Otikfree

Uses

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.

Prednisolone eye drops is used for the treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

Prednisolone tablet, Injection is used forAllergy and anaphylaxis: bronchial asthma, drug hypersensitivity reactions, serum sickness, angioneurotic oedema, anaphylaxis.

Respiratory disease: allergic pneumonitis, asthma, occupational asthma, pulmonary aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body, aspiration of stomach contents, pulmonary sarcoid, drug induced lung disease, adult respiratory distress syndrome, spasmodic croup.

Rheumatic disorders: rheumatoid arthritis, polymyalgia rheumatica, juvenile chronic arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease.

Arteritis/collagenosis: giant cell arteritis/polymyalgia rheumatica, mixed connective tissue disease, polyarteritis nodosa, polymyositis.

Blood disorders: haemolytic anaemia (auto-immune), leukaemia (acute and chronic lymphocytic), lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura.

Cardiovascular disorders: post-myocardial infarction syndrome, rheumatic fever with severe carditis.

Endocrine disorders: primary and secondary adrenal insufficiency, congenital adrenal hyperplasia.

Gastro-intestinal disorders: Crohn's disease, ulcerative colitis, persistent coeliac syndrome (coeliac disease unresponsive to gluten withdrawal), auto-immune chronic active hepatitis, multisystem disease affecting liver, biliary peritonitis.

Infections (with appropriate chemotherapy): helminthic infestations, Herxheimer reaction, infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult), tuberculous meningitis, rickettsial disease.

Muscular disorders: polymyositis, dermatomyositis.

Neurological disorders: infantile spasms, Shy-Drager syndrome, sub-acute demyelinating polyneuropathy.

Ocular disease: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the orbit, giant cell arteritis, malignant ophthalmic Graves disease.

Renal disorders: lupus nephritis, acute interstitial nephritis, minimal change glomerulonephritis.

Skin disorders: pemphigus vulgaris, bullous pemphigoid, systemic lupus erythematosus, pyoderma gangrenosum.

Miscellaneous: sarcoidosis, hyperpyrexia, Behçets disease, immunosuppression in organ transplantation.

Prednisolone is used for the treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

Otikfree is also used to associated treatment for these conditions: Acne 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 candidiasisInflammation, Inflammatory Conditions, Ocular Infections, Irritations and Inflammations, Ocular Inflammation, Organ Transplant Rejection

How Otikfree works

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.

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Dosage

Otikfree dosage

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).

The initial dosage of Prednisolone may vary from 5 mg to 60 mg daily depending on the disorder being treated. Divided daily dosage is usually used.

The appropriate individual dose must be determined by trial and error and must be re-evaluated regularly according to activity of the disease.

In general, initial dosage shall be maintained or adjusted until the anticipated response is observed. The dose should be gradually reduced until the lowest dose, which will maintain an adequate clinical response is reached.

During prolonged therapy, dosage may need to be temporarily increased during periods of stress or during exacerbations of the disease. When the drug is to be stopped, it must be withdrawn gradually and not abruptly.

Intermittent dosage regimen: A single dose of Prednisolone in the morning on alternate days or at longer intervals is acceptable therapy for some patients. When this regimen is practical, the degree of pituitary-adrenal suppression can be minimized.

Use in children: Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible. Treatment should be administered where possible as a single dose on alternate days.

Specific dosage guidelines-

Allergic and skin disorders: initial doses of 5-15 mg daily are commonly adequate.

Collagenosis: Initial doses of 20-30 mg daily are frequently effective. Those with more severe symptoms may require higher doses.

Rheumatoid arthritis: The usual initial dose is 10-15 mg daily. The lowest daily maintenance dose compatible with tolerable symptomatic relief is recommended.

Blood disorders and lymphoma: An initial daily dose of 15-60 mg is often necessary with reduction after an adequate clinical or haematological response. Higher doses may be necessary to induce remission in acute leukaemia.

Adult: Instill one drop into the conjunctival sac two to four times daily. During the initial 24 to 48 hours, the dosing frequency may be increased if necessary. Care should be taken not to discontinue the therapy before completing the course.

Paediatri: Safety and effectiveness in pediatric patients have not been established.

Side Effects

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.

Elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation and delayed wound healing. Fungal and viral infections of the cornea are particularly may develop coincidentally with long-term applications of steroid.

