Gynoril

Gynoril is a combination vaginal anti-infective product indicated for the local (intravaginal) treatment of mixed vaginal infections, where more than one type of organism is responsible for the infection.

Established/labeled uses

• Bacterial vaginosis caused by anaerobic and mixed bacterial flora (e.g. Gardnerella vaginalis and other anaerobes).
• Trichomoniasis (vaginal infection caused by Trichomonas vaginalis), covered by the metronidazole component.
• Vulvovaginal candidiasis (yeast infection caused by Candida species), covered by the nystatin component.
• Vaginal infections with mixed gram-negative bacterial, anaerobic, protozoal, and fungal involvement, where broad local coverage in a single product is clinically useful.

Notes on evidence and use

Gynoril is intended for cases where a mixed or polymicrobial vaginal infection is suspected or confirmed by clinical examination and/or microscopy; it is not intended to replace pathogen-specific therapy when a single organism has been clearly identified and a narrower-spectrum agent is preferred by treatment guidelines. Use should be guided by a physician's assessment.

Each vaginal tablet/pessary of Metronidazole + Neomycin Sulphate + Nystatin + Polymyxin B typically contains:

• Metronidazole (commonly around 500 mg per tablet, depending on manufacturer)
• Neomycin Sulphate (an aminoglycoside antibiotic component, commonly expressed in International Units)
• Nystatin (an antifungal polyene antibiotic, commonly 100,000 IU)
• Polymyxin B (a polypeptide antibiotic component, commonly expressed in International Units)

Exact strengths of each component may vary slightly between manufacturers/brands; the printed pack insert should always be checked for the precise composition of the specific product dispensed.

Gynoril is a fixed-dose combination vaginal tablet (pessary) that brings together four anti-infective agents with complementary spectra of activity: metronidazole (an antiprotozoal/antibacterial active against anaerobes and Trichomonas vaginalis), neomycin sulphate (an aminoglycoside antibiotic active mainly against gram-negative bacteria), nystatin (a polyene antifungal active against Candida species), and polymyxin B (a polypeptide antibiotic active against gram-negative organisms including Pseudomonas).

By combining these four agents in one locally-applied product, Gynoril provides broad-spectrum coverage suitable for vaginal infections in which bacterial, protozoal, and fungal organisms may coexist, reducing the need to identify the exact causative organism before starting local treatment.

Gynoril belongs to the therapeutic class of combination gynecological/vaginal anti-infectives, bringing together an antiprotozoal/nitroimidazole antibacterial (metronidazole), an aminoglycoside antibiotic (neomycin sulphate), a polyene antifungal (nystatin), and a polypeptide antibiotic (polymyxin B) in a single vaginal dosage form.

Metronidazole + Neomycin Sulphate + Nystatin + Polymyxin B acts locally within the vaginal mucosa through the combined mechanisms of its four components:

• Metronidazole is reduced intracellularly by anaerobic bacteria and protozoa, generating reactive intermediates that damage microbial DNA, leading to strand breakage and cell death. This gives activity against anaerobic bacteria (e.g. Gardnerella vaginalis and other organisms associated with bacterial vaginosis) and Trichomonas vaginalis.
• Neomycin Sulphate, an aminoglycoside, binds the bacterial 30S ribosomal subunit and inhibits protein synthesis, causing misreading of mRNA; it is primarily active against aerobic gram-negative bacteria and some gram-positive organisms.
• Nystatin binds ergosterol in the fungal cell membrane, creating pores that increase membrane permeability and cause leakage of intracellular contents, leading to fungal cell death; it is active against Candida albicans and other Candida species.
• Polymyxin B is a cationic polypeptide that binds to and disrupts the bacterial outer cell membrane of gram-negative bacteria (including Pseudomonas aeruginosa), increasing membrane permeability and causing cell death.

Systemic absorption of each component from the vaginal mucosa is generally low, though not negligible, particularly if the vaginal epithelium is inflamed or eroded; this is the basis for the precautions described elsewhere regarding alcohol, anticoagulants, and renal function.

• Wash hands thoroughly before and after inserting Gynoril.
• Insert the tablet deep into the vagina while lying on your back with knees bent, preferably at bedtime, using the applicator provided if supplied with the pack.
• Remain lying down for a few minutes after insertion to minimize leakage.
• A panty liner may be used to protect clothing from any discharge, as the tablet base may not fully dissolve.
• Complete the full prescribed course, even if symptoms improve after a few days.
• Avoid sexual intercourse during the treatment period where possible; if barrier contraception is relied upon, use an alternative method as the product's vehicle may weaken latex condoms/diaphragms (see Interactions).

• Alcohol: Concomitant use of alcohol with Gynoril may cause a disulfiram-like reaction (flushing, throbbing headache, nausea, vomiting, sweating, palpitations) due to the metronidazole component. Alcohol should be avoided during treatment and for at least 24 to 72 hours after the last dose.
• Warfarin and other oral anticoagulants: The metronidazole component may potentiate the anticoagulant effect, increasing prothrombin time/INR and bleeding risk. Patients on warfarin should be monitored more closely for a potentiated effect while using Gynoril.
• Latex barrier contraceptives: The vehicle/base of Gynoril vaginal tablets may weaken latex condoms or diaphragms, reducing their contraceptive and barrier effectiveness. An alternative method of contraception is advised during treatment and for a short period afterward.
• Other nephrotoxic/ototoxic drugs: Concurrent use with other aminoglycosides or nephrotoxic/ototoxic agents should be undertaken cautiously, given the neomycin and polymyxin B components, although systemic absorption from vaginal use is much lower than with systemic administration.

