Econazole nitrate, triamcinolone acetonide.
Each gram contains 10 mg econazole nitrate and 1 mg triamcinolone acetonide.
Excipients/Inactive Ingredients: Benzoic acid, butyhydroxyznisole, disodium edetate, liquid paraffin, oleoyl macrogolglycerides, PEG-6 (and) PEG-32 (and) glycol stearate, purified water.
Pharmacotherapeutic Group: Antifungals For Topical Use, Imidazole and triazole derivatives. ATC Code: D01AC20.
Pharmacology: Pharmacodynamics: Mechanism of action: Econazole nitrate: Econazole nitrate acts by damaging fungal cell membranes, resulting in increased permeability. Sub-cellular membranes in the cytoplasm are damaged. The site of action is most probably the unsaturated fatty acid acyl moiety of membrane phospholipids.
Triamcinolone acetonide: Triamcinolone acetonide is primarily effective because of its anti-inflammatory, antipruritic and vasoconstrictive actions, characteristic of the topical corticosteroid class of drugs. The pharmacologic effects of the topical corticosteroids are well-known; however, the mechanisms of their dermatologic actions are unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.
Pharmacokinetics: Econazole: Absorption: Systemic absorption of econazole is extremely low after topical application to the skin.
Mean peak plasma/serum concentrations of econazole and/or its metabolites were observed 1 to 2 days after dose administration and were <1 ng/mL for the 2% Dermal cream applied to intact skin and 20 ng/mL for the 2% Dermal cream applied to stripped skin. Although most econazole remains on the skin surface (approximately 90%) after application of a 1% cream, concentrations of econazole that have been found in the stratum corneum exceed the minimum inhibitory concentration for dermatophytes, and inhibitory concentrations are achieved in the middermis.
Distribution: Econazole and/or its metabolites in the systemic circulation are extensively bound (>98%) to serum proteins.
Metabolism: Econazole that reaches the systemic circulation is extensively metabolized by oxidation of the imidazole ring, followed by O-dealkylation and glucuronidation.
Excretion: Econazole and its metabolites are eliminated in urine and feces in approximately equal amounts.
Triamcinolone: Absorption: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses (see Dosage & Administration).
Distribution: Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees.
Metabolism: Corticosteroids are metabolized primarily in the liver.
Excretion: Corticosteroids are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
Toxicology: Non-Clinical Information: Econazole: Preclinical effects were observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.
Acute toxicity studies indicate a wide margin of safety. In repeat dose toxicity studies, at high doses (50 mg/kg/day) the liver was identified as a target organ with minimal toxicity and full recovery. Neither significant topical toxicity, phototoxicity, local dermal irritation, vaginal irritation, nor sensitization was noted. Only mild ocular irritation was noted with the cream formulation.
Carcinogenicity and Mutagenicity: No studies on the carcinogenic potential have been conducted due to the short course of proposed clinical therapy and the absence of any significant potential of econazole to be genotoxic in a way that could lead to initiation or promotion of tumor formation.
In various test systems either no or some limited gene-toxicity effects (structural chromosomal deviations) have been shown. Based on an overall assessment of these data and the indicated route of administration including the resulting minimal systemic exposure to econazole, there is little relevance for clinical use.
Reproductive Toxicology: Results of econazole reproduction studies showed no effects on teratogenicity.
Fertility: Results of econazole reproduction studies showed no effects on fertility.
Pregnancy: Low neonatal survival and fetal toxicity was associated only with maternal toxicity. In animal studies, econazole nitrate has shown no teratogenic effects but was foetotoxic in rodents at maternal subcutaneous doses of 20 mg/kg/day and at maternal oral doses of 10 mg/kg/day.
Triamcinolone: As is common with other corticosteroids, lethality in animal models increases with length of exposure, with the principle cause of death related to generalized septicemia presumably due to suppression of the animal's immune-response mechanism.
