FLAZOLE IV

Indications

• Oropharyngeal candidiasis
• Esophageal candidiasis
• Vulvovaginal candidiasis
• Cryptococcal meningitis
• Fungal infections in immunocompromised patients
• Prophylaxis against fungal infections in patients undergoing chemotherapy or bone marrow transplantation

Dosage

Children: Refer to the BNF

Adults: Refer to the BNF for specific dosing guidance based on indication and patient condition.

Mechanism of action

Fluconazole selectively inhibits the fungal enzyme 14-alpha-demethylase, part of the cytochrome P450 complex, which is responsible for the conversion of lanosterol to ergosterol. This inhibition leads to a depletion of ergosterol in the fungal cell membrane, resulting in increased cell membrane permeability and ultimately cell lysis.

Pharmacodynamics

Fluconazole exhibits fungistatic activity against a wide range of fungi. Its effectiveness is particularly notable against Candida spp. and Cryptococcus neoformans. The drug has a high tissue penetration, including the central nervous system, making it effective for treating cryptococcal meningitis. The pharmacodynamic profile suggests that fluconazole's antifungal effect can be enhanced with higher doses, although this must be balanced against potential toxicity.

Pharmacokinetics

Fluconazole is well absorbed after oral administration, with bioavailability exceeding 90%. It has a volume of distribution of approximately 0.7 to 1 L/kg and is extensively distributed in body tissues, including the cerebrospinal fluid. The drug is primarily eliminated via renal excretion, with a half-life ranging from 30 to 50 hours, allowing for once-daily dosing in most cases. Dose adjustments may be necessary in patients with impaired renal function.

Contra-indications

• Hypersensitivity to fluconazole or any of its components
• Concomitant use with certain medications that prolong the QT interval in patients with known heart conditions

Adverse effects

• Nausea
• Headache
• Dizziness
• Abdominal pain
• Diarrhea
• Rash
• Elevated liver enzymes
• Rarely, severe skin reactions such as Stevens-Johnson syndrome

Interactions

• CYP2C19 inhibitors may increase fluconazole levels
• CYP3A4 inducers may decrease fluconazole levels
• Co-administration with warfarin can lead to increased anticoagulant effects
• Use with other drugs that prolong the QT interval may increase the risk of arrhythmias

Precautions

• Use with caution in patients with liver disease
• Monitor renal function in patients with renal impairment
• Assess for potential drug interactions, particularly with long-term therapy

Pregnancy

Fluconazole is classified as a Category D drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fluconazole is excreted in breast milk, and caution is recommended when administering to nursing mothers.

Storage

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

Formulations

• Oral tablets
• Oral suspension
• Intravenous solution

Indications

• Dehydration
• Electrolyte imbalances
• Infections requiring immediate antibiotic therapy
• Pain management in acute settings
• Nutritional support in patients unable to eat
• Chemotherapy administration
• Anesthesia induction and maintenance

Dosage

Children: Refer to the specific drug's prescribing information in the BNF for Children for appropriate dosing guidelines.

Adults: Refer to the specific drug's prescribing information in the BNF for appropriate dosing guidelines.

Mechanism of action

The mechanism of action for intravenous drugs depends on the specific medication administered. Generally, intravenous administration allows for rapid drug distribution throughout the body, achieving high plasma concentrations quickly. This is particularly beneficial for medications that require immediate therapeutic effects.

Pharmacodynamics

Pharmacodynamics varies based on the specific drug administered intravenously. In general, drugs delivered via IV can achieve peak plasma concentrations faster than those taken orally, leading to quicker onset of action. This route is often utilized for drugs that are poorly absorbed in the gastrointestinal tract or for those that require precise titration to achieve the desired therapeutic effect.

Pharmacokinetics

Pharmacokinetics for intravenous drugs typically includes immediate bioavailability since the drug is delivered directly into circulation. Distribution is rapid, and elimination depends on the drug's specific metabolic pathways. Volume of distribution, clearance rates, and half-life can significantly vary based on the drug's properties and patient factors such as age, body weight, and organ function.

Interactions

• ataluren + intravenous aminoglycosides: Severe (increases risk of nephrotoxicity)
• intravenous dantrolene + calcium channel blockers: Severe (increases risk of acute hyperkalaemia and cardiovascular collapse)
• intravenous dantrolene + diltiazem: Severe (increases risk of acute hyperkalaemia and cardiovascular collapse)
• intravenous dantrolene + verapamil: Severe (increases risk of acute hyperkalaemia and cardiovascular collapse)
• intravenous chloramphenicol + antiepileptics: Moderate (increases concentration)
• intravenous chloramphenicol + fosphenytoin: Moderate (increases concentration)
• intravenous chloramphenicol + phenytoin: Moderate (increases concentration)
• miconazole + intravenous benzodiazepines: Moderate (increases exposure)
• intravenous magnesium + calcium channel blockers: Unknown (increases risk of hypotension)
• intravenous magnesium + amlodipine: Unknown (increases risk of hypotension)