itraconazole
Capsule · Oral
Uses
Itraconazole Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. Itraconazole Capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (See CLINICAL PHARMACOLOGY: Special Populations , CONTRAINDICATIONS , WARNINGS , and ADVERSE REACTIONS: Postmarketing Experience for more information.) Description of Clinical Studies Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status. The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. Histoplasmosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=34 combined) in patients with normal or abnormal immune status (not including HIV-infected patients). The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. Histoplasmosis in HIV-infected patients Data from a small number of HIV-infected patients suggested that the response rate of histoplasmosis in HIV-infected patients is similar to that of non-HIV-infected patients. The clinical course of histoplasmosis in HIV-infected patients is more severe and usually requires maintenance therapy to prevent relapse. Aspergillosis Analyses were conducted on data from an open-label, "single-patient-use" protocol designed to make itraconazole available in the U.S. for patients who either failed or were intolerant of amphotericin B therapy (N=190). The findings were corroborated by two smaller open-label studies (N=31 combined) in the same patient population. Most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. Results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin B therapy. Onychomycosis of the toenail Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given Itraconazole Capsules) in which patients with onychomycosis of the toenails received 200 mg of Itraconazole Capsules once daily for 12 consecutive weeks. Results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 54% of patients. Thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). The mean time to overall success was approximately 10 months. Twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of KOH or culture from negative to positive). Onychomycosis of the fingernail Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given Itraconazole Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of Itraconazole Capsules b.i.d., followed by a 3-week period without Itraconazole Capsules, which was followed by a second 1-week pulse of 200 mg of Itraconazole Capsules b.i.d. Results demonstrated mycologic cure in 61% of patients. Fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. The mean time to overall success was approximately 5 months. None of the patients who achieved overall success relapsed.
Dosage and administration
Itraconazole Capsules should be taken with a full meal to ensure maximal absorption. Itraconazole Capsules must be swallowed whole. Itraconazole Capsules are a different preparation than SPORANOX ® (itraconazole) Oral Solution and should not be used interchangeably. Treatment of Blastomycosis and Histoplasmosis The recommended dose is 200 mg once daily (2 capsules). If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100-mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses. Treatment of Aspergillosis A daily dose of 200 to 400 mg is recommended. Treatment in Life-Threatening Situations In life-threatening situations, a loading dose should be used. Although clinical studies did not provide for a loading dose, it is recommended, based on pharmacokinetic data, that a loading dose of 200 mg (2 capsules) three times daily (600 mg/day) be given for the first 3 days of treatment. Treatment should be continued for a minimum of three months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Itraconazole Capsules and SPORANOX ® (itraconazole) Oral Solution should not be used interchangeably. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis. Treatment of Onychomycosis Toenails with or without fingernail involvement The recommended dose is 200 mg (2 capsules) once daily for 12 consecutive weeks. Treatment of Onychomycosis Fingernails only The recommended dosing regimen is 2 treatment pulses, each consisting of 200 mg (2 capsules) b.i.d. (400 mg/day) for 1 week. The pulses are separated by a 3-week period without itraconazole. Use in Patients with Renal Impairment Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS .) Use in Patients with Hepatic Impairment Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations , WARNINGS , and PRECAUTIONS .)
Contraindications
Congestive Heart Failure Itraconazole Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. (See BOXED WARNING , WARNINGS , PRECAUTIONS: Drug Interactions-Calcium Channel Blockers, ADVERSE REACTIONS: Postmarketing Experience , and CLINICAL PHARMACOLOGY: Special Populations .) Drug Interactions Coadministration of a number of CYP3A4 substrates are contraindicated with itraconazole. Some examples of drugs for which plasma concentrations increase are: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin. In addition, coadministration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and coadministration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors. (See PRECAUTIONS: Drug Interactions Section for specific examples.) This increase in drug concentrations caused by coadministration with itraconazole may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia. Some specific examples are listed in PRECAUTIONS: Drug Interactions. Coadministration with venetoclax is contraindicated in patients with CLL/SLL during the dose initiation and ramp-up phase of venetoclax due to the potential for an increased risk of tumor lysis syndrome. Itraconazole should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. Itraconazole is contraindicated for patients who have shown hypersensitivity to itraconazole. There is limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used when prescribing itraconazole to patients with hypersensitivity to other azoles.
