Metromic

Metromic

Manufacturer:

Kusum Healthcare

Distributor:

Kusum Healthcare
Full Prescribing Info
Contents
Metronidazole, miconazole.
Description
Each vaginal suppository contains Metronidazole BP 500 mg, Miconazole nitrate BP 100 mg.
Excipients/Inactive Ingredients: Hard fat.
Action
Pharmacotherapeutic group: Gynecological anti infectives and antiseptics, imidazole derivatives. ATC code: G01AF20.
Pharmacology: Pharmacodynamics: Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories contain miconazole nitrate for antifungal and metronidazole for antibacterial and antitrichomonal effects. Miconazole nitrate which is a synthetic imidazole derivative antifungal has a wide spectrum of activity and is particularly effective against pathogen fungi including Candida albicans. In addition, miconazole nitrate is effective against gram (+) bacteria. Miconazole nitrate shows its effect by ergosterol synthesis in the cytoplasmic membrane. Miconazole nitrate changes permeability of the mycotic cell of candida species and inhibits glucose utilization in vitro.
Metronidazole, a 5-nitroimidazole derivative is an antiprotozoal and an antibacterial agent and is effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria including anaerobic streptococci. Miconazole nitrate and metronidazole have no synergic or antagonistic effects.
Pharmacokinetics: Absorption: Miconazole nitrate: Absorption of miconazole nitrate by the intravaginal route is very low (approximately 1.4% of dose). Following intravaginal application of Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories, miconazole nitrate could not detected in plasma.
Metronidazole: Bioavailability of metronidazole by vaginal route is 20% compared to the oral route. Steady state levels of metronidazole in plasma ranged 1.6-7.2 μg/ml after daily intravaginal application of Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories.
Distribution: Miconazole nitrate: The protein binding rate is 90% - 93%. Its distribution to cerebrospinal fluid is poor; however it is widely distributed to other tissues. Distribution volume is 1400 L.
Metronidazole: It is widely distributed in body tissues and fluids including bile, bone, breast, milk, cerebral abscesses, cerebrospinal fluid, liver and liver abscesses, saliva, seminal fluids and vaginal secretion and achieves concentrations similar to those in plasma. It crosses the placenta and rapidly enters to fetal circulation. Not more than 20% is bound to plasma proteins. Distribution volume is 0.25-0.85 L/kg.
Metabolism: Miconazole nitrate: It is metabolized in liver. Two non-active metabolites found are 2,4- dichlorophenyl-1 H imidazole ethanol and 2,4-dichloromandelic acid.
Metronidazole: It is metabolized in the liver by oxidation, hydroxy metabolite is active. Major metabolites of metronidazole, hydroxy and acetic acid metabolites, are excreted in urine. The hydroxyl metabolite has 30% of biological activity of metronidazole.
Elimination: Miconazole nitrate: Half-life is 24 hours. Less than 1% is excreted in the urine.
Metronidazole: Half-life is 6-11 hours. About 6%-15% of metronidazole dose is excreted with faeces, 60%-80% is unchanged and excreted in urine as its metabolites. Approximately 20% of metronidazole is excreted in the urine as unchanged drug.
Indications/Uses
Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories are indicated for the treatment of candidal vulvovaginitis due to Candida albicans, in bacterial vaginosis due to anaerobic bacteria and Gardnerella vaginalis, in trichomonal vaginitis due to Trichomonas vaginalis and in mixed vaginal infections.
Dosage/Direction for Use
Dosage: One suppository should be inserted high into the vagina at night and in the morning for 7 days. In recurrent cases, application of one suppository in the morning and one suppository at night for 14 days is recommended.
Do not use without consulting a physician.
Route of administration: Vaginal.
Method of administration: Remove the suppository from the strip and insert it deep into the vagina in lying position with the patient's knees bent or in squatting position.
Do not cut the suppositories into parts as such change in storage conditions may cause misdistribution of the active substance.
Overdosage
No data is available on metronidazole overdose when administered via intravaginal route. When introduced into the vagina metronidazole can be absorbed in sufficient quantities to have systemic effects.
When excessive amount of suppositories is applied, systemic effects may occur due to metronidazole, but intravaginal metronidazole is not expected to cause life-threatening symptoms.
Symptomatic and supportive treatment should be instituted. There is no specific antidote for metronidazole. Cure can be provided in individuals who ingested a dose of 12 g of metronidazole.
Symptoms of metronidazole overdose are nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste, ataxia, dizziness, paresthesia, convulsion, leucopenia, darkening of urine; symptoms of miconazole nitrate overdose are sore mouth and throat, anorexia, nausea, vomiting, headache, diarrhea.
In case of accidental ingestion of large amounts of suppositories into the gastrointestinal tract, perform a corresponding lavage technique if necessary.
Contraindications
Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories are contraindicated in case of: Hypersensitivity to the active ingredients or their derivatives.
Drinking alcohol during the treatment or within 3 days after the treatment.
Receiving Disulfiram during the treatment or within 2 weeks.
During the first trimester of pregnancy.
In cases of porphyria, epilepsy, serious liver function disorders.
Special Precautions
Patients should be warned not to take alcohol during the therapy and for 3 days after the end of the treatment because of the possibility of disulfiram-like reactions.
High doses and long term systemic use may cause peripheral neuropathy and convulsion. Should not be used in young females who are not sexually active.
The suppositories base may damage rubber or latex condoms or diaphragms, therefore concurrent use is not recommended.
Other vaginal products (e.g. Tampon, douche or spermicide) should not be used during the treatment.
Sexual partners with Trichomonas vaginalis should be treated at the same time.
In renal insufficiency metronidazole dose should be reduced.
In severe hepatic insufficiency 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 1/3 in patients with hepatic encephalopathy.
