CanesOral

Applies to fluconazole: intravenous solution, oral powder for reconstitution, oral tablet

General

This drug was generally well tolerated. Changes in renal and hematological function test results and hepatic abnormalities reported during therapy with this and comparative agents in some patients, primarily those with serious underlying diseases (e.g., AIDS, cancer); clinical significance and relationship to therapy unclear.

During clinical trials of single-dose therapy, side effects possibly related to therapy were reported in 26% of patients using this drug and 16% of patients using active comparative agents. The most common side effects reported in patients receiving a single 150 mg dose of this drug for vaginitis were headache, nausea, and abdominal pain. Most side effects were of mild to moderate severity.

During clinical trials of multiple-dose therapy, side effects were reported in 16% of patients. Therapy discontinuation occurred in 1.5% and 1.3% of patients due to adverse clinical events and laboratory test abnormalities, respectively. Clinical side effects were reported more often in HIV-infected patients than in non-HIV-infected patients (21% versus 13%), but the patterns in both groups were similar.[Ref]

Nervous system

Rare cases of seizures have been reported, but a causal relationship was difficult to establish, since some of these patients had cryptococcal meningitis or severe underlying disease. Nonetheless, at least 1 case of seizure following a 100 mg oral dose has been reported.

Seizures, dizziness, paresthesia, somnolence, tremor, and vertigo have also been reported during postmarketing experience.[Ref]

Very common (10% or more): Headache (up to 13%)
Uncommon (0.1% to 1%): Seizures, dizziness, paresthesia, somnolence, vertigo, visual field defect, taste perversion, hyperkinesia, hypertonia
Rare (less than 0.1%): Tremor
Frequency not reported: Dysesthesias[Ref]

Gastrointestinal

Very common (10% or more): Nausea, abdominal pain, diarrhea, vomiting
Common (1% to 10%): Dyspepsia
Uncommon (0.1% to 1%): Constipation, flatulence, loose stools, dry mouth
Frequency not reported: General abdominal discomfort[Ref]

Dry mouth, dyspepsia, and vomiting have also been reported during postmarketing experience.[Ref]

Hepatic

Fatal hepatic reactions have occurred primarily in patients with serious underlying medical conditions (primarily AIDS or malignancy) and often taking multiple concomitant medications. One reported patient with AIDS experienced acute hepatic necrosis and hepatic failure about 3 weeks after starting this drug.

Transient hepatic reactions have been reported in patients with no other identifiable risk factors. Liver function returned to baseline after stopping this drug.

Serum transaminase elevations (greater than 8 times the upper limit of normal [8 x ULN]; about 1%) and statistically significant increases in AST have been reported. Serum transaminase elevations have been reported primarily in patients with serious underlying medical conditions (primarily AIDS or malignancy) and often taking multiple concomitant medications, including agents known to be hepatotoxic.

Transaminase elevations greater than 2 to 3 x ULN have also been reported.

Cholestasis, hepatocellular damage, and hepatocellular necrosis have also been reported during postmarketing experience.[Ref]

Very common (10% or more): Increased ALT, increased AST
Uncommon (0.1% to 1%): Serum transaminase elevations, cholestasis, jaundice, increased bilirubin
Rare (less than 0.1%): Serious hepatic reactions, hepatic toxicity (including fatalities), hepatic failure, hepatocellular necrosis, hepatitis, hepatocellular damage
Frequency not reported: Hepatic reactions (ranging from mild transient transaminase elevations to clinical hepatitis, fulminant hepatic failure [including fatalities]), transient hepatic reactions (including hepatitis, jaundice), elevated liver function tests (transient and asymptomatic), cholestatic jaundice, fatal hepatic necrosis, increased plasma levels of hepatic enzymes[Ref]

Dermatologic

Reversible alopecia has been associated with long-term (2 months or longer) therapy.

In patients with serious underlying diseases (primarily AIDS and malignancy), exfoliative skin disorders have resulted in a fatal outcome.

