Metronidazole

Metronidazole has been shown to be carcinogenic in mice and rats (see

). Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the section below.

Metronidazole capsules 375 mg are indicated for the treatment of infection in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures).

Metronidazole capsules 375 mg are indicated in the treatment of asymptomatic infection in 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.

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 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 sexual partner 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 sexual partner should be treated with metronidazole in cases of reinfection.

Metronidazole capsules 375 mg are indicated in the treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess.

In amebic liver abscess, metronidazole capsules 375 mg therapy does not obviate the need for aspiration or drainage of pus.

Metronidazole capsules 375 mg are 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, antimicrobials appropriate for the treatment of the aerobic infection should be used in addition to metronidazole capsules 375 mg.

INTRA-ABDOMINAL INFECTIONS, including peritonitis, intra-abdominal abscess, and liver abscess, caused by

species including the group (), species, species, or species.

SKIN AND SKIN STRUCTURE INFECTIONS caused by

species including the group, species, species, or species.

GYNECOLOGIC INFECTIONS, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused by

species including the group, species, speciesspecies, or species.

BACTERIAL SEPTICEMIA caused by

species including the group or species.

BONE AND JOINT INFECTIONS (as adjunctive therapy) caused by

species including the group.

CENTRAL NERVOUS SYSTEM (CNS) INFECTIONS, including meningitis and brain abscess, caused by

species including the group.

LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, empyema, and lung abscess, caused by

species including the group.

ENDOCARDITIS caused by

species including the group.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of metronidazole capsules 375 mg and other antibacterial drugs, metronidazole capsules 375 mg 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.

 

In the Female: Seven-day course of treatment (375 mg two times daily for seven consecutive days).

A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain treatment. Pregnant patients should not be treated during the first trimester (see

and ).

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.

 

Adults:

750 mg orally three times daily for 5 to 10 days.

750 mg orally three times daily for 5 to 10 days.

35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.

 

In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially.

The usual adult oral dosage is 7.5 mg/kg every 6 hours (approximately 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.

 

For amebiasis patients with severe (Child-Pugh C) hepatic impairment, pharmacokinetic modeling and simulation indicate that the metronidazole capsules 375 mg dose should be reduced by 50%. Therefore, the dosage regimen of metronidazole capsules 375 mg in Child Pugh C patients with amebiasis is 375 mg q8h for 5 to 10 days (see

and ).

For trichomoniasis patients with severe (Child-Pugh C) hepatic impairment, pharmacokinetic modeling and simulation indicate that the frequency of metronidazole administration should be reduced from every 12 hours to every 24 hours. Therefore, the dosage regiment of metronidazole capsules 375 mg in Child Pugh C patients with trichomoniasis is 375 mg q24h for 7 days (see

and ).

Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from a hemodialysis session, supplementation of metronidazole dosage following the hemodialysis session should be considered, depending on the patient’s clinical situation (see

).

The following reactions have been reported during treatment with metronidazole:

The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur. In addition, patients have reported headache, syncope, dizziness, vertigo, incoordination, ataxia, tinnitus, hearing impairment, hearing loss, confusion, dysarthria, irritability, depression, weakness, and insomnia (see ).

The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; abdominal cramping; and constipation.

A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of which may occur during therapy.

Dermatitis bullous, fixed drug eruption, erythematous rash and pruritus. 

Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. Flattening of the T-wave may be seen in electrocardiographic tracings.

Toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (see ), urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne syndrome (latency from drug start to signs of liver failure as short as 2 days) (see ).

Proliferation of in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness.” Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported.

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 capsules 375 mg.

To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Metronidazole capsules USP 375 mg is an oral formulation of the synthetic nitroimidazole antimicrobial agent, 2-methyl-5-nitro-1

-imidazole-1-ethanol, which has the following structural formula:

Metronidazole capsules USP 375 mg contain 375 mg of metronidazole USP. Inactive ingredients include corn starch, FD&C Yellow No. 5, gelatin, iron oxide black, magnesium stearate and titanium dioxide.