 1-(beta-hydroxyethyl)-2-methyl-5-nitroimidazole, which has the following structural formula: Metronidazole tablets contain 250 mg or 500 mg of metronidazole. Inactive ingredients include cellulose, FD&C Blue No. 2 Lake, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, stearic acid, and titanium dioxide. I.V. Injection Metronidazole HCl Sterile IV and Metronidazole Sterile IV, are parenteral dosage forms of the synthetic antibacterial agents 1-(beta-hydroxyethyl)-2-methyl-5 -nitroimidazole hydrochloride and 1-(beta-hydroxyethyl)-methyl- 5-nitroimidazole, respectively. Each single-dose vial of lyophilized Metronidazole IV contains sterile, nonpyrogenic Metronidazole HCl, equivalent to 500 mg metronidazole, and 415 mg mannitol. Each Metronidazole IV RTU (Ready-To-Use) 100-ml single-dose plastic container contains a sterile, nonpyrogenic, isotonic, buffered solution of 500 mg metronidazole, 47.6 mg sodium phosphate, 22.9 mg citric acid, and 790 mg sodium chloride in Water for Injection USP. Metronidazole IV RTU has a tonicity of 310 mOsm/L and a pH of 5 to 7. Each container contains 14 mEq of sodium. The plastic container is fabricated from a specially formulated polyvinyl chloride plastic. Water can permeate from inside the container into the overwrap in amounts insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di 2-ethyhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animal according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. CLINICAL PHARMACOLOGY Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours. The major route of elimination of metronidazole and its metabolites is via the urine (60 to 80% of the dose), with fecal excretion accounting for 6 to 15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation (1-(beta-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5- nitroimidazole-1-yl-acetic acid) and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 ml/min/1.73m2. Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity. Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses. Following oral administration metronidazole is well absorbed with peak plasma concentrations occurring between one and two hours after administration. 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. Decreased renal function dose not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function. Microbiology Trichomonas vaginalis, Entamoeba histolytica. Metronidazole possesses direct trichomonacidal and amebicidal activity against T. vaginalis and E. histolytica. The in vitro minimal inhibitory concentration (MIC) for most strains of these organisms is 1 mcg/ml or less. Anaerobic Bacteria. Metronidazole is active in vitro against most obligate anaerobes, but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Against susceptible organisms, metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Metronidazole has been shown to havein vitro and clinical activity against the following organisms: Anaerobic gram-negative bacilli, including: Bacteroides species including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B vulgatus) Fusobacterium species Anaerobic gram-positive bacilli, including: Clostridium species and susceptible strains of Eubacterium Anaerobic gram-positive cocci, including: Peptococcus nigerns = "urn:schemas-microsoft-com:office:smarttags" /> Peptostreptococcus species Susceptibility Testing: Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to metronidazole; however, the rapid, routine susceptibility testing of individual isolates of anaerobic bacteria is not always practical, and therapy may be started while awaiting these results. Quantitative methods give the most precise estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended.1 Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more of the following strains should be included: Clostridium perfringens A.C. 13124,Bacteroides fragilis ATCC 25285, and Bacteroides thetaiotamicron A.C. 29741. The mode metronidazole M.C. for those three strains are reported to be 0.25, 0.25, and 0.5 mcg/ml, respectively. A clinical laboratory is considered under acceptable control if the results of the control strains are within one doubling dilution of the mode M.C. reported for metronidazole. A bacterial isolate may be considered susceptible if the MIC value for metronidazole is not more than 16 mcg/ml. An organism is considered resistant if the MIC is greater than 16 mcg/ml. A report of "resistant" from the laboratory indicates that the infecting organism is not likely to respond to therapy. INDICATIONS Oral Tablets Symptomatic Trichomoniasis: Metronidazole is indicated for the treatment of symptomatic trichomoniasis in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures). Asymptomatic Trichomoniasis: Metronidazole is indicated in the treatment of asymptomatic females when the organism is associated with endocervicitis, cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite. Treatment of Asymptomatic Consorts: T. vaginalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in the order to prevent reinfection of the partner. The decision as to whether to treat an asymptomatic male partner who has a negative culture or one for whom no culture has been attempted is an individual one. In making this decision, it should be noted that there is evidence that a woman may become reinfected if her consort is not treated. Also, since there can be considerable difficulty in isolating the organism from the asymptomatic male carrier, negative smears and cultures cannot be relied upon in this regard. In any event, the consort