Acute generalized exanthematous pustulosis, drug eruption, increased sweating, exfoliative skin disorders (including Stevens-Johnson syndrome, toxic epidermal necrolysis), and alopecia have also been reported during postmarketing experience.[Ref]

Very common (10% or more): Rash
Common (1% to 10%): Maculopapular erythema
Uncommon (0.1% to 1%): Pruritus, genital pruritus, erythematous rash, dry skin, abnormal skin odor, urticaria, herpes simplex, drug eruption, increased sweating
Rare (less than 0.1%): Angioedema, exfoliative skin disorders (including Stevens-Johnson syndrome, toxic epidermal necrolysis), alopecia, acute generalized exanthematous pustulosis, exfoliative dermatitis
Frequency not reported: Reversible alopecia, exfoliative skin disorders (including fatalities)[Ref]

Metabolic

Very common (10% or more): Increased blood alkaline phosphatase
Uncommon (0.1% to 1%): Hypokalemia, anorexia, decreased appetite
Rare (less than 0.1%): Hypercholesterolemia, hypertriglyceridemia[Ref]

Hypercholesterolemia, hypertriglyceridemia, and hypokalemia have also been reported during postmarketing experience.[Ref]

Hypersensitivity

Rare cases of exfoliative dermatitis and ulcerative eruptions consistent with Stevens-Johnson syndrome have been reported in association with hypersensitivity reactions.

A 52-year-old female experienced a fixed drug eruption (FDE) when administered a single 400 mg oral dose for extensive pityriasis versicolor. Within 12 hours, she noticed 3 oval, painful, eroded, pigmented patches over her trunk with diameters of 3 to 4 cm and erythematous halos. A clinical diagnosis of FDE due to drug therapy was made. The FDE was confirmed when the patient was rechallenged with a 25 mg oral dose.[Ref]

Rare (less than 0.1%): Anaphylactic reaction, anaphylaxis
Frequency not reported: Hypersensitivity reactions (including generalized edema, stridor, hypotension, exfoliative dermatitis, ulcerative eruptions), fixed drug eruption
Postmarketing reports: Anaphylaxis (including angioedema, face edema, pruritus)[Ref]

Cardiovascular

Most reports of QT interval prolongation and torsades de pointes involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications that may have been contributory.

An 11-year-old male with neurofibromatosis-1 presented to the hospital in septic shock secondary to a perforated gastric volvulus. After initial stabilization, the patient underwent total gastrectomy and multiple peritoneal lavages. Culture of peritoneal fluid showed infection with Candida albicans. Therapy was started with fluconazole 150 mg IV every 12 hours. After starting this drug, the patient developed QT prolongation and complex ventricular arrhythmia. The drug was discontinued. Over the subsequent 36-hours, the patient remained in sinus rhythm except for one brief run of ventricular bigeminy. An ECG recorded 5 months after admission (and about 4 months after cessation of all QT-prolonging medications) showed sinus rhythm with normal heart rate and corrected QT interval.

QT prolongation and torsade de pointes have also been reported during postmarketing experience.[Ref]

Rare (less than 0.1%): QT prolongation, torsade de pointes
Frequency not reported: Prolongation of the QT interval on the ECG, palpitations, complex ventricular arrhythmia[Ref]

Hematologic

Anemia, eosinophilia, leukopenia, neutropenia, and thrombocytopenia have been reported, often in patients with severe deep fungal infections or underlying disease.

Spontaneous reports of anemia were more frequent in patients 65 years of age or older than in those between 12 and 65 years of age; however, there is a natural increase in the incidence of anemia in the elderly. A causal relationship to drug exposure could not be determined.

Anemia, leukopenia, neutropenia, agranulocytosis, and thrombocytopenia have also been reported during postmarketing experience.[Ref]

Uncommon (0.1% to 1%): Anemia
Rare (less than 0.1%): Leukopenia, neutropenia, agranulocytosis, thrombocytopenia
Frequency not reported: Eosinophilia[Ref]

Other

Uncommon (0.1% to 1%): Thirst, fatigue, malaise, pain, rigors, asthenia, fever, flushing, hot flushes
Rare (less than 0.1%): Face edema
Frequency not reported: Infection due to resistant microorganisms[Ref]

Fever, asthenia, fatigue, and malaise have also been reported during postmarketing experience.[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Back pain, myalgia
Frequency not reported: Joint pain, finger stiffness[Ref]

Myalgia has also been reported during postmarketing experience.[Ref]

Psychiatric

Uncommon (0.1% to 1%): Insomnia, nervousness

Insomnia has also been reported during postmarketing experience.

Renal

Uncommon (0.1% to 1%): Polyuria, renal pain, changes in renal function tests
Frequency not reported: Membranous nephropathy
Postmarketing reports: Acute renal failure[Ref]

A 58-year-old female with a history of hypertension and cervical cancer experienced membranous nephropathy coincident with this drug. The patient presented with increasing generalized edema accompanied by nausea and indigestion for 3 weeks. Clinical findings showed the patient had stage I membranous nephropathy. At initial presentation, the patient's medication history included amlodipine, hydrochlorothiazide, metoclopramide, and levosulpiride. She did not admit to taking fluconazole. Five months after the initial presentation, the patient returned with reports of increasing pedal edema. At that point, the patient admitted to taking this drug once a week for tinea pedis. The patient went into complete remission when the drug was stopped.

