SPORANOX- itraconazole capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Janssen Pharmaceuticals, Inc.

INN (International Name):

ITRACONAZOLE

Composition:

ITRACONAZOLE 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

SPORANOX ® (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. SPORANOX ® 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: Post-marketing Experiencefor more information.) 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. 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. 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. 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. Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given SPORANOX ® Capsules) in which patients with onychomycosis of the toenails received 200 mg of SPORANOX ® 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). Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given SPORANOX ® Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of SPORANOX ® Capsules b.i.d., followed by a 3-week period without SPORANOX ® , which was followed by a second 1-week pulse of 200 mg of SPORANOX ® 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. SPORANOX ® (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: Post-marketing Experience, and CLINICAL PHARMACOLOGY: Special Populations.) Coadministration of a number of CYP3A4 substrates are contraindicated with SPORANOX ® . 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 InteractionsSection 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. SPORANOX ® should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. SPORANOX ® 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 SPORANOX ® to patients with hypersensitivity to other azoles.

Product summary:

SPORANOX ® (itraconazole) Capsules are available containing 100 mg of itraconazole, with a blue opaque cap and pink transparent body, imprinted with "JANSSEN" and "SPORANOX 100." The capsules are supplied in unit-dose blister packs of 3 × 10 capsules (NDC 50458-290-01) and bottles of 30 capsules (NDC 50458-290-04). Store at controlled room temperature 15°–25°C (59°–77°F). Protect from light and moisture.

Authorization status:

New Drug Application

Summary of Product characteristics

SPORANOX- ITRACONAZOLE CAPSULE
JANSSEN PHARMACEUTICALS, INC.
----------
SPORANOX
(ITRACONAZOLE)
CAPSULES
®
BOXED WARNING
CONGESTIVE HEART FAILURE, CARDIAC EFFECTS AND DRUG INTERACTIONS
Congestive Heart Failure and Cardiac Effects
SPORANOX
(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 SPORANOX
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 POPULATIONSFOR MORE INFORMATION.)
Drug Interactions
COADMINISTRATION OF A NUMBER OF CYP3A4 SUBSTRATES ARE
CONTRAINDICATED WITH SPORANOX
. SOME EXAMPLES OF DRUGS THAT ARE
CONTRAINDICATED FOR COADMINISTRATION WITH SPORANOX
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 VENETOCLAX. SEE
PRECAUTIONS: DRUG INTERA