Most side effects of Gynoril are local and mild, related to the site of application:

• Local vaginal or vulval irritation, itching, or burning sensation
• Increased or altered vaginal discharge
• Local redness or a mild allergic-type reaction at the application site
• Metallic taste in the mouth, occasionally reported due to limited systemic absorption of the metronidazole component
• Nausea or mild gastrointestinal upset (uncommon, related to systemic absorption)
• Rarely, systemic effects related to the aminoglycoside (neomycin) and polypeptide (polymyxin B) components, such as dizziness, have been reported, though vaginal use results in much lower systemic exposure than oral or injectable administration of these agents

Patients should stop use and consult a physician promptly if signs of a significant allergic reaction (rash, swelling, difficulty breathing) occur.

Pregnancy: Gynoril is generally contraindicated during the first trimester of pregnancy, largely as a precaution related to the metronidazole component, even though systemic absorption from vaginal use is considerably lower than with oral metronidazole. In later trimesters, Gynoril should be used only if clearly needed and if the potential benefit justifies the potential risk to the fetus, and only under the direct advice and supervision of a physician.

Lactation: Metronidazole is excreted into breast milk. Because of this, a breastfeeding mother should use Gynoril only on a physician's advice; the physician may recommend temporarily interrupting breastfeeding or expressing and discarding milk for a period after use, weighed against the benefit of treatment.

• Complete the full course: Take/use Gynoril exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, even if symptoms resolve early, to reduce the risk of relapse or antimicrobial resistance.
• Avoid alcohol: Avoid alcoholic beverages during treatment with Gynoril and for at least 24 to 72 hours after finishing the course, because of the risk of a disulfiram-like reaction from the metronidazole component.
• Renal impairment: Use with caution in patients with significant renal impairment, given the potential (though reduced with vaginal use) for nephrotoxicity/ototoxicity from the neomycin and polymyxin B components; physician supervision is advised.
• Barrier contraception: The base of the tablet may weaken latex condoms and diaphragms; use an alternative contraceptive method during treatment if pregnancy prevention is required.
• Avoid intercourse during the treatment course where possible, to allow the medicine to act and to avoid transferring infection to a partner.
• Hypersensitivity: Discontinue immediately and seek medical advice if signs of local or systemic allergic reaction develop.
• Not for other routes: Gynoril vaginal tablets are for intravaginal use only and must not be taken orally, applied to the eyes, or used on broken/open skin.

Overdose is unlikely with correctly used intravaginal Gynoril, since systemic absorption from this route is limited. If a vaginal tablet is accidentally swallowed, or if excessive amounts are used, symptoms such as nausea, vomiting, metallic taste, abdominal discomfort, or dizziness may occur due to the metronidazole and aminoglycoside/polypeptide components.

In case of accidental ingestion or suspected overdose, seek immediate medical attention or contact a poison control center/emergency services rather than attempting home treatment. Bring the medicine pack/leaflet with you if seeking care.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Pregnant women: Contraindicated in the first trimester; use in later trimesters only if clearly needed under physician supervision (see Pregnancy and Lactation).
• Breastfeeding women: Use only on a physician's advice because of metronidazole excretion into breast milk.
• Children and adolescents: Gynoril is not indicated for use in children; safety and efficacy in this population have not been established.
• Elderly: No specific dose adjustment is established for elderly patients using this vaginal product; general precautions regarding renal function still apply if relevant comorbidities exist.
• Patients with renal impairment: Use with caution and physician supervision given the neomycin and polymyxin B components (see Precautions and Warnings).

The typical course of Gynoril is 7 to 10 consecutive nights of vaginal tablet insertion, or as specifically directed by the prescribing physician based on the severity and type of infection. The full prescribed duration should always be completed, even if symptoms improve earlier, to reduce the risk of relapse or incomplete eradication of the infection.

Metronidazole + Neomycin Sulphate + Nystatin + Polymyxin B combines agents from four distinct drug classes: a nitroimidazole antiprotozoal/antibacterial (metronidazole), an aminoglycoside antibiotic (neomycin sulphate), a polyene antifungal antibiotic (nystatin), and a polypeptide (cyclic lipopeptide) antibiotic (polymyxin B), formulated together as a combination vaginal anti-infective.

Metronidazole + Neomycin Sulphate + Nystatin + Polymyxin B works through the combined, complementary actions of its four components applied locally in the vagina: metronidazole damages the DNA of anaerobic bacteria and protozoa; neomycin sulphate inhibits bacterial protein synthesis in susceptible gram-negative organisms; nystatin disrupts the fungal cell membrane of Candida species; and polymyxin B disrupts the outer membrane of gram-negative bacteria. Together, these actions provide broad local coverage against the mixed organisms often responsible for polymicrobial vaginal infections.

Gynoril is formulated and indicated for use in adult women for intravaginal infections. It is not indicated for use in children or adolescents, and the safety and efficacy of Gynoril in the pediatric population have not been established. This product should not be used in pre-pubertal girls or children under any circumstances without specific specialist gynecological/pediatric advice.