Carcinogenicity and Mutagenicity: Long-term animal studies have not been performed to evaluate the carcinogenicity potential of topical corticosteroids. In a 104-week drinking water study in male rats, triamcinolone acetonide caused an increased incidence of hepatocellular adenomas and combined adenomas/carcinomas at a toxic dose of ~5 μg/kg. It was judged that these findings represent a class effect and probably involved glucocorticoid receptors. No other verifiable or relevant carcinogenicity data are available.
Reproductive Toxicology: Triamcinolone (within the human therapeutic range and greater) has been associated with cleft palate in the offspring when given to pregnant mice, rats, rabbits and hamsters, and pulmonary hypoplasia in rats. In non-human primates, administration of triamcinolone (at doses <1 to 20 x clinical dose) has been associated with central nervous system effects, neural tube defects, craniofacial and skeletal abnormalities, and growth retardation.
Fertility: No verifiable data are available.
Pregnancy: No verifiable data are available.
Microbiology: Econazole possesses a broad spectrum of antimycotic activity that has been demonstrated against dermatophytes, yeasts and molds. A clinically relevant action against gram- positive bacteria has also been found.
PEVISONE Cream in all its dosages is indicated for the treatment of dermatomycoses complicated by inflammatory and/or pruritic manifestations of skin disorders.
Dosage: PEVISONE Cream should be applied to the affected area no more than 2 times daily, preferably once in the morning and once in the evening. PEVISONE Cream should not be applied with an occlusive dressing, or to large skin areas of the body.
The duration of treatment with the PEVISONE Cream should be until the inflammatory symptoms subside but no longer than 2 weeks; after 2 weeks of therapy with PEVISONE Cream, continue therapy as needed with a preparation containing econazole or econazole nitrate alone.
Administration: Cream for topical application to the skin.
PEVISONE Cream is for cutaneous application only. Corticosteroids applied to the skin, including triamcinolone, can be absorbed in sufficient amounts to produce systemic effects.
Treatment: In the event of accidental ingestion, treat symptomatically. If PEVISONE Cream is accidentally applied to the eyes, wash with clean water or saline and seek medical attention if symptoms persist.
PEVISONE Cream is contraindicated in individuals who have shown hypersensitivity to any of its ingredients.
Like any other dermatological preparation containing corticosteroids, PEVISONE Cream is contraindicated in specific skin conditions such as tuberculosis, varicella, herpes simplex or other viral infections of the skin, or fresh vaccination sites.
For external use only. PEVISONE Cream is not for ophthalmic or oral use.
If a reaction suggesting hypersensitivity or chemical irritation occurs, treatment should be discontinued.
Corticosteroids applied to the skin can be absorbed in sufficient amounts to produce systemic effects, including adrenal suppression. Systemic absorption may be increased by various factors such as application over a large skin surface area, application to damaged skin, application under occlusive skin dressings and prolonged duration of therapy.
Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA (hypothalamic-pituitary-adrenal) axis suppression and Cushing's syndrome than mature patients because of a higher ratio of skin surface area to body mass. Caution should be exercised when PEVISONE Cream is administered to pediatric patients and treatment should be discontinued if signs of HPA axis suppression or Cushing's syndrome occur.
Repeated application and/or prolonged application of topical corticosteroids in the periorbital region may induce cataracts, ocular hypertension, or increase the risk of glaucoma in patients.
Topical corticosteroids are associated with skin thinning and atrophy, striae, rosacea, perioral dermatitis, acne, telangiectasis, purpura, hypertrichosis, and delayed wound healing.
Topical corticosteroids may lead to increased risk of dermatological superinfection or opportunistic infection.
Effects on Ability to Drive and Use Machines: None known.
Pregnancy: PEVISONE Cream: There are no adequate and well controlled studies on adverse effects from the use of PEVISONE Cream in pregnant women, and no other relevant epidemiological data are available.
PEVISONE Cream should be used in the first trimester of pregnancy only when the physician considers it essential to the welfare of the patient. PEVISONE Cream may be used during the second and third trimester if the potential benefit to the mother outweighs the possible risks to the fetus. Drugs of this class should not be used extensively in large amounts, over large skin surface areas, or for a prolonged period of time in pregnant patients.