Warnings
Hepatic Effects: Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease nor a serious underlying medical condition, and some of these cases developed within the first week of treatment. If clinical signs or symptoms develop that are consistent with liver disease, treatment should be discontinued and liver function testing performed. Continued itraconazole use or reinstitution of treatment with itraconazole is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk. (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS .) Cardiac Dysrhythmias: Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugs such as cisapride, pimozide, methadone, or quinidine concomitantly with itraconazole and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with itraconazole is contraindicated. (See BOXED WARNING , CONTRAINDICATIONS , and PRECAUTIONS: Drug Interactions .) Cardiac Disease: Itraconazole Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. Itraconazole Capsules should not be used for other indications in patients with evidence of ventricular dysfunction unless the benefit clearly outweighs the risk. For patients with risk factors for congestive heart failure, physicians should carefully review the risks and benefits of itraconazole therapy. These risk factors include cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders. Such patients should be informed of the signs and symptoms of CHF, should be treated with caution, and should be monitored for signs and symptoms of CHF during treatment. If signs or symptoms of CHF appear during administration of Itraconazole Capsules, discontinue administration. Itraconazole has been shown to have a negative inotropic effect. When itraconazole was administered intravenously to anesthetized dogs, a dose-related negative inotropic effect was documented. In a healthy volunteer study of itraconazole intravenous infusion, transient, asymptomatic decreases in left ventricular ejection fraction were observed using gated SPECT imaging; these resolved before the next infusion, 12 hours later. Itraconazole has been associated with reports of congestive heart failure. In postmarketing experience, heart failure was more frequently reported in patients receiving a total daily dose of 400 mg although there were also cases reported among those receiving lower total daily doses. Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers. Therefore, caution should be used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHF. Concomitant administration of itraconazole and felodipine or nisoldipine is contraindicated. Cases of CHF, peripheral edema, and pulmonary edema have been reported in the postmarketing period among patients being treated for onychomycosis and/or systemic fungal infections. (See CLINICAL PHARMACOLOGY: Special Populations , CONTRAINDICATIONS , PRECAUTIONS: Drug Interactions , and ADVERSE REACTIONS: Postmarketing Experience for more information.) Pseudoaldosteronism: Pseudoaldosteronism, manifested by the onset of hypertension or worsening of hypertension, and abnormal laboratory findings (hypokalemia, low serum renin and aldosterone, and elevated 11-deoxycortisol), has been reported with itraconazole use in the postmarketing setting. Monitor blood pressure and potassium levels and manage as necessary. Management of pseudoaldosteronism may include discontinuation of Itraconazole Capsules, substitution with an appropriate antifungal drug that is not associated with pseudoaldosteronism, or use of aldosterone receptor antagonists. Interaction Potential: Itraconazole has a potential for clinically important drug interactions. Coadministration of specific drugs with itraconazole may result in changes in efficacy of itraconazole and/or the coadministered drug, life-threatening effects and/or sudden death. Drugs that are contraindicated, not recommended or recommended for use with caution in combination with itraconazole are listed in PRECAUTIONS: Drug Interactions. Interchangeability: Itraconazole Capsules and SPORANOX ® (itraconazole) Oral Solution should not be used interchangeably. This is because drug exposure is greater with the Oral Solution than with the Capsules when the same dose of drug is given. In addition, the topical effects of mucosal exposure may be different between the two formulations. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis.
Precautions
General: Itraconazole Capsules should be administered after a full meal. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism ). Under fasted conditions, itraconazole absorption was decreased in the presence of decreased gastric acidity. The absorption of itraconazole may be decreased with the concomitant administration of antacids or gastric acid secretion suppressors. Studies conducted under fasted conditions demonstrated that administration with 8 ounces of a non-diet cola beverage resulted in increased absorption of itraconazole in AIDS patients with relative or absolute achlorhydria. This increase relative to the effects of a full meal is unknown. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism ). Hepatotoxicity: Rare cases of serious hepatotoxicity have been observed with itraconazole treatment, including some cases within the first week. It is recommended that liver function monitoring be considered in all patients receiving itraconazole. Treatment should be stopped immediately and liver function testing should be conducted in patients who develop signs and symptoms suggestive of liver dysfunction. Neuropathy: If neuropathy occurs that may be attributable to Itraconazole Capsules, the treatment should be discontinued. Immunocompromised Patients: In some immunocompromised patients (e.g., neutropenic, AIDS or organ transplant patients), the oral bioavailability of Itraconazole capsules may be decreased. Therefore, the dose should be adjusted based on the clinical response in these patients. Cystic Fibrosis: If a cystic fibrosis patient does not respond to Itraconazole Capsules, consideration should be given to switching to alternative therapy. For more information concerning the use of itraconazole in cystic fibrosis patients see the prescribing information for SPORANOX ® Oral Solution. Hearing Loss: Transient or permanent hearing loss has been reported in patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated (See BOXED WARNING: Drug Interactions , CONTRAINDICATIONS: Drug Interactions and PRECAUTIONS: Drug Interactions ). The hearing loss usually resolves when treatment is stopped, but can persist in some patients. Information for Patients: The topical effects of mucosal exposure may be different between Itraconazole Capsules and SPORANOX ® (itraconazole) Oral Solution. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis. Itraconazole Capsules should not be used interchangeably with SPORANOX ® (itraconazole) Oral Solution. Instruct patients to take Itraconazole Capsules with a full meal. Itraconazole Capsules must be swallowed whole. Instruct patients about the signs and symptoms of congestive heart failure, and if these signs or symptoms occur during itraconazole administration, they should discontinue itraconazole and contact their healthcare provider immediately. Instruct patients to stop itraconazole treatment immediately and contact their healthcare provider if any signs and symptoms suggestive of liver dysfunction develop. Such signs and symptoms may include unusual fatigue, anorexia, nausea and/or vomiting, jaundice, dark urine, or pale stools. Instruct patients to contact their physician before taking any concomitant medications with itraconazole to ensure there are no potential drug interactions. Instruct patients that hearing loss can occur with the use of itraconazole. The hearing loss usually resolves when treatment is stopped, but can persist in some patients. Advise patients to discontinue therapy and inform their physicians if any hearing loss symptoms occur. Instruct patients that dizziness or blurred/double vision can sometimes occur with itraconazole. Advise patients that if they experience these events, they should not drive or use machines. Drug Interactions: Effect of Itraconazole Capsules on Other Drugs Itraconazole and its major metabolite, hydroxy-itraconazole, are potent CYP3A4 inhibitors. Itraconazole is an inhibitor of the drug transporters P-glycoprotein and breast cancer resistance protein (BCRP). Consequently, Itraconazole Capsules has the potential to interact with many concomitant drugs resulting in either increased or sometimes decreased concentrations of the concomitant drugs. Increased concentrations may increase the risk of adverse reactions associated with the concomitant drug which can be severe or life-threatening in some cases (e.g., QT prolongation, torsade de pointes, respiratory depression, hepatic adverse reactions, hypersensitivity reactions, myelosuppression, hypotension, seizures, angioedema, atrial fibrillation, bradycardia, priapism). Reduced concentrations of concomitant drugs may reduce their efficacy. Table 1 lists examples of drugs that may have their concentrations affected by itraconazole, but it is not a comprehensive list. Refer to the approved product labeling to become familiar with the interaction pathways, risk potential, and specific actions to be taken with regards to each concomitant drug prior to initiating therapy with Itraconazole Capsules. Although many of the clinical drug interactions in Table 1 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with Itraconazole Capsules. Table 1: Drug Interactions with Itraconazole Capsules that Affect Concomitant Drug Concentrations Examples of Concomitant Drugs Within Class Prevention or Management Drug Interactions with Itraconazole Capsules that Increase Concomitant Drug Concentrations and May Increase Risk of Adverse Reactions Associated with the Concomitant Drug Alpha Blockers Alfuzosin Silodosin Tamsulosin Not recommended during and 2 weeks after Itraconazole Capsules treatment. Analgesics Methadone Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Fentanyl Not recommended during and 2 weeks after Itraconazole Capsules treatment.
Side effects
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease nor a serious underlying medical condition. If clinical signs or symptoms develop that are consistent with liver disease, treatment should be discontinued and liver function testing performed. The risks and benefits of itraconazole use should be reassessed. (See WARNINGS: Hepatic Effects and PRECAUTIONS: Hepatotoxicity and Information for Patients .) Adverse Events in the Treatment of Systemic Fungal Infections Adverse event data were derived from 602 patients treated for systemic fungal disease in U.S. clinical trials who were immunocompromised or receiving multiple concomitant medications. Treatment was discontinued in 10.5% of patients due to adverse events. The median duration before discontinuation of therapy was 81 days (range: 2 to 776 days). The table lists adverse events reported by at least 1% of patients. Table 3: Clinical Trials of Systemic Fungal Infections: Adverse Events Occurring with an Incidence of Greater than or Equal to 1% Body System/Adverse Event Incidence (%) (N=602) Gastrointestinal Nausea 11 Vomiting 5 Diarrhea 3 Abdominal Pain 2 Anorexia 1 Body as a Whole Edema 4 Fatigue 3 Fever 3 Malaise 1 Skin and Appendages Rash Rash tends to occur more frequently in immunocompromised patients receiving immunosuppressive medications. 9 Pruritus 3 Central/Peripheral Nervous System Headache 4 Dizziness 2 Psychiatric Libido Decreased 1 Somnolence 1 Cardiovascular Hypertension 3 Metabolic/Nutritional Hypokalemia 2 Urinary System Albuminuria 1 Liver and Biliary System Hepatic Function Abnormal 3 Reproductive System, Male Impotence 1 Adverse events infrequently reported in all studies included constipation, gastritis, depression, insomnia, tinnitus, menstrual disorder, adrenal insufficiency, gynecomastia, and male breast pain. Adverse Events Reported in Toenail Onychomycosis Clinical Trials Patients in these trials were on a continuous dosing regimen of 200 mg once daily for 12 consecutive weeks. The following adverse events led to temporary or permanent discontinuation of therapy. Table 4: Clinical Trials of Onychomycosis of the Toenail: Adverse Events Leading to Temporary or Permanent Discontinuation of Therapy Adverse Event Incidence (%) Itraconazole (N=112) Elevated Liver Enzymes (greater than twice the upper limit of normal) 4 Gastrointestinal Disorders 4 Rash 3 Hypertension 2 Orthostatic Hypotension 1 Headache 1 Malaise 1 Myalgia 1 Vasculitis 1 Vertigo 1 The following adverse events occurred with an incidence of greater than or equal to 1% (N=112): headache: 10%; rhinitis: 9%; upper respiratory tract infection: 8%; sinusitis, injury: 7%; diarrhea, dyspepsia, flatulence, abdominal pain, dizziness, rash: 4%; cystitis, urinary tract infection, liver function abnormality, myalgia, nausea: 3%; appetite increased, constipation, gastritis, gastroenteritis, pharyngitis, asthenia, fever, pain, tremor, herpes zoster, abnormal dreaming: 2%. Adverse Events Reported in Fingernail Onychomycosis Clinical Trials Patients in these trials were on a pulse regimen consisting of two 1-week treatment periods of 200 mg twice daily, separated by a 3-week period without drug. The following adverse events led to temporary or permanent discontinuation of therapy. Table 5: Clinical Trials of Onychomycosis of the Fingernail: Adverse Events Leading to Temporary or Permanent Discontinuation of Therapy Adverse Event Incidence (%) Itraconazole (N=37) Rash/Pruritus 3 Hypertriglyceridemia 3 The following adverse events occurred with an incidence of greater than or equal to 1% (N=37): headache: 8%; pruritus, nausea, rhinitis: 5%; rash, bursitis, anxiety, depression, constipation, abdominal pain, dyspepsia, ulcerative stomatitis, gingivitis, hypertriglyceridemia, sinusitis, fatigue, malaise, pain, injury: 3%. Adverse Events Reported from Other Clinical Trials In addition, the following adverse drug reaction was reported in patients who participated in Itraconazole Capsules clinical trials: Hepatobiliary Disorders: hyperbilirubinemia. The following is a list of additional adverse drug reactions associated with itraconazole that have been reported in clinical trials of SPORANOX ® Oral Solution and itraconazole IV excluding the adverse reaction term "Injection site inflammation" which is specific to the injection route of administration: Cardiac Disorders: cardiac failure, left ventricular failure, tachycardia; General Disorders and Administration Site Conditions: face edema, chest pain, chills; Hepatobiliary Disorders: hepatic failure, jaundice; Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, blood urea increased, gamma-glutamyltransferase increased, urine analysis abnormal; Metabolism and Nutrition Disorders: hyperglycemia, hyperkalemia, hypomagnesemia; Psychiatric Disorders: confusional state; Renal and Urinary Disorders: renal impairment; Respiratory, Thoracic and Mediastinal Disorders: dysphonia, cough; Skin and Subcutaneous Tissue Disorders: rash erythematous, hyperhidrosis; Vascular Disorders: hypotension Postmarketing Experience Adverse drug reactions that have been first identified during postmarketing experience with itraconazole (all formulations) are listed in the table below. Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.
Drug interactions
Drug Interactions: Effect of Itraconazole Capsules on Other Drugs Itraconazole and its major metabolite, hydroxy-itraconazole, are potent CYP3A4 inhibitors. Itraconazole is an inhibitor of the drug transporters P-glycoprotein and breast cancer resistance protein (BCRP). Consequently, Itraconazole Capsules has the potential to interact with many concomitant drugs resulting in either increased or sometimes decreased concentrations of the concomitant drugs. Increased concentrations may increase the risk of adverse reactions associated with the concomitant drug which can be severe or life-threatening in some cases (e.g., QT prolongation, torsade de pointes, respiratory depression, hepatic adverse reactions, hypersensitivity reactions, myelosuppression, hypotension, seizures, angioedema, atrial fibrillation, bradycardia, priapism). Reduced concentrations of concomitant drugs may reduce their efficacy. Table 1 lists examples of drugs that may have their concentrations affected by itraconazole, but it is not a comprehensive list. Refer to the approved product labeling to become familiar with the interaction pathways, risk potential, and specific actions to be taken with regards to each concomitant drug prior to initiating therapy with Itraconazole Capsules. Although many of the clinical drug interactions in Table 1 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with Itraconazole Capsules. Table 1: Drug Interactions with Itraconazole Capsules that Affect Concomitant Drug Concentrations Examples of Concomitant Drugs Within Class Prevention or Management Drug Interactions with Itraconazole Capsules that Increase Concomitant Drug Concentrations and May Increase Risk of Adverse Reactions Associated with the Concomitant Drug Alpha Blockers Alfuzosin Silodosin Tamsulosin Not recommended during and 2 weeks after Itraconazole Capsules treatment. Analgesics Methadone Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Fentanyl Not recommended during and 2 weeks after Itraconazole Capsules treatment. Alfentanil Buprenorphine (IV and sublingual) Oxycodone Based on clinical drug interaction information with itraconazole. Sufentanil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Digoxin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antibacterials Bedaquiline Based on 400 mg bedaquiline once daily for 2 weeks. Concomitant Itraconazole Capsules not recommended for more than 2 weeks at any time during bedaquiline treatment. Rifabutin Not recommended 2 weeks before, during, and 2 weeks after Itraconazole Capsules treatment. See also Table 2 . Clarithromycin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. See also Table 2 . Trimetrexate Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Anticoagulants and Antiplatelets Ticagrelor Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Apixaban Rivaroxaban Vorapaxar Not recommended during and 2 weeks after Itraconazole Capsules treatment. Cilostazol Dabigatran Warfarin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after Itraconazole Capsules treatment. See also Table 2 . Antidiabetic Drugs Repaglinide Saxagliptin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antihelminthics, Antifungals and Antiprotozoals Isavuconazonium Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Praziquantel Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Artemether-lumefantrine Quinine Monitor for adverse reactions. Antimigraine Drugs Ergot alkaloids (e.g., dihydroergotamine, ergotamine) Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Eletriptan Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antineoplastics Irinotecan Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Venetoclax Contraindicated during the dose initiation and ramp-up phase in patients with CLL/SLL. Refer to the venetoclax prescribing information for dosing and safety monitoring instructions. Mobocertinib Avoid use during and 2 weeks after Itraconazole Capsules treatment. Axitinib Bosutinib Cabazitaxel Cabozantinib Ceritinib Cobimetinib Crizotinib Dabrafenib Dasatinib Docetaxel Ibrutinib Lapatinib Nilotinib Olaparib Pazopanib Sunitinib Trabectedin Trastuzumab- emtansine Vinca alkaloids Avoid use during and 2 weeks after Itraconazole Capsules treatment. Entrectinib Pemigatinib Talazoparib Refer to the entrectinib, pemigatinib and talazoparib prescribing information for dosing instructions if concomitant use cannot be avoided. Glasdegib Refer to the glasdegib prescribing information for safety monitoring if concomitant use cannot be avoided. Bortezomib Brentuximab- vedotin Busulfan Erlotinib Gefitinib Idelalisib Imatinib Ixabepilone Nintedanib Panobinostat Ponatinib Ruxolitinib Sonidegib Tretinoin (oral) Vandetanib Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For idelalisib, see also Table 2 . Antipsychotics, Anxiolytics and Hypnotics Alprazolam Aripiprazole Buspirone Cariprazine Diazepam Haloperidol Midazolam (IV) Quetiapine Ramelteon Risperidone Suvorexant Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Zopiclone Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lurasidone Midazolam (oral) Pimozide Triazolam Contraindicated during and 2 weeks after Itraconazole Capsules treatment. Antivirals Daclatasvir Indinavir Maraviroc Monitor for adverse reactions.
Pregnancy
Pregnancy: Teratogenic Effects Itraconazole was found to cause a dose-related increase in maternal toxicity, embryotoxicity, and teratogenicity in rats at dosage levels of approximately 40–160 mg/kg/day (1–4 times the MRHD based on body surface area comparisons), and in mice at dosage levels of approximately 80 mg/kg/day (1 time the MRHD based on body surface area comparisons). Itraconazole has been shown to cross the placenta in a rat model. In rats, the teratogenicity consisted of major skeletal defects; in mice, it consisted of encephaloceles and/or macroglossia. There are no studies in pregnant women. Itraconazole should be used for the treatment of systemic fungal infections in pregnancy only if the benefit outweighs the potential risk. Itraconazole should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. Itraconazole should not be administered to women of childbearing potential for the treatment of onychomycosis unless they are using effective measures to prevent pregnancy and they begin therapy on the second or third day following the onset of menses. Highly effective contraception should be continued throughout itraconazole therapy and for 2 months following the end of treatment. During postmarketing experience, cases of congenital abnormalities have been reported. (See ADVERSE REACTIONS: Postmarketing Experience .)
Pediatric use
Pediatric Use: The efficacy and safety of itraconazole have not been established in pediatric patients. The long-term effects of itraconazole on bone growth in children are unknown. In three toxicology studies using rats, itraconazole induced bone defects at dosage levels as low as 20 mg/kg/day (0.5 times the MRHD of 400 mg based on body surface area comparisons). The induced defects included reduced bone plate activity, thinning of the zona compacta of the large bones, and increased bone fragility. At a dosage level of 80 mg/kg/day (2 times the MRHD based on body surface area comparisons) over 1 year or 160 mg/kg/day (4 times the MRHD based on body surface area comparisons) for 6 months, itraconazole induced small tooth pulp with hypocellular appearance in some rats.
Geriatric use
Geriatric Use: Clinical studies of Itraconazole Capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. It is advised to use Itraconazole Capsules in these patients only if it is determined that the potential benefit outweighs the potential risks. In general, it is recommended that the dose selection for an elderly patient should be taken into consideration, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Transient or permanent hearing loss has been reported in elderly patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated (See BOXED WARNING: Drug Interactions , CONTRAINDICATIONS: Drug Interactions and PRECAUTIONS: Drug Interactions ).
Overdosage
Itraconazole is not removed by dialysis. In the event of accidental overdosage, supportive measures should be employed. Contact a certified poison control center for the most up to date information on the management of Itraconazole Capsules overdosage (1-800-222-1222 or www.poison.org). In general, adverse events reported with overdose have been consistent with adverse drug reactions already listed in this package insert for itraconazole. (See ADVERSE REACTIONS .)
Description
Itraconazole is an azole antifungal agent. Itraconazole is a 1:1:1:1 racemic mixture of four diastereomers (two enantiomeric pairs), each possessing three chiral centers. It may be represented by the following structural formula and nomenclature: (±)-1-[( R *)- sec -butyl]-4-[ p -[4-[ p -[[(2 R *,4 S *)-2-(2,4-dichlorophenyl)-2-(1 H -1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ 2 -1,2,4-triazolin-5-one mixture with (±)-1-[( R *)- sec -butyl]-4-[ p -[4-[ p -[[(2 S *,4 R *)-2-(2,4-dichlorophenyl)-2-(1 H -1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ 2 -1,2,4-triazolin-5-one or (±)-1-[( RS )- sec -butyl]-4-[ p -[4-[ p -[[(2 R ,4 S )-2-(2,4-dichlorophenyl)-2-(1 H -1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ 2 -1,2,4-triazolin-5-one Itraconazole has a molecular formula of C 35 H 38 Cl 2 N 8 O 4 and a molecular weight of 705.64. It is a white to slightly yellowish powder. It is insoluble in water, very slightly soluble in alcohols, and freely soluble in dichloromethane. It has a pKa of 3.70 (based on extrapolation of values obtained from methanolic solutions) and a log (n-octanol/water) partition coefficient of 5.66 at pH 8.1. Itraconazole Capsules contain 100 mg of itraconazole coated on sugar spheres (composed of sucrose, maize starch, and purified water). Inactive ingredients are hard gelatin capsule, hypromellose, polyethylene glycol (PEG) 20,000, titanium dioxide, FD&C Blue No. 1, FD&C Blue No. 2, D&C Red No. 22 and D&C Red No. 28. Meets USP Dissolution Test 2. Chemical Structure
Mechanism of action
Mechanism of Action In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.
How supplied
Itraconazole Capsules are available containing 100 mg of itraconazole, with a blue opaque cap and pink transparent body, imprinted with "PP 100." The capsules are supplied in bottles of 30 capsules (NDC 10147-1700-3). Store at controlled room temperature 15°–25°C (59°–77°F). Protect from light and moisture.
Storage
Store at controlled room temperature 15°–25°C (59°–77°F). Protect from light and moisture.
Patient information
Information for Patients: The topical effects of mucosal exposure may be different between Itraconazole Capsules and SPORANOX ® (itraconazole) Oral Solution. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis. Itraconazole Capsules should not be used interchangeably with SPORANOX ® (itraconazole) Oral Solution. Instruct patients to take Itraconazole Capsules with a full meal. Itraconazole Capsules must be swallowed whole. Instruct patients about the signs and symptoms of congestive heart failure, and if these signs or symptoms occur during itraconazole administration, they should discontinue itraconazole and contact their healthcare provider immediately. Instruct patients to stop itraconazole treatment immediately and contact their healthcare provider if any signs and symptoms suggestive of liver dysfunction develop. Such signs and symptoms may include unusual fatigue, anorexia, nausea and/or vomiting, jaundice, dark urine, or pale stools. Instruct patients to contact their physician before taking any concomitant medications with itraconazole to ensure there are no potential drug interactions. Instruct patients that hearing loss can occur with the use of itraconazole. The hearing loss usually resolves when treatment is stopped, but can persist in some patients. Advise patients to discontinue therapy and inform their physicians if any hearing loss symptoms occur. Instruct patients that dizziness or blurred/double vision can sometimes occur with itraconazole. Advise patients that if they experience these events, they should not drive or use machines.
Label text from the FDA structured product label by Patriot Pharmaceuticals (revised Jan 28, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Itraconazole in 12 products
itraconazole NDC products (12)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 62332-204 | Itraconazole 100 mg/1 Capsule | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-204 | Itraconazole 100 mg/1 Capsule | Alembic Pharmaceuticals Limited | ANDA |
| 60687-299 | Itraconazole 100 mg/1 Capsule | American Health Packaging | ANDA |
| 65162-087 | Itraconazole 10 mg/mL Solution | Amneal Pharmaceuticals LLC | ANDA |
| 65162-630 | Itraconazole 100 mg/1 Capsule | Amneal Pharmaceuticals LLC | ANDA |
| 67877-454 | Itraconazole 100 mg/1 Capsule, Coated Pellets | Ascend Laboratories, LLC | ANDA |
| 50268-450 | Itraconazole 100 mg/1 Capsule | AvPAK | ANDA |
| 31722-006 | Itraconazole 10 mg/mL Solution | Camber Pharmaceuticals, Inc. | ANDA |
| 16714-743 | Itraconazole 100 mg/1 Capsule, Coated Pellets | NorthStar RxLLC | ANDA |
| 16571-245 | Itraconazole 100 mg/1 Capsule | Rising Pharma Holdings, Inc. | ANDA |
| 13668-463 | Itraconazole 100 mg/1 Capsule | Torrent Pharmaceuticals Limited | ANDA |
| 10147-1700 | Itraconazole 100 mg/1 Capsule | Patriot Pharmaceuticals | NDA |
Frequently asked questions
What is itraconazole used for?
Itraconazole Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are…
What are the side effects of itraconazole?
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these… See the full label for the complete list.
Who makes itraconazole?
itraconazole is listed by 11 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, American Health Packaging, Amneal Pharmaceuticals LLC.