it-tra-KON-a-zole

Capsules:

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

Oral solution:

• Treatment of 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; enters breast milk.

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.

Contraindicated in:

• Hypersensitivity
• Cross-sensitivity with other azole antifungals (miconazole, ketoconazole) may occur
• Concurrent use of avanafil, quinidine, dofetilide, disopyramide, dronedarone, pimozide, midazolam (PO), triazolam, ranolazine, eplerenone, irinotecan. isavuconazonium, lomitapide, ivabradine, lurasidone, felodipine, nisoldipine, ergot alkaloids, methadone, simvastatin, lovastatin, ticagrelor
• Concurrent use of colchicine, fesoterodine, and 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
• 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: Congenital abnormalities have occurred; should not be used for treatment of onychomycosis in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Rep: 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.

CV: HF, edema, hypertension.

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

EENT: hearing loss, tinnitus.

Endo: adrenal insufficiency.

F and E: hypokalemia.

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

GU: albuminuria, ↓ libido, erectile dysfunction.

MS: rhabdomyolysis.

Neuro: dizziness, drowsiness, fatigue, headache, malaise, neuropathy.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), fever.

Drug-Drug:

• Itraconazole is a potent inhibitor of the CYP450 3A4 hepatic enzyme, which can ↑ blood levels and effects of other drugs which are metabolized by this system.
• ↑risk of potentially fatal arrhythmias with quinidine, dofetilide, methadone, disopyramide, dronedarone, or pimozide (concurrent use is contraindicated and may result in QTc prolongation, torsades de pointes, ventricular arrhythmias, and sudden death).
• ↑risk of excessive sedation with midazolam (PO) or triazolam; concurrent use is contraindicated.
• ↑risk of adverse CNS reactions with pimozide; concurrent use is contraindicated.
• ↑risk of myopathy with lomitapide, simvastatin or lovastatin; concurrent use contraindicated.
• ↑risk of vasoconstriction with ergot alkaloids, (dihydroergotamine, ergotamine, methylergonovine); concurrent use is contraindicated.
• Significantly ↑ avanafil, nisoldipine, felodipine, isavuconazonium, lurasidone, ranolazine, eplerenone, 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 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.
• May also ↑ blood 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, erlotinib, erythromycin, fentanyl, fluticasone, gefitinib, glecaprevir/pibrentasvir, haloperidol, ibrutinib, imatinib, indinavir, ivacaftor, ixabepilone, lapatinib, lumacaftor/ivacaftor, methylprednisolone, midazolam, nilotinib, ombitasvir/paritaprevir/ritonavir, oral hypoglycemic agents, ponatinib, quetiapine, ramelteon, rifabutin, risperidone, ritonavir, saquinavir, sirolimus, sunitinib, suvorexant, tacrolimus, tenofovir disoproxil fumarate, trabectedin, trimetrexate, vinca alkaloids, andwarfarin.
• May ↑ levels and the negative inotropic effects of calcium channel blockers.
• Absorption of tablets, 200–mg capsules, and oral solution ↓ by antacids, histamine H₂ blockers, sucralfate, proton pump inhibitors, or other agents that increase gastric pH, including the buffer in didanosine (take at least 1 hr before or 2 hr after itraconazole).
• Antacids, histamine H₂ blockers, sucralfate, proton pump inhibitors, or other agents that increase gastric pH may ↑ levels of 65–mg capsules; may need to ↓ itraconazole dose.
• Phenytoin, phenobarbital, nevirapine, isoniazid, rifampin, rifabutin, efavirenz, and carbamazepine↑ metabolism and ↓ blood levels (↑ dosage may be necessary).
• 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.

• 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.

Onmel, Sporanox, Tolsura

Therapeutic Classification: antifungals (systemic)

(Generic available)

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

(blood levels)

• Assess for signs and symptoms of infection (vital signs, lung sounds, sputum, WBC, oral and pharyngeal mucosa, nail beds) before and periodically during therapy.
• Obtain specimens for culture before instituting therapy. Therapy may be started before results are obtained.
• Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

• Monitor hepatic function tests before and periodically during therapy, especially in patients with pre-existing hepatic function abnormalities. Discontinue itraconazole if abnormal values persist or worsen.
  • Monitor serum potassium. May cause hypokalemia.

• 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, anorexia, nausea, vomiting, jaundice, dark urine, or pale stools) or HF (dyspnea, peripheral edema, weight gain) 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.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during 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.

