Ring Out Plus

Ring Out Plus Uses, Dosage, Side Effects, Food Interaction and all others data.

Clobetasol is under investigation for the treatment of Scleroderma. Clobetasol has been investigated for the prevention of Psoriasis and Cutaneous Atrophy Due to Corticosteroids.

Clotrimazole is a broad spectrum antifungal. It also exhibits activity against Trichomonus, Staphylococci, Streptococci and Bacteroides. Clotrimazole kills fungi and yeasts by interfering with their cell membranes. It works by stopping the production of ergosterol, which is an essential component of fungal cell membranes resulting in increased membrane permeability and leakage of essential constituents of the fungal cells. Clotrimazole acts reliably on dermatophytes, yeasts and other fungi; it is also effective against Trichomonas vaginalis and Gram-positive microorganisms (streptococci/ staphylococci) and Gram-negative microorganisms (bacteroides/ Haemophilus vaginalis).

Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal in vitro against Candida albicans and other species of the genus Candida at higher concentrations . Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations .

Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations .

Neomycin is a broad-spectrum aminoglycoside antibiotic drug that is derived from the metabolic products of Streptomyces fradiae. Neomycin is a complex comprised of three components, neomycin A, B, and C. Neomycin B, also known as framycetin, is the most active component of the complex and neomycin C is the isomer of neomycin B, making these two stereoisomers the active components of neomycin. Neomycin A, or neamine, is a moiety that conjoins two molecules of neomycin B and C together. Neomycin is active against both gram-positive and gram-negative organisms and mediates its pharmacological action by binding to bacterial ribosomes and inhibiting protein synthesis, which is crucial for the survival of bacteria.

Neomycin sulfate is the most common form for pharmaceutical preparations; because the compound is a complex, the amount of neomycin in products is measured in units. Neomycin sulfate as monotherapy is available in an oral solution for adjunct use in the treatment of hepatic coma. It is also used in combination with polymyxin B sulfates and hydrocortisone in otic suspensions for use in the treatment of bacterial infections in the external auditory canal, including infections caused by medical procedures in the ear. Neomycin is also used in combination with polymyxin B sulfates and dexamethasone in ophthalmic preparations for use in the treatment of inflammatory conditions and infections in the eye. Neomycin is also available in over-the-counter topical products to prevent minor skin infections.

Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms.

Ring Out Plus
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Ring Out Plus
Generic	Clotrimazole + Neomycin + Clobetasol
Weight	1%
Type	Cream
Therapeutic Class
Manufacturer	Mankind Pharmaceuticals Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

The confirmed indication for Clotrimazole include:

All dermatomycoses due to dermatophytes (e.g. Trichophyton species).
All dermatomycoses due to yeasts (Candida species).
Dermatomycoses due to moulds and other fungi.
Skin diseases showing superinfections with these fungi.

To the dermatomycoses listed under 1-4 belong for example, interdigital myocoses (e.g. athlete’s foot), paronychias (associated with nail mycoses), myocoses in skin folds, Candida vulvitis, Candida balanitis, Pityriasis versicolor, erythrasma.

Clotrimazole rectal preparation is used for vaginal itching, burning and discharge associated with recurrent vaginal yeast infections (Vaginal candidiasis) and also in viginitis due to Candida species as well as Mycotic infections complicated by other microorganisms sensitive to the drug.

Clotrimazole Sterile Eye Ointment is used for the treatment of fungal keratitis due to filamentous fungi and Candida species.

Clotrimazole Ear Drop is used for the treatment of fungal infections of the ear.

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.

Ring Out Plus is also used to associated treatment for these conditions: Balanitis candida, Candidiasis, Dermatitis, Dermatomycoses, Ear infection fungal, Erythrasma, Fungal Vaginal Infections, Fungal skin infection, Genital candidiasis, Inflammation, Mixed Vaginal Infections, Oropharyngeal Candidiasis, Pityriasis versicolor, Pyoderma, Ringworm, Skin Infections, Skin candida, Tinea Corporis, Tinea Cruris, Tinea Pedis, Tinea inguinalis, Trichophytosis, Vaginal Candidiasis, Vaginal Mycosis, Vulvitis, Cutaneous candidiasis, Infection mycotic, Susceptible Bacterial Infections, Symptomatic Tinea Corporis caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Symptomatic Tinea Cruris caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Symptomatic Tinea Pedis caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Tinea versicolor caused by Malassezia infectionAcne 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 Infections

How Ring Out Plus works

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane ,. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth .

Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as CYP51) is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels . The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities .

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.

Dosage

Ring Out Plus dosage

Topical

Wash skin with soap and water and dry thoroughly. Apply a thin layer of the cream or solution 2-3 times daily and gently massage over affected area as directed by the doctor. For Athlete’s foot, pay special attention to the spaces between the toes. Best results in Athlete's foot and ringworm are usually obtained with 4 weeks use of this product. The cream should be applied two or three times daily for one month or for at least two weeks after the disappearance of all signs of infection. If satisfactory results have not occurred within these times consultation with doctor is essential. For best results, follow directions and continue treatment for length of time indicated. The duration of treatment varies; it depends among other factors on the extent and localization of the disease.

Recommended duration of treatment :

Dermatomycoses: 3-4 weeks
Candida vulvitis and candida balanitis: 1-2 weeks
Erythrasma and pityriasis versicolor (approx.): 3 weeks
In fungal infection of the feet, to prevent relapses:Treatment should be continued for about 2 weeks beyond the disappearance of all signs of disease.

