Fluconazole – Antifungal Drug

Background

Fluconazole, commonly known as Diflucan, is an antifungal drug used for the treatment of both systemic and superficial fungal infections in a variety of tissues. It was initially approved by the FDA in 1990. This drug is an azole antifungal, in the same drug family as ketoconazole and itraconazole. Fluconazole has many advantages over the other antifungal drugs including the option of oral administration. The side effect profile of this drug is minimal. It has been demonstrated as an efficacious treatment for vaginal yeast infections in one single dose.

Properties and Characteristics of Fluconazole

Drug class	Antifungal drug
Brand Names	Diflucan
Synonyms	Diflucan, Difluconazole, Fluconazol, Fluconazole, Fluconazolum, Triflucan
Molecular Formula	C13H12F2N6O
Molecular Weight	306.27 g/mol
IUPAC Names	2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol
Structural formula of main components
Pure active ingredient	Fluconazole
Appearance	White crystalline powder
Melting Point	138-140 °C
Solubility	34.9 [ug/mL] slightly soluble in water
Excretion	Renal excretion
Available as	Capsule, Injection, Solution, Powder for suspension
Storage	Should be stored in tight containers at a temperature less than 30 °C
Prescription	Prescription is requried

What is Fluconazole (Diflucan) used for?

• Blastomycosis
• Candida Urinary Tract Infection
• Candidemia
• Coccidioidomycosis
• Coccidioidomycosis — Meningitis
• Cryptococcal Meningitis — Immunocompetent Host
• Cryptococcal Meningitis — Immunosuppressed Host
• Cryptococcosis
• Esophageal Candidiasis
• Fungal Peritonitis
• Fungal Pneumonia
• Fungal Infection Prophylaxis
• Histoplasmosis
• Onychomycosis — Fingernail
• Onychomycosis — Toenail
• Oral Thrush
• Sporotrichosis
• Vaginal Candidiasis
• Fungal Infection — Disseminated
• Systemic Candidiasis

Fluconazole side effects

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Fluconazole may cause serious side effects. Call your doctor at once if you have:

• Fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
• Seizure (convulsions);
• Skin rash or skin lesions;
• Decreased adrenal gland hormones–nausea, vomiting, stomach pain, loss of appetite, feeling tired or light-headed, muscle or joint pain, skin discoloration, craving salty foods; or
• Liver problems–loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects of fluconazole may include:

• Nausea, stomach pain, diarrhea, upset stomach;
• Headache;
• Dizziness; or
• Changes in your sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Mechanism of action

Fluconazole is a very selective inhibitor of fungal cytochrome P450 dependent enzyme lanosterol 14-α-demethylase. This enzyme normally works to convert lanosterol to ergosterol, which is necessary for fungal cell wall synthesis. The free nitrogen atom located on the azole ring of fluconazole binds with a single iron atom located in the heme group of lanosterol 14-α-demethylase. This prevents oxygen activation and, as a result, inhibits the demethylation of lanosterol, halting the process of ergosterol biosynthesis. Methylated sterols are then found to accumulate in the fungal cellular membrane, leading to an arrest of fungal growth. These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane.

Fluconazole resistance may arise from an alteration in the amount or function of the target enzyme (lanosterol 14-α-demethylase), altered access to this enzyme, or a combination of the above.8 Other mechanisms may also be implicated, and studies are ongoing.

Interactions

Medicines that interact with fluconazole may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with fluconazole. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with fluconazole include:

• Anticoagulants or antiplatelet agents (blood thinners), such as warfarin, and clopidogrel (may prolong bleeding time)
• Biologics, such as acalabrutinib, bosutinib, or entrectinib
• Albuterol
• Antibiotics, such as ciprofloxacin, erythromycin, or moxifloxacin
• Anticonvulsants, such as carbamazepine or phenytoin
• Antidepressants, such as amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, imipramine, or nortriptyline
• Antifungals, such as voriconazole
• Antipsychotics, such as clozapine, haloperidol, thioridazine, or ziprasidone
• Aprepitant
• Barbiturates, such as phenobarbital
• Benzodiazepines, such as midazolam or triazolam
• Buspirone
• Cannabidiol
• Cisapride
• Cocaine
• Colchicine
• Corticosteroids, such as fludrocortisone or prednisone
• Diabetes medications, such as glimepiride, glyburide, or glipizide
• Diuretics, such as furosemide or hydrochlorothiazide
• Droperidol
• Estrogens or progestins
• Famotidine
• Heart medications, such as amiodarone, felodipine, sotalol, quinidine, or procainamide
• HIV medications, such as efavirenz or saquinavir
• Lithium
• Medications to lower cholesterol, such as atorvastatin or simvastatin
• Mifepristone
• Migraine medications, such as dihydroergotamine
• Nilotinib
• Omeprazole
• Ondansetron
• Opioids, such as alfentanil, fentanyl, oxycodone, methadone, morphine, or codeine
• Pimozide
• Polyethylene glycol 3350
• Red yeast rice
• Tacrolimus
• Tamoxifen
• Tramadol
• Ziprasidone
• Zolpidem

