Fluconazole major drug interactions

Fluconazole is one the commonly used anti fungal drugs in most of the clinics.

If it is to be used in a cardiac patient then its better to use it with caution or to replace with other anti fungals.

When fluconazole is used along with drugs like clopidogrel, warfarin, phenytoin, ondansetron, amiodarone and statins like atorvastatin it has a great potential to inhibit the metabolism of these drugs and increases their concentration in the blood leading to increased risk of side effects.

 

 Fluconazole is an antifungal medication primarily used to treat and prevent fungal infections. It belongs to a class of drugs known as triazole antifungals. Here are some key aspects of fluconazole:

Mechanism of Action

Fluconazole works by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes. By disrupting the production of ergosterol, fluconazole compromises the integrity of the fungal cell membrane, leading to increased cell permeability and ultimately the death of the fungal cell.

Indications

Fluconazole is prescribed for various fungal infections, including:

1. Candidiasis: This includes infections of the mouth (oral thrush), throat, esophagus, and other body parts.
2. Cryptococcal Meningitis: A serious infection of the brain and spinal cord, commonly seen in immunocompromised patients, such as those with HIV/AIDS.
3. Vaginal Yeast Infections: Fluconazole is often used as a single-dose treatment for uncomplicated cases.
4. Systemic Fungal Infections: These include infections that affect internal organs such as the lungs, blood, and bones.
5. Prophylaxis: It is used to prevent fungal infections in high-risk patients, such as those undergoing chemotherapy or those with compromised immune systems.

Dosage and Administration

Fluconazole is available in several forms, including tablets, oral suspension, and intravenous (IV) solution. The dosage and duration of treatment depend on the type and severity of the infection. For instance:

• Vaginal candidiasis: Typically, a single 150 mg oral dose.
• Oropharyngeal candidiasis: 200 mg on the first day, followed by 100 mg daily.
• Cryptococcal meningitis: Initial dose of 400 mg on the first day, followed by 200-400 mg daily for several weeks or months, depending on the patient’s response and immune status.

Side Effects

Common side effects of fluconazole include:

• Nausea
• Headache
• Stomach pain
• Diarrhea
• Dizziness

Serious but rare side effects may include liver toxicity, severe skin reactions, and QT prolongation (a heart rhythm disorder).

Interactions

Fluconazole can interact with various other medications, potentially altering their effects. Notable interactions include:

• Warfarin: Increased risk of bleeding.
• Phenytoin: Increased levels of phenytoin, leading to toxicity.
• Rifampin: Decreased effectiveness of fluconazole.
• Oral Hypoglycemics: Risk of hypoglycemia.
• Statins: especially atorvastatin requires CYP3A4 for its metabolism, when used with Ketoconazole it may leads to higher serum concentration of statins and causes statin associated muscle symptoms (SAMS).

Contraindications and Precautions

Fluconazole should be used with caution in patients with:

• Liver Disease: Due to the risk of hepatotoxicity.
• Kidney Disease: Dosage adjustments may be necessary.
• Heart Conditions: Particularly those involving arrhythmias, as fluconazole can cause QT prolongation.

Use in Special Populations

• Pregnancy: Fluconazole is categorized as FDA Pregnancy Category D for high doses and long-term use, due to potential teratogenic effects. For single-dose treatment of vaginal candidiasis, it is categorized as Category C.
• Breastfeeding: Fluconazole is excreted in breast milk, but at low levels. The decision to use fluconazole while breastfeeding should consider the benefits and potential risks.

Summary

Fluconazole is a versatile antifungal medication effective against a range of fungal infections. Its relatively favorable safety profile and oral availability make it a convenient choice for both treatment and prophylaxis. However, due to potential side effects and drug interactions, its use should be carefully monitored, particularly in patients with underlying health conditions or those taking multiple medications.