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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Metronidazole (topical): Drug information

Metronidazole (topical): Drug information
(For additional information see "Metronidazole (topical): Patient drug information" and see "Metronidazole (topical): Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • MetroCream;
  • Metrogel;
  • MetroGel-Vaginal [DSC];
  • MetroLotion;
  • Noritate;
  • Nuvessa;
  • Rosadan;
  • Vandazole
Brand Names: Canada
  • Flagyl;
  • Metrogel;
  • Nidagel;
  • Noritate
Pharmacologic Category
  • Antibiotic, Topical
Dosing: Adult

Bacterial vaginosis: Intravaginal:

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% (Nuvessa): 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.

Trichomoniasis: Intravaginal: 10% (Flagyl Cream [Canadian product]): Insert one applicatorful (equal to metronidazole 500 mg) intravaginally once or twice daily for 10 or 20 consecutive days (even during menses).

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

(For additional information see "Metronidazole (topical): Pediatric drug information")

Bacterial vaginosis:

Vaginal gel 0.75%: Adolescents: Intravaginal: One applicatorful (~37.5 mg metronidazole) intravaginally once daily at bedtime for 5 days

Vaginal gel 1.3%: Children ≥12 years and Adolescents: Intravaginal: One applicatorful (~65 mg metronidazole) intravaginally once at bedtime as a single dose

Periorificial dermatitis: Limited data available: Infants ≥6 months, Children, and Adolescents: Topical: 0.75% gel: Apply thin film once or twice daily (Manders 1992; Miller 1994; Nguyen 2006)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

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

Dosing: Geriatric

Refer to adult dosing.

Dosage Forms: US

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]

Generic: 0.75% (45 g)

Gel, External:

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

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

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

Gel, Vaginal:

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

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

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

Lotion, External:

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

Generic: 0.75% (59 mL)

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Cream, External:

Noritate: 1% (45 g) [contains methylparaben, propylparaben, trolamine (triethanolamine)]

Cream, Vaginal:

Flagyl: 10% (60 g) [contains methylparaben, propylparaben, trolamine (triethanolamine)]

Gel, External:

Metrogel: 0.75% (3 g, 60 g); 1% (3 g, 60 g) [contains edetate (edta) disodium, methylparaben, propylene glycol, propylparaben]

Gel, Vaginal:

Nidagel: 0.75% (70 g) [contains edetate (edta) disodium, methylparaben, propylene glycol, propylparaben]

Administration: Adult

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).

Intravaginal: 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.

10% (Flagyl cream [Canadian product]): Administer once or twice daily; do not use applicator after the 7th month of pregnancy.

Administration: Pediatric

Intravaginal: Use only vaginal gel intravaginally; fill applicator with medication; insert the applicator high into the vagina and press the plunger to release the medication; clean the applicator with warm soapy water and rinse well. Do not apply to the eye

Topical: For topical use only. Wash affected areas with a mild cleanser; then apply a thin film of drug to the affected area and rub in. Cosmetics may be used after application (wait at least 5 minutes after using lotion). Do not apply to the eye.

Use: Labeled Indications

Bacterial vaginosis:

Vaginal gel 0.75%: Treatment of bacterial vaginosis

Vaginal gel 1.3%: Treatment of bacterial vaginosis in females ≥12 years of age

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

Trichomoniasis: Flagyl cream [Canadian product]: Treatment of trichomoniasis in females

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Topical:

1% to 10:

Cardiovascular: Hypertension (1%)

Central nervous system: Headache (2%)

Dermatologic: Erythema (≤6%), contact dermatitis (1% to 3%), burning sensation of skin (<3%), exacerbation of acne rosacea (<3%), pruritus (<3%), skin irritation (<3%), stinging of the skin (<3%), xeroderma (≤2%)

Genitourinary: Urinary tract infection (1%)

Hypersensitivity: Local hypersensitivity reaction (3%)

Infection: Influenza (1%)

Respiratory: Upper respiratory tract infection (3%)

Frequent not defined:

Central nervous system: Metallic taste, numbness of extremities, tingling of extremities

Gastrointestinal: Nausea

Ophthalmic: Lacrimation

<1%, postmarketing, and/or case reports: Acne vulgaris, conjunctivitis, eye irritation, peripheral neuropathy, xerostomia

Vaginal:

>10%:

