fluconazole

General

Pronunciation
floo-KON-a-zole

Trade Name(s)

• Canesoral [Canada]

• Diflucan

Pregnancy Category
Category C (single-dose oral treatment of vaginal candidiasis)
Category D (all other indications)

Ther. class.
antifungals
(systemic)

Indications

• PO, IV: Fungal infections caused by susceptible organisms, including:

» Oropharyngeal or esophageal candidiasis ,

» Serious systemic candidal infections,

» Urinary tract infections,

» Peritonitis,

» Cryptococcal meningitis.

• Prevention of candidiasis in patients who have undergone bone marrow transplantation.

• PO: Single-dose oral treatment of vaginal candidiasis.

Unlabelled Use(s):
Prevention of recurrent vaginal yeast infections.

Action

Inhibits synthesis of fungal sterols, a necessary component of the cell membrane.

Therapeutic Effect(s):

• Fungistatic action against susceptible organisms.

• May be fungicidal in higher concentrations.

Spectrum:

• Cryptococcus neoformans .

• Candida spp.

Pharmacokinetics

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed, good penetration into CSF, saliva, sputum, vaginal fluid, skin, eye, and peritoneum. Excreted in breast milk.

Metabolism and Excretion: >80% excreted unchanged by the kidneys; <10% metabolized by the liver.

Half-life: Premature neonates: 46–74 hr; Children: 19–25 hr (PO) and 15–17 hr (IV); Adults: 30 hr (↑ in renal impairment).

TIME/ACTION PROFILE (blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–4 hr	24 hr
IV	rapid	end of infusion	24 hr

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to fluconazole or other azole antifungals;

• Concurrent use with pimozide or voriconazole.

Use Cautiously in:

• Renal impairment (dose ↓ required if CCr <50 mL/min);

• Underlying liver disease;

• OB: Safety not established; congenital defects have occurred with use of high-dose fluconazole (400–800 mg/day);

• Lactation: Usually compatible with breastfeeding;

• Geri: ↑ risk of adverse reactions (rash, vomiting, diarrhea, seizures); consider age-related ↓ in renal function in determining dose.

Adverse Reactions/Side Effects

Incidence of adverse reactions is increased in HIV patients

CNS: headache, dizziness, seizures.

GI: HEPATOTOXICITY, abdominal discomfort, diarrhea, nausea, vomiting.

Derm: EXFOLIATIVE SKIN DISORDERS INCLUDING STEVENS-JOHNSON SYNDROME .

Endo: hypokalemia, hypertriglyceridemia.

Misc: allergic reactions,including anaphylaxis.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• ↑ activity of warfarin .

• Rifampin , rifabutin , and isoniazid ↓ levels.

• Fluconazole at doses >200 mg/day may inhibit the CYP3A4 enzyme system and effect the activity of drugs metabolized by this system.

• ↑ hypoglycemic effects of tolbutamide , glyburide , or glipizide .

• ↑ levels and risk of toxicity from cyclosporine , rifabutin , tacrolimus , theophylline , zidovudine , alfentanil , and phenytoin .

• ↑ levels and effects of benzodiazepines , zolpidem , bispirone , nisoldipine , tricyclic antidepressants , and losartan .

• May ↑ risk of bleeding with warfarin .

• May antagonize effects of amphotericin B .

• May ↑ voriconazole levels; avoid concurrent use.

Route/Dosage

Oropharyngeal Candidiasis

• PO, IV (Adults): 200 mg initially, then 100 mg daily for at least 2 wk..

• PO, IV (Children >14 days): 6 mg/kg initially, then 3 mg/kg/day for at least 2 wk..

• PO, IV (Neonates <14 days, 30–36 weeks gestation): same dose as older children except frequency is q 48 hr; Premature neonates <29 weeks gestation: 5–6 mg/kg/dose q 48–72 hr..

Esophageal Candidiasis

• PO, IV (Adults): 200 mg initially, then 100 mg once daily for at least 3 wk (up to 400 mg/day)..

• PO, IV (Children >14 days): 6 mg/kg initially, then 3–12 mg/kg/day for at least 3 wk..

