Metronidazole, miconazole nitrate.
Each vaginal suppository contains: Metronidazole BP 500 mg, miconazole nitrate BP 100 mg, excipients qs.
Pharmacology: Pharmacodynamics: TRIMIC (Metronidazole + Miconazole Nitrate) vaginal suppository contains metronidazole for antibacterial and antitrichomonal effects and miconazole for antifungal action.
Miconazole nitrate has a wide spectrum of activity. It is particularly effective against pathogen fungi including Candida albicans, in addition to Gram (+) bacteria. Metronidazole is an antibacterial and antiprotozoal agent that is effective against several infections caused by anaerobic bacteria and protozoa such as Gardenerella vaginalis, Trichomonas vaginalis and anaerobic bacteria including anaerobic Streptococci.
Pharmacokinetics: Absorption of miconazole nitrate through the intravaginal route is very low (approximately 1.4% of dose). Bioavailability of metronidazole by this route is 20% compared to the oral route. Steady state level of metronidazole in plasma reaches 1.6-7.2 μg/mL.
Metronidazole is metabolized in the liver. The hydroxyl-metabolite is effective. The half-life of metronidazole is 6-11 hours. Approximately 20% of the dose is excreted unchanged in urine.
It is used in the treatment of candidal vulvovaginitis due to Candida albicans, in bacterial vaginosis due to anaerobic bacteria and Gardenerella vaginalis, in trichomonal vaginitis due Trichomonas vaginalis and in mixed vaginal infections.
In treatment of Vaginitis: Adults and Elderly (>65 years): Usual dose: Insert 1 vaginal suppository at night and in the morning for 7 days or insert 1 vaginal suppository at night for 14 days.
Vaginitis resistant to other treatments or recurrent vaginitis: Insert 1 vaginal suppository at night and in the morning for 14 days.
Children: Not recommended for children.
There is no human experience with overdose of Metronidazole and Miconazole nitrate vaginal suppositories. If large quantities of the product are accidentally taken, an appropriate method of emptying the stomach may be considered necessary. Symptoms of Metronidazole overdose are nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste, movement disorders (ataxia), vertigo, unusual sensations on the skin (paresthesia), cramps, decrease of white blood cells, and darkening of urine.
Symptoms of Miconazole nitrate overdose are nausea, vomiting, sore throat and mouth, decrease appetite, headache and diarrrhea.
In patients hypersensitive to metronidazole, miconazole nitrate or any other ingredients of the product; first trimester of pregnancy; patients with severe liver problems; patients with nervous system diseases; patients with disturbances in hematopoiesis.
Caution should be taken while administering TRIMIC (Metronidazole + Miconazole Nitrate) vaginal suppositories to patients with liver impairment including porphyria, diseases of the nervous system and hematopoiesis.
Pessaries may be used after the first trimester of pregnancy in cases considered essential by a physician, but should be used under control. Breastfeeding should be discontinued during Trimic therapy, since metronidazole appears in milk. Breastfeeding can be started again 24-48 hours after the end of therapy. 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. The base contained in the pessary formulation may interact with certain rubber or latex products, such as 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.
There is no data established for the use of Metronidazole and Miconazole in second and third trimester. The active ingredients are found in the breast milk. Hence Metronidazole and Miconazole if used during pregnancy and lactation should be under medical supervision only if the benefits outweigh the risk.
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Due to metronidazole absorption, the following interactions can be seen if used concomitantly with the drugs below: Alcohol: Alcohol intolerance (disulfiram-like reaction).
Amiodarone: Increase in risk of cardiotoxicity (QT prolongation, Torsades de pointes, cardiac arrest).
Astemizole and terfenadine: Metronidazole inhibits the metabolism of these drugs and increases their plasma concentrations.
Disulfiram: Central nervous system related effects (eg, psychotic reactions).
Phenytoin: Increase in blood levels of phenytoin, decreases in blood levels of metronidazole.
Phenobarbital: Decrease in blood levels of metronidazole.
Fluorouracil: Increase in blood levels and toxicity of fluorouracil.
Carbamazepine: Increase in blood concentration of carbamazepine.
Lithium: Increase in blood levels and lithium toxicity.
Oral anticoagulants: Increase in anticoagulant effect.
Cyclosporine: Increase in cyclosporine toxicity risk.
Cimetidine: Increase in blood levels of metronidazole and the risk of neurologic side effects.
Interference with blood levels of liver enzymes, glucose (hexokinase method), theophylline and procainamide have been observed during the treatment with metronidazole.
Due to miconazole nitrate absorption, the following interactions can be seen if used concomitantly with the drugs below: Acenocoumarol, Anisindione, Dicumarol, Phenindione, Phenprocoumon, Warfarin: Increase in bleeding risk.
Astemizole, cisapride and terfenadine: Miconazole inhibits the metabolism of these drugs and increase their plasma concentrations.
Fentanyl: Increase or prolonged effects of opioid (CNS depression, respiratory depression).
Glimepiride: Increase of hypoglycemic action.
Carbamazepine: Decrease in carbamazepine metabolism.
Oxybutinin: Increase in oxycodone plasma concentration or exposure to oxybutinin.
Oxycodone: Increase in oxycodone plasma concentration and reduction in clearance.
Pimozide: Increase in cardiotoxicity risk (QT prolongation, Torsades de pointes, cardiac arrest).
Cyclosporine: Increase in cyclosporine risk toxicity (renal dysfunction, cholestasis, parasthesias).
Tolterodine: Increase in tolterodine bioavailability in individuals with deficient cytochrome P450 2DC activity.
Trimetrexate: Increase in trimetrexate toxicity (bone marrow suppression, renal and hepatic dysfunction and gastrointestinal ulceration).
Do not use barrier contraceptives like condoms with the use of Vaginal Suppositories since it may lead to breaking of rubber.
How to Use Vaginal Suppositories: Wash hands; do not open vaginal suppositories if it seems soft, hold the foil wrapper under cold water or place it in refrigerator for few minutes to harden it before removing the wrapper; remove one vaginal suppository from the strip ad hold it in fingertips; remove any foil or plastic wrapping stuck to the vaginal suppository; sit or lie down with knees bent and legs apart; gently insert the suppository into the vagina as far as comfortably possible using fingers; wash hands again.
Store at temperatures not exceeding 25°C. Do not freeze. Protect from light.
G01AF01 - metronidazole ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.