Studies in animals have shown reproductive toxicity [fetotoxicity with econazole and teratogenicity for triamcinolone (see as follows)]. However, the risk in humans is unknown.
Econazole nitrate: Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology: Non-Clinical Information under Actions). The significance of this finding in humans is unknown. Systemic absorption of econazole is low (<10%) after topical application to the intact skin in humans.
Triamcinolone acetonide: Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology: Non-Clinical Information under Actions). Limited data in the literature indicate that up to 5% of topically applied triamcinolone to the skin is systemically absorbed in humans.
Breast-feeding: PEVISONE Cream: There are no adequate and well-controlled studies on the topical administration of PEVISONE Cream during breast-feeding. It is not known whether concomitant topical administration of PEVISONE Cream to the skin could result in sufficient systemic absorption to produce detectable quantities in breast milk in humans. Caution should be exercised when PEVISONE Cream is administered to breast-feeding mothers.
Econazole nitrate: Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups. It is not known whether cutaneous administration of topical econazole nitrate could result in sufficient systemic absorption of econazole to produce detectable quantities in breast milk in humans.
Triamcinolone acetonide: No studies in animals relevant to triamcinolone during lactation were identified. It is not known whether topical administration of triamcinolone to the skin could result in sufficient systemic absorption to produce detectable quantities in breast milk in humans.
Fertility: Econazole nitrate: Results of econazole animal reproduction studies showed no effects on fertility (see Pharmacology: Toxicology: Non-Clinical Information under Actions).
Triamcinolone acetonide: No verifiable data are available.
Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of econazole nitrate with triamcinolone acetate based on the comprehensive assessment of the available adverse event information. A causal relationship with of econazole nitrate with triamcinolone acetate cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Trial Data: Adults:
The safety of PEVISONE Cream [econazole nitrate (1%) plus triamcinolone acetonide (0.1%)] was evaluated in 182 adults who participated in 4 clinical trials. Adverse reactions that occurred in ≥ 1% of adults treated with PEVISONE Cream in these studies are listed as follows in Table 1. (See Table 1.)
Click on icon to see table/diagram/image
No adverse reactions were reported in < 1% of adults treated with PEVISONE Cream in the 4 clinical trials.
The safety of PEVISONE Cream [econazole nitrate (1%) plus triamcinolone acetonide (0.1%)] was evaluated in 101 children (ages 3 months to 10 years) who participated in 1 clinical trial. Adverse reactions reported for ≥ 1% of children treated with PEVISONE Cream in this study are shown in Table 2. (See Table 2.)
Click on icon to see table/diagram/image
No adverse reactions were reported in < 1% of children treated with PEVISONE Cream in the 1 clinical trial.
In addition to the adverse reactions reported during clinical studies and listed previously, the following adverse reactions have been reported during postmarketing experience (Table 3). The frequencies are provided according to the following convention: Very common ≥ 1/10; Common ≥ 1/100 and < 1/10; Uncommon ≥ 1/1,000 and < 1/100; Rare ≥ 1/10,000, < 1/1,000; Very rare < 1/10,000, including isolated.
In Table 3, adverse reactions are presented by frequency category based on spontaneous reporting rates. (See Table 3.)
Click on icon to see table/diagram/image
Econazole is a known inhibitor CYP3A4/2C9. However, due to the limited systemic availability after cutaneous application, clinically relevant interactions are unlikely to occur, but have been reported for oral anticoagulants. In patients taking oral anticoagulants, such as warfarin or acenocoumarol, caution should be exercised and the anticoagulant effect should be monitored.
Incompatibilities: Not known.
D01AC20 - imidazoles/triazoles in combination with corticosteroids ; Belongs to the class of imidazole and triazole derivatives. Used in the topical treatment of fungal infection.
Cream (soft white with faint odour) 15 g.