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Fluconazole

Pronunciation

Pronunciation

(floo KOE na zole)

Index Terms

  • Diflucan

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 100 mg (50 mL); 200 mg (100 mL); 400 mg (200 mL)

Solution, Intravenous [preservative free]:

Generic: 200 mg (100 mL); 400 mg (200 mL)

Suspension Reconstituted, Oral:

Diflucan: 10 mg/mL (35 mL); 40 mg/mL (35 mL) [orange flavor]

Generic: 10 mg/mL (35 mL); 40 mg/mL (35 mL)

Tablet, Oral:

Diflucan: 50 mg, 100 mg, 150 mg, 200 mg

Generic: 50 mg, 100 mg, 150 mg, 200 mg

Brand Names: U.S.

  • Diflucan

Pharmacologic Category

  • Antifungal Agent, Oral
  • Antifungal Agent, Parenteral

Pharmacology

Interferes with fungal cytochrome P450 activity (lanosterol 14-α-demethylase), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation

Absorption

Oral: Well absorbed; food does not affect extent of absorption

Distribution

Vd: ~0.6 L/kg; widely throughout body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urine

Relative diffusion blood into CSF: Adequate with or without inflammation (exceeds usual MICs)

CSF:blood level ratio: Normal meninges: 50% to 90%; Inflamed meninges: ~80%

Excretion

Urine (80% as unchanged drug)

Time to Peak

Oral: 1 to 2 hours

Half-Life Elimination

Normal renal function: ~30 hours (range: 20 to 50 hours); Elderly: 46.2 hours; Neonates (gestational age 26 to 29 weeks): 73.6 to 46.6 hours (decreases with increasing postnatal age); Pediatric patients 9 months to 15 years: 19.5 to 25 hours

Protein Binding

Plasma: 11% to 12%

Special Populations: Renal Function Impairment

Pharmacokinetics are markedly affected; there is an inverse relationship between half-life and creatinine clearance.

Use: Labeled Indications

Treatment of candidiasis (esophageal, oropharyngeal, peritoneal, urinary tract, vaginal); systemic candida infections (eg, candidemia, disseminated candidiasis, and pneumonia); cryptococcal meningitis; antifungal prophylaxis in allogeneic bone marrow transplant recipients

Use: Unlabeled

Cryptococcal pneumonia; candidal intertrigo; surgical (perioperative) prophylaxis in high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation; primary antifungal prophylaxis in pediatric oncology patients

Contraindications

Hypersensitivity to fluconazole or any component of the formulation (cross-reaction with other azole antifungal agents may occur, but has not been established; use caution); coadministration of terfenadine in adult patients receiving multiple doses of 400 mg or higher or with CYP3A4 substrates which may lead to QTc prolongation (eg, astemizole, cisapride, erythromycin, pimozide, or quinidine)

Dosing: Adult

The daily dose of fluconazole is the same for both oral and IV administration

Usual dosage range: Oral, IV: 150 mg once or Loading dose: 200 to 800 mg; maintenance: 200 to 800 mg once daily; duration and dosage depend on location and severity of infection

Indication-specific dosing:

Blastomycosis (off-label use): Oral: CNS disease: Consolidation: 800 mg daily for ≥12 months and until resolution of CSF abnormalities (Chapman 2008)

Candidiasis: Oral, IV:

Candidemia (neutropenic and non-neutropenic): Loading dose: 800 mg (12 mg/kg) on day 1, then 400 mg daily (6 mg/kg/day) for 14 days after first negative blood culture and resolution of signs/symptoms. Note: Not recommended for patients with recent azole exposure, critical illness, or if C. krusei or C. glabrata are suspected (Pappas 2009).

Chronic, disseminated: 400 mg daily (6 mg/kg/day) until calcification or lesion resolution (Pappas 2009)

CNS candidiasis (alternative therapy): 400 to 800 mg daily (6 to 12 mg/kg/day) until CSF/radiological abnormalities resolved. Note: Recommended as alternative therapy in patients intolerant of amphotericin B (Pappas 2009).

