Itraconazole for Dandruff, Cradle Cap, and Other Scalp Conditions

INDICATIONS AND USAGE 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 : 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 mg 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 .)

WARNINGS AND PRECAUTIONS Hepatotoxicity : Serious hepatotoxicity, including liver failure and death were reported with the use of itraconazole. Discontinue treatment if signs of liver dysfunction occur ( 5.2 ) Cardiac Dysrhythmias : Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using certain drugs that are metabolized by human CYP450 enzymes concomitantly with oral itraconazole and/or other CYP3A4 inhibitors. ( 4 , 5.3 , 5.5 ) Pseudoaldosteronism : Manifested by the onset or worsening of hypertension, and abnormal laboratory findings. Monitor blood pressure and potassium levels and manage as necessary ( 5.4 ). Peripheral Neuropathy : This has been reported in patients on long-term therapy with itraconazole. Monitor and promptly evaluate neurologic symptoms. ( 5.6 ) Hearing Loss : Reversible or permanent has been reported in patients. Discontinue treatment if hearing loss occurs ( 5.7 ) 5.1 Congestive Heart Failure TOLSURA can cause or exacerbate congestive heart failure (CHF) [see Boxed Warning and Adverse Reactions (6.1) ]. For patients with evidence of ventricular dysfunction such as CHF, history or risk factors for CHF, physicians should carefully review the risks and benefits of TOLSURA 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. Inform such patients of the signs and symptoms of CHF and monitor carefully for signs and symptoms of CHF during treatment. If signs or symptoms of CHF appear or worsen during administration of TOLSURA, reassess the benefit-risk of continuing treatment. When itraconazole was administered intravenously to anesthetized dogs, a dose-related negative inotropic effect was demonstrated. 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 CHF, peripheral edema, and pulmonary edema. In post-marketing experience, heart failure was more frequently reported in patients receiving higher total daily doses of itraconazole of 400 mg although there were also cases reported among those receiving lower total daily doses [see Adverse Reactions (6.2) ] . 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, when co-administering itraconazole and calcium channel blockers, monitor carefully for signs and symptoms of CHF during treatment due to an increased risk of CHF. Concomitant administration of TOLSURA and felodipine or nisoldipine is contraindicated [see Contraindications (4.1) , Drug Interactions (7.1) and Adverse Reactions (6.2) ] 5.2 Hepatotoxicity Itraconazole has been associated with 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, discontinue treatment and perform testing for liver disease. Continued TOLSURA use or reinstitution of treatment with TOLSURA is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk [ see Adverse Reactions (6.1) ]. 5.3 Cardiac Dysrhythmias Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugs such as, pimozide, methadone, or quinidine concomitantly with oral itraconazole and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with TOLSURA is contraindicated [see Boxed Warning , Contraindications (4) and Drug Interactions (7) ]. 5.4 Pseudoaldosteronism Pseudoaldosteronism, manifested by the onset of hypertension or worsening of hypertension, and abnormal laboratory findings (hypokalemia, low serum renin and aldosterone, and elevate 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 TOLSURA, substitution with an appropriate antifungal drug that is not associated with pseudoaldosteronism, or use of aldosterone receptor antagonists. 5.5 Drug Interaction Potential Itraconazole has a potential for clinically important drug interactions [see Drug Interactions (7.1 , 7.2) ] . Co-administration of specific drugs with TOLSURA may result in changes in the efficacy of itraconazole and/or the co-administered drug, life-threatening effects and/or sudden death. [see Boxed Warning , Contraindications (4.1) and Drug Interactions (7.1 , 7.2) ]. 5.6 Peripheral Neuropathy Cases of peripheral neuropathy have been reported in patients on long-term therapy with itraconazole. Monitor for and promptly evaluate neurologic symptoms. If neuropathy attributable to TOLSURA occurs, discontinue treatment. 5.7 Hearing Loss Reversible 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 , Contraindications (4.2) and Drug Interactions (7) ] . The hearing loss usually resolves when treatment is stopped but can persist in some patients. 5.8 Hypersensitivity Reactions TOLSURA is contraindicated in patients with a known hypersensitivity to itraconazole [see Contraindications (4.2) ]. Hypersensitivity reactions have been reported with the use of itraconazole [see Adverse Reactions (6.2) ] . Due to the limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal drugs, careful enquiry about previous hypersensitivity to other azole antifungal drugs should be made when prescribing TOLSURA. If hypersensitivity reactions to TOLSURA occurs, discontinue the drug and institute appropriate therapy.

