Clc M

Uses

Clobetasone preparations are used for the treatment of eczema and dermatitis of all types including atopic eczema, photodermatitis, otitis externa, primary irritant allergic dermatitis (including napkin rash), intertrigo, prurigo nodularis, seborrhoeic dermatitis and insect bite reactions. Clobetasone may be used as a maintenance therapy between courses of one of the more active topical steroids.

Miconazole Topical Cream has an antibacterial effect on Gram-positive bacteria, it may be used in mycoses secondarily infected with such bacteria. Skin and nail infections due to dermatophytes, yeasts and other fungi such as: Tinea capitis, corporis, manuum, pedis, barbae, cruris, unguium or onychomycosis. Pityriasis versicolor, candidiasis of skin and nails, stomatitis angularis, otitis externa.

Miconazole Oral treatment and prevention of fungal infections of the oropharynx and gastrointestinal tract, and of super infections due to Gram-positive bacteria.

Clc M is also used to associated treatment for these conditions: Allergic Contact Dermatitis, Conjunctivitis allergic, Cyclitis, Dermatitis, Eczematous, Episcleritis, Iritis, Keratitis interstitial, Ocular Irritation, Phlyctenular keratoconjunctivitis, Rosacea Keratitis, Scleritis, Vernal Keratoconjunctivitis, Conjunctival hyperemia, Ocular bacterial infections, Ocular lesionAcne Vulgaris, Dermatophytosis, Dermatophytosis of nail, Diaper Dermatitis, Excessive sweating and body odor, Fungal skin infection, Gastrointestinal candidiasis, Infection Mixed, Infections, Fungal of the Skin Folds, Nail candida, Oropharyngeal Candidiasis, Pityriasis versicolor, Ringworm, Seborrheic Dermatitis, Skin candida, Tinea Capitis, Tinea Corporis, Tinea Cruris, Tinea Pedis, Vaginal Candidiasis, Cutaneous candidiasis

How Clc M works

Topically applied clobeyasone are thought to bind with cytoplasmic receptors in the dermal and intradermal cells and to induce inhibitory proteins, thus leading to decreased activity of prostaglandins, kinins, histamine, liposomal enzymes and other endogenous mediators of inflammation. Topical corticosteroids inhibit the migration of macrophages and leukocytes into areas of inflamed skin by reversing vascular dilation and permeability, resulting in decreased erythema, edema and pruritus.

Miconazole is an azole antifungal used to treat a variety of conditions, including those caused by Candida overgrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.

In addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.

Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in Candida, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics. In addition, farnesol is an inhibitor of drug efflux ABC transporters, namely Candida CaCdr1p and CaCdr2p, which may additionally contribute to increased effectiveness of azole drugs.

Dosage

Clc M dosage

Apply to the affected area up to four times a day until improvement occurs, when the frequency of application may be reduced.

For oral administration: Dosage is based on 15 mg/kg/day.

• Adults: 1-2 tea-spoonfuls of gel four times daily
• Children aged 6 years and over: One tea-spoonful of gel four times daily
• Children aged 2-6 years: One tea-spoonful of gel twice daily
• Infants under 2 years: Half tea-spoonful of gel twice daily.

For localised lesions of the mouth:

A small amount of gel may be applied directly to the affected area with a clean finger. For topical treatment of the oropharynx, the gel should be kept in the mouth for as long as possible. Treatment should be continued for up to 2 days after the symptoms have cleared.

For oral candidasis, dental prostheses:

Should be removed at night and brushed with the gel.

The dosage is same for all the ages.

For skin infections: Apply some cream to the lesions twice daily and rub it well with finger until it has fully penetrated the skin. All lesions usually disappear after 2 to 5 weeks. Prolong treatment for some 10 days to prevent relapse.

For nail infections: Clip infected nail as shortly as possible. Apply some cream once daily to the infected nail and rub with your finger, cover nail with a non-perforated occlusive plastic bandage.

Also after loosening of the infected nail (from 2-3 weeks onwards) uniterrupted treatment should be continued until the growth of a new nail has set in and definite cure can be observed (usually after seven months or more).

Side Effects

Local atrophic changes; pigmentation changes & hypertrichosis. Increased liability to infection. Infections may be masked. Acute adrenal insufficiency. Growth retardation in child. Cushingoid symptoms. Amenorrhoea, hyperhidrosis, skin thinning

Topical application of Miconazole Nitrate has almost no side effect.

For oral gel: Occasionally, nausea and vomiting have been reported, and with long term treatment, diarrhoea. In rare instances, allergic reactions have been reported. There are isolated reports of hepatitis, for which the causal relationship with Miconazole has not been established.

Toxicity

Organism : Mouse Test type: LD50 Oral (Reported dose: >6gm/kg) LD50 Subcutaneous ( >3600mg/kg ) Effects : Behavioral : somnolence ( general depressed activity ) Blood changes in spleen

Organism : Mouse Test type: LD50 Route: Intraperitoneal Reported dose: 500 mg/kg

LD50 rat : 1510mg/kg Intraperitoneal LD50 rat >6gm/kg Oral LD 50 rat : > 2600mg/kg subcutaneous

Miconazole overdose has not been reported. Patients experiencing an overdose are at an increased risk of severe adverse effects such as headache, skin irritation, diarrhea, nausea, vomiting, abdominal pain, and dysgeusia. Symptomatic and supportive measures are recommended.