Spontaneous reports of acute renal failure were more frequent in patients 65 years of age or older than in those between 12 and 65 years of age; however, there is a natural increase in the incidence of renal failure in the elderly. A causal relationship to drug exposure could not be determined.[Ref]

Genitourinary

Uncommon (0.1% to 1%): Intermenstrual bleeding, dysmenorrhea, leukorrhea, menorrhagia, uterine spasm, vaginal disorders, female sexual dysfunction

Respiratory

Uncommon (0.1% to 1%): Pharyngitis
Frequency not reported: Respiratory disorders[Ref]

Ocular

Uncommon (0.1% to 1%): Abnormal vision

Some side effects of fluconazole may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Doses up to 400 mg/day have been used.

Comments:
-Optimal therapeutic dose and therapy duration have not been established.

Use: For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia

IDSA Recommendations:
Candidemia in nonneutropenic or neutropenic patients: 800 mg IV or orally on the first day followed by 400 mg IV or orally once a day
Duration of therapy:
-Nonneutropenic patients: 14 days after first negative blood culture and candidemia signs/symptoms resolve
-Neutropenic patients: 2 weeks after Candida cleared from bloodstream (documented) and candidemia symptoms and neutropenia resolve

Chronic disseminated candidiasis in stable patients: 400 mg IV or orally once a day
Duration of therapy: Until lesions have resolved (usually months) and through periods of immunosuppression

Candida osteoarticular infection: 400 mg IV or orally once a day
Duration of therapy:
-Osteomyelitis: 6 to 12 months
-Septic arthritis: At least 6 weeks

CNS candidiasis (after initial regimen of IV amphotericin B): 400 to 800 mg IV or orally once a day
Duration of therapy: Until all signs/symptoms and CSF and radiologic abnormalities resolve

Candida cardiovascular system infection: 400 to 800 mg IV or orally once a day
Duration of therapy:
-Endocarditis: Lifelong suppressive therapy may be indicated.
-Pericarditis or myocarditis: Often several months
-Suppurative thrombophlebitis: At least 2 weeks after candidemia cleared
-Infected pacemaker, implantable cardioverter defibrillator (ICD), or ventricular assist device (VAD): 4 to 6 weeks after device removed; chronic suppressive therapy if VAD not removed

Comments:
-Candidemia in nonneutropenic patients: Recommended as primary therapy; an echinocandin is recommended for moderately severe to severe illness or recent azole exposure; switching to this drug after initial echinocandin is often appropriate.
-Candidemia in neutropenic patients: Recommended as alternative therapy; an echinocandin or IV amphotericin B preferred for most patients; this drug recommended for patients without recent azole exposure and who are not critically ill.
-Recommended as primary therapy for chronic disseminated candidiasis in stable patients, Candida osteoarticular infection, CNS candidiasis, pericarditis/myocarditis, and suppurative thrombophlebitis
-Recommended as alternative therapy for endocarditis and infected pacemaker, ICD, or VAD

Acute infection: 400 mg IV or orally on the first day followed by 200 mg IV or orally once a day
Duration of therapy: 10 to 12 weeks after CSF culture is negative

Comments:
-Dose of 400 mg IV or orally once a day may be used based on clinical judgment of patient response.

IDSA Recommendations:
-Consolidation therapy (after induction therapy): 400 to 800 mg orally once a day for 8 weeks
-Maintenance therapy: 200 mg orally once a day for 6 to 12 months

Comments:
-Preferred agent
-The higher dose (800 mg/day) is recommended for consolidation therapy if the 2-week induction regimen was used.
-Maintenance therapy is recommended to prevent relapse.

Cerebral cryptococcoma:
-Consolidation and maintenance therapy (after induction therapy): 400 to 800 mg orally once a day for 6 to 18 months

Acute infection: 400 mg IV or orally on the first day followed by 200 mg IV or orally once a day
Duration of therapy: 10 to 12 weeks after CSF culture is negative

Comments:
-Dose of 400 mg IV or orally once a day may be used based on clinical judgment of patient response.

