MYCOCORT​ ​CREAM

Indications

• Severe resistant inflammatory skin disorders
• Eczema unresponsive to less potent corticosteroids
• Psoriasis

Dosage

Children: For children aged 1–17 years: apply 1–2 times a day for up to 4 weeks, to be applied thinly.

Adults: Apply 1–2 times a day for up to 4 weeks, to be applied thinly, with a maximum of 50 g of 0.05% preparation per week between courses of more potent corticosteroids.

Mechanism of action

Clobetasol propionate exerts its effects by binding to the glucocorticoid receptor, leading to decreased vasodilation and capillary permeability, reduced leukocyte migration to inflammation sites, and modulation of gene expression. It inhibits the production of pro-inflammatory mediators and promotes the expression of anti-inflammatory genes, resulting in an overall anti-inflammatory effect. The drug also has immunosuppressive properties at higher doses.

Pharmacodynamics

As a corticosteroid, clobetasol propionate significantly inhibits pro-inflammatory signals while promoting anti-inflammatory responses. Its effects can last for an extended duration when applied twice daily. It has a wide therapeutic window, allowing for doses significantly higher than the body's natural corticosteroid production. However, long-term use can lead to suppression of the hypothalamic-pituitary-adrenal axis and increase the risk of infections.

Pharmacokinetics

Clobetasol propionate is well-absorbed through the skin, with systemic absorption dependent on the formulation and application site. Once absorbed, it is distributed throughout the body and metabolized primarily in the liver. Its elimination half-life varies, but the drug is generally excreted in urine. Due to its potency, careful monitoring is required to avoid systemic side effects, particularly with prolonged use.

Adverse effects

• skin atrophy
• telangiectasia
• striae
• systemic absorption leading to adrenal suppression
• burning sensation at application site
• allergic reactions including contact dermatitis

Precautions

• Use with caution in patients with a history of diabetes or hypertension
• Avoid prolonged use on large surface areas
• Monitor for signs of infection at the application site
• Consider potential systemic effects with high doses or extended use

Pregnancy

Clobetasol propionate should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids should be used cautiously.

Breast-feeding

It is not known whether clobetasol propionate is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• 0.05% cream
• 0.05% ointment
• 0.05% foam
• 0.05% scalp application
• 0.05% shampoo

Indications

• Vaginal candidiasis
• Oropharyngeal candidiasis
• Vulvovaginal infections
• Superficial fungal infections

Dosage

Adults: For vaginal candidiasis, miconazole cream is typically applied twice daily, using 5 g inserted into the vagina for 7 days. For oropharyngeal candidiasis, the oral gel is usually administered as 2.5 mL four times a day.

Mechanism of action

Miconazole primarily acts through the inhibition of the CYP450 14α-lanosterol demethylase enzyme, leading to disrupted ergosterol production in fungal cell membranes. This disruption results in increased cell membrane permeability and leakage of essential cellular constituents. Additionally, miconazole inhibits fungal peroxidase and catalase, increasing the production of reactive oxygen species (ROS) which contribute to fungal cell death. Miconazole also elevates intracellular levels of farnesol, which disrupts quorum sensing in Candida, preventing the transition to more virulent forms.

Pharmacodynamics

Miconazole is predominantly applied topically, leading to minimal systemic absorption. Its primary adverse reactions are usually localized to hypersensitivity reactions, with the potential for anaphylaxis in rare cases. Patients using intravaginal miconazole are advised to avoid reliance on other contraceptive methods and not to use tampons simultaneously due to the risk of altered vaginal flora.

Pharmacokinetics

Miconazole is poorly absorbed when applied topically or intravaginally, resulting in low systemic exposure. The pharmacokinetics of miconazole can vary based on the route of administration, but systemic absorption is generally low, thus limiting systemic side effects and interactions. Miconazole is extensively metabolized in the liver, and its metabolites are excreted primarily through the urine.

