Likmez Prescribing Information
Metronidazole has been shown to be carcinogenic in mice and rats. Tumors affecting the liver, lungs, mammary, and lymphatic tissues have been detected in several studies of metronidazole in rats and mice, but not hamsters
LIKMEZ is indicated for the treatment of:
- Symptomatic trichomoniasis caused byTrichomonas vaginalisin adult females and males when the diagnosis is confirmed by appropriate laboratory procedures.
- Asymptomatic trichomoniasis caused byTrichomonas vaginalisin 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.
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.
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 byBacteroidesspecies including theB. fragilisgroup (B.fragilis, B. ovatus, B. thetaiotaomicron, B. vulgatus),Parabacteroides distasonis, Clostridiumspecies,Eubacteriumspecies,Peptococcusspecies,andPeptostreptococcusspecies.
- Skin and skin structure infections caused byBacteroidesspecies including theB. fragilisgroup,Clostridiumspecies,Peptococcusspecies, Peptostreptococcusspecies, andFusobacteriumspecies.
- Gynecologic infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused byBacteroidesspecies including theB. fragilisgroup,Clostridiumspecies,Peptococcusspecies, Peptostreptococcusspecies, andFusobacteriumspecies.
- Bacterial septicemia caused byBacteroidesspecies including theB. fragilisgroup andClostridiumspecies.
- Bone and joint infections, (as adjunctive therapy), caused byBacteroidesspecies including theB. fragilisgroup.
- Central nervous system (CNS) infections, including meningitis and brain abscess, caused byBacteroidesspecies including theB. fragilisgroup.
- Lower respiratory tract infections, including pneumonia, empyema, and lung abscess, caused byBacteroidesspecies including theB. fragilisgroup.
- Endocarditis caused byBacteroidesspecies including theB. fragilisgroup.
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.
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Central and Peripheral Nervous System Effects[see]
5.2 Central and Peripheral Nervous System EffectsEncephalopathy, aseptic meningitis, peripheral neuropathy (including optic neuropathy) and convulsive seizures have been reported with metronidazole. Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole. CNS lesions seen on MRI have also been described as reversible. Peripheral neuropathy, mainly of sensory type has been reported and is characterized by numbness or paresthesia of an extremity. Cases of aseptic meningitis have been reported with metronidazole
[seeAdverse Reactions (6.1)]. Symptoms may occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued. The appearance of abnormal neurological signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy. - Blood Dyscrasias[see)]
5.4 Blood DyscrasiasLIKMEZ 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 metronidazole 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
[seeAdverse Reactions (6.1)].
LIKMEZ (metronidazole) oral suspension is a nitroimidazole antimicrobial. The chemical name of metronidazole is 2-methyl-5-nitro-1H-imidazole-1-ethanol. The structural formula is shown as:
Metronidazole is a white to pale yellow crystalline powder with a molecular formula of C
6H
9N
3O
3and a molecular weight of 171.2 g/mole. The pKa of metronidazole is 14.44 ± 0.10. The pH of a 1% aqueous solution of metronidazole is 5.5-7.5. It is slightly soluble in water, acetone, alcohol, and methylene chloride.
LIKMEZ is an oral suspension containing 500 mg of metronidazole per 5 mL, and the following inactive ingredients: Glycerin, magnesium aluminum silicate, methylparaben, microcrystalline cellulose, natural peppermint flavor, natural strawberry flavor, propylparaben, purified water, sodium phosphate dibasic, sodium phosphate monobasic, sucralose, and sucrose.
LIKMEZ 500 mg/5 mL is supplied as 200 mL of white to slightly brown suspension with characteristic strawberry peppermint flavor packed in white HDPE round bottle with a child‑resistant cap (NDC 81033-066-20).
Store between 20°C to 25°C (68°F to 77°F). Brief exposure to 15°C to 30°C (59°F to 86°F) permitted [See USP Controlled Room Temperature].
Dispense in a tight container as defined in USP. Discard 10 days after opening container.
Metronidazole is a nitroimidazole antimicrobial drug
Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Once metronidazole enters the organism by passive diffusion and activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced; this process includes intracellular electron transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and formation of a short-lived nitroso free radical. Because of this alteration of the metronidazole molecule, a concentration gradient is created and maintained which promotes the drug’s intracellular transport. The reduced form of metronidazole and free radicals can interact with DNA leading to inhibition of DNA synthesis and DNA degradation leading to death of the bacteria. The precise mechanism of action of metronidazole is unclear.
A potential for development of resistance exists against metronidazole.
Resistance may be due to multiple mechanisms that include decreased uptake of the drug, altered reduction efficiency, overexpression of the efflux pumps, inactivation of the drug, and/or increased DNA damage repair.
Metronidazole does not possess any clinically relevant activity against facultative anaerobes or obligate aerobes.
Metronidazole has been shown to be active against most isolates of the following microorganisms, both
Gram-positive anaerobes
Gram-negative anaerobes
Protozoal parasites
The following
Gram-negative anaerobes
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.