it-tra-KON-a-zole

Therapeutic Classification: antifungals (systemic)

Pharmacologic Classification: azoles

Capsules:

• Treatment of the following fungal infections in immunocompromised or nonimmunocompromised patients:
  • Histoplasmosis,
  • Blastomycosis,
  • Aspergillosis in patients refractory or intolerant to amphotericin B,
  • Onychomycosis of fingernails,
  • Onychomycosis of toenails.

Oral solution:

• Oropharyngeal and esophageal candidiasis.

• Inhibits enzymes necessary for integrity of the fungal cell membrane.

• Fungistatic effects against susceptible organisms.

Spectrum:

• Active against Histoplasma capsulatum, Histoplasma duboisii, Blastomyces dermatitidis, Aspergillus flavus, Aspergillus fumigatus, Candida albicans, and Tinea unguium.

Absorption: Absorption is enhanced by food.

Distribution: Tissue concentrations are higher than plasma concentrations. Does not enter CSF.

Protein Binding: Itraconazole: 99.8%; hydroxyitraconazole: 99.5%.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP3A4 isoenzyme and excreted in feces. Hydroxyitraconazole, the major metabolite, has antifungal activity.

Half-life: 21 hr.

(plasma concentrations)

Contraindicated in:

• Hypersensitivity
• Cross-sensitivity with other azole antifungals (miconazole, ketoconazole) may occur
• Concurrent use of avanafil, dofetilide, disopyramide, dronedarone, eplerenone, ergot alkaloids, felodipine, finerenone, irinotecan, isavuconazonium, ivabradine, lomitapide, lovastatin, lurasidone, methadone, midazolam (PO), nisoldipine, pimozide, quinidine, ranolazine, simvastatin, ticagrelor, triazolam, or voclosporin
• Concurrent use of colchicine, fesoterodine, or solifenacin in patients with varying degrees of hepatic or renal impairment
• Concurrent use of eliglustat in patients who are poor or intermediate CYP2D6 metabolizers or patients taking moderate or strong CYP2D6 inhibitors
• Concurrent use of venetoclax in patients with chronic lymphocytic leukemia or small lymphocytic leukemia during the initiation and ramp-up phase of venetoclax
• HF or other evidence of left ventricular dysfunction.

Use Cautiously in:

• Hepatic impairment (dose ↓ may be required)
• Renal impairment
• Achlorhydria or hypochlorhydria (absorption will be ↓)
• Immunocompromised patients (may have ↓ bioavailability)
• OB: Use for systemic infections during pregnancy only if potential maternal benefit justifies potential fetal risk. Should not be used for treatment of onychomycosis in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Should not be used for treatment of onychomycosis in women of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: ↑risk of hearing loss in older adults.

CV: HF, edema, hypertension.

Derm: photosensitivity, pruritus, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: hearing loss, tinnitus.

Endo: adrenal insufficiency.

F and E: hypokalemia.

GI: nausea, abdominal pain, anorexia, diarrhea, flatulence, HEPATOTOXICITY, vomiting.

GU: ↓libido, albuminuria, erectile dysfunction.

MS: RHABDOMYOLYSIS.

Neuro: dizziness, drowsiness, fatigue, headache, malaise, neuropathy.
Misc: fever, (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• ↑risk of potentially fatal arrhythmias with quinidine, dofetilide, methadone, disopyramide, dronedarone, or pimozide; concurrent use contraindicated.
• ↑risk of excessive sedation with midazolam (PO) or triazolam; concurrent use contraindicated.
• ↑risk of adverse CNS reactions with pimozide; concurrent use contraindicated.
• ↑risk of myopathy with lomitapide, simvastatin, or lovastatin; concurrent use contraindicated.
• ↑risk of vasoconstriction with ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine); concurrent use contraindicated.
• Significantly ↑ avanafil, nisoldipine, felodipine, isavuconazonium, lurasidone, ranolazine, eplerenone, finerenone, voclosporin, and irinotecan levels; concurrent use contraindicated.
• Significantly ↑ colchicine, fesoterodine, and solifenacin levels in patients with varying degrees of hepatic or renal impairment; concurrent use contraindicated.
• Significantly ↑ eliglustat levels in patients who are poor or intermediate CYP2D6 metabolizers or those taking moderate or strong CYP2D6 inhibitors; concurrent use contraindicated.
• ↑risk of bradycardia and heart block with ivabradine; concurrent use contraindicated.
• ↑risk of tumor lysis syndrome with venetoclax during initiation and ramp-up phase of venetoclax in patients with chronic lymphocytic leukemia or small lymphocytic leukemia; concurrent use during these dosing phases contraindicated.
• May also ↑ levels and the risk of toxicity from alprazolam, aripiprazole, atorvastatin, axitinib, bortezomib, budesonide, buspirone, busulfan, carbamazepine, cariprazine, cilostazol, clarithromycin, cobicistat, cyclosporine, dabrafenib, dasatinib, dexamethasone, diazepam, digoxin, docetaxel, elbasvir/grazoprevir, eletriptan, entrectinib, erlotinib, erythromycin, fentanyl, fluticasone, gefitinib, glecaprevir/pibrentasvir, haloperidol, ibrutinib, imatinib, ivacaftor, ixabepilone, lapatinib, lumacaftor/ivacaftor, methylprednisolone, midazolam, mobocertinib, nilotinib, oral hypoglycemic agents, pemigatinib, ponatinib, quetiapine, ramelteon, rifabutin, risperidone, ritonavir, sirolimus, sunitinib, suvorexant, tacrolimus, talazoparib, tenofovir disoproxil fumarate, trabectedin, tretinoin (oral), vinca alkaloids, and warfarin.
• May ↑ levels and the negative inotropic effects of calcium channel blockers.
• Absorption of tablets, 200-mg capsules, and oral solution ↓ by antacids, H₂ blockers, sucralfate, proton pump inhibitors, or other agents that increase gastric pH (take 1 hr before or 2 hr after itraconazole).
• Antacids, histamine H₂ blockers, sucralfate, proton pump inhibitors, or other agents that ↑ gastric pH may ↑ levels of 65-mg capsules; may need to ↓ itraconazole dose.
• Phenytoin, phenobarbital, nevirapine, isoniazid, rifampin, rifabutin, efavirenz, and carbamazepine may ↓ levels and effectiveness; ↑ itraconazole dose.
• If hypokalemia occurs, the risk of digoxin toxicity is ↑.

