Fluconazole is a synthetic triazole with antifungal activity. Fluconazole preferentially inhibits fungal cytochrome P-450 sterol C-14 alpha-demethylation, resulting in the accumulation of fungal 14 alpha-methyl sterols, the loss of normal fungal sterols, and fungistatic activity. Mammalian cell demethylation is much less sensitive to fluconazole inhibition.
Fluconazole is an Azole Antifungal. The mechanism of action of fluconazole is as a Cytochrome P450 2C19 Inhibitor, and Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 2C9 Inhibitor. The chemical classification of fluconazole is Azoles.
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Fluconazole is a synthetic antifungal agent of the imidazole class, is used to treat vaginal candidiasis. It inhibits the fungal lanosterol 14 alpha-demethylase which thereby prevents the formation of ergosterol which is an essential component in the fungal cell membrane. It is used for a number of fungal infections.This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts.
Mechanism of action of Fluconazole
Fluconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Fluconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
Indications of Fluconazole
- Vaginal Yeast Infection
- Candida Urinary Tract Infection
- Bone Marrow Transplantation
- Chronic Mucocutaneous Candidiasis
- Fungal Infection, Internal and Disseminated
- Blastomycosis
- Candidemia
- Coccidioidomycosis
- Coccidioidomycosis, Meningitis
- Cryptococcal Meningitis, Immunocompetent Host/Immunosuppressed Host
- Cryptococcosis
- Esophageal Candidiasis
- Fungal Infection Prophylaxis
- Fungal Peritonitis
- Fungal Pneumonia
- Histoplasmosis
- Onychomycosis, Fingernail
- Onychomycosis, Toenail
- Oral Thrush
- Sporotrichosis
- Systemic Candidiasis
- Tinea Corporis
- Tinea Cruris
- Tinea Versicolor
- Candida intertrigo
- Candida pneumonia
- Candidemia
- Esophageal Candidiasis
- Infections, Fungal
- Meningitis, Cryptococcal
- Oropharyngeal Candidiasis
- Peritoneal candidiasis
- Pneumonia cryptococcal
- Vaginal Candidiasis
- Candidiasis infection
- Disseminated Candidiasis
- Urinary tract candidiasis
Therapeutic Indications
- For the treatment of fungal infections.
- Diflucan is indicated in the following fungal infections in adults:
- Acute vaginal candidiasis when local therapy is not appropriate.
- Candidal balanitis when local therapy is not appropriate.
Contraindications of Fluconazole
- have known hypersensitivity to other azole medicines such as ketoconazole;
- are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
- concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
- take SSRIs such as fluoxetine or sertraline.
Dosage of Fluconazole
Strengths
Injected solution
- 2mg/mL
Oral suspension
- 10mg/mL ,40mg/mL
Tablets
- 50mg ,100mg ;150mg ;200mg
Vaginal Candidiasis
- 150 mg orally as a single dose
Infectious Diseases Society of America (IDSA) Recommendations
- Uncomplicated vaginitis: 150 mg orally as a single dose
- Management of recurrent vulvovaginal candidiasis (after 10 to 14 days induction therapy): 150 mg orally once a week for 6 months
- Complicated vulvovaginal candidiasis: 150 mg orally every 72 hours for 3 doses
US CDC Recommendations
- Uncomplicated vulvovaginal candidiasis: 150 mg orally as a single dose
- Initial therapy for recurrent vulvovaginal candidiasis: 100 to 200 mg orally every 72 hours for 3 doses
- Maintenance therapy for recurrent vulvovaginal candidiasis: 100 to 200 mg orally once a week for 6 months
- Severe vulvovaginal candidiasis: 150 mg orally every 72 hours for 2 doses
US CDC, National Institutes of Health (NIH), and IDSA Recommendations for HIV-infected Patients
- Uncomplicated vulvovaginal candidiasis: 150 mg orally as a single dose
- Severe or recurrent vulvovaginal candidiasis: 100 to 200 mg orally once a day for at least 7 days
- Suppressive therapy for vulvovaginal candidiasis: 150 mg orally once a week
Oral Thrush
- Oropharyngeal candidiasis: 200 mg IV or orally on the first day followed by 100 mg IV or orally once a day
- Duration of therapy: At least 2 weeks, to reduce the risk of relapse
IDSA Recommendations
- Moderate to severe oropharyngeal candidiasis: 100 to 200 mg IV or orally once a day for 7 to 14 days
US CDC, NIH, and IDSA Recommendations for HIV-infected Patients
- Initial episodes of oropharyngeal candidiasis: 100 mg orally once a day for 7 to 14 days
- Suppressive therapy for oropharyngeal candidiasis: 100 mg orally once a day or 3 times a week
Candidemia
- Doses up to 400 mg/day have been used.
Fungal Pneumonia
- Doses up to 400 mg/day have been used.
Fungal Infection – Disseminated
- Doses up to 400 mg/day have been used.
Systemic Candidiasis
- Doses up to 400 mg/day have been used.
Esophageal Candidiasis
- 200 mg IV or orally on the first day followed by 100 mg IV or orally once a day
- Duration of therapy: At least 3 weeks and for at least 2 weeks after symptoms resolve
Side Effects of Fluconazole
The most common
- Abdominal or stomach pain
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- Nausea
- liver problems,
- stomach pain,
- vomiting,
- Dizziness
- Burning, itching, stinging, redness, or other sign of irritation at the application site ,rash
- headache,
- increased intracranial pressure,
- meningeal signs,
- reversible hair loss or thinning, and
- fever.
Common
- chills or fever
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- hallucinations
- headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- burning,
- stinging,
- severe pain in your upper stomach spreading to your back, nausea and vomiting;
- signs of congestive heart failure–shortness of breath (even with mild exertion), cough with mucus, fast heartbeats, swelling, rapid weight gain, sleep problems;
Drug Interactions of Fluconazole
Kitoconazole may interact with following drugs, supplements & may change the efficacy of drugs
- medications that use the enzyme such as budesonide , cyclosporine , darifenacin , dihydroergotamine , fentanyl pimozide , quinidine , sirolimus , tacrolimus , terfenadine , fluticasone , eletriptan , lovastatin quetiapine, sildenafil , and simvastatin
- medications that block the enzyme CYP3A4 such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan, delavirdine, and nefazodone
- Erythromycin-containing drugs, including drugs containing erythromycin base, erythyromycin ethylsuccinate, erythromycin lactobionate, or eryrthromyvin stearate
- Quinidine
- as carbamazepine , phenobarbital, phenytoin , rifampin and nimodipine
- methylprednisolone
- midazolam
- triazolam
- digoxin
- phenytoin
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- tapentadol
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, )
- thyroid replacements (e.g., dessicated thyroid, levothyroxine)
- tizanidine
- tramadol
- tricyclic antidepressants (e.g., desipramine, nortriptyline)
- warfarin
Pregnancy & Lactation of Fluconazole
US FDA pregnancy category C
Pregnancy
Most scientific studies suggest that a single 150mg dose of fluconazole during pregnancy will not harm a baby in the womb. Thrush is very common in pregnancy. If you think you have thrush it is best to consult your doctor or midwife who will advise you as to whether treatment is recommended.
Lactation
Fluconazole passes into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this drug. This medication shouldn’t be used in people younger than 6 months.
References
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