Endocarditis, prosthetic valve (off-label use): 400 to 800 mg daily (6 to 12 mg/kg/day) for 6 weeks after valve replacement (as step-down in stable, culture-negative patients); long-term suppression in absence of valve replacement: 400 to 800 mg daily (Pappas 2009)

Endophthalmitis (off-label use): 400 to 800 mg daily (6 to 12 mg/kg/day) for 4 to 6 weeks until examination indicates resolution (Pappas 2009)

Esophageal:

Manufacturer's labeling: Loading dose: 200 mg on day 1, then maintenance dose of 100 to 400 mg daily for 21 days and for at least 2 weeks following resolution of symptoms

Alternative dosing: 200 to 400 mg daily for 14 to 21 days; suppressive therapy of 100 to 200 mg 3 times weekly may be used for recurrent infections (Pappas 2009)

Intertrigo (off-label use): 50 mg daily or 150 mg once weekly (Coldiron 1991; Nozickova 1998; Stengel 1994)

Oropharyngeal:

Manufacturer's labeling: Loading dose: 200 mg on day 1; maintenance dose 100 mg daily for ≥2 weeks. Note: Therapy with 100 mg daily is associated with resistance development (Rex 1995).

Alternative dosing: 100 to 200 mg daily for 7 to 14 days for uncomplicated, moderate-to-severe disease; chronic therapy of 100 mg 3 times weekly is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC) (Pappas 2009)

Osteoarticular: 400 mg daily for 6 to 12 months (osteomyelitis) or 6 weeks (septic arthritis) (Pappas 2009)

Pacemaker (or ICD, VAD) infection (off-label use): 400 to 800 mg daily (6 to 12 mg/kg/day) for 4 to 6 weeks after device removal (as step-down in stable, culture-negative patients); long-term suppression when VAD cannot be removed: 400 to 800 mg daily (Pappas 2009)

Pericarditis or myocarditis: 400 to 800 mg daily for several months (Pappas 2009)

Peritonitis: 50 to 200 mg daily. Note: Some clinicians do not recommend using <200 mg daily (Chen 2004).

Prophylaxis:

Bone marrow transplant: 400 mg once daily. Patients anticipated to have severe granulocytopenia should start therapy several days prior to the anticipated onset of neutropenia and continue for 7 days after the neutrophil count is >1000 mm3.

High-risk ICU patients in units with high incidence of invasive candidiasis: 400 mg once daily (Pappas 2009)

Neutropenic patients: 400 mg once daily for duration of neutropenia (Pappas 2009)

Peritoneal dialysis associated infection (concurrently treated with antibiotics), prevention of secondary fungal infection: 200 mg every 48 hours (Restrepo 2010)

Solid organ transplant: 200 to 400 mg once daily for at least 7 to 14 days (Pappas 2009)

Surgical (perioperative) prophylaxis in high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation (off-label use): IV: 400 mg given in the perioperative period and continued in the postoperative period for ≤28 days. Time of initiation and duration varies with transplant type and operative protocol (Bratzler 2013).

Thrombophlebitis, suppurative (off-label use): 400 to 800 mg daily (6 to 12 mg/kg/day) and as step-down in stable patients for ≥2 weeks (Pappas 2009)

Urinary tract:

Cystitis:

Manufacturer's labeling: UTI: 50 to 200 mg once daily

Asymptomatic, patient undergoing urologic procedure: 200 to 400 mg once daily several days before and after the procedure (Pappas 2009)

Symptomatic: 200 mg once daily for 2 weeks (Pappas 2009)

Fungus balls: 200 to 400 mg once daily (Pappas 2009)

Pyelonephritis: 200 to 400 mg once daily for 2 weeks (Pappas 2009)

Vaginal/Vulvovaginal: Oral:

Uncomplicated: Manufacturer's labeling: 150 mg as a single dose

Complicated or severe: 150 mg every 72 hours for 3 doses (Pappas 2009) or 150 mg every 72 hours for 2 doses (CDC [Workowski 2015])

