1 INDICATIONS AND USAGE TOLSURA is indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised adult 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, anti-fungal therapy should be adjusted accordingly TOLSURA is an azole antifungal indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised adult patients ( 1 ): 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.

Limitations of Use: TOLSURA is not indicated for the treatment of onychomycosis ( 1 ) TOLSURA is NOT interchangeable or substitutable with other itraconazole products ( 1 ) Limitations of Use: TOLSURA is not indicated for the treatment of onychomycosis.

TOLSURA is NOT interchangeable or substitutable with other itraconazole products due to the differences in the dosing between TOLSURA and other itraconazole products.

Therefore, follow the specific dosage recommendations for TOLSURA [see Dosage and Administration (2) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Congestive Heart Failure [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Cardiac Dysrhythmias [see Warnings and Precautions (5.3) ] Pseudoaldosteronism [see Warnings and Precautions (5.4) ] Peripheral Neuropathy [see Warnings and Precautions (5.6) ] Hearing Loss [see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [see Warnings and Precautions (5.8) ] Most common adverse reactions (incidence ≥ 1%) are nausea, rash, vomiting, edema, headache, diarrhea, fatigue, fever, pruritus, hypertension, abnormal hepatic function, abdominal pain, dizziness, hypokalemia, anorexia, malaise, decreased libido, somnolence, albuminuria, impotence ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience 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.

Adverse Reactions in the Treatment of Systemic Fungal Infections Safety data with itraconazole capsules 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).

Table 2 lists adverse reactions reported by at least 1% of patients.

Table 2: Clinical Trials of Systemic Fungal Infections: Adverse Reactions Occurring with an Incidence of ≥1% Body System/Adverse Reaction 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 reactions reported at a rate of <1% included: constipation, gastritis, depression, insomnia, tinnitus, menstrual disorder, adrenal insufficiency, gynecomastia, and male breast pain.

Adverse Reactions Reported from Other Clinical Trials In addition, the following adverse reactions were reported in itraconazole-treated patients who participated in clinical trials: Hepatobiliary Disorders: hyperbilirubinemia; 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, gammaglutamyltransferase 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: hyperhidrosis; Vascular Disorders: hypotension 6.2 Postmarketing Experience Adverse reactions that have been identified during post-marketing experience with itraconazole are listed in Table 3.

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.

Table 3: Postmarketing Reports of Adverse Drug Reactions Blood and Lymphatic System Disorders: Leukopenia, neutropenia, thrombocytopenia Immune System Disorders: Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema Endocrine Disorders: Pseudoaldosteronism Nervous System Disorders: Peripheral neuropathy, paresthesia, hypoesthesia, tremor Eye Disorders: Visual disturbances, including blurred vision and diplopia Ear and Labyrinth Disorders: Transientor permanent hearing loss Respiratory, Thoracic and Mediastinal Disorders: Pulmonary edema, dyspnea Gastrointestinal Disorders: Pancreatitis, dysgeusia Hepatobiliary Disorders: Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity, urticaria Musculoskeletal and Connective Tissue Disorders: Arthralgia Renal and Urinary Disorders: Urinary incontinence, pollakiuria Reproductive System and Breast Disorders: Erectile dysfunction General Disorders and Administration Site Conditions: Peripheral edema Investigations: Blood creatine phosphokinase increased