Clotrimazole cream is odourless, can be washed off and does not stain.

Rectal

First infections: In general, a 3-day treatment is sufficient for Candida vaginitis. On 3 consecutive nights, Clotrimazole 200 mg vaginal preparation is inserted as deeply as possible into the vagina. This is best achieved when lying on one's back with the knees slightly bent.

Re-infections: In general, a 6-day treatment is sufficient. This applies also to mixed infections with the above-mentioned causative organisms. On six consecutive nights, 1 Clotrimazole 100 mgvaginal preparation is inserted as deeply as possible into the vagina. If necessary, 2 Clotrimazole 100 mg(1 in the morning and 1 in the evening) or 1 Clotrimazole 200 mg daily can be used for 6-12 days. Treatment should be timed so as to avoid the menstrual period and be finished before the onset of menstruation. To avoid re-infection, the partner should undergo local treatment with Clotrimazole cream at the same time.

Clotrimazole 500 mg vaginal preparation: Single dose, complete treatment with one vaginal tablet. The tablet should be inserted as deeply as possible into the vagina. This is best achieved when lying on one's back with the knees slightly bent. It is recommended that the treatment should be timed so as to avoid the menstrual period. For prevention of re-infection the partner should be treated locally with Clotrimazole cream at the same time.

Clotrimazolevaginal preparation are colorless and do not stain the underwear.

Eye

Adult: It should be applied thinly and evenly to the conjunctival sac every 4 hours daily or as advised by a physician.

Children: Safety and effectiveness in children have been established for Clotrimazole when used as indicated and in the recommended dosage.

Ear

Instill 2-3 drops of Clarizol Ear Drops in the affected ear two or three times daily.The treatment should be continued for at least two weeks after the disappearance of all signs of infection to prevent re-infection.

For the treatment to become a complete success, reliable and sufficiently long application of Clotrimazole cream is important. The duration of treatment varies; it depends among other factors on the extent and localisation of the disease.

Side Effects

Clotrimazole is generally well tolerated after local application but the few side effects have been reported infrequently like erythema, stinging, blistering, peeling, oedema, pruritus, urticaria and general irritation.

Since there is practically no Clotrimazole absorption through the vaginal skin, no systemic effect is expected. The local tolerance of Clotrimazole vaginal tablet is generally good. Local irritation or burning sensation may occur in a very few cases but these symptoms are not considered harmful.

Rarely patients may experience burning or irritation immediately after applying the ointment.

Toxicity

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps. As with all topical agents, skin sensitization may result .

Oral LD50 (rat): 708 mg/kg; Intraperitoneal LD50 (rat): 445 mg/kg; Subcutaneous LDLO (rat): 10 g/kg; Oral LD50 (mouse): 761 mg/kg; Subcutaneous LDLO (mouse): 10 g/kg; Intraperitoneal LD50 (mouse): 108 mg/kg;

Overdose

This drug poses no risk of acute intoxication, as it is unlikely to occur following a single vaginal or dermal application of an overdose (application over a large area under conditions favorable to absorption) or accidental oral ingestion. There is no specific antidote .

Effects on Fertility

No human studies of the effects of clotrimazole on fertility have been conducted; however, animal studies have not shown any effects on the drug on fertility .

Use in Pregnancy

There are limited data regarding the use of clotrimazole in pregnant women. Animal studies do not show direct or indirect harmful effects on reproduction. Although the topical application of clotrimazole may result in very low serum and tissue levels, the use of clotrimazole topical cream by pregnant women is not recommended unless it is advised by the prescribing physician. Clotrimazole topical cream should not be used in the first trimester of pregnancy unless it is considered by the physician to be essential to patient well-being .

Use in Breastfeeding

Available pharmacodynamic/toxicological studies in animals have shown excretion of clotrimazole/metabolites in breastmilk. Clotrimazole should not be administered during breastfeeding. Although the topical application of clotrimazole has resulted in very low serum and tissue levels, the use of clotrimazole topical cream by lactating women is not recommended unless it recommended by the prescribing physician .

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.

Precaution

If local intolerance develops, consider withdrawal of the medicine and institution of appropriate therapy. Clotrimazole solution is not intended for ophthalmic use. Avoid contact with eyes upon topical application. Children 3 yrs. Pregnancy, lactation. If irritation or sensitivity develops with the use of Clotrimazole ointment, treatment should be discontinued.

Interaction

There have been reports of a heat reaction when this medication used concomitantly with Sofradex drops in the ear.

Antagonism with polyene antibiotics.

Volume of Distribution

The topical form is minimally absorbed in the serum and tissues . Clotrimazole is a lipophilic drug , and has been shown to be secreted in breastmilk in animal studies . There are limited data available regarding the volume of distribution following oral troche administration.

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.

Elimination Route

Because clotrimazole is generally not significantly absorbed, drug interactions are not a major issue with its use .

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

Half Life

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

Clearance

There is limited information on the clearance rate of neomycin.

Elimination Route

Mainly hepatic .

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

Pregnancy & Breastfeeding use

Pregnancy:Clotrimazole is recommended during pregnancy only after first consulting a doctor.

Lactation:Because systemic absorption of clotrimazole following topical application is marginal, there should be no risk for the infant during lactation.