Drug Interactions: Effect of Itraconazole 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 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. 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. Table 1:Drug Interactions with Itraconazole that Affect Concomitant Drug Concentrations Examples of Concomitant Drugs Within Class Prevention or Management Drug Interactions with Itraconazole 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 treatment. Analgesics Methadone Contraindicated during and 2 weeks after itraconazole treatment. Fentanyl Not recommended during and 2 weeks after itraconazole treatment. Alfentanil Buprenorphine (IV and sublingual) Oxycodone a Sufentanil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine a Contraindicated during and 2 weeks after itraconazole treatment. Digoxin a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antibacterials Bedaquiline b Concomitant itraconazole 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 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 treatment. Apixaban Rivaroxaban Vorapaxar Not recommended during and 2 weeks after itraconazole 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 treatment. See also Table 2. Antidiabetic Drugs Repaglinide a Saxagliptin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antihelminthics, Antifungals and Antiprotozoals Isavuconazonium Contraindicated during and 2 weeks after itraconazole treatment. Praziquantel Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Artemether-lumefantrine Quinine a Monitor for adverse reactions. Antimigraine Drugs Ergot alkaloids (e.g., dihydroergotamine, ergotamine) Contraindicated during and 2 weeks after itraconazole treatment. Eletriptan Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antineoplastics Irinotecan Contraindicated during and 2 weeks after itraconazole 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 a Avoid use during and 2weeks after itraconazole treatment. Docetaxel Axitinib Ibrutinib Bosutinib Lapatinib Cabazitaxel Nilotinib Cabozantinib Olaparib a Ceritinib Pazopanib Cobimetinib a Sunitinib Crizotinib Trabectedin Dabrafenib Trastuzumab­ Dasatinib emtansine Vinca alkaloids Avoid use during and 2 weeks after itraconazole treatment. Entrectinib a Pemigatinib a Talazoparib a 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 Nintedanib Brentuximab- Panobinostat vedotin Ponatinib Busulfan a Ruxolitinib Erlotinib Sonidegib Gefitinib b Tretinoin (oral) Idelalisib Vandetanib a ImatinibIxabepilone Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For idelalisib, see also Table 2. Antipsychotics, Anxiolytics and Hypnotics Alprazolam a Midazolam (IV) a Aripiprazole a Quetiapine Buspirone a Cariprazine Ramelteon Diazepam a Risperidone a Haloperidol a Suvorexant Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Zopiclone a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lurasidone Midazolam (oral) a Pimozide Triazolam a Contraindicated during and 2 weeks after itraconazole treatment. Antivirals Daclatasvir Indinavir a Maraviroc Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For indinavir, see also Table 2. Cobicistat Elvitegravir (ritonavir-boosted) Ombitasvir/Paritaprevir/Ritonavir with or without Dasabuvir Ritonavir Saquinavir (unboosted) a Monitor for adverse reactions. See also Table 2. Elbasvir/grazoprevir Glecaprevir/pibrentasvir Tenofovir disoproxil fumarate Not recommended during and 2 weeks after itraconazole treatment. Monitor for adverse reactions. Monitor for adverse reactions. Beta Blockers Nadolol a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Calcium Channel Blockers Felodipine a Nisoldipine Contraindicated during and 2 weeks after itraconazole treatment. Diltiazem Other dihydropyridines Verapamil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For diltiazem, see also Table 2. Cardiovascular Drugs, Miscellaneous Ivabradine Ranolazine Contraindicated during and 2 weeks after itraconazole treatment. Aliskiren a Riociguat Sildenafil (for pulmonary hypertension) Tadalafil (for pulmonary hypertension) Not recommended during and 2 weeks after itraconazole treatment. For sildenafil and tadalafil, see also Urologic Drugs below. Bosentan Guanfacine Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Contraceptives* Dienogest Ulipristal Monitor for adverse reactions. Diuretics Eplerenone Finerenone Contraindicated during and 2 weeks after itraconazole treatment. Gastrointestinal Drugs Cisapride Naloxegol Contraindicated during and 2 weeks after itraconazole treatment. Aprepitant Loperamide a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Netupitant Monitor for adverse reactions. Immunosuppressants Voclosporin Contraindicated during and for 2 weeks after itraconazole treatment. Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after itraconazole treatment. Budesonide (inhalation) a Budesonide (non­-­­­inhalation) Ciclesonide (inhalation) Cyclosporine (IV) a Cyclosporine (non-IV) Dexamethasone a Fluticasone (inhalation) a Fluticasone (nasal)Methylprednisolone a Tacrolimus (IV) a Tacrolimus (oral) Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lipid-Lowering Drugs Lomitapi