Genitourinary: Vaginal discharge (12%)

Infection: Fungal infection (12%)

1% to 10%:

Central nervous system: Headache (2% to 7%), dizziness (2%)

Dermatologic: Pruritus (6%), skin rash (1%)

Gastrointestinal: Gastrointestinal distress (7%), abdominal pain (5%), nausea (≤4%), vomiting (≤4%), dysgeusia (2%), abdominal cramps (1%), decreased appetite (1%), diarrhea (1%)

Genitourinary: Vulvovaginal candidiasis (6% to 10%), cervical candidiasis (≤10%), vaginitis (≤10%), vulvovaginal irritation (9%), pelvic pain (3%), dysmenorrhea (1% to 3%), vulvovaginal pruritus (2%), abnormal uterine bleeding (1%), mastalgia (1%)

Hematologic & oncologic: Abnormal white blood cell differential (2%)

Infection: Infection (1%)

Neuromuscular & skeletal: Muscle cramps (1%)

Respiratory: Pharyngitis (2%)

<1%, postmarketing, and/or case reports: Acne vulgaris, anorexia, asthma, back pain, bloating, breast hypertrophy, constipation, dark urine, depression, diaphoresis, dyspepsia, dysuria, edema (labial), fatigue, flatulence, flu-like symptoms, gingivitis, heavy menstrual bleeding, hypersensitivity reaction, increased thirst, insomnia, lactation, leukorrhea, mucous membrane disease, pain, pyelonephritis, rhinitis, salpingitis, urinary frequency, urinary tract infection, urticaria, vomiting, xerostomia

Contraindications

Hypersensitivity to metronidazole, parabens, or other ingredients of the formulation or other nitroimidazole derivatives; use of alcohol or propylene glycol during therapy and for up to 24 hours after therapy discontinuation (vaginal gel only); use of disulfiram within the past 2 weeks (vaginal gel only).

Flagyl cream [Canadian product]: Additional contraindications: Active neurological disorders; history of blood dyscrasia, hypothyroidism or hypoadrenalism.

Nidagel [Canadian product]: Additional contraindications: Use during the first trimester of pregnancy.

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; consumption of alcoholic beverages during therapy with vaginal gel is contraindicated during and for up to 72 hours after therapy. Do not administer the vaginal gel to patients who have taken disulfiram within the past 2 weeks. Patients should avoid vaginal intercourse during treatment.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

None known.

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 Risk D: Consider therapy modification

Disulfiram: MetroNIDAZOLE (Topical) may enhance the adverse/toxic effect of Disulfiram. In particular, the risk for CNS toxicities such as psychosis may be increased. 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. Risk D: 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. Risk C: Monitor therapy

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

Pregnancy Considerations

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. Most studies have not shown an increased risk of adverse events to the fetus following maternal use during pregnancy (CDC [Workowski 2015]).

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]). When used for the treatment of inflammatory lesions and erythema of rosacea, topical antibiotics, including metronidazole, are considered compatible with pregnancy (Murase 2014).

Breast-Feeding Considerations

Metronidazole and its active hydroxyl metabolite are present in breast milk following oral administration at concentrations similar to the maternal plasma concentrations. However, systemic absorption is less following topical or vaginal application.

The manufacturer warns of the risk of carcinogenicity in patients exposed to metronidazole based on animal studies; theoretically, this risk is also present in breastfeeding infants exposed to metronidazole via breast milk. Therefore, some manufacturers recommend a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. Alternately, some manufacturers suggest breastfeeding be interrupted during maternal treatment for bacterial vaginosis. Milk can be expressed and discarded during treatment and for 48 hours after therapy ends; the infant can be fed stored breast milk or formula. When used for the treatment of inflammatory lesions and erythema of rosacea, topical antibiotics, including metronidazole, are considered compatible with breastfeeding (Murase 2014).

