Nystatin
Nystatin is an antifungal antibiotic produced by the growth of Streptomyces noursei, which is yellowish powder, very slightly soluble in water. Nystatin has fungicidal activity depending on fungal concentrations and sensitivity. Nystatin is inactive against normal bacteria of the body. It is active against yeasts, including Candida albicans.
Mechanism of action: The antifungal activity is probably due to the binding of sterols in the cell membranes of the fungus with a resultant change in membrane permeability. Nystatin is well tolerated even with long-term treatment without drug resistance. Nystatin has an anti-superinfectious action against Candida albicans in the gastrointestinal tract during antibiotic treatment.
Metronidazole
Metronidazole is a 5-nitroimidazole derivative with broad-spectrum activity against protozoa including amoeba, Giardia and anaerobic bacteria.
The mechanism of action of metronidazole is not known. In the parasite, the 5-nitro group of the drug is reduced to cytotoxic mediators. These substances bind to the helical structure of DNA molecule that breaks the fibers and eventually killing the cell. Effective mean concentration of metronidazole is 8 micrograms per ml or less for most protozoa and susceptible bacteria. The minimum inhibitory concentration (MIC) of susceptible bacteria is about 0.5 microgram per ml. An isolated bacteria is considered to be susceptible to the drug if the MIC does not exceed 16 microgram.
Metronidazole is a very potent drug in the treatment of protozoal infections such as Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Metronidazole has a bactericidal effect on Bacteroides, Fusobaterium and anaerobic bacteria, but has no effect on aerobic bacteria.
Metronidazole is only resistant in a few instances. However, if an alone dose of metronidazole is used in the treatment of Campylobacter/H. pylori, drug resistance develops rapidly. When infected with both anaerobic and aerobic bacteria, metronidazole should be combined with other antimicrobials.
Trichomonas vaginalis infection can be treated with orally or locally metronidazole. Both men and women must be treated because men can carry a germ without leaving any symptom. In many cases, both vaginal tablet and oral tablet should be combined.
In case of bacterial cervicitis/vaginitis, metronidazole makes vaginal microflora return to normal in the majority of patients. Metronidazole does not affect the normal vaginal microflora.
Metronidazole is the standard drug of persistent diarrhea and weight loss caused by Giardia. Metronidazole is the first choice for acute dysentery and severe amoebic liver abscess with different dosage.
If abdominal infections accompanied with abscesses such as appendiceal abscess, post-operative bowel infections and liver abscess, and gynecological infections such as infectious endometritis and abscesses, metronidazole should be combined with a betalactam antibiotic e.g., a new generation cephalosporin.
Bacterodes fragillis or Melaninogenicus usually causes pleural infections and inflammations leading to abscess after phlegm-aspirating procedure, necrotizing pneumonia associated with lung abscess, and purulent pleurisy. In such instances, a combination of metronidazole or clindamycin with a betalatam antibiotic should be recommended. Cerebral abscess or dental infections caused by anaerobic and anaerobic bacteria are also treated according to the above principle.
Since metronidazole is active against Bacteroides, it is often used as a standard drug in the prevention of diseases before gastrointestinal surgeries. Most standard regimes are a combination of metronidazole and a betatalam antibiotic e.g., a new generation cephalosporin. This principle helps to prevent abscesses after appendectomy.
Metronidazole is used in the treatment of Clostridium difficile-associated diarrhea. In this case vancomycin should not be recommended because of a resistance to vancomycin.
Metronidazole-resistant strains have been shown to contain ferredoxin. Ferredoxine is a metronidazole degrading catalyst in these strains. Ferredoxine is reduced but not completely lost. This perhaps explains why infections with these resistant strains responds to higher and longer doses of metromodazole.
Neomycin sulfate
Neomycin sulfate is an aminoglycoside with a mechanism and spectrum similar to gentamicin sulphate. Neomycin-susceptible bacteria include Staphylococcus aureus, Escherichia coli, Haemophilus influenza, Klebsiella, Enterobacter, Neissaria. Neomycin is inactive against Pseudomonas aeruginosa, Serratia marcescens, Streptococci including Streptococcus pneumoniae or haemolytic Streptococcus. Neomycin must not be administered intravenously or systemically because of its toxicity. Neomycin is used in the local treatment of ear, eye, skin infections or it is used as an antiseptic for gastrointestinal tract before surgerial procedures. Even with the routes (oral, dripping into the abdomen, covering on skin lesions), neomycin is absorbed that are sufficient to cause reversibly partial or total deafness. Neomycin acts as a skeletal neuromuscular which is similar to but stronger than other aminoglycosides. Dripping into the abdomen can cause respiratory depression or apnea.
