Neo-Penotran^® Forte (Suppositories) Instructions for Use

Marketing Authorization Holder

Exeltis Ilac San. Ve Tic., A.S. (Turkey)

Manufactured By

Exeltis Ilac San. Ve Tic., A.S. (Turkey)

ATC Code

G01AF20 (Imidazole derivative combinations)

Active Substances

Metronidazole (Rec.INN registered by WHO)

Miconazole (Rec.INN registered by WHO)

Dosage Form

Neo-Penotran® Forte

Vaginal suppositories 750 mg+200 mg: 7 pcs. incl. with applicator fingers

Dosage Form, Packaging, and Composition

Vaginal suppositories in the form of a flat body with a rounded end, white or almost white in color.

Excipients: Witepsol S55 – 1.55 g.

7 pcs. – plastic blisters (1) complete with fingertip applicators – cardboard packs.

Clinical-Pharmacological Group

A drug with antibacterial, antiprotozoal, and antifungal action for topical use in gynecology

Pharmacotherapeutic Group

Combined antimicrobial agent (antimicrobial and antiprotozoal agent + antifungal agent)

Pharmacological Action

A drug with antibacterial, antiprotozoal, and antifungal action for topical use in gynecology.

The drug contains Metronidazole, which has antibacterial and antiprotozoal action, and Miconazole, which has an antifungal effect.

Metronidazole is active against Gardnerella vaginalis, Trichomonas vaginalis, anaerobic bacteria, including anaerobic streptococcus.

Miconazole nitrate has a broad spectrum of action. It is especially active against pathogenic fungi, including Candida albicans, and is also active against gram-positive bacteria.

Pharmacokinetics

Absorption

The bioavailability of Metronidazole with intravaginal application is 20% compared to oral administration. After vaginal administration at steady state, the plasma concentration of Metronidazole was 1.6-7.2 µg/ml. Systemic absorption of Miconazole nitrate with this route of administration is very low (approximately 1.4% of the dose), Miconazole nitrate was not detected in plasma.

Metabolism and Excretion

Metronidazole is metabolized in the liver. The hydroxyl metabolite is active.

The T_1/2 of Metronidazole is 6-11 hours. Approximately 20% of the dose is excreted unchanged by the kidneys.

Indications

• Vaginal candidiasis;
• Bacterial vaginosis;
• Trichomonal vaginitis;
• Vaginitis caused by mixed infections.

ICD codes

Dosage Regimen

The drug is administered intravaginally, 1 suppository at night for 7 days.

For recurrent vaginitis or vaginitis resistant to other types of treatment, Neo-Penotran^® Forte should be used for 14 days.

Vaginal suppositories should be inserted deep into the vagina using the disposable fingertip applicators contained in the package.

For elderly patients over 65 years of age, no dose adjustment is required.

Adverse Reactions

In rare cases, hypersensitivity reactions (skin rash) and such side effects as abdominal pain, headache, vaginal itching, burning, and irritation of the vagina may be observed.

Local reactions Miconazole nitrate, like all other antifungal agents based on imidazole derivatives that are administered into the vagina, may cause vaginal irritation (burning, itching) (2-6%). Due to inflammation of the vaginal mucosa in vaginitis, vaginal irritation (burning, itching) may increase after the insertion of the first suppository or by the third day of treatment. These complications quickly disappear as treatment continues. In case of severe irritation, treatment should be discontinued.

Systemic side effects occur very rarely, since with vaginal absorption the plasma level of Metronidazole is very low. Side effects associated with the systemic absorption of Metronidazole include: hypersensitivity reactions (rarely), leukopenia, ataxia, mental changes (anxiety, mood lability), seizures; rarely – diarrhea, dizziness, headache, loss of appetite, nausea, vomiting, abdominal pain or cramps, change in taste sensations, constipation, dry mouth, metallic taste, increased fatigue.

Contraindications

• First trimester of pregnancy;
• Porphyria;
• Epilepsy;
• Severe liver dysfunction;
• Patients under 18 years of age due to insufficient data on use in this age category, virgins;
• Hypersensitivity to the active components of the drug or their derivatives.

Use in Pregnancy and Lactation

The drug can be used after the first trimester of pregnancy under medical supervision, provided that the intended benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding should be discontinued during treatment, as Metronidazole passes into breast milk. Breastfeeding can be resumed 24-48 hours after the end of treatment.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Pediatric Use

Contraindication: patients under 18 years of age due to insufficient data on use in this age category, virgins.

Geriatric Use

For elderly patients over 65 years of age, no dose adjustment is required.

Special Precautions

Preclinical data indicate the absence of a specific risk to humans, based on the results of standard safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity studies.

It is necessary to avoid alcohol consumption during treatment and for at least 24-48 hours after the end of the course due to the possible development of disulfiram-like reactions.

Caution should be exercised when using suppositories simultaneously with contraceptive diaphragms and condoms due to possible damage to the rubber by the suppository base.

In patients with trichomonal vaginitis, simultaneous treatment of the sexual partner is necessary.

The patient should be informed that the suppositories should not be swallowed or used in any other way.

Changes in the results of determining the level of liver enzymes, glucose (hexokinase method), theophylline, and procainamide in the blood are possible.

Effect on ability to drive vehicles and operate machinery

The drug does not affect the ability to drive vehicles and operate machinery.

Overdose

There are no data on overdose in humans with the intravaginal use of Metronidazole. However, when administered into the vagina, Metronidazole can be absorbed in amounts sufficient to cause systemic effects.

Symptoms of Metronidazole overdose nausea, vomiting, abdominal pain, diarrhea, generalized itching, metallic taste in the mouth, movement disorders (ataxia), dizziness, paresthesia, seizures, peripheral neuropathy (including after prolonged use in high doses), leukopenia, darkening of urine.

Symptoms of Miconazole nitrate overdose have not been identified.

Treatment: if a large number of suppositories are accidentally ingested, gastric lavage may be performed if necessary. Improvement after this can be achieved in persons who have ingested up to 12 g of Metronidazole. There is no specific antidote. Symptomatic and supportive therapy is recommended.

Drug Interactions

The interaction of Metronidazole with ethanol can cause disulfiram-like reactions.

With simultaneous use of Neo-Penotran Forte with oral anticoagulants, an enhancement of the anticoagulant effect is noted.

With simultaneous use of Neo-Penotran Forte with phenytoin, a decrease in the concentration of Metronidazole in the blood is noted with a simultaneous increase in the concentration of phenytoin.

With simultaneous use of Neo-Penotran Forte with phenobarbital, a decrease in the concentration of Metronidazole in the blood is noted.

With simultaneous use of Neo-Penotran Forte with disulfiram, side effects from the CNS (psychotic reactions) are possible.

With simultaneous use of Neo-Penotran Forte with cimetidine, the concentration of Metronidazole in the blood may increase and the risk of neurological side effects may increase.

With simultaneous use of Neo-Penotran Forte with lithium, an increase in lithium toxicity may be observed.

With simultaneous use of Neo-Penotran Forte with astemizole and terfenadine, Metronidazole and Miconazole inhibit the metabolism of these substances and increase their plasma concentrations.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F). Do not store in the refrigerator.

Shelf Life

The shelf life is 2 years.

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.