Recurrent: 150 mg once daily for 10 to 14 days, followed by 150 mg once weekly for 6 months (Pappas 2009) or fluconazole 100 mg, 150 mg, or 200 mg every 72 hours (day 1, 4, and 7) for a total of 3 doses, then 100 mg, 150 mg, or 200 mg once weekly for 6 months (CDC [Workowski 2015])

Coccidioidomycosis, treatment (off-label use):

HIV-infected (HHS [OI adult 2015]):

Meningeal infections (consultation with specialist is advised): IV, Oral: 400 to 800 mg once daily; patients who complete initial therapy should be considered for lifelong suppressive therapy using fluconazole 400 mg once daily if CD4 counts remain <250 cells/mm3.

Mild infections (eg, focal pneumonia): Oral: 400 mg once daily; patients who complete initial therapy should be considered for lifelong suppressive therapy using fluconazole 400 mg once daily if CD4 counts remain <250 cells/mm3.

Non-HIV infected (off-label use): Oral, IV:

Disseminated, extrapulmonary: 400 mg once daily (some experts use 2000 mg daily [Galgiani 2005])

Meningitis: 400 mg once daily (some experts use initial doses of 800 to 1000 mg daily), lifelong duration (Galgiani 2005)

Pneumonia, acute, uncomplicated: 200 to 400 mg daily for 3 to 6 months (Catanzaro 1995; Galgiani 2000)

Pneumonia, chronic progressive, fibrocavitary: 200 to 400 mg daily for 12 months (Catanzaro 1995; Galgiani 2000)

Pneumonia, diffuse: Consolidation after amphotericin B induction: 400 mg daily for 12 months (lifelong in chronically immunosuppressed) (Galgiani 2005)

Coccidioidomycosis, prophylaxis (off-label use): Oral:

HIV-infected patients (HHS [OI adult 2015]):

Primary prophylaxis in patients with a new positive IgM or IgG serologic test who live in disease-endemic areas and have CD4 counts <250 cells/mm3: 400 mg once daily

Chronic suppressive therapy (secondary prophylaxis): 400 mg once daily

Solid organ transplant (off-label use): Note: Prophylaxis regimens in this setting have not been established; the following regimen has been proposed for transplant recipients who maintain residence in a Coccidioides spp endemic area.

Previous history >12 months prior to transplant: 200 mg once daily for 6 to 12 months (Vikram 2009; Vucicevic 2011)

Previous history ≤12 months prior to transplant: 400 mg once daily, lifelong treatment (Vikram 2009; Vucicevic 2011)

Positive serology before or at transplant: 400 mg once daily, lifelong treatment; if serology is negative at 12 months, consider a dose reduction to 200 mg daily (Vikram 2009; Vucicevic 2011)

No history (at risk for de novo post-transplant disease): some clinicians treat with 200 mg daily for 6 to 12 months (Vucicevic 2011)

Cryptococcosis:

Meningitis:

Manufacturer's labeling: Oral, IV: 400 mg for 1 dose, then 200 to 400 mg once daily for 10 to 12 weeks following negative CSF culture

Alternate dosing: HIV-infected:

Induction (alternative to preferred therapy): Oral, IV: 800 to 1,200 mg once daily with concomitant flucytosine for 6 weeks (Perfect 2010) or 400 to 800 mg once daily with concomitant flucytosine for at least 2 weeks (HHS [OI adult 2015]) or 1,200 mg once daily as monotherapy for at least 2 weeks (HHS [OI adult 2015])

Consolidation (preferred therapy): Oral, IV: 400 mg once daily for at least 8 weeks (HHS [OI adult 2015])

Maintenance (suppression) (preferred therapy): Oral: 200 mg once daily for at least 12 months; maintenance therapy may be stopped if the following criteria are fulfilled: induction, consolidation, and at least 12 months of maintenance therapy has been completed, patient remains asymptomatic from cryptococcal infection, and CD4 count ≥100 cells/mm3 for ≥3 months and HIV RNA suppressed in response to effective ART (HHS [OI adult 2015])

