MICOGEL F

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

• Eczema
• Psoriasis
• Contact dermatitis
• Allergic dermatitis
• Seborrheic dermatitis

Dosage

Children: Refer to specific product information or clinical guidelines for appropriate dosing in children, as it varies by formulation and condition treated.

Adults: Refer to specific product information or clinical guidelines for appropriate dosing, as it varies by formulation and condition treated.

Mechanism of action

Acetonide exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells, leading to the translocation of the receptor-ligand complex into the nucleus. This complex then influences the expression of specific genes, resulting in decreased production of pro-inflammatory cytokines and increased production of anti-inflammatory proteins. This modulation of gene expression contributes to its anti-inflammatory and immunosuppressive effects.

Pharmacodynamics

The pharmacodynamics of acetonide involve its ability to inhibit the migration of leukocytes to sites of inflammation, reduce the production of inflammatory mediators such as prostaglandins and leukotrienes, and suppress the immune response. The potency and duration of action can vary based on the specific formulation and concentration used.

Pharmacokinetics

Acetonide is absorbed through the skin when applied topically, with systemic absorption depending on the formulation, application area, and duration of use. It undergoes hepatic metabolism, and its metabolites are excreted primarily through the urine. The half-life and clearance rates can vary based on individual patient factors and specific formulations.

Contra-indications

• Hypersensitivity to acetonide or any component of the formulation.
• Active or untreated infections at the site of application.

Adverse effects

• Local irritation or burning sensation at the application site.
• Skin thinning or atrophy with prolonged use.
• Systemic effects such as adrenal suppression with high doses or prolonged therapy.

Interactions

• Increased risk of systemic effects when used with other corticosteroids.
• Potentially altered metabolism when administered with CYP3A4 inhibitors or inducers.

Precautions

• Use with caution in patients with a history of tuberculosis or other infections.
• Monitor for signs of adrenal insufficiency in patients on high doses.
• Avoid application to large areas of the body or under occlusive dressings.

Pregnancy

Acetonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare professional before use.

Breast-feeding

Limited data available. Use with caution as it may be excreted in breast milk. Consult with a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical solution

Indications

• Atopic dermatitis
• Psoriasis
• Contact dermatitis
• Seborrheic dermatitis
• Allergic rhinitis
• Asthma
• Eczema

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations for pediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated and the formulation used.

Mechanism of action

Flucinolone exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells. This receptor-ligand complex translocates to the nucleus, where it regulates the expression of genes involved in inflammation and immune response. The anti-inflammatory action is primarily due to the inhibition of pro-inflammatory cytokines, suppression of leukocyte infiltration, and stabilization of lysosomal membranes.

Pharmacodynamics

The pharmacodynamics of flucinolone involve its ability to modulate the immune response and decrease inflammation. It reduces the production of inflammatory mediators such as prostaglandins and leukotrienes, leading to decreased redness, swelling, and pain associated with inflammatory conditions. Additionally, flucinolone has an impact on metabolism, influencing glucose levels and protein synthesis in target tissues.

Pharmacokinetics

Flucinolone is typically well-absorbed when applied topically, with systemic absorption varying based on the formulation and the site of application. It is metabolized predominantly in the liver, and the metabolites are excreted primarily via the kidneys. The half-life of flucinolone can be influenced by factors such as the route of administration and individual patient characteristics.

Contra-indications

• Hypersensitivity to flucinolone or any component of the formulation
• Active infections (viral, bacterial, or fungal) in the area to be treated
• Rosacea or perioral dermatitis

Adverse effects

• Skin thinning or atrophy
• Telangiectasia
• Striae
• Burning or itching at the site of application
• Systemic absorption leading to adrenal suppression (with prolonged use)

Interactions

• May enhance the effects of other topical corticosteroids
• Caution with concurrent use of other immunosuppressive agents

Precautions

• Use with caution in patients with a history of hormonal disorders
• Monitor for signs of local or systemic infection
• Avoid prolonged use on large surface areas or under occlusive dressings

Pregnancy

Flucinolone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Systemic absorption may occur, which poses risks.

Breast-feeding

Caution is advised when using flucinolone while breastfeeding. It is recommended to avoid application on the breast unless necessary.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical solution
• Topical lotion

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.