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (suspension or tablets)

For cryptococcal meningitis:

• Adults—400 milligrams (mg) on the first day, followed by 200 mg once a day for at least 10 to 12 weeks. Your doctor may adjust your dose as needed.
• Children 6 months to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 12 milligrams (mg) per kilogram (kg) of body weight on the first day, followed by 6 mg per kg of body weight once a day, for at least 10 to 12 weeks.
• Children younger than 6 months of age—Use and dose must be determined by your doctor.

For esophageal candidiasis:

• Adults—200 milligrams (mg) on the first day, followed by 100 mg once a day for at least 3 weeks. Your doctor may increase your dose as needed.
• Children 6 months to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 6 milligrams (mg) per kilogram (kg) of body weight on the first day, followed by 3 mg per kg of body weight once a day, for at least 3 weeks.
• Children younger than 6 months of age—Use and dose must be determined by your doctor.

For oropharyngeal candidiasis:

• Adults—200 milligrams (mg) on the first day, followed by 100 mg once a day for at least 2 weeks.
• Children 6 months to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 6 milligrams (mg) per kilogram (kg) of body weight on the first day, followed by 3 mg per kg of body weight once a day, for at least 2 weeks.
• Children younger than 6 months of age—Use and dose must be determined by your doctor.

For other infections that may occur in different parts of the body:

• Adults—Doses of up to 400 milligrams (mg) per day.
• Children 6 months to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 6 to 12 milligrams (mg) per kilogram (kg) of body weight per day.
• Children younger than 6 months of age—Use and dose must be determined by your doctor.

For prevention of candidiasis during bone marrow transplantation:

• Adults—400 milligrams (mg) once a day.
• Children—Use and dose must be determined by your doctor.

For urinary tract infections or peritonitis:

• Adults—50 to 200 milligrams (mg) per day.
• Children—Use and dose must be determined by your doctor.

For vaginal candidiasis:

• Adults—150 milligrams (mg) once a day.
• Children—Use and dose must be determined by your doctor.

If you take more Fluconazole Capsules than you should

Taking too many capsules at once may make you unwell. Contact your doctor or your nearest hospital casualty department at once. The symptoms of a possible overdose may include hearing, seeing, feeling and thinking things that are not real (hallucination and paranoid behaviour). Symptomatic treatment (with supportive measures and gastric lavage if necessary) may be adequate.

Pregnancy, breastfeeding and fertility while taking fluconazole

Fluconazole and pregnancy

You can take fluconazole in pregnancy if other treatments have not worked.

If you have thrush, ask your GP for advice about treatment. Your doctor will probably prescribe clotrimazole or a similar antifungal medicine. This may be as a cream or as a soft tablet (a pessary) that you put into your vagina.

If the thrush does not go away, they may prescribe a single dose (150mg) of fluconazole. They’ll discuss the risks and benefits to you and your baby.

If the fungal infection is more serious, your doctor may recommend a higher dose of fluconazole.

Fluconazole and breastfeeding

If your doctor or health visitor says your baby is healthy, you can take fluconazole when you’re breastfeeding.

There is not much information about how much fluconazole passes into breast milk, but information shows that the amounts are fairly high compared to most other medicines. However, the amounts are still lower than doses used to treat babies who have a fungal infection themselves.

It’s been used for many years without side effects in breastfed babies. Occasionally, mild side effects have been reported, such as being sick or diarrhoea.

Fluconazole is sometimes used to treat a fungal infection of the breast, known as breast candidiasis. However, the amount that passes into breast milk is not enough to treat the baby if they also have a fungal infection. Your baby will need their own treatment.

If you notice that your baby is not feeding as well as usual, or has an upset stomach such as being sick or diarrhoea, or if you have any other concerns about your baby, then talk to your midwife, health visitor, pharmacist or doctor.

Fluconazole and fertility

There is no evidence to suggest that fluconazole reduces fertility in either men or women.