FUNGARIN

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

• Pain management
• Nausea and vomiting
• Anxiety
• Oral infections
• Mucosal ulceration

Dosage

Children: Refer to BNF for Children for age-appropriate dosing information.

Adults: Refer to specific product guidelines and BNF for appropriate dosing as it varies widely based on the drug and condition treated.

Mechanism of action

Oromucosal drugs can act through several mechanisms depending on the active ingredient. Generally, they may exert their effects locally at the site of application or systemically after absorption into the bloodstream. For example, certain analgesics may inhibit cyclooxygenase enzymes, reducing the production of pro-inflammatory mediators. Other drugs may interact with specific receptors in the central nervous system, modulating pain perception or other physiological responses.

Pharmacodynamics

The pharmacodynamics of oromucosal medications depend on their formulation and active ingredients. These drugs typically provide rapid onset of action due to the rich vascularization in the oral mucosa, allowing for swift systemic absorption. The efficacy can vary based on factors such as the drug's pH, solubility, and the presence of absorption enhancers.

Pharmacokinetics

Pharmacokinetics for oromucosal drugs varies widely based on the substance used. Generally, drugs administered via this route are rapidly absorbed into the systemic circulation, with peak plasma concentrations often occurring within minutes. Bioavailability may be influenced by the drug's formulation and the presence of salivary enzymes. The elimination half-life and metabolism will depend on the specific drug involved.

Pregnancy

The safety of oromucosal preparations during pregnancy has not been established. Use should be avoided unless clearly needed.

Breast-feeding

It is unknown whether oromucosal agents are excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

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.