Elderly patients (over 65 years): same recommendations as for the rest of the patients.
Should not be used in girls who are not sexually mature.
Not to be swallowed or applied by other routes.
Systemic administration of metronidazole may affect driving and using machines. In comparison with systemic use, topical metronidazole is absorbed in vagina in low concentrations. Patients should be warned about the potential for dizziness, ataxia, fatigue and weakness and advised not to drive or operate machinery if these symptoms occur.
Additional information on special populations: No interaction study has been conducted on special populations.
Effects on Ability to Drive and Use Machines: Systemic administration of metronidazole may affect driving and using machines. In comparison with systemic use, topical metronidazole is absorbed in vagina in low concentrations. Patients should be warned about the potential for dizziness, ataxia, fatigue and weakness and advised not to drive or operate machinery if these symptoms occur.
Use in Children: No interaction study has been conducted in children.
Use In Pregnancy & Lactation
General advice: Pregnancy category is C.
Women of childbearing potential/birth control (contraception): Since the effects of active ingredients in metronidazole and miconazole nitrate suppositories for fetus and newborn growth are not clearly known, women who must use this product should avoid pregnancy with a proper birth control method.
Pregnancy: Preclinical studies on animals regarding the pregnancy, embryonal/fetal growth, perinatal and/or postnatal growth are insufficient. Potential risk for human is not known.
There is insufficient data regarding the use of metronidazole and miconazole nitrate suppositories in the first trimester of pregnancy. Therefore, Metronidazole + Miconazole (Metromic) 500 mg/100 mg Vaginal Suppositories should not be used in the first trimester of pregnancy. In the second and third trimesters, benefit/risk ratio should be evaluated by a physician, should not be used unless it is necessary.
Lactation: Breastfeeding should be discontinued, since metronidazole appears in milk. Breastfeeding can be started again 24-48 hours after the end of treatment.
Reproduction/fertility: There is no evidence regarding hazardous effect on human and animal fertility when metronidazole or miconazole nitrate is administered alone.
Adverse Reactions
The frequency of adverse events listed as follows is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
The frequency of systemic side/adverse 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 are greatly reduced while the treatment continues. If there is severe irritation, the treatment should be stopped.
Undesirable effects regarding systemic use of active substances of Metronidazole + Miconazole (Metromic) 500 mg/ 100 mg Vaginal Suppositories are listed as follows: Blood and lymphatic system disorders: Not known: Leucopenia.
Immune system disorders: Not known: Hypersensitivity reactions, allergic reactions, anaphylaxis may occur in severe cases.
Psychiatric disorders: Uncommon: Depression.
Very rare: Mental alterations.
Nervous system disorders: Common: Dizziness, headache.
Not known: Tiredness or weakness, ataia, convulsion, peripheral neuropathy due to intensive and/or prolonged metronidazole therapy.
Gastrointestinal disorders: Not known: Taste changes, metallic taste, nausea, vomiting, constipation, dry mouth, diarrhea, lack of appetite, abdominal pain or cramp.
General disorders and administration site conditions: Very common: Vaginal discharge.
Common: Vaginitis, vulvovaginal irritation, pelvic discomfort.
Uncommon: Feeling of thirst.
Rare: Vaginal burning, itching, irritation, rash.
Not known: Local irritation and hypersensitivity, contact dermatitis.
These adverse effects are observed rarely since blood concentration of metronidazole and miconazole is much lower when administered via intravaginal route.
For suspected adverse drug reaction, report to FDA: www.fda.gov.ph and contact Kusum Healthcare Private Limited Branch Office at (02) 245-9048 and/or e-mail: khpl.philippines@gmail.com.
Please seek medical attention immediately at the first sign of any adverse drug reaction shall appear.
Drug Interactions
Metronidazole, after being absorbed can cause reaction when used along with the following drugs: Alcohol: alcohol intolerance (disulfiram-like reaction).
Amiodaron: 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.
Carbamazepine: increase in blood concentration of carbamazepine.
Cimetidine: increase in blood level of metronidazole and the risk of neurologic side effects.
Cyclosporine: increase in cyclosporine toxicity.
Disulfiram: central nervous system related effects (e.g. psychotic reactions).
Fluorouracil: increase in blood levels of fluorouracil and toxicity.
Lithium: increase in lithium toxicity.
Oral anticoagulants: increase in anticoagulant effect (increase in bleeding risk).
Phenytoin: increase in blood levels of phenytoin, decrease in blood levels of metronidazole.
Phenobarbital: decrease in blood levels of metronidazole.
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 as follows: Acenocoumarol, anisindione, dicumarol, phenindione, phenprocoumon, warfarin: increase in bleeding risk.
Astemizole, cisapride and terfenadine: miconazole inhibits the metabolism of these drugs and increases their plasma concentrations.
Carbamazepine: reduction in carbamazepine metabolism.
Cyclosporine: increase risk of cyclosporine toxicity (renal dysfunction, cholestasis, parasthesias).
Fentanyl: increase or prolonged effects of opioid (CNS depression, respiratory depression).
Glimepiride: increase of hypoglycemic action.
Oxybutynin: increase in plasma concentration or exposure to oxybutinin, (dry mouth, constipation, headache).
Oxycodone: increase in oxycodone plasma concentration and reduction in clearance.
Phenytoin and phosphenytoin: increase risk of phenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor).
Pimozide: increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).
Trimetrexate: increase in trimetrexate toxicity (bone marrow suppression, renal and hepatic dysfunction and gastrointestinal ulceration).
Storage
Store at temperatures not exceeding 30°C. Do not freeze.
ATC Classification
G01AF01 - metronidazole ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.
G01AF04 - miconazole ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.
Presentation/Packing
Vag supp (white to light yellow color torpedo shaped) 14's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in