FDA label 6fe166f1-5229-4e4c-b502-e98c5849150e

5 WARNINGS AND PRECAUTIONS Central and Peripheral Nervous System Effects: Convulsive seizures and peripheral neuropathy have been reported in patients treated with oral or intravenous metronidazole; Discontinue promptly if abnormal neurologic signs develop. ( 5.1 ) Carcinogenicity in Animals: Metronidazole has been shown to be carcinogenic in mice and rats; unnecessary use should be avoided ( 5.2 , 13.1 ) Interference with laboratory tests: Metronidazole may interfere with certain serum chemistry laboratory values ( 5.3 ) 5.1 Central and Peripheral Nervous System Effects Use of oral or intravenous metronidazole is associated with convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or parethesia of an extremity [ see Adverse Reactions ( 6.2 ) ]. VANDAZOLE should be administered with caution to patients with central nervous system diseases. Discontinue VANDAZOLE promptly if a patient develops abnormal neurologic signs. 5.2 Carcinogenicity in Animals Metronidazole has been shown to be carcinogenic in mice and rats [ see Carcinogenesis, Mutagenesis, Impairment of Fertility ( 13.1 ) ]. Unnecessary use of metronidazole should be avoided. Use of VANDAZOLE should be reserved for the treatment of bacterial vaginosis [ see Indications and Usage ( 1 ) ] 5.3 Interference with Laboratory Tests Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminostransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and glucose hexokinase. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide-adenine dinucleotides (NAD + NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7. Consider postponing chemistry laboratory tests to after treatment with VANDAZOLE.

6 ADVERSE REACTIONS Adverse reactions occurring in ≥ 1% of patients are: fungal infection, headache, pruritus, abdominal pain, nausea, dysmenorrhea, pharyngitis, rash, infection, diarrhea, breast pain, and metrorrhagia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-888-838-2872, X6351 or drug.safety@tevausa.com; or FDA at 1-800-FDA-1088 or 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 data described below reflect exposure to VANDAZOLE compared to another formulation of vaginal metronidazole in 220 women in a single trial. The population was non-pregnant females (age range 18 to 72 years, the mean was 33 years +/- 11 years) with bacterial vaginosis. The racial demographic of those enrolled was 71 (32%) of White, 143 (65%) of Black, 3 (1%) of Hispanic, 2 (1%) of Asian, and 1 (0%) of other. Patients administered an applicator full of VANDAZOLE intravaginally once daily at bedtime for 5 days. There were no deaths or serious adverse reactions related to drug therapy in the clinical trial. VANDAZOLE was discontinued in 5 patients (2.3%) due to adverse reactions. The incidence of all adverse reactions in VANDAZOLE-treated patients was 42% (92/220). Adverse reactions occurring in ≥ 1% of patients were: fungal infection* (12%), headache (7%), pruritus (6%), abdominal pain (5%), nausea (3%), dysmenorrhea (3%), pharyngitis (2%), rash (1%), infection (1%), diarrhea (1%), breast pain (1%), and metrorrhagia (1%). * Known or previously unrecognized vaginal candidiasis may present more prominent symptoms during therapy with VANDAZOLE. Approximately 10% of patients treated with VANDAZOLE developed Candida vaginitis during or immediately after therapy. Additional uncommon events, reported by < 1% of those women treated with VANDAZOLE included: General: allergic reaction, back pain, flu syndrome, mucous membrane disorder, pain Gastrointestinal: anorexia, constipation, dyspepsia, flatulence, gingivitis, vomiting Nervous System: depression, dizziness, insomnia Respiratory System: asthma, rhinitis Skin and Appendages: acne, sweating, urticaria Urogenital System: breast enlargement, dysuria, female lactation, labial edema, leucorrhea, menorrhagia, pyleonephritis, salpingitis, urinary frequency, urinary tract infection, vaginitis, vulvovaginal disorder 6.2 Other Metronidazole Formulations Other Vaginal Formulations Other reactions that have been reported in association with the use of other formulations of metronidazole vaginal gel include: unusual taste and decreased appetite. Topical (Dermal) Formulations Other reactions that have been reported in association with the use of topical (dermal) formulations of metronidazole include skin irritation, transient skin erythema, and mild skin dryness and burning. None of these adverse reactions exceeded an incidence of 2% of patients. Oral and Parenteral Formulations The following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of metronidazole: Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings. 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. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia. [ see Warnings and Precautions (5.1) ] Gastrointestinal: Abdominal discomfort, nausea, vomiting, diarrhea, an unpleasant metallic taste, anorexia, epigastric distress, abdominal cramping, constipation, “furry” tongue, glossitis, stomatitis, pancreatitis, and modification of taste of alcoholic beverages. Genitourinary: Overgrowth of Candida in the vagina, dyspareunia, decreased libido, proctitis. Hematopoietic: Reversible neutropenia, reversible thrombocytopenia. Hypersensitivity Reactions: Urticaria; erythematous rash; Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing; nasal congestion; dryness of the mouth, vagina, or vulva; fever; pruritus; fleeting joint pains [ see Contraindications ( 4.1 ) ]. Renal: Dysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, darkened urine.

<table width="378" ID="id_d8fee834-3d0a-49e8-a994-8d89407bc0ed"> <col width="35.7%"/> <col width="64.3%"/> <tbody> <tr ID="id_f1baa8d2-47e9-43f6-ae25-225a87d913fe"> <td align="left" valign="top" styleCode="Toprule Botrule"> <content styleCode="italics">General:</content> <content styleCode="italics"> </content> </td> <td align="left" valign="top" styleCode="Botrule">allergic reaction, back pain, flu syndrome, mucous membrane disorder, pain </td> </tr> <tr ID="id_a28a8a84-5a47-42f3-9ca2-82eec66b3a00"> <td align="left" valign="top" styleCode="Botrule"> <content styleCode="italics">Gastrointestinal:</content> </td> <td align="left" valign="top" styleCode="Botrule">anorexia, constipation, dyspepsia, flatulence, gingivitis, vomiting </td> </tr> <tr ID="id_084d7395-2456-43ae-b95c-77abc171a6af"> <td align="left" valign="top" styleCode="Botrule"> <content styleCode="italics">Nervous System:</content> </td> <td align="left" valign="top" styleCode="Botrule">depression, dizziness, insomnia </td> </tr> <tr ID="id_94cdbcd2-e6a2-4deb-8ddc-16bfec837bcb"> <td align="left" valign="top" styleCode="Botrule"> <content styleCode="italics">Respiratory System:</content> </td> <td align="left" valign="top" styleCode="Botrule">asthma, rhinitis </td> </tr> <tr ID="id_6b1c4d01-fe91-4aec-a448-cfa78ef6000a"> <td align="left" valign="top" styleCode="Botrule"> <content styleCode="italics">Skin and Appendages:</content> </td> <td align="left" valign="top" styleCode="Botrule">acne, sweating, urticaria </td> </tr> <tr ID="id_9fa2f4f9-e37e-4075-8535-28779a4a6ae1"> <td align="left" valign="top" styleCode="Botrule"> <content styleCode="italics">Urogenital System:</content> <content styleCode="italics"> </content> </td> <td align="left" valign="top" styleCode="Botrule">breast enlargement, dysuria, female lactation, labial edema, leucorrhea, menorrhagia, pyleonephritis, salpingitis, urinary frequency, urinary tract infection, vaginitis, vulvovaginal disorder </td> </tr> </tbody> </table>