ITRACONAZOLE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ITRACONAZOLE (UNII: 304NUG5GF4) (ITRACONAZOLE - UNII:304NUG5GF4)

Available from:

Alembic Pharmaceuticals Inc.

INN (International Name):

ITRACONAZOLE

Composition:

ITRACONAZOLE 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Itraconazole capsules    are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: 1. Blastomycosis, pulmonary and extrapulmonary 2. Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non- meningeal histoplasmosis, and 3. 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:  1. Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and 2. 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: Post-marketing 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 of 200 mg of itraconazole capsules   b.i.d., followed by a 3-week period without itraconazole, which was followed by a second 1-week course 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. 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 WARNINGS, WARNINGS, PRECAUTIONS: Drug Interactions-Calcium Channel Blockers, ADVERSE REACTIONS: Post-marketing 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 are 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.

Product summary:

Itraconazole capsules are supplied as follows: 100 mg: Blue opaque cap/pink transparent body size “0” hard gelatin capsules having imprinting “A” on cap with black ink and “175” on body with black ink filled with white to off-white pellets.  NDC 62332-204-30        Bottle of    30 Capsules NDC 62332-204-90        Bottle of    90 Capsules NDC 62332-204-71        Bottle of    500 Capsules NDC 62332-204-10        Unit Dose Capsules of  100 (Blisters of 10) NDC 62332-204-04        7 Blister Packs x 4 Capsules Each (7 Day Treatment Pack) Store between 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Keep out of reach of children. Medication Guide available at http://www.alembicusa.com/medicationguide.aspx or call 1-866-210-9797. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Panelav 389350, Gujarat, India Manufactured for: Alembic Pharmaceuticals, Inc. Bedminster, NJ 07921, USA Revised: 02/2024

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

ITRACONAZOLE - ITRACONAZOLE CAPSULE
ALEMBIC PHARMACEUTICALS INC.
----------
ITRACONAZOLE CAPSULES
RX ONLY
BOXED WARNING
CONGESTIVE HEART FAILURE, CARDIAC EFFECTS AND DRUG INTERACTIONS
CONGESTIVE HEART FAILURE AND CARDIAC EFFECTS:
• 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. IF SIGNS OR
SYMPTOMS OF CONGESTIVE HEART FAILURE OCCUR DURING ADMINISTRATION OF
ITRACONAZOLE CAPSULES, DISCONTINUE ADMINISTRATION.
• WHEN ITRACONAZOLE WAS ADMINISTERED INTRAVENOUSLY TO DOGS AND
HEALTHY
HUMAN VOLUNTEERS, NEGATIVE INOTROPIC EFFECTS WERE SEEN. (SEE
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS: DRUG INTERACTIONS,
ADVERSE REACTIONS: POST-MARKETING EXPERIENCE, AND CLINICAL
PHARMACOLOGY: SPECIAL POPULATIONS FOR MORE INFORMATION.)
DRUG INTERACTIONS:
• COADMINISTRATION OF A NUMBER OF CYP3A4 SUBSTRATES ARE
CONTRAINDICATED WITH ITRACONAZOLE CAPSULES. SOME EXAMPLES OF DRUGS
THAT ARE CONTRAINDICATED FOR COADMINISTRATION WITH ITRACONAZOLE
CAPSULES
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.
• COADMINISTRATION WITH COLCHICINE, FESOTERODINE, AND SOLIFENACIN IS
CONTRAINDICATED IN SUBJECTS WITH VARYING DEGREES OF RENAL OR HEPATIC
IMPAIRMENT.
• COADMINISTRATION WITH ELIGLUSTAT IS CONTRAINDICATED IN SUBJECTS
THAT ARE
POOR OR INTERMEDIATE METABOLIZERS OF CYP2D6 AND IN SUBJECTS TAKING
STRONG OR MODERATE CYP2D6 INHIBITORS.
• COADMINISTRATION WITH VENETOCLAX IS CONTRAINDICATED IN PATIENTS
WITH
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL)
DURING THE DOSE INITIATION AND RAMP-UP PHASE OF VENET