1 INDICATIONS AND USAGE LIKMEZ is a nitroimidazole antimicrobial indicated for Trichomoniasis in adults ( 1.1 ) Amebiasis in adults and pediatric patients ( 1.2 ) Anaerobic Bacterial Infections in adults ( 1.3 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of LIKMEZ and other antibacterial drugs, LIKMEZ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria ( 1.4 ).

1.1 Trichomoniasis LIKMEZ is indicated for the treatment of: Symptomatic trichomoniasis caused by Trichomonas vaginalis in adult females and males when the diagnosis is confirmed by appropriate laboratory procedures.

Asymptomatic trichomoniasis caused by Trichomonas vaginalis in adult females when the organism is associated with endocervicitis, cervicitis, or cervical erosion.

Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, treat sexual partners of patients simultaneously to prevent re-infection.

1.2 Amebiasis LIKMEZ is indicated for the treatment of acute intestinal amebiasis (amoebic dysentery) and amebic liver abscess in adults and pediatric patients.

In amebic liver abscess, treatment with LIKMEZ does not obviate the need for aspiration or drainage of pus.

1.3 Anaerobic Bacterial Infections LIKMEZ is indicated in the treatment of the following serious infections caused by susceptible anaerobic bacteria in adults: Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B.

fragilis group ( B.

fragilis, B.

ovatus, B.

thetaiotaomicron, B.

vulgatus ), Parabacteroides distasonis, 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.

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.

Bacterial septicemia caused by Bacteroides species including the B.

fragilis group and Clostridium species.

Bone and joint infections, (as adjunctive therapy), caused by Bacteroides 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.

Indicated surgical procedures should be performed in conjunction with LIKMEZ therapy.

In a mixed aerobic and anaerobic infection, antimicrobials appropriate for the treatment of aerobic infection should be used in addition to LIKMEZ.

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

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Central and Peripheral Nervous System Effects [ see Warnings and Precautions (5.2) ] Blood Dyscrasias [ see Warnings and Precautions (5.4 )] Common adverse reactions include nausea, headache, anorexia, vomiting, diarrhea, abdominal cramping, epigastric distress, and constipation.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Saptalis Pharmaceuticals, LLC at 1-833-727-8254 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following reactions have been reported during treatment with metronidazole: Central and Peripheral Nervous System: 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.

Persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole.

In addition, headache, syncope, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia have been reported.

Gastrointestinal: 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; and abdominal cramping and constipation.

Mouth: A sharp, unpleasant metallic taste is not unusual.

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

Dermatologic: Erythematous rash and pruritus.

Hematopoietic: Reversible neutropenia (leukopenia); reversible thrombocytopenia.

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.

Hypersensitivity: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Renal: 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.

Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness".

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 LIKMEZ.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of metronidazole.

Because these reactions are 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.

The 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 (4.4) ] .