Tergynan

Uses

Neomycin is an aminoglycoside antibiotic agent used orally and topically to treat a wide variety of infections in the body.

Oral neomycin sulfate is indicated as an adjunctive therapy in hepatic coma (portal-system encephalopathy) by reducing ammonia-forming bacteria in the intestinal tract. It is strongly recommended that oral neomycin is only used in infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the risk of the development of drug-resistant bacteria.

Neomycin, in combination with polymyxin B sulfates and hydrocortisone in otic suspensions, is used in the treatment of superficial bacterial infections of the external auditory canal caused by organisms susceptible to the antibiotics. This otic formulation is also used in the treatment of infections of mastoidectomy and fenestration cavities caused by organisms susceptible to the antibiotics.

The ophthalmic solution containing neomycin in combination with polymyxin B sulfates and dexamethasone is used to treat steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial infection exists.

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

Trichomoniasis: Tinidazole is used for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection.

Giardiasis: Tinidazole is used for the treatment of giardiasis caused by Giardia duodenalis in both adults and pediatric patients older than three years of age. Sections or subsections omitted from the full prescribing information are not listed.

Amebiasis: Tinidazole is used for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not used for the treatment of asymptomatic cystpassage.

Bacterial Vaginosis: Tinidazole is used for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women.

Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tinidazole and other antibacterialdrugs, Tinidazole should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Tergynan is also used to associated treatment for these conditions: Acne pustular, Allergic Contact Dermatitis, Allergy Skin, Atopic Dermatitis (AD), Atopic Dermatitis (AD) of the external ear canal, Bacterial diarrhoea, Burns, Carbuncle, Cradle Cap, Dermatitis, Dermatitis, Contact, Dermatitis, Eczematous, Diarrhoea, Discoid Lupus Erythematosus (DLE), Ear infection bacterial, Ear infection bacterial caused by susceptible bacteria, Gastrointestinal Infections, Hepatic coma, Hidradenitis Suppurativa (HS), Hot Water Burns (Scalds), Impetigo, Impetigo contagious, Infantile Eczema, Infected Wounds, Infected skin ulcer, Infection of the outer ear caused by susceptible bacteria, Infectious diarrhea, Inflammatory Reaction caused by Acne, Intertrigo, Itching caused by Infection, Lichen Planus (LP), Localized Infection caused by susceptible bacteria, Nail infection, Neurodermatitis, Otitis Externa, Postoperative Wound Infection, Psoriasis Vulgaris (Plaque Psoriasis), Pustular Dermatosis, Radiodermatitis, Secondarily Infected Eczema, Secondary Bacterial Infection, Skin Burns, Skin Infections, Skin Infections, Bacterial, Skin Irritation, Skin Ulcer, Solar erythema, Abrasions, Blistering caused by Staphylococcus, Erythematous eruptions, Intertriginous erythema of the anogenital, Ocular bacterial infections caused by susceptible bacteria, Resistant to other corticosteroids Dermatosis, Susceptible Bacterial 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 candidiasisAmebiasis, Bacterial Vaginosis (BV), Candidal Vulvovaginitis, Giardiasis, Mixed Vaginal Infections, Nongonococcal urethritis, Sexually Transmitted Disease (STD), Trichomonas Vaginalis Infection, Trichomoniasis

How Tergynan works

Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation.

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.

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar.

Dosage

Tergynan dosage

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.

Prevention of Postoperative Infections :

• Adult: A single oral dose of 2g approximately 12 hours before surgery.
• Children less than 12 years: Data are not available to allow dosage recommendations for children below the age of 12 years in the prophylaxis of anaerobic infections.

Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners with the same dose and at the same time Giardiasis:

• Adults: a single 2 g dose taken with food.
• Pediatric patients older than three years of age: a single dose of 50 mg/kg (up to 2 g) with food

Amebiasis, Intestinal:

• Adults: 2 g per day for 3 days with food.
• Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food

Amebic liver abscess:

• Adults: 2 g per day for 3-5 days with food.
• Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food

Bacterial vaginosis: Non-pregnant, adult women: 2 g once daily for 2 days taken with food, or 1 g once daily for 5 days taken with food.

Should be taken with food. Take during or immediately after meals.

Side Effects

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.

Reported side effects have generally been infrequent, mild and self-limiting. Side effects from the gastrointestinal tract include nausea, vomiting, anorexia, diarrhoea and metallic taste. Hypersensitivity reactions, occasionally severe, may occur in rare cases in the form of skin rash, pruritis, urticaria and angioneurotic oedema. As with related compounds, tinidazole may produce transient leukopenia. Other rarely reported side-effects are headache, tiredness, furry tongue and dark urine.