• PO, IV (Neonates <14 days, 30–36 weeks gestation): same dose as older children except frequency is q 48 hr; Premature neonates <29 weeks gestation: 5–6 mg/kg/dose q 48–72 hr..

Vaginal Candidiasis

• PO (Adults): 150-mg single dose; prevention of recurrence (unlabeled)—150 mg daily for 3 days then weekly for 6 mo..

Systemic Candidiasis

• PO, IV (Adults): 400 mg/day initially, then 200–800 mg/day for 28 days..

• PO, IV (Children > 14 days): 6–12 mg/kg/day for 28 days..

• PO, IV (Neonates <14 days, 30–36 weeks gestation): same dose as older children except frequency is q 48 hr; Premature neonates <29 weeks gestation: 5–6 mg/kg/dose q 48–72 hr..

Cryptococcal Meningitis

• PO, IV (Adults): Treatment—400 mg once daily until favorable clinical response, then 200–800 mg once daily for at least 10–12 wk after clearing of CSF; change to oral therapy as soon as possible. Suppressive therapy—200 mg once daily..

• PO, IV (Children >14 days): 12 mg/kg/day initially, then 6–12 mg/kg/day for at least 10–12 wk after clearing of CSF; change to oral therapy as soon as possible. Suppressive therapy—6 mg/kg/day..

• PO, IV (Neonates <14 days, 30–36 weeks gestation): same dose as older children except frequency is q 48 hr; Premature neonates <29 weeks gestation: 5–6 mg/kg/dose q 48–72 hr..

Prevention of Candidiasis after Bone Marrow Transplant

• PO, IV (Adults): 400 mg once daily; begin several days before procedure if severe neutropenia is expected, and continue for 7 days after ANC >1000 /mm³..

• PO, IV (Children >14 days): 10–12 mg/kg/day, not to exceed 600 mg/day..

Renal Impairment

• PO, IV (Adults): CCr 11–50 mL/min—50% of the usual dose..

Availability

• Tablets: 50 mg, 100 mg, 150 mg, 200 mg

» Cost:
Generic: 50 mg $99.98/30, 100 mg $109.97/30, 150 mg $49.99/12, 200 mg $248.95/30.

• Powder for oral suspension (orange flavor): 10 mg/mL, 40 mg/mL

» Cost:
Generic: 10 mg/mL $27.99/35 mL, 40 mg/mL $109.98/35 mL.

• Premixed infusion: 2 mg/mL in 100- or 200-mL bottles/containers

Assessment

• Assess infected area and monitor CSF cultures before and periodically during therapy.

• Specimens for culture should be taken before instituting therapy. Therapy may be started before results are obtained.

• Assess patient for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis), therapy must be discontinued immediately.

Lab Test Considerations

• Monitor BUN and serum creatinine before and periodically during therapy; patients with renal dysfunction will require dose adjustment.

» Monitor liver function tests before and periodically during therapy. May cause ↑ AST, ALT, serum alkaline phosphate, and bilirubin concentrations.

Potential Nursing Diagnoses

• Risk for infection (Indications)

Implementation

• Do not confuse Diflucan (fluconazole) with Diprivan (propofol).

• PO: Shake oral suspension well before administration.

IV Adminstration:

• pH:
3.5–8.0.

• Intermittent Infusion:

Diluent: Premixed infusions are pre-diluted and ready to use. Do not unwrap until ready to use. Do not administer solution that is cloudy or has a precipitate. Check for leaks by squeezing inner bag. If leaks are found, discard container as unsterile.
Concentration: 2 mg/mL.

• Rate:
Infuse over 1–2 hr. Do not exceed a rate of 200 mg/hr. Pedi: For children receiving doses >6 mg/kg/day, give over 2 hr.