Contra-indications

• Hypersensitivity to miconazole or any of its excipients
• Recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
• Undiagnosed vaginal bleeding
• Oestrogen-dependent tumors (e.g. breast cancer in first-degree relatives)
• Acute porphyrias
• Severe diabetes (increased risk of heart disease)

Adverse effects

• Dysmenorrhoea
• Skin reactions
• Increased risk of gallbladder disease
• Migraine or migraine-like headaches
• Abdominal pain
• Dysuria
• Nausea
• Pelvic cramps
• Vaginal hemorrhage
• Angioedema

Interactions

• Miconazole + antihistamines (non-sedating): Severe (increases exposure)
• Miconazole + mizolastine: Severe (increases exposure)
• Miconazole + oral benzodiazepines: Severe (increases exposure)
• Miconazole + ergometrine: Severe (increases exposure)
• Miconazole + ergotamine: Severe (increases exposure)
• Miconazole + alkylating agents: Moderate (increases concentration)
• Miconazole + busulfan: Moderate (increases concentration)
• Miconazole + antiarrhythmics: Moderate (increases exposure)
• Miconazole + disopyramide: Moderate (increases exposure)
• Miconazole + benzodiazepines: Moderate (increases exposure)

Precautions

• Caution in patients with history of breast cancer
• Monitor breast status regularly in women on oestrogen therapy
• Risk of endometrial cancer with prolonged use of oestrogens
• Risk of ovarian cancer with long-term use of combined HRT
• Increased risk of venous thromboembolism in women using combined or oestrogen-only HRT

Pregnancy

Pregnant women may require a longer duration of treatment, usually about 7 days, to clear the infection. Caution is advised.

Breast-feeding

Manufacturer advises caution; no specific information available.

Indications

• Severe eczema
• Psoriasis
• Contact dermatitis
• Lichen planus
• Seborrheic dermatitis
• Dermatitis herpetiformis
• Nummular eczema

Dosage

Children: Refer to the BNF for Children for specific dosing guidance, as clobetasol is typically used in children with caution and under medical supervision.

Adults: Apply a thin layer to the affected area once or twice daily, depending on the severity of the condition and the area involved. Treatment should be limited to the shortest duration necessary to control symptoms.

Mechanism of action

Clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. Its anti-inflammatory activity is believed to stem from the induction of phospholipase A2 inhibitory proteins, known as lipocortins. These proteins are thought to regulate the production of inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid, a precursor to these mediators, from membrane phospholipids.

Pharmacodynamics

Clobetasol works by modulating the immune response and inflammatory process in the skin. By limiting the release of pro-inflammatory substances, clobetasol reduces the signs and symptoms of inflammation, such as redness, swelling, and itching. Its vasoconstrictive properties also contribute to its efficacy by reducing blood flow to the affected area, further diminishing inflammation.

Pharmacokinetics

Clobetasol is well-absorbed through the skin, and its absorption can be influenced by the condition of the skin barrier and the vehicle in which it is delivered. It is primarily metabolized in the liver and excreted via the urine. The pharmacokinetic profile of clobetasol indicates a relatively short systemic half-life due to its rapid metabolism, minimizing the risk of systemic side effects when used topically as directed.

Contra-indications

• Hypersensitivity to clobetasol or any of its excipients
• Viral infections (e.g., herpes simplex, chickenpox)
• Bacterial infections
• Fungal infections
• Rosacea
• Acne vulgaris

Adverse effects

• Burning sensation
• Itching
• Skin atrophy
• Telangiectasia
• Striae
• Systemic effects (with prolonged use)

Precautions

• Use with caution in patients with a history of steroid sensitivity
• Long-term use may lead to adrenal suppression
• Monitor for signs of local or systemic infections
• Not recommended for use on the face or in intertriginous areas without medical advice

Pregnancy

Clobetasol should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available on the use of topical corticosteroids in pregnancy.

Breast-feeding

Caution is advised when using clobetasol during breastfeeding. It is not known if it is excreted in human milk.

Storage

Store at room temperature, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Topical lotion

Mechanism of action

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.

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Clobetasol propionate is generally applied twice daily so the duration of action is long. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Mechanism of action

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.

Pharmacodynamics

Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.

Mechanism of action

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.