Diflucan

Action

Alters cellular membrane, increasing permeability and leakage of essential elements needed for fungal growth. At higher concentrations, may be fungicidal.

Availability

Injection: 2 mg/ml in 100- or 200-ml bottles or containers

Powder for oral suspension: 50 mg/5 ml in 35-ml bottle, 200 mg/5 ml in 35-ml bottle

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

Indications and dosages

➣ Oropharyngeal candidiasis

Adults: 200 mg P.O. or I.V. on first day, followed by 100 mg/day for at least 2 weeks

Children: 6 mg/kg P.O. or I.V. on first day, followed by 3 mg/kg/day for at least 2 weeks

➣ Esophageal candidiasis

Adults: 200 mg P.O. or I.V. on first day, followed by 100 mg/day for 3 weeks and then for 2 weeks after symptom resolution. Up to 400 mg/day may be used in severe cases.

Children: 6 mg/kg P.O. or I.V. on first day, followed by 3 mg/kg/day for 3 weeks and for at least 2 weeks after symptom resolution

➣ Candidal urinary tract infection; peritonitis

Adults: 50 to 200 mg P.O. or I.V. daily

➣ Systemic candidiasis

Adults: 400 mg P.O. or I.V. on first day, followed by 200 mg/day for 4 weeks and for at least 2 weeks after symptom resolution

Children: 6 to 12 mg/kg/day P.O. or I.V.

➣ Vaginal candidiasis

Adults: 150 mg P.O. as a single dose

➣ Cryptococcal meningitis

Adults: 400 mg P.O. or I.V. on first day, followed by 200 or 400 mg/day for 10 to 12 weeks after cerebrospinal fluid (CSF) is negative

Children: 12 mg/kg P.O. or I.V. on first day, followed by 6 mg/kg/day for 10 to 12 weeks after CSF is negative

➣ Suppression of cryptococcal meningitis in patients with AIDS

Adults: 200 mg/day P.O. or I.V.

➣ To prevent candidiasis after bone marrow transplantation

Adults: 400 mg/day P.O. or I.V. for several days before and 7 days after neutrophil count rises above 1,000 cells/mm³

Dosage adjustment

• Renal impairment

• Elderly patients

Contraindications

• Hypersensitivity to drug or its components

• Concurrent use of terfenadine (not available in U.S.) in patients receiving fluconazole at multiple doses of 400 mg or higher and other drugs known to prolong QT interval and that are metabolized via CYP3A4, such as cisapride, astemizole (not available in U.S.), pimozide, and quinidine

Precautions

Use cautiously in:

• hypersensitivity to other azole antifungals

• renal impairment or hepatic disease

• potentially proarrhythmic conditions

• concurrent use of erythromycin because of potential for increased risk of prolonged QT interval, torsades de pointes, and consequently sudden death (avoid use)

• pregnant or breastfeeding patients

• children younger than 6 months.

Administration

☞ Limit single I.V. infusion to 200 mg/hour or less, using infusion pump.

• Don't piggyback with other I.V. infusions.

• Keep overwrap on I.V. bag until just before use.

• Know that plastic container may be opaque (from moisture absorbed during sterilization). This doesn't affect drug and will decrease over time.

• Be aware that powder for oral suspension contains sucrose and shouldn't be used in patients with hereditary fructose intolerance, glucose-galactose malabsorption, and sucrase-isomaltase deficiency.

Adverse reactions

CNS: headache, dizziness

CV: QT interval prolongation, torsades de pointes

GI: nausea, vomiting, diarrhea, dyspepsia, abdominal discomfort

Hematologic: leukopenia, thrombocytopenia

Hepatic: hepatotoxicity

Skin: rash, pruritus, exfoliative skin disorders (including Stevens-Johnson syndrome)

Other: altered taste, anaphylaxis

Interactions

Drug-drug. Alfentanil, cyclosporine, phenytoin, rifabutin, tacrolimus, theophylline, zidovudine: increased blood levels of these drugs, greater risk of toxicity

Benzodiazepines, buspirone, losartan, nisoldipine, tricyclic antidepressants, zolpidem: increased blood levels and effects of these drugs

CYP3A4 inducers: inhibited CYP3A4 enzyme system, altered actions of CYP3A4 inducers (with fluconazole dosages above 200 mg/day)

Glipizide, glyburide, tolbutamide: increased hypoglycemic effect of these drugs

Rifampin: increased rifampin blood level, decreased fluconazole blood level

Thiazide diuretics: increased fluconazole blood level

Warfarin: increased warfarin activity

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, bilirubin, gamma-glutamyltransferase, hepatic enzymes: increased levels

Platelets, white blood cells: decreased counts

Patient monitoring

☞ Stay alert for signs and symptoms of anaphylaxis. Stop drug immediately if these occur.

☞ Monitor liver function test results and hematologic studies; discontinue drug if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole.

☞ Assess for rash; if lesions develop, monitor patient. Stop drug and notify prescriber if lesions progress (may signal Stevens-Johnson syndrome).

• Be aware that patients with human immunodeficiency virus have greater risk of adverse reactions.

Patient teaching

☞ Teach patient how to recognize and immediately report signs and symptoms of allergic response.

• Urge patient to contact prescriber if rash occurs, to determine whether Stevens-Johnson syndrome is developing.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Advise patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.

• Tell female patient to inform prescriber if she is pregnant or breastfeeding.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.