ADVERSE REACTIONS 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 Reported in Oropharyngeal or Esophageal Candidiasis Trials U.S. adverse experience data are derived from 350 immunocompromised patients (332 HIV seropositive/AIDS) treated for oropharyngeal or esophageal candidiasis. Table 3 below lists adverse events reported by at least 2% of patients treated with itraconazole oral solution in U.S. clinical trials. Data on patients receiving comparator agents in these trials are included for comparison. Table 3: Summary of Adverse Events Reported by ≥ 2% of Itraconazole Treated Patients in U.S. Clinical Trials (Total) Body System/ Adverse Event Itraconazole Total (n = 350 * ) % All controlled studies (n = 272) % Fluconazole (n = 125 † ) % Clotrimazole (n = 81 ‡ ) % Gastrointestinal disorders Nausea 11 10 11 5 Diarrhea 11 10 10 4 Vomiting 7 6 8 1 Abdominal pain 6 4 7 7 Constipation 2 2 1 0 Body as a whole Fever 7 6 8 5 Chest pain 3 3 2 0 Pain 2 2 4 0 Fatigue 2 1 2 0 Respiratory disorders Coughing 4 4 10 0 Dyspnea 2 3 5 1 Pneumonia 2 2 0 0 Sinusitis 2 2 4 0 Sputum increased 2 3 3 1 Skin and appendages disorders Rash 4 5 4 6 Increased sweating 3 4 6 1 Skin disorder unspecified 2 2 2 1 Central/peripheral nervous system Headache 4 4 6 6 Dizziness 2 2 4 1 Resistance mechanism disorders Pneumocystis carinii infection 2 2 2 0 Psychiatric disorders Depression 2 1 0 1 * Of the 350 patients, 209 were treated for oropharyngeal candidiasis in controlled studies, 63 were treated for esophageal candidiasis in controlled studies and 78 were treated for oropharyngeal candidiasis in an open study. † Of the 125 patients, 62 were treated for oropharyngeal candidiasis and 63 were treated for esophageal candidiasis. ‡ All 81 patients were treated for oropharyngeal candidiasis. Adverse events reported by less than 2% of patients in U.S. clinical trials with itraconazole included: adrenal insufficiency, asthenia, back pain, dehydration, dyspepsia, dysphagia, flatulence, gynecomastia, hematuria, hemorrhoids, hot flushes, implantation complication, infection unspecified, injury, insomnia, male breast pain, myalgia, pharyngitis, pruritus, rhinitis, rigors, stomatitis ulcerative, taste perversion, tinnitus, upper respiratory tract infection, vision abnormal, and weight decrease. Edema, hypokalemia and menstrual disorders have been reported in clinical trials with itraconazole capsules. Adverse Events Reported from Other Clinical Trials A comparative clinical trial in patients who received intravenous itraconazole followed by itraconazole oral solution or received Amphotericin B reported the following adverse events in the itraconazole intravenous/ itraconazole oral solution treatment arm which are not listed above in the subsection “Adverse Events Reported in Oropharyngeal or Esophageal Candidiasis Trials” or listed below as postmarketing reports of adverse drug reactions: serum creatinine increased, blood urea nitrogen increased, renal function abnormal, hypocalcemia, hypomagnesemia, hypophosphatemia, hypotension, tachycardia and pulmonary infiltration. In addition, the following adverse drug reactions were reported in patients who participated in itraconazole oral solution clinical trials: Cardiac Disorders: cardiac failure; General Disorders and Administration Site Conditions: edema; Hepatobiliary Disorders: hepatic failure, hyperbilirubinemia; Metabolism and Nutrition Disorders: hypokalemia; Reproductive System and Breast Disorders: menstrual disorder The following is a list of additional adverse drug reactions associated with itraconazole that have been reported in clinical trials of itraconazole capsules and itraconazole IV excluding the adverse reaction term “Injection site inflammation” which is specific to the injection route of administration: Cardiac Disorders: left ventricular failure; Gastrointestinal Disorders: gastrointestinal disorder; General Disorders and Administration Site Conditions: face edema; Hepatobiliary Disorders: jaundice, hepatic function abnormal; Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, gamma-glutamyltransferase increased, urine analysis abnormal; Metabolism and Nutrition Disorders: hyperglycemia, hyperkalemia; Nervous System Disorders: somnolence; Psychiatric Disorders: confusional state; Renal and Urinary Disorders: renal impairment; Respiratory, Thoracic and Mediastinal Disorders: dysphonia; Skin and Subcutaneous Tissue Disorders: rash erythematous; Vascular Disorders: hypertension In addition, the following adverse drug reaction was reported in children only who participated in itraconazole oral solution clinical trials: mucosal inflammation. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Postmarketing Experience Adverse drug reactions that have been first identified during postmarketing experience with itraconazole (all formulations) are listed in Table 4 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. Table 4: 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 Metabolism and Nutrition Disorders: Hypertriglyceridemia Nervous System Disorders: Peripheral neuropathy, paresthesia, hypoesthesia, tremor Eye Disorders: Visual disturbances, including vision blurred and diplopia Ear and Labyrinth Disorders: Transient or permanent hearing loss Cardiac Disorders: Congestive heart failure, bradycardia Respiratory, Thoracic and Mediastinal Disorders: Pulmonary edema Gastrointestinal Disorders: Pancreatitis Hepatobiliary Disorders: Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis, reversible increases in hepatic enzymes 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 There is limited information on the use of itraconazole during pregnancy. Cases of congenital abnormalities including skeletal, genitourinary tract, cardiovascular and ophthalmic malformations as well as chromosomal and multiple malformations have been reported during postmarketing experience. A causal relationship with itraconazole has not been established (see CLINICAL PHARMACOLOGY: Special Populations , CONTRAINDICATIONS , WARNINGS, and PRECAUTIONS: Drug Interactions for more information).