Vandazole

Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Warfarin (Coumadin)
• Astemizole (Hismanal)
• Disulfiram (Antabuse)
• Busulfan (Busulfex, Myleran)
• Lithium (Lithobid)
• Phenobarbital
• Phenytoin (Dilantin)
• Cimetidine (Tagamet)
• Vitamins        

This is not a complete list of metronidazole drug interactions. Ask your doctor or pharmacist for more information.

Take or use metronidazole exactly as prescribed. Do not drink alcohol while taking or using any form of metronidazole. Alcohol can cause upset stomach, vomiting, stomach cramps, headaches, sweating, and flushing when used at the same time as metronidazole.

Oral forms:

Metronidazole comes in tablet and capsule forms and is taken two or three times a day. Take metronidazole with food to minimize stomach upset.  Do not chew, divide, or break extended release metronidazole tablets. Swallow metronidazole tablets whole.

Topical forms:

Metronidazole comes in gel, cream, and lotion forms and is applied to the skin one or two times a day. The affected skin should be washed with mild soap 15-20 minutes before applying metronidazole. The gel, cream, or lotion should be applied in a thin layer and gently rubbed into the skin. Moisturizers and cosmetics may be applied once the gel, cream, or lotion has dried.

Topical metronidazole may increase sensitivity to sunlight. Avoid unnecessary or prolonged exposure to sunlight. Wear protective clothing, sunscreen, and sunglasses.

Injectable forms:

Metronidazole is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of metronidazole at the same time.

You should not use this medicine if you are allergic to metronidazole, or if:

• you are allergic to parabens or polyethylene glycol;

• you recently drank alcohol; or

• you took disulfiram (Antabuse) within the past 14 days.

To make sure metronidazole vaginal is safe for you, tell your doctor if you have:

• a seizure disorder;

• a blood cell disorder (such as anemia, or low platelets); or

• peripheral vascular disease such as Raynaud's syndrome.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant.

Metronidazole vaginal can pass into breast milk and may harm a nursing baby. Do not breast-feed within 24 hours after using this medicine. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

Metronidazole vaginal is not approved for use by anyone younger than 18 years old.

An overdose of metronidazole vaginal is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.

Vandazole is a vaginal gel 0.75% in a 70 g tube with 5 vaginal applicators (each applicator delivers approximately 5 g of gel containing 37.5 mg of metronidazole, USP).

The intravaginal administration of a single 5 gram dose of Vandazole results in relatively lower mean systemic exposure to metronidazole that is approximately 2% to 5% of that achieved following a 500 mg oral dose of metronidazole [see Clinical Pharmacology (12.3)]. The following drug interactions were reported for oral metronidazole.

Disulfiram

Use of oral metronidazole has been associated with psychotic reactions in alcoholic patients who are using disulfiram concurrently. Vandazole should not be used by patients who have taken disulfiram within the last two weeks [see Contraindications (4.2)].

Alcoholic Beverages

Use of oral metronidazole has been associated with a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) to alcohol. Alcoholic beverages and preparations containing ethanol or propylene glycol should not be consumed during and for at least three days after Vandazole therapy [see Contraindications (4.3)].

Coumarin and Other Oral Anticoagulants

Use of oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when Vandazole is prescribed for patients on this type of anticoagulant therapy. In patients on oral anticoagulants, consider monitoring prothrombin time, international normalized ratio (INR), and other coagulation parameters while on Vandazole.

Lithium

Short-term use of oral metronidazole has been associated with elevation of serum lithium concentrations and, in a few cases signs of lithium toxicity, in patients stabilized on relatively high doses of lithium. Use Vandazole with caution in patients treated with lithium and consider monitoring lithium serum concentrations while on Vandazole.

Cimetidine

Use of oral metronidazole with cimetidine may prolong the half-life and decrease plasma clearance of metronidazole. No dose adjustment of Vandazole is necessary.

Pregnancy

Pregnancy Category B

Vandazole should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women.

There are published data from case-control studies, cohort studies, and two meta-analyses that include more than 5000 pregnant women who used metronidazole systemically during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition, more than ten randomized, placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of systemic antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Oral reproductive toxicity studies have been performed in mice at doses up to six times the recommended human dose based on body surface area comparisons and have revealed no evidence of impaired fertility or harm to the fetus. However, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed.

Animal studies have shown that metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Because animal reproduction studies are not always predictive of human response, and because metronidazole crosses the placental barrier and is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Caution should be exercised when Vandazole is administered to a nursing woman. Following oral metronidazole administration, concentrations of metronidazole in human milk are similar to concentrations in plasma. Since some metronidazole is systemically absorbed following vaginal administration of metronidazole, excretion in human milk is possible.

Because of the potential for tumorigenicity shown for metronidazole in animal studies, a decision should be made whether to discontinue nursing or to discontinue Vandazole, taking into account the importance of the therapy to the mother. A nursing mother may choose to pump and discard her milk for the duration of Vandazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula.

Pediatric Use

The safety and efficacy of Vandazole in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. The safety and efficacy of Vandazole in pre-menarchal females have not been established.

Geriatric Use

Clinical studies with Vandazole did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other reported clinical experience in using metronidazole gel, 1% has not identified differences in responses between elderly and younger patients.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Metronidazole has shown evidence of carcinogenic activity after chronic oral administration in mice and rats. Pulmonary tumors and lymphomas were reported in several oral mouse studies in which mice were dosed at 75 mg/kg and above (about 5 times the clinical human dose based on body surface area comparison). Malignant liver tumors were reported in male mice dosed at doses equivalent to a human dose of 41 mg/kg/day (33 times the recommended clinical dose based on body surface area comparisons). Chronic oral dosing of metronidazole in rats at doses above 150 mg/kg (about 20 times the clinical human dose based on body surface area comparison) has resulted in mammary and hepatic tumors. Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative. Although no life-time studies were performed to evaluate the carcinogenic potential of Vandazole (metronidazole vaginal gel, 0.75%), published data have shown that intravaginal administration of metronidazole to Wistar rats for 5 days, at doses 26 times the recommended human dose based on body surface area comparisons, has resulted in an increased frequency of micronuclei in rat vaginal mucosal cells.

Metronidazole has shown mutagenic activity in a number of in vitro assay systems. In addition, a dose dependent increase in the frequency of micronuclei was observed in mice after intraperitoneal injections. An increase in chromosome aberrations has been reported in one study of patients with Crohn’s disease who were treated with 200 to 1200 mg/day of metronidazole for 1 to 24 months. However, in a second study, no increase in chromosome aberrations was reported in patients with Crohn’s disease who were treated with metronidazole for 8 months.

Fertility studies have been performed in mice up to six times the recommended human oral dose (based on mg/m2) and have revealed no evidence of impaired fertility.

More frequent side effects include: cervical candidiasis and vaginitis. See below for a comprehensive list of adverse effects.