FLUCONAZOLE (fluconazole)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Congenital long QT syndrome
Torsades de pointes

There are 8 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Hypokalemia
Hypomagnesemia
Pregnancy
Prolonged QT interval

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver
Kidney disease with likely reduction in glomerular filtration rate (GFr)

There are 25 severe adverse reactions.

More Frequent	Less Frequent
None.	Allergic dermatitis Pruritus of skin Skin rash

Rare/Very Rare

Abnormal hepatic function tests Acute generalized exanthematous pustulosis Acute hepatic failure Adrenocortical insufficiency Agranulocytosis Anaphylaxis Angioedema Cholestasis DRESS syndrome Exfoliative dermatitis Hepatitis Hepatocellular damage Hypokalemia Jaundice Leukopenia Neutropenic disorder Prolonged QT interval Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Torsades de pointes Toxic epidermal necrolysis

There are 24 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Nausea	Acute abdominal pain Anorexia Diarrhea Dizziness Drowsy Dyspepsia Vomiting

Rare/Very Rare
Alopecia Dysgeusia Facial edema Fatigue Fever General weakness Hypercholesterolemia Hyperhidrosis Hypertriglyceridemia Insomnia Malaise Myalgia Paresthesia Tremor Vertigo

FDA alerted clinicians in April 2016 that it is reviewing safety data regarding use of oral fluconazole during pregnancy and advised cautious prescribing of the drug until the review is completed. There are no adequate and controlled studies to date using fluconazole in pregnant women. Congenital abnormalities have been reported in infants born to women who received high-dose fluconazole (400-800 mg daily) for the treatment of serious, life-threatening fungal infections during most or all of the first trimester.

These reports have involved a rare and distinct pattern of birth defects that includes brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease and are similar to those reported in animal reproduction studies. Based on these data, FDA reclassified high-dose fluconazole (400-800 mg daily) as pregnancy category D (i.e., there is positive evidence of human fetal risk based on human data, but potential benefits of the drug in pregnant women with serious or life-threatening conditions may be acceptable despite its risks). Because human data available at that time did not identify an increased risk of congenital anomalies with the use of fluconazole administered as a single 150-mg oral dose for the treatment of vulvovaginal candidiasis, the single-dose oral fluconazole regimen was classified by FDA as pregnancy category C (see Users Guide).

Data from a recent Danish study designed to assess the association between use of oral fluconazole during pregnancy and risk of spontaneous abortion and stillbirth indicate an increased risk of spontaneous abortion (i.e., miscarriage during gestational weeks 7 through 22) in pregnant women treated with oral fluconazole (most women received a total cumulative dose of 150-300 mg) compared with matched control pregnancies not exposed to oral fluconazole. Therefore, FDA alerted clinicians that it is reviewing data from the Danish study and additional data and, after completing the review, will communicate its conclusions and updated recommendations regarding use of the single-dose 150-mg oral fluconazole regimen during pregnancy. The US Centers for Disease Control and Prevention (CDC) states that topical (intravaginal) azole antifungals (not oral fluconazole) should be used for the treatment of vulvovaginal candidiasis during pregnancy.

The Infectious Diseases Society of America (IDSA) states that use of fluconazole for the treatment of serious fungal infections (e.g., blastomycosis+, candidiasis, histoplasmosis+, coccidioidomycosis+, cryptococcosis) should be avoided during pregnancy. Patients who are pregnant or actively trying to become pregnant should talk to their clinician about alternatives for treatment of vulvovaginal candidiasis. If fluconazole is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

In several reproduction studies in pregnant rabbits receiving oral fluconazole dosages of 5, 10, 20, 25, or 75 mg/kg once daily during organogenesis, maternal weight gain was impaired at all dosage levels and abortions occurred with the 75-mg/kg dosage (approximately 20-60 times the usual human dosage); no adverse fetal effects were detected. In studies in pregnant rats receiving oral fluconazole during organogenesis, maternal weight gain was impaired and placental weights were increased at dosages of 25 mg/kg once daily. Although there were no fetal effects in rats receiving oral fluconazole in a dosage of 5 or 10 mg/kg once daily, increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification occurred in those receiving oral dosages of 25 mg/kg or greater once daily.

When oral fluconazole dosages of 80 mg/kg once daily (approximately 20-60 times the usual human dosage) to 320 mg/kg once daily were used in these rats, there was an increase in embryolethality and fetal abnormalities (i.e., wavy ribs, cleft palate, abnormal craniofacial ossification). These adverse effects in rats may be attributed to a species-specific effect of fluconazole on estrogen synthesis since lowered estrogen is known to cause effects on pregnancy, organogenesis, and parturition. There is no evidence to date that estrogen concentrations are decreased in women receiving fluconazole. (See Cautions: Other Adverse Effects.)

Fluconazole is distributed into human milk in concentrations similar to those achieved in plasma. Administration of a single 150-mg oral dose to several nursing women resulted in peak plasma fluconazole concentrations of 2.61 mcg/mL (range: 1.57-3.65 mcg/mL). Fluconazole should be used with caution in nursing woman.

No enhanced Geriatric Use information available for this drug.