Miconazole has an oral LD₅₀ of 500 mg/kg in rats.

Precaution

May be absorbed in sufficient amounts to cause systemic effects when applied topically to large areas, broken skin or under occlusive dressings. Peptic ulcer, osteoporosis, psychoses or severe psychoneuroses. Not to be used indiscriminately for pruritus. CHF or hypertension. Diabetes mellitus, epilepsy, glaucoma, infectious diseases, ocular herpes simplex, chronic renal failure and uraemia. Active or doubtfully quiescent tuberculosis. Local treatment of eye disorders. Elderly. Prolonged use on the face.

If the concomitant use of Miconazole and anticoagulants is envisaged, the anticoagulant effect should be carefully monitored and titrated. It is advisable to monitor Miconazole and phenytoin levels, if they are used concomitantly. Particularly in infants and young children, caution is required to ensure that the gel does not obstruct the throat. Hence, the gel should not be applied to the back of the throat and the full dose should be divided into smaller portions. Observe the patient for possible choking.

Interaction

Potentially hazardous interactions- none has been reported. Potentially useful interactions- none has been reported.

Miconazole can inhibit the metabolism of drugs metabolised by the Cytochrome P450-3A and -2C9 families. This can result in an increase or prolongation of their effects, including side effects. Miconazole Oral Gel should not be used during treatment with the following drugs: terfenadine, astemizole,mizolastine, cisapride, triazolam, oral midazolam, dofetilide, quinidine, pimozide, CYP3A4 metabolised HMG-CoA reductase inhibitors such as simvastatin and lovastatin.

Volume of Distribution

The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.

A 1200 mg miconazole vaginal suppository resulted in a calculated apparent volume of distribution of 95 546 L while a 100 mg vaginal cream yielded an apparent volume of distribution of 10 911L.

Elimination Route

Absorption is dependent on many drug-related factors including: intrinsic properties of the steroid itself; concentration of the drug (increased concentration generally leads to more drug being absorbed but may plateau at higher concentrations); vehicle used (optimized or augmented vehicles > ointments or gels > creams or lotions); duration of exposure; frequency of application; combination with other products that break down the skin barrier and increase absorption (e.g., salicylic acid, urea). Patient-related factors that influence absorption include: patient age (infants and children absorb topical medications more quickly and to a greater degree than adults, and have a greater total skin surface to body weight ratio; the elderly have thinner skin and absorb drug more readily); disruption of the skin due to inflammation or disease (e.g., absorption increased in atopic dermatitis); total skin area treated; skin site treated (absorption is much greater from thin-skinned areas such as scalp, face, eyelid, axilla, and scrotum than from areas with thicker skin such as forearm, knee, elbow, palm and sole); absorption is increased with increased temperature or humidity of the skin or the environment; occlusion of the treated skin (via plastic wrap, oily vehicles, dressings, tape, diapers, tight-fitting clothing, etc.) can increase absorption up to 10-fold.

Miconazole given to healthy volunteers as a single 50 mg oral tablet produced a mean C_max of 15.1 ± 16.2 mcg/mL, a mean AUC_0-24 of 55.2 ± 35.1 mcg*h/mL, and a median T_max of 7 hours (range 2.0-24.1). In these patients measurable plasma concentrations ranged from 0.5 to 0.83 mcg/mL.

Topical miconazole is absorbed poorly into the systemic circulation. In pediatric patients aged 1-21 months given multiple topical applications of miconazole ointment for seven days, the plasma miconazole concentration was less than 0.5 ng/mL in 88% of the patients, with the remaining patients having a concentration of 0.57 and 0.58 ng/mL, respectively. Similarly, patients. administered with a vaginal 1200 mg ovule had a mean C_max of 10.71 ng/mL, mean T_max of 18.4 hours, and mean AUC_0-96 of 477.3 ng*h/mL.

Half Life

N/A

Miconazole has a terminal half-life of 24 hours.

Elimination Route

Clobetasone and its metabolites are excreted in urine.

Miconazole is excreted through both urine and feces; less than 1% of unchanged miconazole is recovered in urine.

Pregnancy & Breastfeeding use

There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of fetal development including cleft palate and intrauterine growth retardation. There may therefore be a very small risk of such effects in the human fetus.

In animals, Miconazole has shown no teratogenic effects but is foetotoxic at high oral doses. The significance of this to man is unknown. However, as with other imidazoles, Miconazole Oral Gel should be avoided in pregnant women if possible. The potential hazards should be balanced against the possible benefits. It is not known whether Miconazole is excreted in human milk. Caution should be exercised when prescribing Miconazole Oral Gel to nursing mothers.

Only small amounts of Miconazole cream are absorbed following local administration. However as with other imidazoles, Miconazole nitrate should be used with caution during pregnancy.

Contraindication

Pregnancy (in high doses), Presence of acute infections, Treatment of rosacea, Leg ulcers, Acne vulgaris, Widespread plaque psoriasis. Child <1 yr.

Miconazole is contraindicated in patients with known hypersensitivity to the active drug.

Acute Overdose

Acute overdosage is very unlikely to occur, in the case of chronic overdosage or misuse the features of hypercorticism may appear and in this situation topical steroids should be discontinued.

In general, Miconazole is not highly toxic. In the event of accidental overdosage, vomiting and diarrhoea may occur.

Storage Condition

Store below 30˚ C. Do not freeze. Protect from light.

Store away from direct heat. Keep out of reach of children.

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