INDICATIONS AND USAGE Treatment of Anaerobic Bacterial Infections Metronidazole Injection is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

Indicated surgical procedures should be performed in conjunction with Metronidazole Injection therapy.

In a mixed aerobic and anaerobic infection, antibacterial drugs appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole Injection.

Metronidazole Injection 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 in adults and pediatric patients less than 4 months of age.

• Skin and Skin Structure Infections caused by Bacteroides species including the B.

fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus species and Fusobacterium species in adults.

• Gynecologic Infections , including endometritis, endomyometritis, tubo-ovarian abscess and postsurgical vaginal cuff infection, caused by Bacteroides species including the B.

fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus species and Fusobacterium species in adults.

• Bacterial Septicemia caused by Bacteroides species including the B.

fragilis group and Clostridium species in adults.

• Bone and Joint Infections , as adjunctive therapy, caused by Bacteroides species including the B.

fragilis group in adults.

• Central Nervous System (CNS) Infections , including meningitis and brain abscess, caused by Bacteroides species including the B.

fragilis group in adults.

• Lower Respiratory Tract Infections , including pneumonia, empyema and lung abscess, caused by Bacteroides species including the B.

fragilis group in adults.

• Endocarditis caused by Bacteroides species including the B.

fragilis group in adults.

Prophylaxis Indication The prophylactic administration of Metronidazole Injection preoperatively, intraoperatively and postoperatively may reduce the incidence of postoperative infection in adult patients undergoing elective colorectal surgery which is classified as contaminated or potentially contaminated.

Prophylactic use of Metronidazole Injection 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 ).

Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole Injection and other antibacterial drugs, Metronidazole Injection 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.

WARNINGS Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole.

Symptoms can be serious and potentially life threatening.

If symptoms or signs of SCARs develop, discontinue Metronidazole injection immediately and institute appropriate therapy.

Central and Peripheral Nervous System Effects Severe neurological disturbances, including encephalopathy, cerebellar symptoms, convulsive seizures, peripheral neuropathy, optic neuropathy, and aseptic meningitis, have been reported in patients treated with metronidazole.

Encephalopathy associated with metronidazole may manifest as confusion or decreased level of consciousness, and is associated with widespread lesions on magnetic resonance imaging (MRI) of the brain.

Cerebellar toxicity associated with metronidazole may manifest as ataxia, dizziness, dysarthria, nystagmus and saccadic pursuit and is accompanied by T2 flair lesions within the dentate nuclei seen on MRI.

Cerebellar toxicity may concurrently occur with encephalopathy, peripheral neuropathy or seizures.

CNS symptoms and CNS lesions are generally reversible within days to weeks upon discontinuation of Metronidazole Injection.

Peripheral neuropathy, usually symmetric and mainly of sensory type is characterized by numbness or paresthesia of an extremity.

Symptoms may be prolonged after drug discontinuation.

Aseptic meningitis may occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued (see ADVERSE REACTIONS ).

Advise patients to report neurologic symptoms that occur during metronidazole administration.

Discontinue metronidazole treatment if any abnormal neurologic symptoms occur such as ataxia, dizziness, confusion or any other CNS adverse reaction (see ADVERSE REACTIONS ).

ADVERSE REACTIONS The following reactions have been reported during treatment with metronidazole formulations: INFECTIONS AND INFESTATIONS: Vaginal candidiasis BLOOD AND LYMPHATIC SYSTEM DISORDERS: Agranulocytosis, Leukopenia, Neutropenia, Thrombocytopenia, Eosinophilia IMMUNE SYSTEM DISORDERS: Anaphylactic reaction, Hypersensitivity METABOLISM AND NUTRITION DISORDERS: Decreased appetite PSYCHIATRIC DISORDERS: Confusional state, Depression, Insomnia, Decreased libido NERVOUS SYSTEM DISORDERS: Encephalopathy, Seizure, Neuropathy peripheral, Ataxia, Dizziness, Hypoesthesia, Paresthesia, Dysgeusia, Headache, Nystagmus, Aseptic meningitis, Somnolence, Dysarthria, Numbness, Syncope EYE DISORDERS: Optic neuropathy, Saccadic eye movement EAR AND LABYRINTH DISORDERS: Vertigo, tinnitus, hearing impairment, hearing loss CARDIAC DISORDERS: 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, Tachycardia, Palpitation RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Dyspnea GASTROINTESTINAL DISORDERS: Pancreatitis, Abdominal pain, Diarrhea, Nausea, Vomiting, Asthenia, Proctitis HEPATOBILIARY DISORDERS: Hepatotoxicity/Liver Failure in patients with Cockayne syndrome (see CONTRAINDICATIONS ), Jaundice SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Swelling face, Pruritus, Urticaria, Hyperhidrosis, Erythema, Rash; Stevens-Johnson syndrome, Fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (see WARNINGS ) MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Muscle spasms, Arthralgia, Myalgia RENAL AND URINARY DISORDERS: Chromaturia, Dysuria Hepatic: 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 CONTRAINDICATIONS ) REPRODUCTIVE: Dyspareunia GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site reaction, Malaise, Face edema, Edema peripheral, Chest pain, Chills, INVESTIGATIONS: Hepatic enzyme increased.

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 Injection.