NDC Code^*

• 0259- Merz Pharmaceuticals, LLC
  • 0259-1420- Onmel
    • 0259-1420-28- 2 BLISTER PACK in 1 CARTON (0259-1420-28) > 14 TABLET in 1 BLISTER PACK (0259-1420-14)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-5100- Itraconazole
    • 0378-5100-93- 30 CAPSULE in 1 BOTTLE, PLASTIC (0378-5100-93)

• 10147- Patriot Pharmaceuticals, LLC
  • 10147-0150- itraconazole
    • 10147-0150-1- 150 mL in 1 BOTTLE (10147-0150-1)

• 10147- Patriot Pharmaceuticals
  • 10147-1700- itraconazole
    • 10147-1700-3- 30 CAPSULE in 1 BOTTLE (10147-1700-3)

• 10147- Patriot Pharmaceuticals
  • 10147-1700- itraconazole
    • 10147-1700-7- 7 POUCH in 1 DOSE PACK (10147-1700-7) > 1 BLISTER PACK in 1 POUCH > 4 CAPSULE in 1 BLISTER PACK

• 13668- Torrent Pharmaceuticals Limited
  • 13668-463- Itraconazole
    • 13668-463-05- 500 CAPSULE in 1 BOTTLE (13668-463-05)

• 13668- Torrent Pharmaceuticals Limited
  • 13668-463- Itraconazole
    • 13668-463-30- 30 CAPSULE in 1 BOTTLE (13668-463-30)

• 13668- Torrent Pharmaceuticals Limited
  • 13668-463- Itraconazole
    • 13668-463-37- 28 CAPSULE in 1 CARTON (13668-463-37)

• 13668- Torrent Pharmaceuticals Limited
  • 13668-463- Itraconazole
    • 13668-463-90- 90 CAPSULE in 1 BOTTLE (13668-463-90)

• 13668- Torrent Pharmaceuticals Limited
  • 13668-463- Itraconazole
    • 13668-463-98- 4 CAPSULE in 1 BLISTER PACK (13668-463-98)

• 16714- NorthStar RxLLC
  • 16714-743- Itraconazole
    • 16714-743-01- 7 BLISTER PACK in 1 CARTON (16714-743-01) > 4 CAPSULE, COATED PELLETS in 1 BLISTER PACK

• 16714- NorthStar RxLLC
  • 16714-743- Itraconazole
    • 16714-743-02- 30 CAPSULE, COATED PELLETS in 1 BOTTLE (16714-743-02)

• 16729- Accord Healthcare Inc.
  • 16729-271- Itraconazole
    • 16729-271-10- 30 CAPSULE in 1 BOTTLE (16729-271-10)

• 46708- Alembic Pharmaceuticals Limited
  • 46708-204- ITRACONAZOLE
    • 46708-204-04- 28 CAPSULE in 1 CARTON (46708-204-04)

• 46708- Alembic Pharmaceuticals Limited
  • 46708-204- ITRACONAZOLE
    • 46708-204-10- 100 CAPSULE in 1 CARTON (46708-204-10)

• 46708- Alembic Pharmaceuticals Limited
  • 46708-204- ITRACONAZOLE
    • 46708-204-30- 30 CAPSULE in 1 BOTTLE (46708-204-30)

• 46708- Alembic Pharmaceuticals Limited
  • 46708-204- ITRACONAZOLE
    • 46708-204-71- 500 CAPSULE in 1 BOTTLE (46708-204-71)

• 46708- Alembic Pharmaceuticals Limited
  • 46708-204- ITRACONAZOLE
    • 46708-204-90- 90 CAPSULE in 1 BOTTLE (46708-204-90)

• 49884- Par Pharmaceutical, Inc.
  • 49884-239- Itraconazole
    • 49884-239-11- 30 CAPSULE in 1 BOTTLE (49884-239-11)

• 50268- AvPAK
  • 50268-450- Itraconazole
    • 50268-450-12- 20 BLISTER PACK in 1 BOX, UNIT-DOSE (50268-450-12) > 1 CAPSULE in 1 BLISTER PACK (50268-450-11)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-290- SPORANOX
    • 50458-290-01- 3 BLISTER PACK in 1 CARTON (50458-290-01) > 10 CAPSULE in 1 BLISTER PACK

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-290- SPORANOX
    • 50458-290-04- 30 CAPSULE in 1 BOTTLE (50458-290-04)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-290- SPORANOX
    • 50458-290-28- 7 POUCH in 1 DOSE PACK (50458-290-28) > 1 BLISTER PACK in 1 POUCH > 4 CAPSULE in 1 BLISTER PACK

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-295- SPORANOX
    • 50458-295-15- 150 mL in 1 BOTTLE (50458-295-15)

