Metronidazole- Altfarm (Suppositories) Instructions for Use

Marketing Authorization Holder

Altpharm LLC (Russia)

ATC Code

G01AF01 (Metronidazole)

Active Substance

Metronidazole (Rec.INN registered by WHO)

Dosage Forms

	Metronidazole-Altfarm	Vaginal suppositories 250 mg: 10 pcs.
		Vaginal suppositories 500 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Vaginal suppositories white or white with a yellowish tint, torpedo-shaped.

Excipients: macrogol 1500 (polyethylene oxide 1500) – 2.04 g, macrogol 400 (polyethylene oxide 400) – 0.11 g.

5 pcs. – contour cell packs (2) – cardboard packs.

Vaginal suppositories white or white with a yellowish tint, torpedo-shaped.

Excipients: macrogol 1500 (polyethylene oxide 1500) – 1.805 g, macrogol 400 (polyethylene oxide 400) – 0.095 g.

5 pcs. – contour cell packs (2) – cardboard packs.

Clinical-Pharmacological Group

Antiprotozoal drug with antibacterial activity

Pharmacotherapeutic Group

Antimicrobial and antiprotozoal agent

Pharmacological Action

An antiprotozoal and antibacterial drug, belongs to the 5-nitroimidazole derivatives. The mechanism of action involves the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa.

The reduced 5-nitro group of metronidazole interacts with the DNA of the microorganism cell, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Metronidazole is active against protozoa Trichomonas vaginalis, Entamoeba histolytica, and also against gram-negative anaerobes Bacteroides spp. (B. fragilis, B. ovatus, B.distasonis, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp., and some gram-positive anaerobes Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains of Eubacterium.

The minimum inhibitory concentration (MIC) for these strains is 0.125-6.25 µg/ml.

Aerobic microorganisms and facultative anaerobes are not sensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), Metronidazole acts synergistically with antibiotics effective against common aerobes.

Pharmacokinetics

Absorption

After intravaginal administration, Metronidazole undergoes systemic absorption (about 56%).

Distribution

Penetrates into breast milk and most tissues, passes through the blood-brain barrier and placenta. Plasma protein binding is less than 20%.

Metabolism

Metabolized in the liver by hydroxylation, oxidation, and glucuronidation. The activity of the main metabolite (2-hydroxymetronidazole) is 30% of the activity of the parent compound.

Excretion

Excreted by the kidneys – 60-80% of the systemically active drug dose (20% of this amount unchanged), by the intestines – 6-15% of the systemically active drug dose.

Indications

• Urogenital trichomoniasis (including urethritis, vaginitis);
• Nonspecific vaginitis of various etiologies, confirmed by clinical and microbiological data.

ICD codes

Dosage Regimen

The drug is used intravaginally.

The suppository is inserted into the vagina with the pointed end, as deep as possible.

For treatment of trichomonal vaginitis, use 1 suppository at a dose of 250 mg, 2 times/day (morning and evening) or 1 suppository at a dose of 500 mg 1 time/day for 10 days.

For treatment of nonspecific vaginitis, use 1 suppository at a dose of 500 mg 2 times/day for 7 days.

Sexual intercourse should be avoided during the course of treatment.

Adverse Reactions

Common – 1-10%; infrequent – 0.1-1%; rare – 0.01-0.1%; very rare – less than 0.01%, including isolated cases.

Local reactions infrequent – vulvitis (itching, burning pain or redness of the mucous membrane in the external genital area); thick, white mucous vaginal discharge without odor or with a faint odor; sensation of burning or irritation of the penis in the sexual partner.

Allergic reactions infrequent – urticaria, itching, rash.

From the urinary system rare – frequent urination; in rare cases, red-brown discoloration of urine may be observed, due to the presence of a water-soluble pigment formed as a result of metronidazole metabolism.

From the digestive system infrequent – change in taste sensations, including metallic taste, decreased appetite; rare – nausea, vomiting, cramping abdominal pain; common – constipation or diarrhea, dryness of the oral mucosa.

From the nervous system rare – dizziness, headache.

From the hematopoietic organs and hemostasis system very rare – leukopenia or leukocytosis.

After drug withdrawal, vaginal candidiasis may develop.

Contraindications

• Leukopenia;
• Impaired coordination of movements;
• Organic lesions of the CNS (including epilepsy);
• Hepatic insufficiency (in case of prescribing large doses);
• Pregnancy;
• Breastfeeding period;
• Hypersensitivity to metronidazole or other nitroimidazole derivatives.

With caution: history of leukopenia.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency (in case of prescribing large doses).

Special Precautions

Treatment with metronidazole should not last more than 10 days and should not be repeated more often than 2-3 times a year.

Simultaneous treatment of sexual partners is recommended.

When treating trichomonal vaginitis in women and trichomonal urethritis in men, it is necessary to refrain from sexual intercourse.

In vaginitis caused by Trichomonas vaginalis, simultaneous treatment of the sexual partner with oral metronidazole is advisable.

In case of using the drug together with oral metronidazole, especially during a repeated course, monitoring of the peripheral blood picture is necessary (risk of leukopenia). In case of leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

Alcohol consumption is contraindicated during treatment (disulfiram-like reactions may develop: cramping abdominal pain, nausea, vomiting, headache, sudden flushing of the face).

Effect on ability to drive vehicles and mechanisms.

During treatment, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as the drug may cause dizziness.

Overdose

Symptoms nausea, vomiting, ataxia.

Treatment specific antidote is absent, symptomatic and supportive therapy.

Drug Interactions

Compatible with sulfonamides and antibiotics.

During treatment with metronidazole, alcohol consumption should be avoided (causes alcohol intolerance).

Metronidazole should not be combined with disulfiram, since the interaction of these drugs may lead to depression of consciousness and the development of neurological symptoms. Metronidazole should not be prescribed to patients who have taken disulfiram within the last two weeks.

With simultaneous use with warfarin and other indirect anticoagulants, Metronidazole enhances their effect, leading to an increase in prothrombin time.

It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide).

Under the influence of barbiturates, the effect of metronidazole may be reduced, because its inactivation in the liver is accelerated.

Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its serum concentration and an increased risk of adverse events.

With simultaneous administration with lithium preparations, the concentration of the latter in plasma may increase.

Storage Conditions

Store in a dry, light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.