should be treated with Metronidazole in cases of reinfection. Amebiasis: Metronidazole is indicated in the treatment of acute intestinal amebiasis (amebic dysentery and amebic liver abscess. In amebic liver abscess. Metronidazole therapy does not obviate the need for aspiration or drainage of pus. Anaerobic Bacterial Infections: Metronidazole is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Metronidazole therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole. In the treatment of most serious anaerobic infections, Metronidazole IV RTU (metronidazole) is usually administered initially. This may be followed by oral therapy with Metronidazole at the discretion of the physician. Intra-Abdominal Infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostridium species,Eubacterium species, Peptococcus niger, and Peptostreptococcus species. Skin and Skin Structure Infections caused by Bacteroides species including the B. fragilis group, Clostridium species,Peptococcus niger, Peptostreptococcus species, and Fusobacterium species. Gynecological Infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused byBacteroides species including the B. fragilis group,Clostridium species, Peptococcus niger, and Peptostreptococcus species. Bacterial Septicemia caused by Bacteroides species including theB. fragilis group, and Clostridium species. Bone and Joint Infections, as adjunctive therapy, caused byBacteroides species including the B. fragilis group. Central Nervous System (CNS) Infections, including meningitis and brain abscess, caused by Bacteroides species including the B. fragilis group. Lower Respiratory Tract Infections, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. fragilis group. Endocarditis caused by Bacteroides species including the B. fragilis group. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Flagyl and other antibacterial drugs, Flagyl 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. IV Injection Treatment of Anaerobic Infections: Metronidazole IV is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Metronidazole IV therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole IV. Metronidazole IV is effective in Bacteroides fragilis infections resistant to clindamycin, chloramphenicol, and penicillin. Intra--Abdominal Infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. Vulgatus), Clostridium species, Eubacterium species, Peptococcus species, and Peptostreptococcus species. Skin and Skin Structure Infections, caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus species, and Fusobacterium species. Gynecological Infections, including endometritis, endomyometritis, tubo- ovarian abscess, and postsurgical vaginal cuff infection, caused byBacteroides species including the B. fragilis group,Clostridium species, Peptococcus species, and Peptostreptococcus species. Bacterial Septicemia, caused by Bacteroides species including theB. fragilis group, and Clostridium species. Bone and Joint Infection, as adjunctive therapy, caused byBacteroides species including the B. fragilis group. Central Nervous System (CNS) Infections, including meningitis and brain abscess, caused by Bacteroides species including the B. Fragilis group. Lower Respiratory Tract Infections, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. Fragilis group. Endocarditis, caused by the Bacteroides species, including theB. Fragilis group. Prophylaxis The prophylactic administration of Metronidazole IV preoperatively, intraoperatively, intraoperatively, and postoperatively may reduce the incidence of postoperative infection in patients undergoing elective colorectal surgery which is classified as contaminated or potentially contaminated. Prophylactic use of Metronidazole IV should be discontinued within 12 hours after surgery. If there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism(s) so that appropriate therapy may be given (See DOSAGE AND ADMINISTRATION). DOSAGE AND ADMINISTRATION Oral Tablets In elderly patients the pharmacokinetics of metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly. Trichomoniasis In the Female: One-day treatment: two grams of Metronidazole, given either as a single dose or in two divided doses of one gram each given in the same day. Seven-day course of treatment: 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears, signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen. 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 of the female long enough to treat sexual contacts. Further, some patients may tolerate one course of therapy better than the other. Pregnant patients should not be treated during the first trimester with either regimen. If treated during the second or third trimester, the one-day course of therapy should not be used, as it results in higher serum levels which reach the fetal circulation. (See CONTRAINDICATIONS and PRECAUTIONS.) 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 for the female. Amebiasis Adults: For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days. For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days. Children: 36 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days. ''' Anaerobic Bacterial Infections''' In the treatment of most serious anaerobic infections, Metronidazole HCl IV or Metronidazole IV RTU is usually administered initially. 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-hours 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. Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Close monitoring of plasma metronidazole levels2 and toxicity is recommended. The dose of Metronidazole should not be specifically reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis. Store below 86F (30C) and protect from light. Intravenous Injection In elderly patients the pharmacokinetics of metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly. Treatment of Anaerobic Infections The recommended dosage schedule for adults is: Loading Dose: 15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult). Maintenance Dose: 7.5 mg/kg infused over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose. Parenteral therapy may be changed to oral Metronidazole when conditions warrant, based upon the severity of the disease and the response of the patient to Metronidazole IV treatment. The usual adult oral dosage is 7.5 mg/kg every six hours. A maximum of 4 g should not be exceeded during a 24-hour period. Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in te plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Close monitoring of plasma metronidazole levels1 and toxicity is recommended. In patients receiving Metronidazole in whom gastric secretions are continuously removed by nasogastric aspiration, sufficient Metronidazole may be removed in the aspirate to cause a reduction in serum levels. The dose of Metronidazole should not be specifically rescued in anuric patients since accumulated metabolites may be rapidly removed by dialysis. 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. Prophylaxis For surgical; prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is: 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery; followed by 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose. It is important that (1) administration of the initial preoperative dose be completed approximately one hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and (2) Metronidazole IV be administered, if necessary, at 6- hours intervals to maintain effective drug levels. Prophylactic use of Metronidazole IV should be limited to the day of surgery only, following the above guidelines. CAUTION: Metronidazole IV is to be administered by slow intravenous drip infusion only, either as a continuous or intermittent infusion. IV admixtures containing metronidazole and other drugs should be avoided. Additives should not be introduced into the Metronidazole IV RTU solution. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion. DO NOT USE EQUIPMENT CONTAINING ALUMINUM (EG, NEEDLES, CANNULAE) T.A. WOULD C.M. IN CONTACT WITH THE DRUG SOLUTION. Metronidazole IV Metronidazole IV cannot be given by direct intravenous injection (IV bolus) because of the low pH (0.5 to 2.0) of the reconstituted product. Metronidazole IV MUST BE FURTHER DILUTED AND NEUTRALIZED FOR IV INFUSION. Metronidazole IV is prepared for use in two steps: NOTE: ORDER OF MIXING IS IMPORTANT Reconstitution Dilution in intravenous solution followed by pH neutralization with sodium bicarbonate injection into the dilution. Reconstitution: To prepare the solution, add 4.4 ml of one of the following diluents and mix thoroughly; Sterile Water for Injection, USP; Bacteriostatic Water for Injection, USP; 0.9% Sodium Chloride Injection, USP; or Bacteriostatic 0.9% Sodium Chloride Injection, USP. The resultant approximate withdrawal volume is 5.0 ml with an approximate concentration of 100 mg/ml. The pH of the reconstituted product will be in the range will be in the range of 0.5 to 2.0. Reconstituted Metronidazole IV is clear, and pale yellow to yellow-green in color. Dilution in Intravenous Solution: Properly reconstituted Metronidazole HCl IV may be added to a glass or plastic IV container not to exceed a concentration of 8 mg/ml. Any of the following intravenous solutions may be used: 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; or Lactated Ringer's Injection, USP. Neutralization Is Required Prior To Administration The final product should be mixed thoroughly and used within 24 hours. Neutralization For Intravenous Infusion: Neutralize the intravenous solution containing Metronidazole HCl IV with approximately 5 mEq of sodium bicarbonate injection for each 500 mg of Metronidazole HCl IV used. Mix thoroughly. The pH of the neutralized intravenous solution will be approximately 6.0 to 7.0. Carbon dioxide gas will be generated with neutralization. It may be necessary to relieve gas pressure within the container. Note: When the contents of one vial (500 mg) are diluted and neutralized to 100 ml, the resultant concentration is 5 mg/ml. Do not exceed an 8 mg/ml concentration of Metronidazole HCl IV in the neutralized intravenous solution, since neutralization will decrease the aqueous solubility and precipitation may occur. DO NOT REFRIGERATE NEUTRALIZED SOLUTION; otherwise, precipitation may occur. Metronidazole IV RTU (Ready To Use) Metronidazole IV RTU is a ready-to-use isotonic solution. NO DILUTION OR BUFFERING IS REQUIRED. Do not refrigerate. Each container of Metronidazole IV RTU contains 14 mEq of sodium. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if cloudy or precipitated or if the seal is not intact. Use sterile equipment. It is recommended that the intravenous administration apparatus be replaced at least once every 24 hours. Store Metronidazole HCl IV, prior to reconstitution, should be stored below 86F (30C) and protected from light. Metronidazole IV RTU should be stored at controlled room temperature , 59 to 86F (15 to 30C), and protected from light during storage. HOW SUPPLIED Flagyl 250-mg tablets are round, blue, film coated, with SEARLE and 1831 debossed on one side and FLAGYL and 250 on the other side; bottles of 50 and 100. Flagyl 500-mg tablets are oblong, blue, film coated, with FLAGYL debossed on one side and 500 on the other side; bottles of 50 and 100. Storage and Stability: Store below 77F (25C) and protect from light. WARNINGS Convulsive Seizures and Peripheral Neuropathy Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of Metronidazole therapy. Metronidazole should be administered with caution to patients with central nervous system diseases. PRECAUTIONS General Tablets/IV Injection: Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with Metronidazole and requires treatment with a candicidal agent. Prescribing metronidazole in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Laboratory Tests Tablets/IV Injection: Metronidazole is a nitroimidazole and should be used with care in patients with evidence of or history of blood dyscrasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended before and after therapy for trichomoniasis and amebiasis, especially if a second course of therapy is necessary, and before and after therapy for anaerobic infection. Drug/Laboratory Test Interactions Tablets/IV Injection: Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotine adenine dinucleotide (NAD+<-> NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7. Carcinogenesis, Mutagenesis, and Impairment of Fertility Tumorigenicity studies in rodents: Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats. Prominent among the effects in the mouse was pulmonary tumorigenesis. This has been observed in all six reported studies in that species, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). At very high dose levels (approx. 500 mg/kg/day) there was statistically significant increase in the incidence of malignant liver tumors in males. Also, the published results of one of the mouse studies indicate an increase in the incidence of malignant lymphomas as well as pulmonary neoplasms associated with lifetime feeding of the drug. All these effects are statistically significant. Several long-term, oral-dosing studies in the rat have been completed. There were statistically significant increase in the incidence of various neoplasms, particularly in mammary and hepatic tumors, among female rats administered metronidazole over those noted in the concurrent female control groups. Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative. Mutagenicity Studies Although metronidazole has shown mutagenic activity in a number of in vitro assay systems, studies in mammals (in vivo) have failed to demonstrate a potential for genetic damage. Fertility studies have been performed in mice at doses up to six times the maximum recommended human dose based on mg/m2 and have revealed no evidence of impaired fertility. Pregnancy Teratogenic Effects-Pregnancy Category B. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to metronidazole. Metronidazole administered intraperitoneally to pregnant mice at approximately the human dose caused fetotoxicity; administered orally to pregnant mice, no fetotoxicity was observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed (see CONTRAINDICATIONS.) Use of Metronidazole for trichomoniasis in the second and third trimesters should be restricted to those in whom local palliative treatment has been inadequate to control symptoms. Use of Flagyl (metronidazole) for trichomoniasis in pregnancy should be carefully evaluated because metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known (see above). Nursing Mothers Tablets: Because of the potential for tumorigenicity shown for metronidazole in mouse and rat 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. Metronidazole is secreted in breast milk in concentrations similar to those found in plasma. Pediatric Use Safety and effectiveness in children have not been established, except for the treatment of amebiasis. Geriatric use: Decreased renal function does not alter the single-dose harmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function. Therefore, in elderly patients, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly OVERDOSE Tablets 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 studies 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 every other day. Treatment: There is no specific antidote for Metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy. IV Injection Use of dosages of metronidazole HCl IV higher than those recommended has been reported. These include the use of 27 mg/kg three times a day for 20 days, and the use of 75 mg/kg as a single loading dose followed by 7.5 mg/kg maintenance doses. No adverse reactions were reported in either of the two cases. 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 off 6 to 10.4 g every other day. Treatment: There is no specific antidote for overdose; therefore, management of the patient should consist of symptomatic and supportive therapy. CONTRAINDICATIONS Tablets/IV Metronidazole is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives. Additional Information for Tablets In patients with trichomoniasis, Metronidazole is contraindicated during the first trimester of pregnancy. (see WARNINGS.) PATIENT INFORMATION Alcoholic beverages should be avoided while taking Metronidazole and for at least one day afterward. See DRUG INTERACTIONS. Patients should be counseled that antibacterial drugs including Flagyl should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Flagyl is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Flagyl or other antibacterial drugs in the future.
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