Pulmonary (immunocompetent) (off-label use): 400 mg once daily for 6 to 12 months (Perfect 2010)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

The daily dose of fluconazole is the same for oral and IV administration

Usual dosage range: Oral, IV: Loading dose: 6 to 12 mg/kg/dose; maintenance: 3 to 12 mg/kg/dose once daily; duration and dosage depend on location and severity of infection

Indication-specific dosing:

Candidiasis: Oral, IV:

Esophageal:

Manufacturer’s recommendation: Loading dose: 6 mg/kg/dose; maintenance: 3-12 mg/kg/dose once daily for 21 days and for at least 2 weeks following resolution of symptoms (maximum: 600 mg/day)

HIV-exposed/-infected: Loading dose: 6 mg/kg/dose once on day 1; maintenance: 3 to 6 mg/kg/dose once daily for 4 to 21 days (maximum: 400 mg/day) (CDC 2009)

Relapse suppression (HIV-exposed/-infected): 3 to 6 mg/kg/dose once daily (maximum: 200 mg/day) (CDC 2009)

Invasive disease (alternative therapy): 5 to 6 mg/kg/dose every 12 hours for ≥28 days (maximum: 600 mg/day) (CDC 2009)

Oropharyngeal:

Manufacturer’s recommendation: Loading dose: 6 mg/kg/dose; maintenance: 3 mg/kg/dose once daily for ≥2 weeks (maximum: 600 mg/day)

HIV-exposed/-infected: 3 to 6 mg/kg/dose once daily for 7 to 14 days (maximum: 400 mg/day) (CDC 2009)

Surgical (perioperative) prophylaxis in high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation (off-label use): IV: 6 mg/kg given in the perioperative period and continued in the postoperative period for ≤28 days (maximum dose 400 mg). Time of initiation and duration varies with transplant type and operative protocol (Bratzler 2013).

Coccidioidomycosis: Oral, IV:

Children: Meningeal infection, or in a stable patient with diffuse pulmonary or disseminated disease (HIV-exposed/-infected):

Treatment: 5 to 6 mg/kg/dose twice daily (maximum daily dose: 800 mg/day) (CDC 2009) followed by chronic suppressive therapy (see below)

Relapse suppression: 6 mg/kg/dose once daily (maximum daily dose: 400 mg/day) (CDC 2009)

Adolescents: Treatment, primary prophylaxis, or chronic suppressive therapy (secondary prophylaxis): Refer to adult dosing.

Cryptococcosis: Oral, IV:

Meningitis: Manufacturer's labeling: 12 mg/kg/dose for 1 dose, then 6 to 12 mg/kg/day for 10-12 weeks following negative CSF culture

HIV-exposed/-infected:

CNS disease (alternative therapy in patients intolerant of amphotericin B):

Children:

Induction: 12 mg/kg/dose for 1 dose, then 6 to 12 mg/kg/day (maximum: 800 mg/day) for ≥2 weeks (in combination with flucytosine) (CDC 2009)

Consolidation: 10 to 12 mg/kg/day for 8 weeks (Perfect 2010) or 12 mg/kg/dose for 1 dose, then 6 to 12 mg/kg/day (maximum: 800 mg/day) for 8 weeks (CDC 2009)

Maintenance (suppression): 6 mg/kg/day (maximum: 200 mg/day) (CDC 2009; Perfect 2010)

Adolescents: Refer to adult dosing.

Non-CNS disease, disseminated (including severe pulmonary disease) (alternative therapy; off-label use): Induction: 12 mg/kg/dose for 1 dose, then 6 to 12 mg/kg/day (maximum: 600 mg/day) (CDC 2009)

Non-CNS disease, localized (including isolated pulmonary disease) (off-label use): 12 mg/kg/dose for 1 dose, then 6 to 12 mg/kg/day (maximum: 600 mg/day). Note: Duration depends upon infection site and severity (CDC 2009). For patients with pulmonary disease (not delineated by severity), the IDSA recommends a duration of 6 to 12 months (Perfect 2010).

