Betacin Plus

Uses

Indicated in atopic, infantile & discoid eczema; prurigo nodularis; Psoriasis (excluding widespread plague psoriasis); lichen simplex or planus; contact sensitivity reactions; seborrhoeic dermatitis; discoid lupus erythematosus & adjunct to systemic steroid therapy in generalized erythroderma.

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

Betacin Plus is also used to associated treatment for these conditions: Acute Gouty Arthritis, Adrenal cortical hypofunctions, Alopecia Areata (AA), Ankylosing Spondylitis (AS), Berylliosis, Blepharitis allergic, Blepharoconjunctivitis, Bullous dermatitis herpetiformis, Bursitis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Conjunctivitis, Corneal Inflammation, Dermatitis, Eczematous, Dermatomyositis, Dermatosis, Discoid Lupus Erythematosus (DLE), Edema of the cerebrum, Epicondylitis, Episcleritis, External ear inflammation, Eye allergy, Hypercalcemia of Malignancy, Inflammatory Reaction of the ear, Iridocyclitis, Iritis, Itching caused by Allergies, Keloid Scars, Keratitis interstitial, Keratoconjunctivitis, Leukemias, Lichen Planus (LP), Lichen simplex chronicus, Lupus Erythematosus, Malignant Lymphomas, Multiple sclerosis exacerbation, Mycosis Fungoides (MF), Necrobiosis lipoidica diabeticorum, Nephrotic Syndrome, Ocular Inflammation, Ocular injuries, Ophthalmia, Sympathetic, Pemphigus, Plaque psoriasis of the body, Plaque psoriasis of the scalp, Polymyositis, Post-Surgical Ocular Inflammation, Pruritus, Psoriasis, Psoriasis Vulgaris (Plaque Psoriasis), Psoriatic Arthritis, Psoriatic plaque, Pulmonary Tuberculosis (TB), Pure Red Cell Aplasia, Regional Enteritis, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Scleritis, Secondary thrombocytopenia, Severe Asthma, Severe Atopic Dermatitis, Skin Infections, Stevens-Johnson Syndrome, Systemic Lupus Erythematosus (SLE), Temporal Arteritis, Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Uveitis, Verrucous Lichen Planus (LP), Acquired immune hemolytic anemia, Acute nonspecific tenosynovitis, Acute rheumatic carditis, Bacterial blepharitis, Corticosteroid-responsive dermatoses, Eczematous rash, Exfoliative erythroderma, Granuloma annulare lesions, Idiopathic eosinophilic pneumonias, Non-suppurative Thyroiditis, Ocular bacterial infections, Severe Allergic rhinitis, Severe Contact dermatitis, Severe Serum sickness, Severe Transfusion Reactions, Severe drug hypersensitivity reactions, Superficial ocular infections, Symptomatic Sarcoidosis, Synovitis of osteoarthritisAcne 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 candidiasis

How Betacin Plus works

Glucocorticoids inhibit neutrophil apoptosis and demargination, and inhibit NF-Kappa B and other inflammatory transcription factors. They also inhibit phospholipase A2, leading to decreased formation of arachidonic acid derivatives. In addition, glucocorticoids promote anti-inflammatory genes like interleukin-10.

Corticosteroids like betamethasone can act through nongenomic and genomic pathways. The genomic pathway is slower and occurs when glucocorticoids activate glucocorticoid receptors and initiate downstream effects that promote transcription of anti-inflammatory genes including phosphoenolpyruvate carboxykinase (PEPCK), IL-1-receptor antagonist, and tyrosine amino transferase (TAT). On the other hand, the nongenomic pathway is able to elicit a quicker response by modulating T-cell, platelet and monocyte activity through the use of existing membrane-bound receptors and second messengers.

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.

Dosage

Betacin Plus dosage

Apply sparingly to the affected area 2 to 3 times daily until an improvement occurs.

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

Burning, itching, irritation, dryness, folliculitis, hypertrychosis acneiform eruptions, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliariamay be reported.

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

Chronic high doses of glucocorticoids can lead to the development of cataracts, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

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.

Precaution

Avoid long-term therapy particularly in infant & children; the treated area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. Avoid contact with eyes.

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

Increased hyperglycaemia and hypokalaemia with thiazide diuretics. Increased incidence of peptic ulcer or GI bleeding with concurrent NSAIDs admin. Response to anticoagulants altered. Dose of antidiabetics and antihypertensives needs to be increased. Decreases serum concentration of salicylates and antimuscarinic agents.

Potentially Fatal: Reduced efficacy with concurrent use of carbamazepine, phenytoin, primidone, barbiturates and rifampicin. Enhanced effect in women taking oestrogens or oral contraceptives.

Volume of Distribution

In a study that included Indian women of reproductive age, the volume of distribution following a single intramuscular dose of betamethasone phosphate was 94,584±23,539 mL(s).

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.

Elimination Route

The absorption and potency of any topical corticosteroid including betamethasone depends on the vehicle in which the steroid is delivered. For example, betamethasone dipropionate 0.05% ointment is classified as a highly potent topical steroid, while betamethasone dipropionate 0.05% cream or lotion is considered to be moderately potent.

There are several structural modifications that can determine the potency of a topical corticosteroid. For example, corticosteroids containing a halogen at specific carbons, or that contain esters are more potent due to enhanced lipophilicity. As such, there is a marked difference between topical products containing betamethasone dipropionate vs. betamethasone valerate. Betamethasone dipropionate contains 2 esters which enhances its potency, while betamethasone valerate has only one ester and is less potent.

It should be noted that the use of occlusive dressings with topical steroids significantly increases the absorption, increasing the risk for adverse effects.

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.

Half Life

In a study that included Indian women of reproductive age, the half-life following a single intramuscular dose of betamethasone phosphate was 10.2 ± 2.5 hours.

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

Clearance

In a study that included Indian women of reproductive age, the CL/F following a single intramuscular dose of betamethasone phosphate was 6,466 ± 805 mL/hour.

There is limited information on the clearance rate of neomycin.

Elimination Route

Corticosteroids are eliminated predominantly in the urine.

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.

Pregnancy & Breastfeeding use

There are no adequate and well controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids and should not be used extensively for a prolonged period. Caution should be excercised when topical corticosteroids are administered in nursing women.

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

Betamethasone is contraindicated in patients with a history of hypersensitivity to any of the components of the preparation. Betamethasone Eye/Ear/Nasal Drops is contraindicated in Herpes simplex virus infection of the eye; known sensitivity or allergy to any ingredient; red eye due to unknown causes; viral or fungal infections in the treatment area; tuberculosis, glaucoma etc.

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.

Acute Overdose

Long-term intensive topical use may lead to systemic effects

Storage Condition

Protect from light. Do not freeze. Store between 15 °C and 30 °C.

Store at 20° to 25°C. Avoid freezing.

Innovators Monograph

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