Drug-Food:

• Food↑ absorption.

Aspergillosis

• PO (Adults): 200 mg once or twice daily for 3 mo OR 130 mg once or twice daily for 3 mo.

Blastomycosis, Histoplasmosis

• PO (Adults): 200 mg once daily; may be ↑ by 100 mg/day up to 200 mg twice daily; continue therapy for 3 mo; OR 130 mg once daily; may be ↑ by 65 mg/day up to 130 mg twice daily; continue therapy for 3 mo.

Onychomycosis

• PO (Adults): Toenail fungus: 200 mg once daily for 12 consecutive wk. Fingernail fungus: 200 mg twice daily for 1 wk, then 3 wk without therapy, then 200 mg twice daily an additional wk–6 mo.

Candidiasis

• PO (Adults): Oropharyngeal candidiasis: 200 mg (20 mL) daily for 1–2 wk. Oropharyngeal candidiasis unresponsive to fluconazole: 100 mg (10 mL) twice daily for at least 2–4 wk. Esophageal candidiasis: 100 mg (10 mL) once daily for at least 3 wk.

(Generic available)

• Capsules: 65 mg; 100 mg;
• Oral solution (cherry caramel): 10 mg/mL;

• Assess for signs and symptoms of infection (elevated WBC, fever, rhonchi/congestion, cough/sputum) before and periodically during therapy.
• Obtain specimens for culture before instituting therapy. Therapy may be started before results are obtained.
• Assess for signs and symptoms of hypersensitivity reactions (fever, malaise, fatigue, muscle or joint aches, skin pain or rash, blisters, peeling, oral lesions, conjunctivitis). Discontinue therapy and provide supportive care.
• Assess for signs and symptoms of HF and/or left ventricular dysfunction (dyspnea, rales, peripheral edema, weight gain). If signs and/or symptoms of HF occur, discontinue therapy.
• Monitor for signs and symptoms of hepatic impairment (abnormal LFTs, jaundice, fatigue, dark urine, pale stools) or pancreatitis (abdominal pain, nausea, vomiting); discontinue if severe and provide supportive care.
• Monitor for symptoms of peripheral neuropathy (numbness/tingling in hands and feet) or hearing loss. If symptoms develop, discontinue therapy.

• Verify negative pregnancy test before starting therapy.
• Monitor LFTs and bilirubin before and periodically during therapy, especially in patients with pre-existing hepatic impairments. Discontinue if abnormal values persist or worsen.
  • Monitor serum potassium. May cause hypokalemia.

• Do not interchange capsules and oral solution. Only oral solution is effective for oropharyngeal candidiasis. Oral solution is not recommended for initial treatment of patients at risk for systemic candidiasis.
• Administer with a full meal to minimize nausea and vomiting and to increase absorption.
  • Do not administer with antacids or other medications that may increase gastric pH; may decrease absorption of itraconazole.
• PO: Administer capsules with food, preferably a full meal.DNC: Swallow capsules whole; do not chew, crush, or break capsules. Do not interchange with other itraconazole products.
• Oral Solution: Administer without food if possible. Swish solution in mouth vigorously, 10 mL at a time, for several seconds; then swallow.

• Explain purpose and side effects of isavuconazonium to patient. Instruct patient to take medication as directed, even if feeling better. Doses should be taken at the same time each day. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• May occasionally cause drowsiness, dizziness, or blurred vision. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional immediately if signs and symptoms of liver dysfunction (unusual fatigue, ↓ appetite, nausea, vomiting, jaundice, dark urine, or pale stools), HF (shortness of breath, swelling, weight gain), or peripheral neuropathy (numbness/tingling in hands feet) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise patient to use sunscreen and wear protective clothing to prevent photosensitivity reactions.
• May cause hearing loss; usually resolves when treatment is stopped, but can persist. Advise patient to discontinue therapy and notify health care professional if any hearing loss symptoms occur.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and for 2 mo after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected.

• Resolution of clinical and laboratory indications of fungal infections. Minimal treatment for systemic fungal infections is 3 mo. Inadequate period of treatment may lead to recurrence of active infection.

Onmel, Sporanox, Tolsura