Primary antifungal prophylaxis in pediatric oncology patients (guideline recommendations; Science 2014): Oral, IV:

Allogeneic hematopoietic stem cell transplant (HSCT): Infants ≥1 month, Children, and Adolescents <19 years: 6 to 12 mg/kg/day (maximum: 400 mg/day), begin at the start of conditioning; continue until engraftment

Allogeneic HSCT with grades 2 to 4 acute graft-versus-host-disease (GVHD) or chronic extensive GVHD: Begin with GVHD diagnosis, continue until GVHD resolves:

Infants ≥1 month and Children <13 years: 6 to 12 mg/kg/day (maximum: 400 mg/day)

Adolescents ≥13 years (where posaconazole is contraindicated): 6 to 12 mg/kg/day (maximum: 400 mg/day)

Autologous HSCT with neutropenia anticipated >7 days: Infants ≥1 month, Children, and Adolescents <19 years: 6 to 12 mg/kg/day (maximum: 400 mg/day), begin at the start of conditioning; continue until engraftment

Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS): Infants ≥1 month, Children, and Adolescents <19 years: 6 to 12 mg/kg/day (maximum: 400 mg/day) during chemotherapy associated neutropenia; alternative antifungals may be suggested for children ≥13 years in centers with a high local incidence of mold infections or if fluconazole is not available

Dosing: Renal Impairment

Manufacturer's labeling: Note: Renal function estimated using the Cockcroft-Gault formula

No adjustment for vaginal candidiasis single-dose therapy

For multiple dosing in adults, administer loading dose of 50 to 400 mg, then adjust daily doses as follows (dosage reduction in children should parallel adult recommendations):

CrCl >50 mL/minute: No dosage adjustment necessary

CrCl ≤50 mL/minute (no dialysis): Reduce dose by 50%

End-stage renal disease on intermittent hemodialysis (IHD):

Manufacturer's labeling: 100% of daily dose (according to indication) after each dialysis session; on nondialysis days, patient should receive a reduced dose according to their CrCl.

Alternate recommendations: Doses of 200 to 400 mg every 48 to 72 hours or 100 to 200 mg every 24 hours have been recommended. Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions (Heintz 2009).

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 400 to 800 mg followed by 200 to 400 mg every 24 hours

CVVHD/CVVHDF: Loading dose of 400 to 800 mg followed by 400 to 800 mg every 24 hours (CVVHD or CVVHDF) or 800 mg every 24 hours (CVVHDF)

Note: Higher maintenance doses of 400 mg every 24 hours (CVVH), 800 mg every 24 hours (CVVHD), and 500 to 600 mg every 12 hours (CVVHDF) may be considered when treating resistant organisms and/or when employing combined ultrafiltration and dialysis flow rates of ≥2 L/hour for CVVHD/CVVHDF (Heintz 2009; Trotman 2005).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Administration

IV: Do not use if cloudy or precipitated. Infuse over ~1 to 2 hours; do not exceed 200 mg/hour.

Oral: May be administered without regard to meals.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Compatibility

Stable in D5W, LR, NS.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, ampicillin, calcium gluconate, cefotaxime, ceftriaxone, cefuroxime, chloramphenicol, diazepam, digoxin, erythromycin lactobionate, furosemide, haloperidol, hydroxyzine, imipenem/cilastatin, pantoprazole, pentamidine, sulfamethoxazole/trimethoprim.

Storage

Tablet: Store at <30°C (86°F).

Powder for oral suspension: Store dry powder at <30°C (86°F). Following reconstitution, store at 5°C to 30°C (41°F to 86°F). Discard unused portion after 2 weeks. Do not freeze.

