Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L

Metronidazole, miconazole nitrate (Forte-L: with lidocaine).

Neo-Penotran: Each vaginal suppository contains metronidazole 500 mg and miconazole nitrate 100 mg.
Neo-Penotran Forte: Each vaginal suppository contains metronidazole 750 mg and miconazole nitrate 200 mg.
Neo-Penotran Forte-L: Each vaginal suppository contains metronidazole 750 mg, miconazole nitrate 200 mg and lidocaine 100 mg.

Pharmacology: Pharmacodynamics: Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L contains miconazole nitrate for antifungal effect and metronidazole for antibacterial and antitrichomonal effects, and also lidocaine for local anesthetic effect.
Miconazole nitrate which is a synthetic imidazole derivative antifungal agent has a wide spectrum of activity and is particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole nitrate is effective against gram-positive bacteria. Miconazole nitrate shows its effect during ergosterol synthesis in the cytoplasmic membrane. Miconazole nitrate changes permeability of the mycotic cell of Candida spp and inhibits glucose utilization in vitro.
Metronidazole, a 5-nitroimidazole derivative, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa eg, Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria including anaerobic Streptococci.
Miconazole nitrate and metronidazole have no synergistic or antagonistic effect when administered concomitantly.
Neo-Penotran Forte-L contains lidocaine which stabilizes the neuronal membrane by inhibiting the conduction of impulses, thereby producing local anesthetic action.
Pharmacokinetics: Absorption: Miconazole Nitrate: Absorption of miconazole nitrate through the intravaginal route is very low (approximately 1.4% of the dose). Following intravaginal application of Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L vaginal suppositories daily for 3 days, miconazole nitrate could not be detected in plasma.
Distribution: Metronidazole: Bioavailability of metronidazole by the intravaginal route is 20% compared to the oral administration. Steady-state level of metronidazole in plasma have reached 1.6-7.2 mcg/mL after application of Neo-Penotran and ranged 1.1-5 mcg/mL after application of Neo-Penotran Forte or daily administration of Neo-Penotran Forte-L vaginal suppository once daily for 3 days.
Biotransformation: Metronidazole is metabolized in the liver by oxidation. Major metabolites of metronidazole, hydroxyl and acetic metabolites are excreted in the urine. The hydroxyl metabolite has 30% of biologic activity of metronidazole.
Elimination: The t_½ of metronidazole is 6-11 hrs. After oral or IV application of metronidazole, 60-80% of the dose is excreted renally and as metabolites. Approximately 20% of the dose is excreted unchanged in the urine.
Lidocaine: The onset of its action is 3-5 min. Lidocaine is absorbed following topical administration to injured or abraded skin and mucous membranes and metabolized rapidly by the liver. The metabolites and unchanged drug (10% of the dose administered) are excreted by the kidneys. Following intravaginal application of the vaginal suppository daily for 3 days, lidocaine was absorbed minimally and levels in plasma ranged 0.04-1 mcg/mL.

Treatment of vaginal candidiasis caused by Candida albicans, bacterial vaginitis caused by anaerobic bacteria and Gardnerella vaginalis, trichomonal vaginitis caused by Trichomonas vaginalis and mixed vaginal infections.

Adults and Elderly (>65 years): Neo-Penotran: Unless advised otherwise by a physician, insert 1 ovule at night and 1 ovule in the morning for 7 days.
In recurrent cases, or when vaginitis has resisted other treatments, 1 ovule should be inserted high into the vagina at night and in the morning for 14 days.
Neo-Penotran Forte/Neo-Penotran Forte L: Unless advised otherwise by a physician, insert 1 supp high into the vagina at night for 7 days. In recurrent cases, or when vaginitis has resisted other treatments, application of 1 supp at night for 14 days is recommended.
Administration: The ovule/supp should be applied in lying position and inserted high into the vagina. If possible do not stand up for half an hour after placing the suppository.
Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L should not be used without consulting a physician.
Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L is not to be swallowed or administered by other routes.

There is no human experience with overdose of Neo-Penotran/Neo-Penotran Forte. Metronidazole could be absorbed in sufficient amounts to produce systemic effects.
Symptoms: Due to Metronidazole: Nausea, vomiting, abdominal pain, diarrhea, pruritus, metallic taste, ataxia, vertigo, paresthesia, convulsion, leukopenia and darkening of urine.
Due to Miconazole Nitrate: Nausea, vomiting, sore throat and mouth, anorexia, headache and diarrhea.
Treatment: If accidental ingestion of large quantities of Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L occurs, an appropriate method of gastric emptying may be considered if considered desirable. There exist no specific antidote, symptomatic treatment can be applied. Cure can be provided in persons who ingested a dose of metronidazole 12 g.

Known hypersensitivity to any active ingredients or derivatives of Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L. Patients with severe liver function disorders (including porphyria), nervous system disorders (eg, epilepsy) and hematopoiesis.
Use in pregnancy: Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L is contraindicated for use during the 1st trimester of pregnancy in women.

