Quadriderm Af

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.

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.

Blepharitis, blepharoconjunctivitis, conjunctivitis, dacryocystitis, keratitis, keratoconjunctivitis, acute meibomianitis, and corneal ulcers caused by susceptible organisms. Otorrhea associated with external otitis, chronic suppurative otitis media or subacute purulent otitis media; or postoperative otorrhea, such as that following fenestration, mastoidectomy or tympanoplasty.

Gentamicin cream is used for the topical treatment of the primary and secondary bacterial infections of the skin caused by the organisms sensitive to Gentamicin. Gentamicin may clear infections that have not responded to other topical antibiotics.

Quadriderm Af 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 osteoarthritisBalanitis 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 infectionBacterial Conjunctivitis, Bacterial Infections, Bacterial Peritonitis, Bacterial dacryocystitis, Blepharoconjunctivitis, Central Nervous System Infections, Conjunctivitis allergic, Corneal infection, Dermatitis infected, Ecthyma, Eczematous dermatitis infected, Folliculitis, Furunculosis, Gram-negative enteric bacilli neonatal sepsis, Impetigo contagious, Inflammation, Keratitis bacterial, Keratoconjunctivitis, Meibomianitis, Meningitis, Bacterial, Ocular Inflammation, Pustular Psoriasis (PP), Pustular acne, Pyoderma Gangrenosum, Seborrheic Dermatitis, Septicemia gram-negative, Skin Infections, Skin Infections, Bacterial, Skin and Subcutaneous Tissue Bacterial Infections, Sycosis barbae, Bacterial blepharitis, Bacterial corneal ulcers, Bacterial dermatoses, Complicated Bacterial Urinary Tract Infections, Complicated Respiratory tract infection bacterial, Corticosteroid-responsive dermatoses, Ocular bacterial infections, Severe Endocarditis enterococcal, Severe Infection Pseudomonas aeruginosa, Severe Staphylococcal infection

How Quadriderm Af 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.

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 .

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane.[A233320] Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site.[A232324, A232329] Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit.[A232329, A232339] Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation.[A232344] Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.

Dosage

Quadriderm Af dosage

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

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.

Eye: 1-2 drops instilled in affected eye up to 6 times a day or more frequently if required (severe infections may require 1-2 drops every 15-20 minutes initially, reducing the frequency of instillation gradually as the infection is controlled).

Ear: The area should be cleaned and 2-3 drops should be instilled every 3-4 times a day and at night, or more frequently if required.

A small amount of Gentamicin should be applied gently to the affected areas three to four times daily. The area treated may be covered with a gauze dressing if desired. Before applying the medication the affected area should be properly cleaned.

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

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.

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.

In patients with dermatoses treated with gentamicin, irritation (erythema and pruritus) had been reported in small number of cases. Itching, redness, swelling or other signs of irritation may develop. With the eye/ear drop bacterial and corneal ulcer have developed during treatment with gentamicin. Most frequently reported adverse reactions are ocular burning and irritation upon drug instillation, non specific conjunctivitis, conjunctival epithelial defects, and conjunctival hyperemia.

Gentamicin cream is well tolerated. There has been no evidence of irritation and sensitization after using Gentamicin cream.

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.

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 .

As with other aminoglycosides, nephrotoxicity and ototoxicity are associated with gentamicin. Signs of nephrotoxicity include an increase in plasma creatinine and urea, while signs of ototoxicity include issues with balance, nausea, tinnitus, and hearing loss. It is important to note that aminoglycoside-induced nephrotoxicity is typically reversible, while ototoxicity is more likely to be permanent. The risk of both toxicities increases with long-term gentamicin therapy. Gentamicin is considered to be more vestibulotoxic than cochleotoxic compared to other aminoglycosides. Unfortunately, gentamicin-related ototoxicity does not correlate with cumulative dosing, peak and trough levels, or dosing schedule. The unpredictability of ototoxicity supports close monitoring of the patient throughout treatment. In cases of toxicity or overdose, the medication should be discontinued immediately; hemodialysis may be initiated to lower gentamicin serum concentrations.

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.

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.

If these occurs or if irritation, sensitization develops, treatment with gentamicin should be discontinued and appropriate therapy instituted. Gentamicin ear/eye drops is not for injection. It should never be injected subconjunctivally, nor it should be directly introduced into the anterior chamber of the eye.

Use of topical antibiotics occasionally cause overgrowth of nonsusceptible organisms including fungi. If this occurs or if irritation, sensitisation or super infection develops, treatment with Gentamicin should be discontinued and appropriate therapy should be instituted.

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.

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

Antagonism with polyene antibiotics.

None has been reported so far with topical and Eye/Ear drops.

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 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.

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.

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

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.

One study assessing the pharmacokinetics of gentamicin in children and adults reported a mean half-life of 75 minutes after intravenous administration. The mean half-life associated with intramuscular administration was about 29 minutes longer. Fever and anemia may result in a shorter half-life although dose adjustments are not usually necessary. Severe burns are also associated with a shorter half-life and may result in lower gentamicin serum concentrations.

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.

The renal clearance of gentamicin is comparable to individual creatinine clearance.

Elimination Route

Corticosteroids are eliminated predominantly in the urine.

Mainly hepatic .

Gentamicin is excreted primarily by the kidneys. In patients with normal renal function, 70% or more of an initial gentamicin dose can be recovered in the urine within 24 hours. Excretion of gentamicin is significantly reduced in patients with renal impairment.

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: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.

Consideration should be given the possibility of foetal ototoxicity when gentamicin is applied topically to large denuded areas of skin. For Gentamicin Eye/Ear Drops safety profile in pregnancy is not yet established and should be administered when considered essential.

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.

Hypersensitivity to clotrimazole.

Gentamicin is contraindicated in individuals with a history of sensitivity reaction to any of its components. Use of topical Gentamicin may occasionally allow overgrowth of nonsusceptible organisms, including fungi.

Acute Overdose

Long-term intensive topical use may lead to systemic effects

Supportive measures should be taken incase of accidental oral ingestion.

In case of accidental oral ingestion, supportive measures should be taken.

Storage Condition

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

Store at a cool and dry place. Protect from light. Do not freeze.

To avoid contamination, do not touch the tip of the container to the eye, eyelid or any surface.

Innovators Monograph

You find simplified version here Quadriderm Af