Injection: Store injection in glass at 5°C to 30°C (41°F to 86°F). Store injection in plastic flexible containers with overwrap at 20°C to 25°C (68°F to 77°F). Do not freeze. Do not unwrap unit until ready for use.

Drug Interactions

Alfentanil: Fluconazole may increase the serum concentration of Alfentanil. Management: Monitor for increased anesthetic and respiratory depressant effects if alfentanil is combined with fluconazole. Consider using lower initial doses of alfentanil or an alternative anesthetic. Consider therapy modification

Amitriptyline: May enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Amitriptyline. Monitor therapy

Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Monitor therapy

Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination

AtorvaSTATin: Fluconazole may increase the serum concentration of AtorvaSTATin. Monitor therapy

Avanafil: Fluconazole may increase the serum concentration of Avanafil. Management: Limit avanafil to a maximum dose of 50 mg per 24-hour period in any patient who is also receiving a moderate inhibitor of CYP3A4 such as fluconazole. Consider therapy modification

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy

Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Consider therapy modification

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor or temporarily stopping budesonide therapy during CYP3A4 inhibitor use. Monitor patients closely for signs/symptoms of corticosteroid excess. Consider therapy modification

Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification

BusPIRone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of BusPIRone. Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification

Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Busulfan. Isavuconazonium considerations are addressed in separate monographs. Monitor therapy

Calcium Channel Blockers: Fluconazole may increase the serum concentration of Calcium Channel Blockers. Exceptions: Clevidipine. Monitor therapy

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy

CarBAMazepine: Fluconazole may increase the serum concentration of CarBAMazepine. Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Isavuconazonium considerations are addressed in separate monographs. Avoid combination

Citalopram: Fluconazole may enhance the QTc-prolonging effect of Citalopram. Fluconazole may increase the serum concentration of Citalopram. Management: If this combination cannot be avoided, consider a lower dose of citalopram and monitor closely for QTc prolongation and arrhythmias. Avoid combination

Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a strong CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification

CycloSPORINE (Systemic): Fluconazole may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy

CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Monitor therapy

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg/day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification

Didanosine: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Consider therapy modification

Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Avoid combination

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification

Eplerenone: Fluconazole may increase the serum concentration of Eplerenone. Management: Reduce the starting dose of eplerenone to 25 mg/day; monitor patients closely for increased eplerenone effects. Consider therapy modification

Erythromycin (Systemic): Fluconazole may enhance the QTc-prolonging effect of Erythromycin (Systemic). Fluconazole may increase the serum concentration of Erythromycin (Systemic). Avoid combination

Etravirine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Applicable Isavuconazonium considerations are addressed in separate monographs. Etravirine may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. Consider therapy modification

Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Avoid combination

Fluvastatin: Fluconazole may increase the serum concentration of Fluvastatin. Management: Limit fluvastatin maximum adult dose to 20 mg twice daily, and monitor for toxic effects of fluvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities), during concomitant treatment. Consider therapy modification

Fosphenytoin: Fluconazole may increase the serum concentration of Fosphenytoin. Consider therapy modification

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Canadian labeling recommends an initial 50% reduction in guanfacine dose with further dose titration as needed. However, US labeling does not call for any specific guanfacine dose reduction with this combination. Monitor therapy

Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Hydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Hydrocodone. Monitor therapy

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: If a moderate CYP3A inhibitor must be used, consider reducing the dose of ibrutinib to 140mg daily and monitor closely for signs of toxicity. Avoid combination

Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination

Losartan: Fluconazole may decrease the serum concentration of Losartan. Specifically, fluconazole may decrease the serum concentration of E3174, the more potent active metabolite of losartan. Monitor therapy

Lovastatin: Fluconazole may increase the serum concentration of Lovastatin. Monitor therapy

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant use of grapefruit products. Consider therapy modification

Methadone: Fluconazole may enhance the QTc-prolonging effect of Methadone. Fluconazole may increase the serum concentration of Methadone. Management: Monitor patients closely for evidence of methadone toxicities, including but not limited to respiratory depression and QT-prolongation/torsades de pointes, if combined with fluconazole. Methadone dose reductions may be required. Consider therapy modification

