INDICATIONS AND 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.

TREATMENT OF ANAEROBIC 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 post-surgical vaginal cuff infection, caused by Bacteroides species including the B.

fragilis group, Clostridium species, Peptococcus species, and Peptostreptococcus 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 and other antibacterial drugs, metronidazole 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 antimicrobial 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: Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole products.

Since persistent peripheral neuropathy has been reported in some patients receiving prolonged oral administration of metronidazole, patients should be observed carefully.

The appearance of abnormal neurologic signs demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy.

ADVERSE REACTIONS The following are the most serious adverse reactions reported in patients treated with metronidazole and are also described elsewhere in the labeling: convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy (characterized mainly by numbness or paresthesia of an extremity) (see WARNINGS ).

The following adverse reactions associated with the use of metronidazole products were identified in clinical studies or postmarketing reports or published literature.

Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

GASTROINTESTINAL: Nausea, anorexia, vomiting, abdominal discomfort, diarrhea, an unpleasant metallic taste, epigastric distress, abdominal cramping, constipation and pancreatitis.

MOUTH: A sharp metallic taste.

Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy with metronidazole.

HEMATOPOIETIC: Reversible neutropenia (leukopenia); thrombocytopenia, eosinophilia.

HEPATOBILIARY DISORDERS: Hepatotoxicity and liver failure especially in patients with Cockayne syndrome (see CONTRAINDICATIONS ), jaundice.

CARDIOVASCULAR: 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.

SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Stevens-Johnson syndrome, Fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), erythematous rash, bullae, pruritus, swelling face, urticaria, and hyperhidrosis.

CENTRAL NERVOUS SYSTEM: Encephalopathy, aseptic meningitis, convulsive seizures, optic neuropathy, peripheral neuropathy (mainly numbness or paresthesia of an extremity), dizziness, vertigo, incoordination, ataxia, confusion, psychosis, dysarthria, irritability, depression, weakness, headache, tinnitus, hearing impairment, hearing loss, and insomnia.

LABORATORY INVESTIGATIONS: Hepatic enzymes increased.

HYPERSENSITIVITY: Toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (see WARNINGS ), anaphylaxis, angioedema, hypotension, flushing, nasal congestion, and dryness of mouth (or vagina or vulva).

RENAL: Dysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, and darkened urine.

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 ).

LOCAL REACTIONS: Thrombophlebitis after intravenous infusion.

This reaction can be minimized or avoided by avoiding prolonged use of indwelling intravenous catheters.

OTHER ADVERSE REACTIONS: Fever, hiccup, proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness”.

If patients receiving metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache.

A modification of the taste of alcoholic beverages has also 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 Injection.

Darkened Urine: Instances of darkened urine have also been reported, and this manifestation has been the subject of a special investigation.

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.

To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 866-770-7144 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.