Patients should be warned not to take alcohol during the therapy and for at least 2 days after the end of a course of treatment because of the possibility of disulfiram-like reactions.
High doses and long-term systemic use may cause peripheral neuropathy and convulsion.
The base contained in the vaginal suppository formulation may interact with certain rubber or latex products eg, those used in vaginal contraceptive diaphragms or condoms, therefore concurrent use is not recommended.
Sexual partners of patients with Trichomonas vaginalis should be treated at the same time.
Metronidazole dose must be reduced in renal failure.
In serious liver function failures, metronidazole clearance may be impaired. Metronidazole may increase encephalopathy symptoms due to increased plasma levels and therefore should be used carefully in hepatic encephalopathy patients. The daily dose of metronidazole must be reduced to ⅓ in patients with hepatic encephalopathy. The t_½ of lidocaine may be prolonged ≥2-folds in patients with impaired liver function. Impaired renal function does not affect the pharmacokinetics of lidocaine but may increase accumulation of metabolites.
Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte L is not recommended for use in virgins.
Use in pregnancy & lactation: See Use in Pregnancy & Lactation section for further information.
Use in children: Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L is not recommended for children.

Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L is contraindicated for use during the 1st trimester of pregnancy in women.
Pregnancy Category B for metronidazole and lidocaine and pregnancy category C for miconazole. After the 1st trimester of pregnancy, Neo-Penotran/Neo-Penotran Forte/Neo-Penotran Forte-L may be used in cases considered essential by a physician, but should be used under control.
Breastfeeding should be discontinued since metronidazole appears in the milk. It can be started again 24-48 hrs after the end of treatment. It is not known whether lidocaine is excreted in human milk; therefore, caution should be observed when Neo-Penotran Forte L is administered to a nursing woman.

Neo-Penotran: There were no deaths or serious adverse events in clinical trials. Medical events judged to be common, uncommon and rare are listed as follows. Unless the percentages are otherwise stipulated, the occurrence of individual adverse reactions was <1%.
Vaginal Disorders: Vaginal irritation (burning, itching) 2-6%. Owing to the inflammation of the vaginal mucosa in vaginitis, vaginal irritation can be seen after the administration of the first ovule or towards the 3rd day of the treatment. These complaints disappear quickly when the treatment continues. If there is severe irritation, the physician should be informed because it may be necessary to stop the treatment.
Gastrointestinal Disorders: Abdominal pain or cramps (3%), metallic taste (1.7%), constipation, dry mouth, seldom diarrhea, lack of appetite, vomiting, nausea.
Nervous System Disorders: Headache, ataxia, dizziness, mental changes, peripheral neuropathy after overdose or long period of usage, cramps.
Skin Disorders: Rash.
Blood Disorders: Decreased white blood cells.
Neo-Penotran Forte/Neo-Penotran Forte L: Hypersensitivity reactions (skin rash) and side effects eg, abdominal pain, headache, vaginal itching, burning and irritation may be observed rarely. The incidence of systemic side effects is very rare since after intravaginal administration of metronidazole, very low plasma levels are observed (2-12% compared to oral route). Miconazole nitrate can cause vaginal irritation (burning, itching) as all other imidazole derivative antifungal drugs applied intravaginally (2-6%). These symptoms may be prevented with the local anesthetic action of lidocaine. If there is severe irritation, treatment should be discontinued. Side effects due to systemic use of metronidazole are hypersensitivity reactions (rare), leukopenia, ataxia, mental changes, peripheral neuropathy at overdose and after long period of usage, convulsion, seldom diarrhea, constipation, dizziness, headache, lack of appetite, vomiting, nausea, abdominal pain or cramps, seldom taste changes, dry mouth, metallic or bad taste, tiredness. These side effects occur very rarely because of low blood levels of metronidazole after intravaginal application.

Due to metronidazole absorption, interactions may be seen if used concomitantly with any of the following drugs: Alcohol: Alcohol intolerance (disulfiram-like reaction).
Oral Anticoagulants: Increase in the anticoagulant effect.
Phenytoin: Increase in phenytoin blood levels, decrease in metronidazole blood levels.
Phenobarbital: Decrease in metronidazole blood levels.
Disulfiram: CNS-related effects (eg, psychotic reactions) may occur.
Cimetidine: Metronidazole blood levels and the risk of neurologic side effects may increase.
Lithium: Increase in lithium toxicity may be observed.
Astemizole and Terfenadine: Metronidazole and miconazole inhibit the metabolism of these drugs and increase their plasma concentrations.
Interference with blood levels of liver enzymes, glucose (hexokinase method), theophylline and procainamide have been observed during treatment with metronidazole.

Store at temperatures not exceeding 30°C.

Preparations for Vaginal Conditions

G01AF20 - combinations of imidazole derivatives ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.

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