Suppression of relapse in patients with AIDS: 200 mg IV or orally once a day

IDSA Recommendations:
HIV-infected patients:
-Induction therapy: 800 to 2000 mg orally once a day for 6 to 12 weeks, depending on regimen
-Consolidation therapy (after induction therapy): 400 mg orally once a day for at least 8 weeks
-Maintenance (suppressive) and prophylactic therapy: 200 mg orally once a day for at least 12 months

Comments:
-Recommended as an alternative for induction therapy; use is not encouraged.
-Preferred agent for consolidation therapy and maintenance and prophylactic therapy

Organ transplant recipients:
-Consolidation therapy (after induction therapy): 400 to 800 mg orally once a day for 8 weeks
-Maintenance therapy: 200 to 400 mg orally once a day for 6 to 12 months

Comments:
-Preferred agent

Cerebral cryptococcoma:
-Consolidation and maintenance therapy (after induction therapy): 400 to 800 mg orally once a day for 6 to 18 months

US CDC, NIH, and IDSA Recommendations for HIV-infected Patients:
-Induction therapy: 400 to 1200 mg IV or orally once a day for at least 2 weeks
-Consolidation therapy (after at least 2 weeks successful induction therapy): 400 mg IV or orally once a day for at least 8 weeks
-Maintenance therapy: 200 mg orally once a day for at least 1 year

Comments:
-Recommended for use in alternative regimens for induction therapy; dose depends on regimen (i.e., used with amphotericin B, flucytosine, or alone).
-Recommended as preferred regimen for consolidation therapy; should be followed by maintenance therapy
-Recommended as preferred regimen for maintenance therapy

IDSA Recommendations:
-Mild to moderate pulmonary infection or mild to moderate disseminated infection without CNS involvement: 400 to 800 mg orally once a day for at least 6 to 12 months
-CNS infection (after initial regimen of IV amphotericin B): 800 mg orally once a day for at least 12 months and until CSF abnormalities resolve

Comments:
-Recommended as alternative therapy for mild to moderate pulmonary infection or mild to moderate disseminated infection without CNS involvement
-Recommended as follow-up therapy for CNS infection

IDSA Recommendations:
Cutaneous or lymphocutaneous infection: 400 to 800 mg IV or orally once a day
Duration of therapy: 2 to 4 weeks after all lesions resolve (usually 3 to 6 months total)

Comments:
-Recommended as alternative therapy; should only be used if other agents are not tolerated

Oropharyngeal candidiasis:
2 weeks or younger (gestational age 26 to 29 weeks): 3 mg/kg IV or orally every 72 hours
Older than 2 weeks: 6 mg/kg IV or orally on the first day followed by 3 mg/kg IV or orally once a day
Duration of therapy: At least 2 weeks, to reduce the risk of relapse

US CDC, NIH, IDSA, PIDS, and AAP Recommendations for HIV-exposed and HIV-infected Children: 6 to 12 mg/kg orally once a day
Maximum dose: 400 mg/dose
Duration of therapy: 7 to 14 days

Comments:
-Recommended as preferred therapy; oral fluconazole recommended for moderate or severe oropharyngeal candidiasis.

US CDC, NIH, and IDSA Recommendations for HIV-infected Adolescents:
-Initial episodes: 100 mg orally once a day for 7 to 14 days
-Suppressive therapy: 100 mg orally once a day or 3 times a week

Comments:
-Recommended as preferred oral therapy
-Unless frequent or severe recurrences, suppressive therapy generally not recommended

US CDC, NIH, IDSA, PIDS, and AAP Recommendations for HIV-exposed and HIV-infected Children:
Meningeal infection: 12 mg/kg IV or orally once a day
Maximum dose: 800 mg/dose

Secondary prophylaxis: 6 mg/kg orally once a day
Maximum dose: 400 mg/dose
Duration of therapy: Lifelong

Comments:
-Recommended as preferred therapy
-Secondary prophylaxis should follow treatment of meningeal infection.

US CDC, NIH, and IDSA Recommendations for HIV-infected Adolescents:
-Meningeal infection: 400 to 800 mg IV or orally once a day
-Chronic suppressive therapy: 400 mg orally once a day

Comments:
-Recommended as preferred therapy for meningeal infection and chronic suppressive therapy
-A specialist should be consulted for meningeal infections.
-Since relapse is common (80%), suppressive therapy should be lifelong.

• May be taken with or without food.

• Take fluconazole at least two hours before drugs used for acid suppression such as proton pump inhibitors (for example omeprazole).

• Ensure you finish the course as prescribed by your doctor.

• Try to take fluconazole at the same time each day.

• Peak levels of fluconazole are reached within one to two hours of oral administration. However, signs of infection may take longer to abate.
• One single oral dose is usually sufficient to treat vaginal candidiasis.

View as a slideshow