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination

Nateglinide: Fluconazole may increase the serum concentration of Nateglinide. Monitor therapy

Nevirapine: Fluconazole may increase the serum concentration of Nevirapine. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Monitor therapy

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination

Ospemifene: Fluconazole may increase the serum concentration of Ospemifene. Avoid combination

OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Consider therapy modification

Parecoxib: Fluconazole may increase the serum concentration of Parecoxib. Management: Use the lowest possible dose of parecoxib in patients who are taking fluconazole. Consider therapy modification

Phenytoin: Fluconazole may increase the serum concentration of Phenytoin. Consider therapy modification

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy

Pimozide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the arrhythmogenic effect of Pimozide. Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Pimozide. This increase in serum concentrations may lead to QTc interval prolongation and ventricular arrhythmias. Applicable Isavuconazonium considerations are addressed in separate monographs. Avoid combination

Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Avoid combination

PredniSONE: Fluconazole may increase the serum concentration of PredniSONE. Monitor therapy

Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Monitor therapy

Proton Pump Inhibitors: Fluconazole may increase the serum concentration of Proton Pump Inhibitors. Monitor therapy

QuiNIDine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of QuiNIDine. Applicable Isavuconazonium considerations are addressed in separate monographs. Avoid combination

Ramelteon: Fluconazole may increase the serum concentration of Ramelteon. Monitor therapy

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Consider therapy modification

Red Yeast Rice: Fluconazole may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Monitor therapy

Rifamycin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Consider therapy modification

Ruxolitinib: Fluconazole may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. Consider therapy modification

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy

Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Monitor therapy

Sildenafil: Fluconazole may increase the serum concentration of Sildenafil. Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination

Simvastatin: Fluconazole may increase the serum concentration of Simvastatin. Monitor therapy

Sirolimus: Fluconazole may increase the serum concentration of Sirolimus. Management: Sirolimus dose adjustments will likely be needed when starting/stopping any azole antifungal. Clinical data suggest sirolimus (adult) dose reductions of 50-90% will be needed when starting an azole antifungal, but specific guidelines are lacking. Consider therapy modification

Solifenacin: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Solifenacin. Applicable Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification

Sulfonylureas: Fluconazole may increase the serum concentration of Sulfonylureas. Management: Seek alternatives when possible. If used together, monitor closely for increased effects of sulfonylureas if fluconazole is initiated/dose increased, or decreased effects if fluconazole is discontinued/dose decreased. Consider therapy modification

SUNItinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of SUNItinib. Applicable Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Consider therapy modification

Tacrolimus (Systemic): Fluconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely and adjust oral tacrolimus dose as necessary when concomitantly administered with fluconazole. Reduced doses of tacrolimus will likely be required. Consider therapy modification

Tadalafil: Fluconazole may increase the serum concentration of Tadalafil. Monitor therapy

Temsirolimus: Fluconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to fluconazole. Monitor sirolimus concentrations in all patients receiving fluconazole or any systemic azole antifungal. Consider therapy modification

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tipranavir: Fluconazole may increase the serum concentration of Tipranavir. Management: Limit fluconazole adult maximum dose to 200 mg/day in patients treated with tipranavir. Consider therapy modification

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tofacitinib: Fluconazole may increase the serum concentration of Tofacitinib. Management: Reduce the adult dose of tofacitinib to 5 mg daily in patients receiving moderate CYP3A4 inhibitors that strongly inhibit CYP2C19 (e.g., fluconazole, sitaxentan). Consider therapy modification

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Avoid combination

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Avoid combination

Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination

Vardenafil: Fluconazole may increase the serum concentration of Vardenafil. Management: Limit vardenafil doses to a maximum of 5 mg per 24-hour period in patients receiving concurrent therapy with a moderate CYP3A4 inhibitor such as fluconazole. Consider therapy modification

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy

Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Fluconazole may increase the serum concentration of Vitamin K Antagonists. Consider therapy modification

Voriconazole: Fluconazole may increase the serum concentration of Voriconazole. Avoid combination

Zidovudine: Fluconazole may decrease the metabolism of Zidovudine. Monitor therapy

Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Zolpidem. Applicable Isavuconazonium considerations are addressed in separate monographs. Monitor therapy

Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification

Adverse Reactions

Frequency not always defined.

