Metronidazole

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.

Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Once metronidazole enters the organism by passive diffusion and is activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced, this process includes intra-cellular 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 bacteria. The precise mechanism of action of metronidazole is unclear.

Dosage, rate of administration, and duration of treatment are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition and concomitant treatment, and on the patient’s clinical and laboratory response to the treatment. Recommended Dosage for the Treatment of Anaerobic Bacterial Infections The recommended dosage schedule for adults for the treatment of anaerobic infections is presented in the Table 1: Table 1. Recommended Dosage Schedule for the Treatment of Anaerobic Bacterial Infections in Adults Loading Dose 15 mg/kg infused intravenously over one hour (approximately 1 gram for a 70-kg adult). Maintenance Dosage 7.5 mg/kg infused intravenously over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.

• Hypersensitivity Metronidazole Injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives. • Psychotic Reaction with Disulfiram Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks. • Interaction with Alcohol Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing.

WARNING Metronidazole has been shown to be carcinogenic in mice and rats. Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS AND USAGE section below. 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.

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.

• Disulfiram Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer Metronidazole Injection to patients who have taken disulfiram within the last two weeks. • Alcoholic Beverages Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with Metronidazole Injection. • Warfarin and other Oral Anticoagulants Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages.

Store at controlled room temperature (77°F or 25°C) and protect from light during storage.