General side-effects include leucocytosis, hypersensitivity including anaphylaxis, thromboembolism, nausea, and malaise.

Toxicity

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.

The oral LD₅₀ of prednisolone acetate in mice is 1680 mg/kg. Patients experiencing an overdose of oral prednisolone acetate may experience an increased severity in the adverse effects of corticosteroids. Overdose of oral prednisolone acetate may be treated by gastric lavage or inducing vomiting if the overdose was recent, as well as supportive and symptomatic therapy. Chronic overdosage may be treated by dose reduction or treating patients on alternate days. An overdose by the ophthalmic route is not expected to cause problems.

Precaution

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.

Shake the bottle well before use. Prolonged use of corticosteroids may result in damage to the optic nerve and defects in vision. If this product is used for longer period of time, intraocular pressure should be routinely monitored.

Caution is necessary when oral corticosteroids, including Prednisolone, are prescribed in patients with the following conditions like-Tuberculosis, Hypertension, Congestive heart failure, Liver failure, Renal insufficiency, Diabetes mellitus or in those with a family history of diabetes, Osteoporosis, Patients with a history of severe affective disorders and particularly those with a previous history of steroid-induced psychoses, Epilepsy, Peptic ulceration, Previous Steroid Myopathy.

Undesirable effects may be minimized by using the lowest effective dose for the minimum period and by administering the daily requirement as a single morning dose on alternate days. Frequent patient review is required to titrate the dose appropriately against disease activity.

Interaction

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.

Hepatic microsomal enzyme inducers: Drugs which can cause liver enzyme induction such as phenobarbitone, phenytoin, rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may reduce the therapeutic efficacy of corticosteroids by increasing the rate of metabolism.

Non-steroidal anti-inflammatory drugs: Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of Gl ulceration.

Anticoagulants: Response to anticoagulants may be reduced or, less often, enhanced by corticosteroids.

Vaccines: Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

Oestrogens: Oestrogens may potentiate the effects of glucocorticoids and dosage adjustment may be required if oestrogens are added to or withdrawn from a stable dosage regimen.

Other: The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids and the hypokalaemic effect of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

Volume of Distribution

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.

The volume of distribution of the active metabolite, prednisolone, is 0.22/0.7L/kg.

Elimination Route

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.

Prednisolone acetate oral suspension given at a dose equivalent to 15mg prednisolone has a C_max of 321.1ng/hr, a T_maxof 1-2 hours, and an AUC of 1999.4ng*hr/mL. The absorption pharmacokinetics of prednisolone acetate are not significantly different from a comparable dose of prednisolone.

Half Life

Miconazole has a terminal half-life of 24 hours.

Oral prednisolone acetate has a plasma half life of 2-3 hours.

Clearance

Data regarding the clearance of prednisolone acetate is not readily available.

Elimination Route

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

Prednisolone acetate is predominantly excreted in the urine.

Pregnancy & Breastfeeding use

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.

Pregnancy: Prednisolone Acetate is pregnancy category C. So, this drug should be used during pregnancy only if clearly needed.

Lactation: Corticosteroids are excreted in small amounts in breast milk and infants of mothers taking pharmacological doses of steroids should be monitored carefully for signs of adrenal suppression.

Contraindication

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

Prednisolone (Eye drops) is contraindicated in viral diseases of the cornea, conjunctiva and known hypersensitivity to any of the ingredients of Prednisolone (Eye drops) or other corticosteroids.

Systemic infections unless specific anti-infective therapy is employed. Hypersensitivity to any ingredient. Ocular herpes simplex because of possible perforation.

Special Warning

Use in the elderly: Treatment of elderly patients, particularly if long term, should be planned bearing in mind the more serious consequences of the common side effects of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, hypokalemia, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

May need to increase dose in patients with hyperthyroidism to achieve therapeutic effects.

Acute Overdose

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

A one-time accidental overdose of Prednisolone Ophthalmic Suspension generally will not cause acute problems. Long time overdose may show general side-effects. In accidental overdose sufficient water should be taken to dilute the medication.

Report of acute toxicity and/or death following overdose of glucocorticoids are rare. No specific antidote is available; treatment is supportive and symptomatic. Serum electrolytes should be monitored.

Storage Condition

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

Store in a cool, dry place and protect from light. Keep out of the reach of children. Protect from freezing. Shake well before using.

Innovators Monograph

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