Cardiovascular: Angioedema (rare)

Central nervous system: Headache (2% to 13%), dizziness (1%)

Dermatologic: Rash (2%)

Gastrointestinal: Nausea (2% to 7%), abdominal pain (2% to 6%), vomiting (2% to 5%), diarrhea (2% to 3%), dysgeusia (1%), dyspepsia (1%)

Hepatic: Alkaline phosphatase increased, ALT increased, AST increased, hepatic failure (rare), hepatitis, jaundice

Miscellaneous: Anaphylactic reactions (rare)

Postmarketing and/or case reports: Agranulocytosis, alopecia, cholestasis, diaphoresis, drug eruption, exanthematous pustulosis, fatigue, fever, hypercholesterolemia, hypertriglyceridemia, hypokalemia, insomnia, leukopenia, malaise, myalgia, neutropenia, paresthesia, QT prolongation, seizure, somnolence, Stevens-Johnson syndrome, thrombocytopenia, torsade de pointes, toxic epidermal necrolysis, tremor, vertigo, weakness, xerostomia

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Cases of QTc prolongation and torsade de pointes associated with fluconazole use have been reported (usually high dose or in combination with agents known to prolong the QT interval); use caution in patients with concomitant medications or conditions which are arrhythmogenic.

• CNS effects: May occasionally cause dizziness or seizures; use caution driving or operating machinery.

• Hepatotoxicity: Serious (and sometimes fatal) hepatic toxicity (eg, hepatitis, cholestasis, fulminant hepatic failure) has been observed. Monitor patients who develop abnormal liver function tests for the development of more severe hepatic injury; discontinue fluconazole if signs and symptoms consistent with liver disease develop.

• Hypersensitivity reactions: Anaphylaxis has been reported rarely; use with caution in patients with hypersensitivity to other azoles.

• Skin reactions: Rare exfoliative skin disorders have been observed; fatal outcomes have been reported in patients with serious concomitant diseases. Monitor patients with deep seated fungal infections closely for rash development and discontinue if lesions progress. In patients with superficial fungal infections who develop a rash attributable to fluconazole, treatment should also be discontinued.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with preexisting hepatic impairment; monitor liver function closely and discontinue if symptoms consistent with liver disease develop.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be necessary.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Sucrose: Oral suspension contains sucrose; avoid use in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Monitoring Parameters

Periodic liver function tests (AST, ALT, alkaline phosphatase) and renal function tests, potassium

Pregnancy Risk Factor

C (single dose for vaginal candidiasis)/D (all other indications)

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. When used in high doses, fluconazole is teratogenic in animal studies. Following exposure during the first trimester, case reports have noted similar malformations in humans when used in higher doses (400 mg/day) over extended periods of time (Aleck 1997). Abnormalities reported include abnormal facies, abnormal calvarial development, arthrogryposis, brachycephaly, cleft palate, congenital heart disease, femoral bowing, thin ribs and long bones. Use of lower doses (150 mg as a single dose) does not suggest an increase risk to the fetus. Most azole antifungals, including fluconazole, are recommended to be avoided during pregnancy (Pappas 2009). Only topical azole antifungals are recommended for the treatment of vulvovaginal candidiasis in pregnant women (CDC [Workowski 2015]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, dyspepsia, or dysgeusia. Have patient report immediately to prescriber signs of hypokalemia, signs of hepatic impairment, severe dizziness, syncope, considerable nausea, significant diarrhea, paresthesia, chills, pharyngitis, ecchymosis, or hemorrhaging (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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