Itraconazole

A to Z Drug Facts

 Action Inhibits synthesis of ergosterol, which is a vital component of fungal cell membranes. Also inhibits endogenous respiration, causes accumulation of phospholipids and unsaturated fatty acids within fungal cells, and disrupts chitin synthesis.

 Indications

Capsules/Injection: Treatment of blastomycosis, aspergillosis, and histoplasmosis fungal infections. Capsules: Treatment of onychomycosis of the toenail or fingernail due to dermatophytes in nonimmunocompromised patients. Oral solution: Treatment of oropharyngeal and esophageal candidiasis. Unlabeled use(s): Treatment of other fungal infections (superficial mycoses [eg, dermatophytoses]; systemic mycoses [eg, candidiasis, cryptococcus]; and miscellaneous fungal infections [eg, SC mycoses, cutaneous Leishmaniasis]).

 Contraindications Coadministration with pimozide, quinidine, triazolam, or oral midazolam, HMG-CoA reductase inhibitors metabolized by the P450 3A enzyme system (eg, lovastatin, simvastatin); not for treatment of onychomycosis in pregnant women or women contemplating pregnancy.

 Route/Dosage

Blastomycosis, aspergillosis, histoplasmosis

ADULTS: PO 200 to 400 mg/day. Give doses > 200 mg in 2 divided doses. IV 200 mg bid for 4 doses, followed by 200 mg/day. Infuse over 1 hour. Continue IV for 14 days followed by PO for ³ 3 months and until clinical parameters and laboratory tests indicate active fungal infection has subsided. An inadequate treatment period may lead to recurrence.

Life-threatening situations

PO Give loading dose of 200 mg tid for 3 days. Continue treatment for ³ 3 months and until clinical parameters and laboratory tests indicate active fungal infection has subsided. Inadequate period of treatment may lead to recurrence.

Onychomycosis, toenails with or without fingernail involvement

ADULTS: PO 200 mg/day for 12 consecutive weeks.

Onychomycosis, fingernails only

ADULTS: PO 2 treatment pulses separated by a 3-week period without itraconazole. Each pulse consisting of 200 mg bid for 1 week.

Oropharyngeal candidiasis

ADULTS: PO, oral solution 200 mg (20 ml)/day for 1 to 2 weeks. For patients unresponsive to treatment with fluconazole tablets, 100 mg (10 ml) bid.

Esophageal candidiasis

ADULTS: PO, oral solution 100 to 200 mg/day (10 to 20 ml) for a minimum of 3 weeks. Continue treatment for 2 weeks following resolution of symptoms.

 Interactions

Buspirone: May elevate buspirone plasma concentrations. Adjust buspirone dose as needed. Calcium blockers (eg, amlodipine, felodipine, nifedipine): Edema has occurred with concomitant dihydropyridine calcium blockers. Cyclosporine plus HMG-CoA reductase inhibitors: There are rare reports of rhabdomyolysis in renal transplant patients receiving this drug combination. Increased cyclosporine levels may occur. Monitor cyclosporine levels; reduce cyclosporine dose by 50% when using itraconazole doses > 100 mg/day. Didanosine: May decrease therapeutic effects of itraconazole. Administer itraconazole ³ 2 hours before didanosine. Digoxin: Increased digoxin levels. Monitor frequently. H₂-antagonists: Reduced plasma itraconazole levels. Hypoglycemic agents: Hypoglycemia may occur. Monitor blood glucose. Midazolam (oral), triazolam: Elevated plasma levels of these drugs; may potentiate and prolong their hypnotic and sedative effects. Sedative effects of parenteral midazolam may be prolonged. Oral contraceptives: Efficacy may be reduced by itraconazole. Phenytoin: Reduced plasma itraconazole levels; altered phenytoin metabolism. Pimozide, quinidine: Increased levels may result in life-threatening cardiac dysrhythmias and death. Do not use with itraconazole. Rifampin: Decreased itraconazole levels with decreased effectiveness. Sulfonylurea: Hypoglycemia may occur. Tacrolimus: Increased tacrolimus plasma concentrations. Warfarin: Increased warfarin levels with possible bleeding.

 Lab Test Interferences None well documented.

 Adverse Reactions

OTHER: Incidence and type of reactions vary depending on usage and route of administration. CV: Hypertension; orthostatic hypotension; vasculitis. CNS: Headache; dizziness; decreased libido; somnolence; vertigo; anxiety; depression; abnormal dreaming. DERM: Rash; pruritus; increased sweating. GI: Nausea; vomiting; diarrhea; abdominal pain; anorexia; flatulence; constipation; dyspepsia; gingivitis; ulcerative stomatitis; gastritis; gastroenteritis; increased appetite; general GI disorders. GU: Impotence; albuminuria; cystitis; abnormal renal function; menstrual disorders. HEPA: Abnormal liver function; elevated liver enzyme; bilirubinemia; ALT increased; hepatic function abnormal; jaundice; AST increased. META: Hypokalemia; alkaline phosphatase increased; BUN increased; hypomagnesemia. RESP: Coughing; dyspnea; pneumonia; sinusitis; sputum increased; rhinitis; upper respiratory tract infection; pharyngitis. OTHER: Edema; fatigue; fever; malaise; myalgia; bursitis; pain; injury; chest pain; back pain; pneumocystis-carinii infection; herpes zoster; application site reaction; vein disorder; asthenia; tremor; hypertriglyceridemia.

 Precautions

Pregnancy: Category C. Lactation: Excreted in breast milk. Weigh benefits to mother against potential risk to infant. Children: Safety and efficacy not established. Patients 6 mo to 16 yr of age have been treated with no serious adverse effects reported; however, the long-term effect in children is unknown. Hepatitis: Rare cases of hepatitis have been reported. HIV-infected patients: Absorption may be decreased in HIV-infected individuals with hypochlorhydria. Renal function impairment: Do not use injection in patients with severe renal dysfunction (creatinine clearance < 30 ml/min).

 Administration/Storage

• Do not use capsules and oral solution interchangeably.
• Administer capsules after a full meal to increase absorption; administer oral solution without food.
• For injection, use only the components provided in the kit; do not substitute. Not for IV bolus injection.
• Use only a dedicated infusion line for administration. Do not introduce concomitant medication in the same bag or through the same line.
• Add the full contents (25 ml) of the ampule into the infusion bag provided.
• Store at room temperature. Protect from light and freezing. Refrigerate the reconstituted injection or store at room temperature for up to 48 hr.

 Assessment/Interventions

• Obtain patient history, including drug history and any allergies.
• Ensure that fungal cultures have been obtained before beginning therapy.
• Obtain baseline liver function test results. Ensure that liver function tests are performed 2 wk after initial administration. In patients receiving extended drug therapy, repeat these tests at routine intervals to monitor for signs of liver dysfunction.
• Monitor potassium levels after initial administration and repeat routinely with extended therapy.
• Notify physician if appetite loss, nausea, vomiting, sleeplessness, signs of liver dysfunction, dark urine, jaundice, or pruritus occur.
• Report decreased potassium levels to physician and give appropriate supplements as prescribed.

 Patient/Family Education

• Instruct patient to take drug with or without food, depending on doseform.
• Tell patient to report the following symptoms to the physician: Nausea, vomiting, diarrhea, headache, rash, swelling, fever, itching, dizziness, inability to sleep, yellowing skin, pale stools, or dark urine.
• Instruct patient to notify physician of any medication change.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts