|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(i tra KOE na zole)
Generic Available (U.S.)
Yes: Capsule
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral capsules: Treatment of susceptible fungal infections in immunocompromised and immunocompetent patients including blastomycosis and histoplasmosis; indicated for aspergillosis (in patients intolerant/refractory to amphotericin B), and onychomycosis of the toenail and fingernail (in nonimmunocompromised patients)
Oral solution: Treatment of oral and esophageal candidiasis
Use: Dental
Treatment of susceptible fungal infections in immunocompromised and immunocompetent patients including blastomycosis and histoplasmosis; has activity against Aspergillus, Candida, Coccidioides, Cryptococcus, Sporothrix, and chromomycosis. Useful in superficial mycoses including dermatophytoses (eg, tinea capitis), pityriasis versicolor, sebopsoriasis, vaginal and chronic mucocutaneous candidiases; systemic mycoses including candidiasis, meningeal and disseminated cryptococcal infections, paracoccidioidomycosis, coccidioidomycoses; miscellaneous mycoses such as sporotrichosis, chromomycosis, leishmaniasis, fungal keratitis, alternariosis, zygomycosis.
Pregnancy Risk Factor
C
Pregnancy Considerations
Should not be used to treat onychomycosis during pregnancy. Effective contraception should be used during treatment and for 2 months following treatment. Congenital abnormalities have been reported during postmarketing surveillance, but a causal relationship has not been established.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to itraconazole (use caution in patients with a history of hypersensitivity to other azoles), any component of the formulation; concurrent administration with cisapride, dofetilide, ergot derivatives, levomethadyl, lovastatin, midazolam (oral), nisoldipine, pimozide, quinidine, simvastatin, or triazolam; treatment of onychomycosis (or other non-life-threatening indications) in patients with evidence of ventricular dysfunction, heart failure (HF) or a history of HF; treatment of onychomycosis in patients who are pregnant or intend on becoming pregnant
Warnings/Precautions
Boxed warnings:
• Heart failure: See “Concerns related to adverse effects”
• High potential for interactions: See “Concurrent drug therapy issues” below.
• Onychomycosis: See “Disease-related concerns” below.
Concerns related to adverse effects:
• Hearing loss: Transient or permanent hearing loss has been reported. Quinidine (a contraindicated drug) was used concurrently in several of these cases. Hearing loss usually resolves after discontinuation, but may persist in some patients.
• Heart failure:[U.S. Boxed Warning]: Negative inotropic effects have been observed following intravenous administration. Discontinue or reassess use if signs or symptoms of heart failure (HF) occur during treatment. CHF has been reported, particularly in patients receiving a total daily oral dose of 400 mg. Use with caution in patients with risk factors for HF (COPD, renal failure, edematous disorders, ischemic or valvular disease).
• Hepatotoxicity: Rare cases of serious hepatotoxicity (including liver failure and death) have been reported (including some cases occurring within the first week of therapy); hepatotoxicity was reported in some patients without pre-existing liver disease or risk factors. Use with caution in patients with pre-existing hepatic impairment; monitor liver function closely and dosage adjustment may be warranted. Not recommended for use in patients with active liver disease, elevated liver enzymes, or prior hepatotoxic reactions to other drugs unless the expected benefit exceeds the risk of hepatotoxicity.
• Neuropathy: Discontinue if signs or symptoms of neuropathy occurs during treatment.
Disease-related concerns:
• Cystic fibrosis: Large differences in itraconazole pharmacokinetic parameters have been observed in cystic fibrosis patients receiving the solution; if a patient with cystic fibrosis does not respond to therapy, alternate therapies should be considered.
• Onychomycosis: [U.S. Boxed Warning]: Not recommended for treatment of onychomycosis in patients with ventricular dysfunction or a history of HF.
• Renal impairment: Use with caution in patients with renal impairment; limited information is available.
Concurrent drug therapy issues:
• Calcium channel blockers (CCBs): May cause additive negative inotropic effects when used concurrently with itraconazole. Itraconazole may also inhibit the metabolism of CCBs. Therefore, use caution with concurrent use of itraconazole and CCBs due to an increased risk of heart failure. Concurrent use of itraconazole and nisoldipine is contraindicated.
• High potential for interactions: [U.S. Boxed Warning]: Serious cardiovascular adverse events including, QT prolongation, ventricular tachycardia, torsade de pointes, cardiac arrest and/or sudden death have been observed due to increased cisapride, pimozide, quinidine, dofetilide or levomethadyl concentrations induced by itraconazole; concurrent use contraindicated. Additionally, the following drugs metabolized by the CYP 3A4 isoenzyme system are also contraindicated: Ergot derivatives, lovastatin, midazolam (oral), simvastatin, and triazolam.
Dosage form specific issues:
• Oral/esophageal candidiasis: Only the oral solution has proven efficacy; mucosal exposure may vary between the oral solution and capsules
• Oral solution: Initiation of treatment with oral solution is not recommended in patients at immediate risk for systemic candidiasis (eg, patients with severe neutropenia).
• Product interchangeability: Due to differences in bioavailability, oral capsules and oral solution cannot be used interchangeably.
Adverse Reactions
>10%: Gastrointestinal: Nausea (11%), diarrhea (3% to 11%)
1% to 10%:
Cardiovascular: Edema (4%), hypertension (3%), chest pain (3%)
Central nervous system: Fever (3% to 7%), headache (4%), fatigue (2% to 3%), dizziness (2%), depression (2%)
Dermatologic: Rash (4% to 9%), pruritus (3%)
Endocrine & metabolic: Hypokalemia (2%)
Gastrointestinal: Vomiting (5% to 7%), abdominal pain (2% to 6%), constipation (2%)
Hepatic: LFTs abnormal (3%)
Respiratory: Rhinitis (5% to 9%), cough (4%), dyspnea (2%), pneumonia (2%), sinusitis (2%), sputum increased (2%)
Miscellaneous: Diaphoresis increased (3%)
<2%, postmarketing, and/or case reports: Adrenal insufficiency, albuminuria, allergic reactions, alopecia, anaphylactoid reactions, anaphylaxis, angioedema, anorexia, arrhythmia, arthralgia, asthenia, blurred vision, diplopia, dysgeusia, dyspepsia, dysphagia, erythema multiforme, exfoliative dermatitis, flatulence, gastritis, gynecomastia, hearing loss, heart failure, hematuria, hepatic failure, hepatitis, hepatotoxicity, hepatitis, hot flashes, hypertriglyceridemia, hypoesthesia, impotence, insomnia, leukocytoclastic dermatitis, leukopenia, libido decreased, malaise, menstrual disorders, myalgia, neutropenia, pancreatitis, paresthesia, peripheral neuropathy, photosensitivity, pollakiuria, pulmonary edema, pharyngitis, rigors, serum sickness, somnolence, Stevens-Johnson syndrome, stomatitis ulcerative, thrombocytopenia, taste perversion, tinnitus, toxic epidermal necrolysis, urinary incontinence, urticaria, vasculitis
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (strong), P-glycoprotein
Drug Interactions
Alfentanil: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Aliskiren: Itraconazole may increase the serum concentration of Aliskiren. Risk X: Avoid combination
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Itraconazole. Management: Administer itraconazole at least 1 hour after and 2 hours before administration of any antacids. Itraconazole oral suspension may be less sensitive to the effects of decreased gastric acidity. Risk D: Consider therapy modification
Aprepitant: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Aprepitant. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Decrease aripiprazole dose to 50% of the usual dose with concomitant use of strong CYP3A4 inhibitors or to 25% of usual dose with concomitant use of strong CYP3A4 and 2D6 inhibitors or with use of a strong 3A4 inhibitor in a poor 2D6 metabolizer Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: The following combinations are specifically contraindicated: itraconazole with alprazolam, estazolam, oral midazolam, or triazolam; ketoconazole with alprazolam, estazolam, or triazolam. Consider initial dose reductions of other benzodiazepines. Exceptions: Quazepam. Risk D: Consider therapy modification
Boceprevir: May increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Boceprevir. Management: Limit maximum adult itraconazole dose to 200 mg daily in patients receiving boceprevir, due to a possible increase in itraconazole concentrations. Risk D: Consider therapy modification
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosentan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Bosentan. Risk C: Monitor therapy
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Risk C: Monitor therapy
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
BusPIRone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Busulfan. Risk C: Monitor therapy
Calcium Channel Blockers: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
CarBAMazepine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CarBAMazepine. Risk C: Monitor therapy
Cardiac Glycosides: Itraconazole may increase the serum concentration of Cardiac Glycosides. Management: Consider preemptive cardiac glycoside dose adjustments with initiation / changes / discontinuation of itraconazole. Risk D: Consider therapy modification
Ciclesonide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ciclesonide. Specifically, concentrations of the active des-ciclesonide metabolite may be increased. Risk C: Monitor therapy
Cilostazol: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Cilostazol. Risk D: Consider therapy modification
Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Risk X: Avoid combination
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Risk X: Avoid combination
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Monitor for signs and symptoms of adrenal suppression if inhaled budesonide or mometasone are coadministered with a strong CYP3A4 inhibitor. Avoid combining inhaled fluticasone with any strong CYP3A4 inhibitor. Exceptions: Beclomethasone; Beclomethasone (Oral Inhalation); Triamcinolone; Triamcinolone (Systemic). Risk C: Monitor therapy
Corticosteroids (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Didanosine: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Risk D: Consider therapy modification
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
DOCEtaxel: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of DOCEtaxel. Risk D: Consider therapy modification
Dofetilide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Dofetilide. Risk X: Avoid combination
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Itraconazole. Risk D: Consider therapy modification
Eletriptan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Eletriptan. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Eplerenone: Itraconazole may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Ergot Derivatives: Itraconazole may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Erlotinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Erlotinib. Risk C: Monitor therapy
Eszopiclone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Eszopiclone. Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Risk X: Avoid combination
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Fexofenadine: Itraconazole may increase the serum concentration of Fexofenadine. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk X: Avoid combination
Fosaprepitant: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosaprepitant. Specifically, concentrations of aprepitant are likely to be increased. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification
Gefitinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Gefitinib. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This specifically applies to oral antifungal administration, and the interaction may be different depending on specific dosage form being used. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Risk C: Monitor therapy
H2-Antagonists: May decrease the serum concentration of Itraconazole. Management: When this combination is used, the itraconazole should be administered with a cola beverage (8 ounces). Itraconazole oral suspension may be less sensitive to this interaction. Monitor patient response to itraconazole closely. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider use of HMG-CoA reductase inhibitors posing the least rhabdomyolysis risk (e.g. fluva- or pravastatin), and monitor for signs/symptoms of rhabdomyolysis. Do not use keto- or itraconazole with lova- or simvastatin, or posaconazole with simvastatin. Exceptions: Fluvastatin; Pitavastatin; Rosuvastatin. Risk D: Consider therapy modification
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Imatinib: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Imatinib. Risk C: Monitor therapy
Irinotecan: Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Irinotecan. Risk D: Consider therapy modification
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Decrease ivacaftor dose to 150 mg twice a week in patients also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Risk X: Avoid combination
Losartan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Risk C: Monitor therapy
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Risk C: Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Macrolide Antibiotics: May decrease the metabolism of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Macrolide Antibiotics. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification
Methadone: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Methadone. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects. Risk D: Consider therapy modification
Nevirapine: May decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Paliperidone: Itraconazole may decrease the metabolism of Paliperidone. Risk C: Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
Pazopanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pazopanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib adult dose to 400 mg. Further dose reductions may also be required. Risk D: Consider therapy modification
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Pimozide. Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Protease Inhibitors: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Protease Inhibitors. Management: Limit indinavir adult dose to 600 mg every 8 hours with itraconazole or ketoconazole. With ritonavir, limit ketoconazole adult dose to 200 mg/day. Limit fluconazole, itraconazole, and ketoconazole to 200 mg (adult dose) with tipranavir/ritonavir. Risk D: Consider therapy modification
Proton Pump Inhibitors: May decrease the serum concentration of Itraconazole. Risk D: Consider therapy modification
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Risk C: Monitor therapy
QuiNIDine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of QuiNIDine. Management: Itraconazole, voriconazole, and posaconazole are specifically contraindicated with quinidine. Use of quinidine with any azole antifungal may require quinidine dose adjustment and should be done with caution and close monitoring. Risk X: Avoid combination
Ramelteon: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ramelteon. Risk C: Monitor therapy
Ranolazine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ranolazine. Risk X: Avoid combination
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Repaglinide: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Repaglinide. Management: Concurrent use of an azole antifungal with both repaglinide and gemfibrozil should be avoided. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Rivaroxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk X: Avoid combination
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: Reduce ruxolitinib initial adult dose to 10 mg twice daily in patients receiving strong CYP3A4 inhibitors whose platelet count is 100*10^9/L or greater. Avoid in patients with lower platelet count. Risk D: Consider therapy modification
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Management: Limit saxagliptin adult dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) when used with a strong CYP3A4 inhibitor. Monitor for decreased saxagliptin levels/effects if discontinuing CYP3A4 inhibitor. Risk D: Consider therapy modification
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: When used for treatment of pulmonary arterial hypertension, use of sildenafil with strong CYP3A4 inhibitors should be avoided. When used for erectile dysfunction, starting dose should be reduced to 25 mg. Max dose with ritonavir is 25 mg per 48 hours. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination
Sirolimus: Itraconazole may increase the serum concentration of Sirolimus. Management: Sirolimus dose adjustments will likely be needed when starting/stopping any azole antifungal. Clinical data suggest sirolimus (adult) dose reductions of 50-90% will be needed when starting an azole antifungal, but specific guidelines are lacking. Risk D: Consider therapy modification
Solifenacin: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Solifenacin. Risk D: Consider therapy modification
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Risk C: Monitor therapy
Sucralfate: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk C: Monitor therapy
SUNItinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of SUNItinib. Risk D: Consider therapy modification
Tacrolimus: Itraconazole may increase the serum concentration of Tacrolimus. Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with itraconazole. Tacrolimus dose reductions will likely be required. The magnitude of this interaction may be greater in older patients. Risk D: Consider therapy modification
Tacrolimus (Systemic): Itraconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with itraconazole. Tacrolimus dose reductions will likely be required. The magnitude of this interaction may be greater in older patients. Risk D: Consider therapy modification
Tacrolimus (Topical): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving strong CYP3A4 inhibitors may vary based on indication and/or international labeling. Consult appropriate product labeling. Risk D: Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination
Telaprevir: Itraconazole may increase the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Itraconazole. Management: Doses of itraconazole greater than 200 mg/day are not recommended in patients receiving telaprevir. Use extra caution when using these drugs in combination. Risk D: Consider therapy modification
Temsirolimus: Itraconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to itraconazole. Monitor sirolimus concentrations in all patients receiving itraconazole or any systemic azole antifungal. Risk D: Consider therapy modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Tolterodine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk D: Consider therapy modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of long-acting tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Risk X: Avoid combination
Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. Consult appropriate product labeling for specific recommendations. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
VinBLAStine: Itraconazole may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: Itraconazole may enhance the adverse/toxic effect of VinCRIStine. Itraconazole may increase the serum concentration of VinCRIStine. Risk D: Consider therapy modification
Vinorelbine: Itraconazole may enhance the adverse/toxic effect of Vinorelbine. Itraconazole may increase the serum concentration of Vinorelbine. Management: Monitor for increased toxic effects of vinorelbine if itraconazole is being received/initiated/dose increased. Decreased vinorelbine doses may be required. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Itraconazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Ziprasidone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ziprasidone. Risk C: Monitor therapy
Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Zolpidem. Management: Consider using a lower starting dose of zolpidem in patients receiving systemic azole antifungals. Monitor patients closely for increased magnitude and/or duration of zolpidem effects when using this combination. Risk D: Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food:
Capsules: Absorption enhanced by food and possibly by gastric acidity. Cola drinks have been shown to increase the absorption of the capsules in patients with achlorhydria or those taking H2-receptor antagonists or other gastric acid suppressors. Grapefruit/grapefruit juice may increase serum levels. Management: Take capsules immediately after meals. Avoid grapefruit juice.
Solution: Food decreases the bioavailability and increases the time to peak concentration. Management: Take solution on an empty stomach 1 hour before or 2 hours after meals.
Herb/Nutraceutical: St John's wort may decrease itraconazole levels.
Storage
Capsule: Store at room temperature, 15°C to 25°C (59°F to 77°F). Protect from light and moisture.
Oral solution: Store at ≤25°C (77°F); do not freeze.
Mechanism of Action
Interferes with cytochrome P450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Pharmacodynamics/Kinetics
Absorption: Requires gastric acidity; capsule better absorbed with food, solution better absorbed on empty stomach
Distribution: Vd (average): 796 ± 185 L or 10 L/kg; highly lipophilic and tissue concentrations are higher than plasma concentrations. The highest concentrations: adipose, omentum, endometrium, cervical and vaginal mucus, and skin/nails. Aqueous fluids (eg, CSF and urine) contain negligible amounts.
Protein binding, plasma: 99.8%; metabolite hydroxy-itraconazole: 99.5%
Metabolism: Extensively hepatic via CYP3A4 into >30 metabolites including hydroxy-itraconazole (major metabolite); appears to have in vitro antifungal activity. Main metabolic pathway is oxidation; may undergo saturation metabolism with multiple dosing.
Bioavailability: Variable, ~55% (oral solution) in 1 small study; Note: Oral solution has a higher degree of bioavailability (149% ± 68%) relative to oral capsules; should not be interchanged
Half-life elimination: Oral: Single dose: ~21 hours, steady state: 64 hours; Cirrhosis (single dose): 37 hours (range 20-54 hours)
Time to peak, plasma: Capsules: 3-5 hours; Oral solution: 2-3 hours
Excretion: Urine (<0.03% active drug, 40% as inactive metabolites); feces (~3% to 18%)
Dosage
Oral:
Usual dosage ranges:
Children: Efficacy and safety have not been established; a small number of patients 3-16 years of age have been treated with 100 mg/day for systemic fungal infections with no serious adverse effects reported. A dose of 5 mg/kg once daily was used in a pharmacokinetic study using the oral solution in patients 6 months to 12 years; duration of study was 2 weeks.
Adults: 100-400 mg/day; doses >200 mg/day are given in 2 divided doses; length of therapy varies from 1 day to >6 months depending on the condition and mycological response
Indication-specific dosing:
Infants and Children (HIV-exposed/-positive; unlabeled use; CDC, 2009):
Candidiasis:
Oropharyngeal: Oral solution: 2.5 mg/kg/dose twice daily (maximum: 200 mg/day [400 mg/day if fluconazole-refractory]) for 7-14 days
Esophageal: Oral solution: 5 mg/kg/day once daily or divided twice daily for 4-21 days
Coccidioidomycosis:
Treatment: Oral: 5-10 mg/kg/dose twice daily for 3 days, followed by 2-5 mg/kg/dose orally twice daily (maximum: 400 mg/day)
Relapse prevention: Oral: 2-5 mg/kg/dose twice daily (maximum: 400 mg/day)
Cryptococcus: Relapse prevention: Oral solution: 5 mg/kg/dose once daily (maximum: 200 mg/day)
Histoplasmosis:
Treatment of mild disseminated disease: Oral solution: 2-5 mg/kg/dose 3 times daily for 3 days (9 doses), followed by twice daily for 12 months (maximum: 200 mg/dose)
Consolidation treatment for moderate-severe to severe disseminated disease, including CNS infection (following appropriate induction therapy): 2-5 mg/kg/dose 3times daily for 3 days, followed by 2-5 mg/kg/dose (maximum: 200 mg/dose) twice daily for 12 months for non-CNS-disseminated disease or for ≥12 months for CNS infection
Relapse prevention: Oral solution: 5 mg/kg/dose twice daily (maximum: 400 mg/day)
Adults:
Aspergillosis, invasive (salvage therapy): Duration of therapy should be a minimum of 6-12 weeks or throughout period of immunosuppression: Oral: 200-400 mg/day; Note: 2008 IDSA guidelines recommend 600 mg/day for 3 days, followed by 400 mg/day
Appropriate use: Itraconazole should NOT be used for voriconazole-refractory aspergillosis since the same antifungal and/or resistance mechanism(s) may be shared by both agents. Itraconazole oral solution and capsule formulations are not bioequivalent or interchangeable. Due to variable bioavailability of oral preparations, therapeutic drug monitoring advisable.
Aspergillosis, allergic (ABPA, sinusitis): 200 mg/day; may be used in conjunction with corticosteroids
Blastomycosis: 200 mg 3 times/day for 3 days, then 200 mg twice daily for 6-12 months; in moderately-severe to severe infection, therapy should be initiated with ~2 weeks of amphotericin B (Chapman, 2008)
Brain abscess: Cerebral phaeohyphomycosis (dematiaceous): 200 mg twice daily for at least 6 months with amphotericin
Candidiasis:
Oropharyngeal: Oral solution: 200 mg once daily for 1-2 weeks; in patients unresponsive or refractory to fluconazole: 100 mg twice daily (clinical response expected in 1-2 weeks)
Esophageal: Oral solution: 100-200 mg once daily for a minimum of 3 weeks; continue dosing for 2 weeks after resolution of symptoms
Coccidioidomycosis: 200 mg twice daily
Histoplasmosis: 200 mg 3 times/day for 3 days, then 200 mg twice daily (or once daily in mild-moderate disease) for 6-12 weeks in mild-moderate disease or ≥12 months in progressive disseminated or chronic cavitary pulmonary histoplasmosis; in moderately-severe to severe infection, therapy should be initiated with ~2 weeks of a lipid formation of amphotericin B (Wheat, 2007)
Long-term suppression therapy: 200 mg/day (AIDSinfo guidelines, 2008)
Meningitis:
Coccidioides: 400-800 mg/day
Coccidioides, HIV-positive (unlabeled use): 200 mg 3 times/day for 3 days, then 200 mg twice daily; maintenance: 200 mg twice daily life-long (AIDSinfo guidelines, 2008)
Appropriate use: Fluconazole is preferred for meningeal infections.
Onychomycosis: 200 mg once daily for 12 consecutive weeks; alternative “pulse-dosing” may be considering for fingernail involvement only: 200 mg twice daily for 1 week; repeat 1-week course after 3-week off-time
Penicilliosis, HIV-positive (unlabeled use): 200 mg twice daily for 8-10 weeks (in severely-ill patients, initiate therapy with 2 weeks of amphotericin B); maintenance: 200 mg/day (AIDSinfo guidelines, 2008)
Pneumonia:
Coccidioides: Mild-to-moderate: 200 mg twice daily
Coccidioides, HIV-positive (focal pneumonia): 200 mg 3 times/day for 3 days, then 200 mg twice daily (AIDSinfo guidelines, 2008)
Protothecal infection: 200 mg once daily for 2 months
Sporotrichosis:
Lymphocutaneous: 100-200 mg/day for 3-6 months
Osteoarticular and pulmonary: 200 mg twice daily for 1-2 years (may use amphotericin B initially for stabilization)
Dosing adjustment in renal impairment: The FDA-approved labeling states to use with caution in patients with renal impairment. The following guidelines have been used by some clinicians:
Aronoff, 2007:
Clcr >10 mL/minute: No adjustment recommended
Clcr <10 mL/minute: Administer 50% of normal dose
Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).
Dosing adjustment in hepatic impairment: Use caution in patients with hepatic impairment
Dental Usual Dosing
Oropharyngeal candidiasis: Adults: Oral solution: 200 mg once daily for 1-2 weeks; in patients unresponsive or refractory to fluconazole: 100 mg twice daily (clinical response expected in 1-2 weeks)
Administration: Oral
Doses >200 mg/day are given in 2 divided doses; do not administer with antacids. Capsule and oral solution formulations are not bioequivalent and thus are not interchangeable. Capsule absorption is best if taken with food, therefore, it is best to administer itraconazole after meals; solution should be taken on an empty stomach. When treating oropharyngeal and esophageal candidiasis, solution should be swished vigorously in mouth, then swallowed.
Monitoring Parameters
Liver function in patients with pre-existing hepatic dysfunction, and in all patients being treated for longer than 1 month; serum concentrations particularly for oral therapy (due to erratic bioavailability with capsule formulation); renal function
Reference Range
Serum concentrations may be performed to assure therapeutic levels. Itraconazole plus the metabolite hydroxyitraconazole concentrations should be >1 mcg/mL (not to exceed 10 mcg/mL).
Timing of serum samples: Obtain level after ~2 weeks of therapy, level may be drawn anytime during the dosing interval.
Dietary Considerations
Capsule: Take with food.
Solution: Take without food, if possible.
Patient Education
Treatment for some fungal infections may take several weeks or months. Take capsule immediately after meals; take solution on empty stomach (1 hour before or 2 hours after meals). Frequent blood tests may be required with prolonged therapy. May cause dizziness, drowsiness, nausea, vomiting, or anorexia. Report any rash, any change in hearing acuity, difficulty breathing, or chest pain. Report any signs and symptoms of liver dysfunction (eg, unusual fatigue, anorexia, nausea and/or vomiting, jaundice [yellowing of skin or sclera], dark urine, pale stool) so that the appropriate laboratory testing can be done.
Geriatric Considerations
No specific data for the elderly. Transient or permanent hearing loss reported in the elderly; several reports include concurrent administration of quinidine.
Additional Information
Due to potential toxicity, the manufacturer recommends confirmation of diagnosis testing of nail specimens prior to treatment of onychomycosis.
Cardiovascular Considerations
Itraconazole has negative inotropic properties and cases of new heart failure (HF) or exacerbation of HF have been reported. Itraconazole is contraindicated for the treatment of onychomycosis in patients with HF. The benefit:risk for therapy in the treatment of other types of fungal infections should be carefully considered in each patient, particularly those with HF and in heart transplant recipients. If indicated after cardiac, renal, or liver transplantation, itraconazole can increase cyclosporine levels by up to 50% at high doses. It also increases serum levels of lovastatin and simvastatin by up to 20-fold, as well as other HMG-CoA reductase inhibitors (except fluvastatin and rosuvastatin), by inhibiting CYP3A4. This is important since many post-transplantation patients are also hyperlipidemic and on HMG-CoA reductase inhibitors. Itraconazole may also increase levels of digoxin, disopyramide, dofetilide, and quinidine. The simultaneous administration of these medications may increase the risk of cardiotoxicity. Edema has been reported in patients concurrently receiving itraconazole and calcium channel blockers (CCBs). CCBs may cause additive negative inotropic effects when used concurrently with itraconazole. Use caution with concurrent use of itraconazole and CCBs due to an increased risk of HF. Concurrent use of itraconazole and dofetilide, nisoldipine and quinidine is contraindicated.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
In vitro resistance to itraconazole has been observed in C. krusei, C. glabrata and C. tropicalis isolates. These are generally the least susceptible Candida species.
Mental Health: Effects on Mental Status
May cause sedation
Mental Health: Effects on Psychiatric Treatment
Contraindicated with oral midazolam, pimozide, and triazolam
Nursing: Physical Assessment/Monitoring
Evaluate hepatic status and hypersensitivity history prior to treatment. Assess results of LFTs.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 100 mg
Sporanox®: 100 mg
Solution, oral:
Sporanox®: 10 mg/mL (150 mL) [contains propylene glycol; cherry-caramel flavor]
Pricing: U.S. (www.drugstore.com)
Capsules (Itraconazole)
100 mg (28): $239.97
100 mg (30): $251.98
Capsules (Sporanox)
100 mg (30): $439.99
Solution (Sporanox)
10 mg/mL (150): $217.99
Extemporaneously Prepared
Note: Commercial oral solution is available (10 mg/mL)
A 20 mg/mL oral suspension may be made with capsules. Empty the contents of forty 100 mg capsules and add 15 mL of Alcohol, USP. Let stand for 5 minutes. Crush the beads in a mortar and reduce to a fine powder. Mix while adding a 1:1 mixture of Ora-Sweet® and Ora-Plus® in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label "shake well" and "refrigerate". Stable for 56 days refrigerated.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Ahmad SR, Singer SJ, and Leissa BG, “Congestive Heart Failure Associated With Itraconazole,” Lancet, 2001, 357(9270):1766-7.
Amichai B and Grunwald MH, “Adverse Drug Reactions of the New Oral Antifungal Agents - Terbinafine, Fluconazole, and Itraconazole,” Int J Dermatol, 1998, 37(6):410-5.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.
Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf
Chapman SW, Dismukes WE, Proia LA, et al, “Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2008, 46(12):1801-12.
Cleary JD, Taylor JW, and Chapman SW, “Itraconazole in Antifungal Therapy,” Ann Pharmacother, 1992, 26(4):502-9.
Cowie F, Meller ST, Cushing P, et al, “Chemoprophylaxis for Pulmonary Aspergillosis During Intensive Chemotherapy,” Arch Dis Child, 1994, 70(2):136-8.