• Y-Site Compatibility:

» acyclovir

» aldesleukin

» alemtuzumab

» alfentanil

» allopurinol

» amifostine

» amikacin

» aminocaproic acid

» aminophylline

» amiodarone

» anidulafungin

» argatroban

» ascorbic acid

» atracurium

» atropine

» aztreonam

» benztropine

» bivalirudin

» bumetanide

» calcium chloride

» caspofungin

» cefazolin

» cefepime

» cefoxitin

» ceftaroline

» cisatracurium

» cisplatin

» cyanocobalamin

» cyclophosphamide

» cyclosporine

» cytarabine

» dactinomycin

» daptomycin

» dexamethasone sodium phosphate

» dexmedetomidine

» diltiazem

» diphenhydramine

» dobutamine

» docetaxel

» dopamine

» doxorubicin liposome

» doxycycline

» droperidol

» enalaprilat

» ephedrine

» epinephrine

» epirubicin

» epoetin alfa

» eptifibatide

» ertapenem

» erythromycin

» esmolol

» etoposide

» etoposide phosphate

» famotidine

» fenoldopam

» fentanyl

» filgrastim

» fludarabine

» fluorouracil

» folic acid

» foscarnet

» ganciclovir

» gemcitabine

» gentamicin

» glycopyrrolate

» granisetron

» heparin

» hydrocortisone

» hydromorphone

» idarubicin

» ifosfamide

» immune globulin IV

» indomethacin

» insulin

» irinotecan

» isoproterenol

» ketorolac

» labetalol

» lansoprazole

» leucovorin

» levofloxacin

» lidocaine

» linezolid

» lorazepam

» magnesium sulfate

» mannitol

» mechlorethamine

» melphanan

» meperidine

» meropenem

» metaraminol

» methotrexate

» methoxamine

» methyldopate

» methylprednisolone sodium succinate

» metoclopramide

» metoprolol

» metronidazole

» midazolam

» milrinone

» mitoxantrone

» morphine

» multivitamins

» mycophenolate

» nafcillin

» nalbuphine

» naloxone

» nesiritide

» nitroglycerin

» nitroprusside

» norepinephrine

» octreotide

» ondansetron

» oxacillin

» oxaliplatin

» oxytocin

» paclitaxel

» palonosetron

» pamidronate

» pancuronium

» papaverine

» pemetrexed

» penicillin G

» pentazocine

» pentobarbital

» phenobarbital

» phentolamine

» phenylephrine

» phytonadione

» piperacillin/tazobactam

» potassium acetate

» potassium chloride

» procainamide

» prochlorperazine

» promethazine

» propofol

» propranolol

» protamine

» pyridoxime

» quinapristin-dalfopristin

» ranitidine

» remifentanil

» rituximab

» rocuronium

» sargramostim

» sodium acetate

» sodium bicarbonate

» streptokinase

» succinylcholine

» sufentanil

» tacrolimus

» telavancin

» teniposide

» theophylline

» thiotepa

» ticarcillin/clavulanate

» tigecycline

» tirofiban

» tobramycin

» tolazoline

» trastuzumab

» trimetaphan

» vancomycin

» vasopressin

» vecuronium

» verapamil

» vincristine

» vinorelbine

» voriconazole

» zidovudine

» zoledronic acid

• Y-Site Incompatibility:

» amphotericin B cholesteryl

» amphotericin B colloidal

» amphotericin B lipid complex

» ampicillin

» dantrolene

» diazepam

» diazoxide

» pantoprazole

» trimethoprim/sulfamethoxazole

Patient/Family Teaching

• Instruct patient to take medication as directed, even if feeling better. Doses should be taken at the same time each day. Take missed doses as soon as remembered, but not if almost time for next dose. Do not double doses.

• Instruct patient to notify health care professional if skin rash, abdominal pain, fever, or diarrhea becomes pronounced, if signs and symptoms of liver dysfunction (unusual fatigue, anorexia, nausea, vomiting, jaundice, dark urine, or pale stools) occur, if unusual bruising or bleeding occur, or if no improvement is seen within a few days of therapy.

Evaluation/Desired Outcomes

• Resolution of clinical and laboratory indications of fungal infections. Full course of therapy may require weeks or months of treatment after resolution of symptoms.

• Prevention of candidiasis in patients who have undergone bone marrow transplantation.

• Decrease in skin irritation and vaginal discomfort in patients with vaginal candidiasis. Diagnosis should be reconfirmed with smears or cultures before a second course of therapy to rule out other pathogens associated with vulvovaginitis. Recurrent vaginal infections may be a sign of systemic illness.