Mechanism of Action

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

Pharmacodynamics and Pharmacokinetics

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

Pricing: US

Cream (MetroCream External)

0.75% (per gram): $16.68

Cream (metroNIDAZOLE External)

0.75% (per gram): $1.90 - $12.22

Cream (Noritate External)

1% (per gram): $39.13

Cream (Rosadan External)

0.75% (per gram): $13.05

Gel (Metrogel External)

1% (per gram): $7.53

Gel (metroNIDAZOLE External)

0.75% (per gram): $3.64 - $7.10

1% (per gram): $5.04

Gel (metroNIDAZOLE Vaginal)

0.75% (per gram): $1.54 - $2.28

Gel (Nuvessa Vaginal)

1.3% (per gram): $44.20

Gel (Rosadan External)

0.75% (per gram): $13.05

Gel (Vandazole Vaginal)

0.75% (per gram): $2.33

Kit (Rosadan External)

0.75% (cream) (per each): $587.11

0.75%(gel) (per each): $587.12

Lotion (MetroLotion External)

0.75% (per mL): $14.62

Lotion (metroNIDAZOLE External)

0.75% (per mL): $4.19 - $4.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Acea Gel (GB, IE);
  • Epaq (CR, DO, GT, HN, NI, PA, SV);
  • Geloderm (CL);
  • Li Fu (CN);
  • Metroderme (PT);
  • Metrogel (CR, DE, DO, GB, GT, HN, NI, PA, SV, TW);
  • Metrogyl (LK);
  • Metrogyl Gel (TH, VN);
  • Metrosa (EE, LV, NL);
  • Nidazea (BE);
  • Robaz (GR, PH, TH);
  • Rosaced gel (BE, FR);
  • Rosagel (EG);
  • Rosiced (NL, PT);
  • Roza (TR);
  • Rozacreme (FR);
  • Rozagel (FR);
  • Rozex (AR, AT, AU, BE, BR, CH, CO, CZ, DK, EE, ES, FI, FR, GB, HK, IE, IL, IT, JP, KR, KW, LB, LU, LV, MY, NL, NO, NZ, PE, PL, PY, SA, SE, SG, UY, VE, ZA);
  • Trogel (BD);
  • Zidoval (IL);
  • Zyomet Gel (MT)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  2. American Academy of Pediatrics (AAP). In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
  3. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  4. Flagyl Cream (metronidazole) [product monograph]. Laval, Quebec, Canada: Sanofi-aventis Canada Inc; September 2021.
  5. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. doi:10.1542/peds.99.2.268 [PubMed 9024461]
  6. Manders SM, Lucky AW. Perioral dermatitis in childhood. J Am Acad Dermatol. 1992;27:688-692. [PubMed 1430388]
  7. MetroCream (metronidazole) [prescribing information]. Fort Worth, TX: Galderma Laboratories, L.P.; January 2017.
  8. Metrogel (metronidazole) [prescribing information]. Fort Worth, TX: Galderma Laboratories LP; October 2021. [PubMed Metrogel.2019.06]
  9. Metrogel vaginal (metronidazole) [prescribing information]. Scottsdale, AZ: Medicis; January 2012.
  10. MetroLotion (metronidazole) [prescribing information]. Fort Worth, TX: Galderma Laboratories; February 2017.
  11. Metronidazole gel [prescribing information]. Bridgewater, NJ: Valeant; March 2014.
  12. Metronidazole vaginal gel [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; March 2014.
  13. Miller SR, Shalita AR. Topical metronidazole gel (0.75%) for the treatment of perioral dermatitis in children. J Am Acad Dermatol. 1994;31:847-848. [PubMed 7962733]
  14. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. J Am Acad Dermatol. 2014;70(3):401. [PubMed 24528911]
  15. Nguyen V, Eichenfield LE. Periorificial dermatitis in children and adolescents. J Am Acad Dermatol. 2006;55:781-785. [PubMed 17052482]
  16. Nidagel (metronidazole) [product monograph]. Laval, Quebec, Canada: Bausch Health, Canada Inc; August 2021.
  17. Noritate (metronidazole) 1% cream [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC; June 2020.
  18. Nuvessa (metronidazole) [prescribing information]. Florham Park, NJ: Exeltis USA Inc; August 2018.
  19. Rosadan cream (metronidazole) [prescribing information]. Fairfield, NJ: Medimetriks Pharmaceuticals, Inc; December 2014.
  20. Rosadan gel (metronidazole) [prescribing information]. Fairfield, NJ: Medimetriks Pharmaceuticals, Inc; June 2013.
  21. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  22. Vandazole (metronidazole) [prescribing information]. Maple Grove, MN: Upsher-Smith Laboratories, LLC; February 2021.
  23. Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137. [PubMed 26042815]
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