Toxicity

The oral LD₅₀ of neomycin sulfate in mouse is > 8 g/kg. The subcutaneous LD₅₀ is 200 mg/kg in rat and 190 mg/kg in mouse. The intraperitoneal LD₅₀ in mouse is 305 mg/kg. The oral Lowest published toxic dose (TDLo) in woman is 12600 mg/kg/7D.

Because of low absorption, acute overdosage from oral neomycin is not likely to occur. However, prolonged administration of neomycin should be avoided because of the possibility of some systemic absorption and the risk of neurotoxicity, ototoxicity, and/or nephrotoxicity. Hemodialysis will remove neomycin from the blood. While nephrotoxicity and ototoxicity have been reported in otherwise patients without compromised renal function, the risk for developing these toxicities is increased in patients with renal impairment. Like other aminoglycosides, neomycin may cause fetal harm and total irreversible bilateral congenital deafness when administered in pregnant women.

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.

There are no reported overdoses with tinidazole in humans. In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.

Precaution

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

Compounds of similar chemical structure have produced various neurological disturbances such as dizziness, vertigo, uncoordination, and ataxia. If, during therapy with tinidazole, abnormal neurological signs develop, therapy should be discontinued. Use in Pregnancy & Lactation: Tinidazole is contraindicated during the first trimester of pregnancy. While there is no evidence that tinidazole is harmful during the late stages of pregnancy, its use during the last two trimesters requires that the potential benefits outweigh the possible risk to mother and foetus. Tinidazole is excreted in breast milk in concentrations similar to those seen in serum. Tinidazole can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose.

Interaction

The following interactions were reported with metronidazole, which is chemically-related to tinidazole.

Alcohol, disulfiram: Avoid during tinidazole use and for 3 days afterward because cramps, nausea, vomiting, headaches, and flushing may occur.

Anticoagulants, oral (eg, warfarin): Anticoagulant effects may be increased. Anticoagulant dose may need to be adjusted during coadministration and for up to 8 days after discontinuation.

Cholestyramine: Bioavailability of tinidazole may be decreased. Cyclosporine, lithium, tacrolimus: Levels may be elevated by tinidazole, increasing the risk of toxicity.

Drugs that induce CYP3A4 (eg, fosphenytoin, phenobarbital, phenytoin, rifampin): May increase metabolism of tinidazole, decreasing plasma levels and therapeutic effect.

Drugs that inhibit CYP3A4 (eg, cimetidine, ketoconazole): May prolong t½ and decrease tinidazole Cl, increasing plasma levels and risk of adverse reactions.

Fluorouracil: Cl may be decreased by tinidazole, increasing the risk of adverse reactions

Fosphenytoin, phenytoin: The t½ may be prolonged and Cl reduced by tinidazole, increasing the risk of adverse reactions.

Oxytetracycline: Therapeutic effect of tinidazole may be decreased.

Volume of Distribution

The small fraction of absorbed neomycin is rapidly distributed in the tissues. The amount of systemically absorbed neomycin is reported to increase cumulatively with each repeated dose administered until a steady state is reached.

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

• 50 L

Elimination Route

Neomycin is poorly absorbed from the gastrointestinal tract. Gastrointestinal absorption of the drug may be increased if inflammatory or ulcerative gastrointestinal disease is present.

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

Rapidly and completely absorbed under fasting conditions. Administration with food results in a delay in T_max of approximately 2 hours and a decline in C_max of approximately 10% and an AUC of 901.6 ± 126.5 mcg hr/mL.

Half Life

There is limited information on the half-life of neomycin.

The elimination half-life is 13.2±1.4 hours and the plasma half-life is 12 to 14 hours.

Clearance

There is limited information on the clearance rate of neomycin.

Elimination Route

The small absorbed fraction of neomycin is excreted by the kidney. The unabsorbed portion of the drug is excreted unchanged in the feces.

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

Tinidazole crosses the placental barrier and is secreted in breast milk. Tinidazole is excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.

Pregnancy & Breastfeeding use

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

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

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.

As with other compounds of similar structure, tinidazole, is contraindicated in patients having, or with a history of, blood dyscrasias although no persistent haematological abnormalities have been noted in clinical or animal studies. Tinidazole should be avoided in patients with organic neurological disorders. Tinidazole should not be administered to patients with known hypersensitivity to the compound.

Special Warning

Renal Impairment: Haemodialysis: Additional dose equal to half the usual dose at the end of haemodialysis.

Storage Condition

Store at 20° to 25°C. Avoid freezing.

Store at room temperature & protected from light.

Innovators Monograph

You find simplified version here Tergynan