• 51862- Mayne Pharma Inc.
  • 51862-462- Tolsura
    • 51862-462-60- 60 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (51862-462-60)

• 60687- American Health Packaging
  • 60687-299- Itraconazole
    • 60687-299-25- 30 BLISTER PACK in 1 BOX, UNIT-DOSE (60687-299-25) > 1 CAPSULE in 1 BLISTER PACK (60687-299-95)

• 62332- Alembic Pharmaceuticals Inc.
  • 62332-204- ITRACONAZOLE
    • 62332-204-04- 28 CAPSULE in 1 CARTON (62332-204-04)

• 62332- Alembic Pharmaceuticals Inc.
  • 62332-204- ITRACONAZOLE
    • 62332-204-10- 100 CAPSULE in 1 CARTON (62332-204-10)

• 62332- Alembic Pharmaceuticals Inc.
  • 62332-204- ITRACONAZOLE
    • 62332-204-30- 30 CAPSULE in 1 BOTTLE (62332-204-30)

• 62332- Alembic Pharmaceuticals Inc.
  • 62332-204- ITRACONAZOLE
    • 62332-204-71- 500 CAPSULE in 1 BOTTLE (62332-204-71)

• 62332- Alembic Pharmaceuticals Inc.
  • 62332-204- ITRACONAZOLE
    • 62332-204-90- 90 CAPSULE in 1 BOTTLE (62332-204-90)

• 63629- Bryant Ranch Prepack
  • 63629-8168- Itraconazole
    • 63629-8168-1- 30 CAPSULE, COATED PELLETS in 1 BOTTLE (63629-8168-1)

• 65162- Amneal Pharmaceuticals LLC
  • 65162-087- Itraconazole
    • 65162-087-74- 150 mL in 1 BOTTLE, GLASS (65162-087-74)

• 65162- Amneal Pharmaceuticals LLC
  • 65162-630- Itraconazole
    • 65162-630-03- 30 CAPSULE in 1 BOTTLE (65162-630-03)

• 67877- Ascend Laboratories, LLC
  • 67877-454- Itraconazole
    • 67877-454-05- 500 CAPSULE, COATED PELLETS in 1 BOTTLE (67877-454-05)

• 67877- Ascend Laboratories, LLC
  • 67877-454- Itraconazole
    • 67877-454-30- 30 CAPSULE, COATED PELLETS in 1 BOTTLE (67877-454-30)

• 67877- Ascend Laboratories, LLC
  • 67877-454- Itraconazole
    • 67877-454-84- 3 BLISTER PACK in 1 CARTON (67877-454-84) > 10 CAPSULE, COATED PELLETS in 1 BLISTER PACK (67877-454-33)

• 67877- Ascend Laboratories, LLC
  • 67877-454- Itraconazole
    • 67877-454-90- 90 CAPSULE, COATED PELLETS in 1 BOTTLE (67877-454-90)

• 68382- Zydus Pharmaceuticals (USA) Inc.
  • 68382-697- itraconazole
    • 68382-697-01- 100 CAPSULE in 1 BOTTLE (68382-697-01)

• 68382- Zydus Pharmaceuticals (USA) Inc.
  • 68382-697- itraconazole
    • 68382-697-06- 30 CAPSULE in 1 BOTTLE (68382-697-06)

• 68382- Zydus Pharmaceuticals (USA) Inc.
  • 68382-697- itraconazole
    • 68382-697-10- 1000 CAPSULE in 1 BOTTLE (68382-697-10)

• 68382- Zydus Pharmaceuticals (USA) Inc.
  • 68382-697- itraconazole
    • 68382-697-77- 10 BLISTER PACK in 1 CARTON (68382-697-77) > 10 CAPSULE in 1 BLISTER PACK (68382-697-30)

• 70771- Cadila Healthcare Limited
  • 70771-1208- itraconazole
    • 70771-1208-0- 1000 CAPSULE in 1 BOTTLE (70771-1208-0)

• 70771- Cadila Healthcare Limited
  • 70771-1208- itraconazole
    • 70771-1208-1- 100 CAPSULE in 1 BOTTLE (70771-1208-1)

• 70771- Cadila Healthcare Limited
  • 70771-1208- itraconazole
    • 70771-1208-3- 30 CAPSULE in 1 BOTTLE (70771-1208-3)

• 70771- Cadila Healthcare Limited
  • 70771-1208- itraconazole
    • 70771-1208-4- 10 BLISTER PACK in 1 CARTON (70771-1208-4) > 10 CAPSULE in 1 BLISTER PACK (70771-1208-2)