Since neomycin is used locally and quite commonly, broad drug resistance has been reported, typically Staphylococcus staphylococcus, Salmonella, Shigella and Escherichia coli. Cross-resistance occurs frequently between kanamycin, neomycin, framycetin and paromomycin.
Pharmacokinetic properties
Nystatin
Nystatin is poorly absorbed by the gastrointestinal tract and is not absorbed through the skin and mucosa when used locally. Nystatin is excreted primarily in faeces as unchanged.
Metronidazole
Metronidazole is rapidly and completely absorbed after oral administration and reaches plasma concentrations of about 10 microgram/ml one hour after a 500-mg dosing. Linear correlations between dose and plasma concentrations occurred in the dose range of 200-2000 mg. Repeated dosing every 6-8 hours causes an accumulation. The plasma half-life of metronidazole is about 8 hours and the distribution volume is approximately equal to the volume of water in the body (0.6-0.8 liters/kg). Approximately 10-20% of the drug is bound to plasma proteins. Metronidazole penetrates well into body tissues and fluids, saliva and breast milk. Treatment concentrations also obtained in cerebrospinal fluid.
The half-life of hydroxy metabolites is 9.5-19.2 hours in patients with normal renal function. Over 90% of the oral dose is eliminated by the kidneys for 24 hours, mainly hydroxy metabolites (30-40%) and acid form (10-22%). Less than 10% is excreted in parenteral form. About 14% of the dose is excreted in faeces.
In patients with renal failure, the half-life of the maternal form is unchanged and that of the hydroxy metabolites lasts 4- to 17-fold. Metronidazole metabolism may be affected by severe liver failure. Metronidazole can be excluded from the body by hemodialysis.
The pharmacokinetics of intravenous metronidazole is similar to that of oral metronidazole.
If a single dose of 5 g of gel is inserted into the vagina (equivalent to 37.5 mg of metronidazole), mean serum metronidazole concentration was 237 nanogram per ml (152-368 nanogram per ml). This concentration was approximately 2% of mean serum maximum metronidazole concentraion after an oral administration of 500 mg metronidazole (mean Cmax of 12.785 nanogram per ml). These peak concentrations are achieved 6-12 hours after vaginal administration of gel and 1-3 hours after oral administration of metronidazole.
The drug exposure (the AUC) when administered as a single vaginal dose of 5 g of metronidazole gel (equivalent to 37.5mg) is about 4% AUC when taken an oral single of 500 mg metronidazole (4977 nanogram-hour/ml and 125000 nanogram-hour/ml). Comparison of AUCs (mg-mg) of two administrations demonstrated that vaginal absorption of metronidazole is only half that of oral administration when administered equally.
Neomycin sulfate
Neomycin is poorly absorbed from the gastrointestinal tract; approximately 97% of the oral dose is excreted unchanged in faeces. Oral doses of 3 g produce peak plasma concentrations of up to 4 μg/ml. Vaginal absorption is similar. Drug absorption may be increased if inflamed or injured mucosa occurs. After absorption neomycin is rapidly excreted by the kidneys in active form. The plasma half-life of neomycin is approximately 2-3 hours.
Contraindications
Hypersensitivity to any ingredients of the drug.
Precautions
The drug should be discontinued if there are any signs of hypersensitivity.
Interactions
To avoid interactions among drugs, inform your physician or pharmacist about the drugs you are taking.
Pregnancy and lactation
Safety in pregnant and lactating women has not been proven. Therefore, this medicine should not be used during pregnancy, especially in the first 3 months of pregnancy and during lactation.
Dosage & administration
- Dosage: One tablet should be inserted deeply into the vagina at bedtime for 10 consecutive days. In case of fungal infection, the duration of treatment can be increased to 20 days.
- Method of administration: Immerse the tablet in water for 10-15 seconds before inserting deeply into the vagina. This is best performance in a lying position and patients should be keep this position for 15 minutes.
If a dose is forgotten, it should be taken as soon as the patient remembers. However, if this time is too close to the next dose, skip the missed dose and insert the next tablet as usual.
Adverse effects
Fastgynax can cause allergic reactions.
Symptoms of pricking or local irritation for the first few days of treatment has been rarely occur.
Systemic side effects: As with all topical medications, a small amount of the ingredients can be absorbed through the mucosa.
Inform your doctor about any side effects that may occur during the treatment.
Overdose
In the case of accidental oral administration of high doses of the drug, the patient should be promptly notified the medical staff to take timely supportive measures.
Shelf-life: 24 months from the manufacturing date.
Storage: Store in cool dry places, below 28oC, protect from direct light.
Specifications: Manufacturer’s.
Registration number: VD-10371-10