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MetroNIDAZOLE (Topical)


General


Pronunciation

(met roe NYE da zole)


Brand Names: U.S.

  • MetroCream
  • Metrogel
  • MetroGel-Vaginal
  • MetroLotion
  • Noritate
  • Nuvessa
  • Rosadan
  • Vandazole
  • Vitazol [DSC]

Indications


Use: Labeled Indications

Bacterial vaginosis: Vaginal gel: Treatment of bacterial vaginosis

Rosacea: Topical: Treatment of inflammatory lesions and erythema of rosacea


Contraindications


Hypersensitivity to metronidazole, parabens, or other ingredients of the formulation or other nitroimidazole derivatives; use of disulfiram within the past 2 weeks; use of alcohol or propylene glycol during therapy or within 24 hours (Nuvessa only) or 3 days of therapy discontinuation.


Dosing and Administration


Dosing: Adult

Bacterial vaginosis: Vaginal:

0.75% (Vandazole): One applicatorful (~37.5 mg metronidazole) intravaginally once daily for 5 days

0.75% (MetroGel-vaginal, other products): One applicatorful (~37.5 mg metronidazole) intravaginally once or twice daily for 5 days

1.3%: One applicatorful (~65 mg metronidazole) intravaginally as a single dose

Rosacea: Topical:

0.75%: Apply and rub a thin film twice daily, morning and evening, to entire affected areas after washing.

1%: Apply thin film to affected area once daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturers labeling.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling; use with caution in severe hepatic impairment.


Administration

Topical: No disulfiram-like reactions have been reported after topical application, although metronidazole can be detected in the blood. Apply to clean, dry skin. Cosmetics may be used after application (wait at least 5 minutes after using lotion).

Vaginal: For vaginal use only. Applicator may be inserted in any comfortable position. Hold the applicator by the barrel, gently insert into the vagina as far as possible without causing discomfort.. Press the plunger until it stops and withdraw the applicator. Patients should not use intravaginal products (eg, tampons, douches) or engage in vaginal intercourse for the duration of treatment. Discard applicator after use.

0.75%: Administer once in morning and evening if using twice daily; if daily, use at bedtime.

1.3%: Administer as a single dose at bedtime.


Storage

Topical cream, gel, lotion: Store at 20 � �C to 25 � �C (68 � �F to 77 � �F).

Vaginal gel: Store at 15 � �C to 30 � �C (59 � �F to 86 � �F); do not refrigerate or freeze. Avoid exposure to extreme heat.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

MetroCream: 0.75% (45 g) [contains benzyl alcohol]

Noritate: 1% (60 g) [contains methylparaben, propylparaben, trolamine (triethanolamine)]

Rosadan: 0.75% (45 g) [contains benzyl alcohol]

Vitazol: 0.75% (60 g [DSC]) [contains benzyl alcohol]

Generic: 0.75% (45 g)

Gel, External:

Metrogel: 1% (55 g, 60 g) [contains methylparaben, propylparaben]

Rosadan: 0.75% (45 g) [contains edetate disodium, methylparaben, propylene glycol, propylparaben]

Generic: 0.75% (45 g); 1% (55 g, 60 g)

Gel, Vaginal:

MetroGel-Vaginal: 0.75% (70 g) [contains edetate disodium, methylparaben, propylene glycol, propylparaben]

Nuvessa: 1.3% (5 g) [contains benzyl alcohol, methylparaben, polyethylene glycol, propylene glycol, propylparaben]

Vandazole: 0.75% (70 g) [contains methylparaben, propylparaben]

Generic: 0.75% (70 g)

Kit, External:

Rosadan: 0.75% [contains benzyl alcohol]

Rosadan: 0.75% [contains edetate disodium, methylparaben, propylene glycol, propylparaben]

Lotion, External:

MetroLotion: 0.75% (59 mL) [contains benzyl alcohol]

Generic: 0.75% (59 mL)


Drug Interactions

Alcohol (Ethyl): MetroNIDAZOLE (Topical) may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Management: Warn patients and monitor for signs and symptoms of a disulfiram-like reaction if patients consume alcohol while using topical metronidazole. Some manufacturers of vaginal metronidazole products list alcohol use within 24 to 72 hours as a contraindication Consider therapy modification

Disulfiram: MetroNIDAZOLE (Topical) may enhance the adverse/toxic effect of Disulfiram. Management: Warn patients and monitor for the development of serious CNS toxicity if topical metronidazole is used in a patient taking disulfiram. Some manufacturers of vaginal metronidazole products list disulfiram use within 2 weeks as a contraindication. Consider therapy modification

