Metronidazole Injection

This medication is given by injection into a vein by a health care professional, usually 3 or 4 times a day or as directed by your doctor. This medication should be given slowly over 1 hour. The dosage is based on your medical condition and response to treatment.If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, use this drug at evenly spaced intervals.Continue to use this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria/protozoa to continue to grow, which may result in a return of the infection.Your doctor may direct you to start taking this medication by mouth instead of by vein when you are able to take medications by mouth or when your condition allows the switch.Tell your doctor if your condition persists or worsens.

Do not use needles or IV tubing that contains aluminum because this metal may cause this medication to discolor.Treatment of a certain infection (trichomoniasis) may require that sexual partners be treated as well to avoid re-infection. During treatment, avoid sexual intercourse, or always use latex or polyurethane condoms/dental dams.Do not share this medication with others.This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in that case.Laboratory and/or medical tests (e.g., cultures, white blood cell counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Metronidazole Injection, USP RTU, is a parenteral dosage form of the synthetic antibacterial agent 1-(β-hydroxyethyl)-2-methyl-5-nitroimidazole.

Metronidazole Injection, USP RTU, in 100 mL VIAFLEX Plus single dose plastic container, is a sterile, nonpyrogenic, iso-osmotic, buffered solution of 500 mg Metronidazole, USP, 790 mg Sodium Chloride, USP, 47.6 mg Dibasic Sodium Phosphate Dried, USP and 22.9 mg Citric Acid Anhydrous, USP. Metronidazole Injection, USP RTU has an osmolarity of 310 mOsmol/L (calc) and a pH of 5.5 (4.5 to 7.0). Each container contains 14 mEq of sodium.

The plastic container is fabricated from a specially formulated polyvinyl chloride plastic. Water can permeate from inside the container into the overwrap in amounts insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.

The most serious adverse reactions reported in patients treated with metronidazole injection have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged oral administration of metronidazole, patients should be observed carefully if neurologic symptoms occur and a prompt evaluation made of the benefit/risk ratio of the continuation of therapy.

The following reactions have also been reported during treatment with Metronidazole Injection, USP RTU.

Gastrointestinal: Nausea, vomiting, abdominal discomfort, diarrhea and an unpleasant metallic taste.

Hematopoietic: Reversible neutropenia (leukopenia).

Dermatologic: Erythematous rash and pruritus.

Central Nervous System: Encephalopathy, aseptic meningitis, optic neuropathy, headache, dizziness, syncope, ataxia, confusion and dysarthria.

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

Local Reactions: Thrombophlebitis after intravenous infusion. This reaction can be minimized or avoided by avoiding prolonged use of indwelling intravenous catheters.

Other: Fever. Instances of a 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.

The following adverse reactions have been reported during treatment with oral metronidazole:

Gastrointestinal: Nausea, sometimes accompanied by headache, anorexia and occasionally vomiting; diarrhea, epigastric distress, 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 effective therapy.

Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.

Central Nervous System: Encephalopathy, aseptic meningitis, convulsive seizures, optic neuropathy, peripheral neuropathy, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness and insomnia.

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

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

Other: 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. Rare cases of pancreatitis, which abated on withdrawal of the drug, have been reported.

Crohn's disease patients 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, USP RTU.

Use of dosages of intravenous metronidazole higher than those recommended has been reported. These include the use of 27 mg/kg three times a day for 20 days, and the use of 75 mg/kg as a single loading dose followed by 7.5 mg/kg maintenance doses. No adverse reactions were reported in either of the two cases.

Single oral dose of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported included nausea, vomiting and ataxia.

Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.

Treatment: There is no specific antidote for overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Not hungry.
• Stomach cramps.
• Metallic taste.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about metronidazole injection, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about metronidazole injection. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using metronidazole injection.

Review Date: October 4, 2017

Treatment of Anaerobic Infections

Metronidazole Injection, USP is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with metronidazole therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in addition to metronidazole.

Metronidazole 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.

Skin and Skin Structure Infections caused by Bacteroides species including B. fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus species and Fusobacterium species.

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, 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.

Prophylaxis

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

Prophylactic use of Metronidazole Injection, USP 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).

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 antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Use of dosages of intravenous metronidazole hydrochloride higher than those recommended has been reported. These include the use of 27 mg/kg three times a day for 20 days, and the use of 75 mg/kg as a single loading dose followed by 7.5 mg/kg maintenance doses. No adverse reactions were reported in either of the two cases.

Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported included nausea, vomiting, and ataxia.

Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.

Treatment of Overdosage

There is no specific antidote for metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.

Metronidazole Injection, USP, sterile, is supplied in 100 mL single dose flexible containers, each containing 500 mg (5 mg/mL) of metronidazole (List 7811).

Unit of Sale	Concentration	Each
NDC 0409-7811-10 Case containing 24	500 mg/100 mL (5 mg/mL)	NDC 0409-7811-09 100 mL single dose flexible container
NDC 0409-7811-17 Case containing 80	500 mg/100 mL (5 mg/mL)	NDC 0409-7811-27 100 mL single dose flexible container

Metronidazole Injection, USP should be stored at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature] and protected from light during storage.

LAB-0872-1.0

October 2016