Fladystin

Uses

Metronidazole is used for:

• All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
• Trichomoniasis
• Giardiasis
• Bacterial vaginosis
• Acute ulcerative gingivitis
• Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
• Anaerobically-infected leg ulcers and pressure sores
• Acute dental infections (e.g. acute pericoronitis and acute apical infections)
• Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
• Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Nystatin Cream is used for the treatment of cutaneous or mucocutaneous mycotic infections caused by Candida albicans and other susceptible Candida species. This cream is not used for systemic, oral, intravaginal or ophthalmic use.

Nystatin tablet is an antifungal antibiotic active against a wide range of yeasts and yeast like fungi including Candida albicans. It is used for the prevention and treatment of Candida infections of oral cavity, esophagus and intestinal tract. It provides effective prophylaxis against oral candidiasis in those born of mothers with vaginal candidiasis. It is used for the prophylaxis of Candida overgrowth during courses of broadspectrum antibiotics

Fladystin is also used to associated treatment for these conditions: Abscess, Intra-Abdominal, Acne Rosacea, Amebiasis, Anaerobic Infection, Bacteremia, Bacterial Endocarditis, Bacterial Peritonitis, Bacterial Vaginosis (BV), Balantidiasis, Bloodstream Infections, Bone and Joint Infections, Brain abscess, CNS Infection, Candidal Vulvovaginitis, Clostridium Difficile Infection (CDI), Empyema, Endometritis, Endomyometritis, Facial Rosacea, Giardiasis, Gynaecological infection, Helicobacter Pylori Infection, Infection, Bacteroides, Intraabdominal Infections, Lower Respiratory Infection, Lower respiratory tract infection bacterial, Lung Abscess, Meningitis, Mixed Vaginal Infections, Parasitic infection NOS, Periodontitis, Pneumonia, Postoperative Infections, Pouchitis, Septicemia bacterial anaerobic, Skin and Subcutaneous Tissue Bacterial Infections, Tetanus, Trichomonal Vaginitis, Trichomonas Vaginitis, Tubo-ovarian abscess, Urethritis, Vulvovaginitis, Asymptomatic Trichomoniasis, Entamoeba histolytica, Hepatic abscess, Refractory Sinusitis, Skin and skin-structure infections, Symptomatic Trichomoniasis, Asymptomatic InfectionsAnal candidiasis, Candidiasis, Invasive, Intestinal Candidiasis, Mixed Vaginal Infections caused by Trichomonas Vaginalis, candida albicans, Oral Candidiasis, Pruritus Ani, Pruritus Vulvae, Skin candida, Trichomonas Vaginitis, Vaginal Candidiasis, Vulvovaginal Candidiasis, Corticosteroid-responsive dermatoses, Cutaneous candidiasis

How Fladystin works

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.

Nystatin is a channel-forming ionophore, meaning it exerts its therapeutic effect via formation of a membrane-spanning pore in the fungal plasma membrane. The formation of this pore results in a change in membrane permeability that allows for leakage of intracellular contents and the subsequent disruption of electrochemical gradients necessary for proper cell function. Selectivity for fungal cells over mammalian cells is due to nystatin’s greater binding affinity for ergosterol, a key sterol found in fungal cell walls, as opposed to its mammalian counterpart, cholesterol.

Dosage

Fladystin dosage

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days;

• For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

• For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days);

• For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

• For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
• For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

• For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

• For Tablet: Adults- 2 g single dose;
• For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

• For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

• For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

• For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
• For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
• For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d.
• For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

• For Tablet: Adults- 2 g as a single dose
• For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d.
• For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d
• For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d
• For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

• Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
• Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

• Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
• Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

• For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
• For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

Children:

• In intestinal and oral candidiasis (thrush): 1,00,000 units (1 ml) should be dropped into the mouth four times daily.The longer the suspension is kept in contact with the affected area in the mouth, before swallowing, the greater will be its effect.
• For prophylaxis in the newborn:The suggested dose is 1,00,000 units (1 ml) once daily or as prescribed by the physician.

Adult:

• For the treatment of intestinal or esophageal candidiasis: 5,00,000 units (5 ml) by mouth 3 or 4 times daily. The dose may be doubled, if required.
• For prophylaxis of intestinal candidiasis in adults: 10,00,000 units (10 ml) daily.
• For prophylaxis to suppress the over growth of Candida albicans in patients receiving broad spectrum antibiotic therapy: 10,00,000 units (10 ml) daily.
• For the treatment of dental sores and oral infection: 1,00,000 units (1 ml) suspension should be dropped into the mouth four times daily.

Elderly: Older people with intestinal candidiasis who are unable to swallow tablets should be given 5,00,000 units (5 ml) suspension four times daily.

Adults and Pediatric Patients (Neonates and Older): Apply liberally to affected areas twice daily or as indicated until healing is complete.

Pediatric Use: Safety and effectiveness have been established in the pediatric population from birth to 16 years.

Geriatric Use: Clinical studies with nystatin cream did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Side Effects

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

Nystatin cream: The frequency of adverse events reported in patients using nystatin cream is less than 0.1%. The more common events that were reported include allergic reactions, burning, itching, rash, eczema, and pain on application.

Nystatin tablet: Nausea, vomiting and diarrhoea have occasionally been reported with high doses of Nystatin. No systemic effects or allergic reactions have been associated with its oral dose.

Toxicity

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

The oral LD₅₀ in rats is 10 g/kg. There have been no reports of serious toxic effects following overdosage of nystatin - doses in excess of five million units daily have resulted in nausea and gastrointestinal upset with no other associated effects.

Precaution

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

Nystatin cream should not be used for the treatment of systemic, oral, intravaginal or ophthalmic infections. If irritation or sensitization develops, treatment should be discontinued and appropriate measures taken as indicated. It is recommended that KOH smears, cultures, or other diagnostic methods be used to confirm the diagnosis of cutaneous or mucocutaneous candidiasis and to rule out infection caused by other pathogens.

Absorption from the gastrointestinal tract is negligible, therefore no special precaution is required to apply in pregnancy and lactation

Interaction

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

Volume of Distribution

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

Nystatin is not absorbed into the systemic circulation and thus does not undergo distribution.

Elimination Route

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Systemic absorption of nystatin is minimal following oral administration, and no detectable plasma concentrations are attained following topical or vaginal administration.

Half Life

The elimination half-life of metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

Clearance

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

Elimination Route

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

The majority of orally administered nystatin is eliminated unchanged in the feces.

Pregnancy & Breastfeeding use

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

Pregnancy Category C. Animal reproduction studies have not been conducted with any nystatin cream. It also is not known whether this cream can cause fetal harm when used by a pregnant woman or can affect reproductive capacity. Nystatin cream should be prescribed for a pregnant woman only if the potential benefit to the mother outweighs the potential risk to the fetus.

Nursing Mothers: It is not known whether nystatin is excreted in human milk. Caution should be exercised when nystatin is prescribed for a nursing woman.

Mouth/Throat/PO/Topical: Pregnancy catagory C

Vaginal: Pregnancy catagory A

Contraindication

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

Nystatin cream is contraindicated in patients with a history of hypersensitivity to any of its components.

There is no known contraindication to the use of Nystatin oral.

Storage Condition

Store in a cool and dry place. Protect from light and moisture. Keep out of the reach of children

Store at 20° to 25°C. Avoid freezing.

Innovators Monograph

You find simplified version here Fladystin