Lopinavir: MetroNIDAZOLE (Topical) may enhance the adverse/toxic effect of Lopinavir. Specifically, the use of topical metronidazole with lopinavir/ritonavir solution (which contains 42% alcohol) may result in a disulfiram-like reaction. Monitor therapy

Tipranavir: MetroNIDAZOLE (Topical) may enhance the adverse/toxic effect of Tipranavir. Monitor therapy


Adverse Reactions


Topical: Frequency not always defined:

Cardiovascular: Hypertension

Central nervous system: Headache

Dermatologic: Burning sensation of skin ( ≤2%), erythema ( ≤2%), skin irritation ( ≤2%), xeroderma ( ≤2%), acne vulgaris, contact dermatitis, pruritus, skin rash

Gastrointestinal: Metallic taste, nausea, unusual taste, xerostomia

Local: Hypersensitivity reaction

Neuromuscular & skeletal: Numbness of extremities, peripheral neuropathy, tingling of extremities

Ophthalmic: Eye irritation

Respiratory: Flu-like symptoms

Vaginal:

>10%: Genitourinary: Vaginal discharge (12%)

1% to 10%:

Central nervous system: Headache (2% to 5%), dizziness (2%)

Gastrointestinal: Gastrointestinal distress (7%), nausea and vomiting (2% to 4%), metallic taste (2%; or unusual taste), abdominal cramps (1%), decreased appetite (1%), diarrhea (1%)

Genitourinary: Cervical candidiasis (10%; or vaginitis), vulvovaginal irritation (9%), vulvovaginal candidiasis (6%), pelvic pain (3%), vulvovaginal pruritus (2%), dysmenorrhea (1%)

<1% (Limited to important or life-threatening): Bloating, dark urine, depression, skin rash, xerostomia


Warnings/Precautions


Concerns related to adverse effects:

- Carcinogenic: Possibly carcinogenic based on animal data. Unnecessary use should be avoided.

- CNS effects: Aseptic meningitis, encephalopathy, seizures, and neuropathies (peripheral and optic) have been reported with systemic metronidazole, especially with increased doses and chronic treatment; peripheral neuropathy has also been reported with topical products; monitor and consider discontinuation of therapy if signs/symptoms occur. Use with caution in patients with CNS diseases. Discontinue immediately if abnormal neurologic signs develop.

- Eye irritation: May cause tearing of the eye; avoid contact with the eyes. In the event of accidental contact, wash out immediately.

- Hepatic impairment: Use with caution in patients with severe liver impairment due to potential accumulation.

- Superinfection: Prolonged use may result in fungal or bacterial superinfection. Approximately 6% to 10% of women treated with the vaginal gel developed Candida vaginitis during or immediately after treatment.

Disease-related concerns:

- Blood dyscrasias: Use with caution in patients with or history of blood dyscrasias.

Dosage form related concerns:

- Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity ( "gasping syndrome " �) in neonates; the "gasping syndrome " � consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer 's labeling.

- Vaginal gel: Disulfiram-like reaction to ethanol has been reported with systemic metronidazole and may occur with the vaginal gel; consider avoidance of alcoholic beverages during therapy with vaginal gel. Do not administer the vaginal gel to patients who have taken disulfiram within the past 2 weeks. Patients should avoid vaginal intercourse during treatment.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Metronidazole crosses the placenta and rapidly distributes into the fetal circulation following oral administration. The amount of metronidazole available systemically following topical application is less in comparison to oral doses. Although the vaginal products are not indicated for use in pregnant patients, bacterial vaginosis has been associated with adverse pregnancy outcomes; current guidelines recommended metronidazole for the treatment of symptomatic bacterial vaginosis in pregnancy (CDC [Workowski 2015]).


Actions


Pharmacology

After diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms


Absorption

Topical: Concentrations achieved systemically after application of the 1 g topical gel and cream are <1% of those obtained after a 250 mg oral dose

Vaginal gel: Concentrations achieved systemically after application of 5 g vaginal gel (containing either 37.5 mg or 65 mg metronidazole) are ~2 % of those obtained after a 500 mg oral dose


Time to Peak

Serum:

Topical cream: 8 to 12 hours

Topical gel: 6 to 10 hours

Vaginal gel: 4 to 18 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience application site irritation, scaling, itching, stinging, burning, diarrhea, headache, nausea, menstrual pain, or dry skin. Have patient report immediately to prescriber burning or numbness feeling, seizures, severe skin irritation, vaginal discharge, or severe vaginal irritation (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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