De Backer M, De Vroey C, Lesaffre E, et al, “Twelve Weeks of Continuous Oral Therapy for Toenail Onychomycosis Caused by Dermatophytes: A Double-Blind Comparative Trial of Terbinafine 250 mg/day Versus Itraconazole 200 mg/day,” J Am Acad Dermatol, 1998, 38(5 Pt 3):S57-63.
Denning DW, Lee JY, Hostetler JS, et al, “NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis,” Am J Med, 1994, 97(2):135-44.
Grant SM and Clissold SP, “Itraconazole. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use in Superficial and Systemic Mycoses,” Drugs, 1989, 37(3):310-44.
“Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents,” June 18, 2008. Available at http://aidsinfo.nih.gov
Haria M, Bryson HM, and Goa KL, “Itraconazole: A Reappraisal of Its Pharmacological Properties and Therapeutic Use in the Management of Superficial Fungal Infections,” Drugs, 1996, 51(4):585-620.
Heintz BH, Matzke GR, Dager WE, “Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis,” Pharmacotherapy, 2009, 29(5):562-77.
Heymann WR and Manders SM, “Itraconazole-Induced Acute Generalized Exanthemic Pustulosis,” J Am Acad Dermatol, 1995, 33(1):130-1.
Jennings TS and Hardin TC, “Treatment of Aspergillosis With Itraconazole,” Ann Pharmacother, 1993, 27(10):1206-11.
Kauffman CA and Carver PL, “Antifungal Agents in the 1990s. Current Status and Future Developments,” Drugs, 1997, 53(4):539-49.
Kintzel PE, Rollins CJ, Yee WJ, et al, “Low Itraconazole Serum Concentrations Following Administration of Itraconazole Suspension to Critically Ill Allogenic Bone Marrow Transplant Recipients,” Ann Pharmacother, 1995, 29(2):140-3.
Lyman CA and Walsh TJ, “Systemically Administered Antifungal Agents. A Review of Their Clinical Pharmacology and Therapeutic Applications,” Drugs, 1992, 44(1):9-35.
Mohr J, Johnson M, Cooper T, et al, “Current Options in Antifungal Pharmacotherapy,” Pharmacotherapy, 2008, 28(5):614-45.
Mouy R, Veber F, Blanche S, et al, “Long-Term Itraconazole Prophylaxis Against Aspergillus Infections in Thirty-Two Patients With Chronic Granulomatous Disease,” J Pediatr, 1994, 125(6 Pt 1):998-1003.
Neuvonen PJ and Suhonen R, “Itraconazole Interacts With Felodipine,” J Am Acad Dermatol, 1995, 33(1):134-5.
Neuvonen PJ, Backman JT, and Niemi M, “Pharmacokinetic Comparison of the Potential Over-The-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin,” Clin Pharmacokinet, 2008, 47(7):463-74.
Terrell CL, “Antifungal Agents. Part II. The Azoles,” Mayo Clin Proc, 1999, 74(1):78-100.
Tobon AM, Franco L, Espinal D, et al, “Disseminated Histoplasmosis in Children: The Role of Itraconazole Therapy,” Pediatr Infect Dis J, 1996; 15:1002-8.
Trepanier EF and Amsden GW, “Current Issues in Onchomycosis,” Ann Pharmacother, 1998, 32(2):204-14.
Tucker RM, Haq Y, Denning DW, et al, “Adverse Effects Associated With Itraconazole in 189 Patients on Chronic Therapy,” J Antimicrob Chemother, 1990, 26(4):561-6.
Varhe A, Olkkola KT, and Neuvonen PJ, “Oral Triazolam is Potentially Hazardous to Patients Receiving Systemic Antimycotics Ketoconazole or Itraconazole,” Clin Pharmacol Ther, 1994, 56(6 Pt 1):601-7.
Walsh TJ, Anaissie EJ, Denning DW, et al, “Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America,” Clin Infect Dis, 2008, 46(3):327-60.
Wheat J, Freifeld AG, Kleiman MB, et al, “Clinical Practice Guidelines for the Management of Patients With Histoplasmosis: 2007 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2007, 45(7):807–25.
Wheat J, Hafner R, Korzun AH, et al, “Itraconazole Treatment of Disseminated Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome,” Am J Med, 1995, 98(4):336-42.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
| 
