FDA label 2c506c07-df63-e1ee-e063-6394a90a0bb1

BOXED WARNING Congestive Heart Failure, Cardiac Effects and Drug Interactions Congestive Heart Failure and Cardiac Effects: If signs or symptoms of congestive heart failure occur during administration of Itraconazole Oral Solution, continued Itraconazole Oral Solution use should be reassessed. When itraconazole was administered intravenously to dogs and healthy human volunteers, negative inotropic effects were seen. (See CONTRAINDICATIONS , WARNINGS , PRECAUTIONS : Drug Interactions , ADVERSE REACTIONS: Postmarketing Experience , and CLINICAL PHARMACOLOGY: Special Populations for more information.) Drug Interactions Coadministration of a number of CYP3A4 substrates are contraindicated with Itraconazole Oral Solution. Some examples of drugs that are contraindicated for coadministration with Itraconazole Oral Solution 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 Interactions Section for specific examples. Coadministration with itraconazole can cause elevated plasma concentrations of these drugs and 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. See CONTRAINDICATIONS and WARNINGS Sections, and PRECAUTIONS: Drug Interactions Section for specific examples.

WARNINGS Hepatic Effects Itraconazole Oral Solution 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 Oral Solution use or reinstitution of treatment with Itraconazole Oral Solution 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 Oral Solution and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with Itraconazole Oral Solution is contraindicated. (See BOXED WARNING , CONTRAINDICATIONS , and PRECAUTIONS: Drug Interactions .) Cardiac Disease Itraconazole Oral Solution should not be used 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 Oral Solution 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 Oral Solution, monitor carefully and consider other treatment alternatives which may include discontinuation of Itraconazole Oral Solution 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 Oral Solution 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 Oral Solution 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 CONTRAINDICATIONS , CLINICAL PHARMACOLOGY: Special Populations , 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 Oral Solution, substitution with an appropriate antifungal drug that is not associated with pseudoaldosteronism, or use of aldosterone receptor antagonists. Interaction Potential Itraconazole Oral Solution 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 Oral Solution and SPORANOX ® (itraconazole) Capsules/Itraconazole Capsules 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. Only Itraconazole Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis. Hydroxypropyl-β-cyclodextrin Itraconazole Oral Solution contains the excipient hydroxypropyl-β-cyclodextrin which produced adenocarcinomas in the large intestine and exocrine pancreatic adenocarcinomas in a rat carcinogenicity study. These findings were not observed in a similar mouse carcinogenicity study. The clinical relevance of these adenocarcinomas is unknown. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, and Impairment of Fertility .) Treatment of Severely Neutropenic Patients Itraconazole Oral Solution as treatment for oropharyngeal and/or esophageal candidiasis was not investigated in severely neutropenic patients. Due to its pharmacokinetic properties, Itraconazole Oral Solution is not recommended for initiation of treatment in patients at immediate risk of systemic candidiasis.

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 Oral Solution 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 Oral Solution 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 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 Oral Solution Treated Patients in U.S. Clinical Trials (Total) Body System/ Adverse Event Itraconazole Total (n = 350 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. ) % All controlled studies (n = 272) % Fluconazole (n = 125 Of the 125 patients, 62 were treated for oropharyngeal candidiasis and 63 were treated for esophageal candidiasis. ) % Clotrimazole (n = 81 All 81 patients were treated for oropharyngeal candidiasis. ) % 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 Adverse events reported by less than 2% of patients in U.S. clinical trials with Itraconazole Oral Solution 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. Postmarketing Experience Adverse drug reactions that have been first identified during postmarketing experience with Itraconazole Oral Solution (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 Oral Solution 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 Oral Solution has not been established. (See CLINICAL PHARMACOLOGY: Special Populations , CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS: Drug Interactions for more information.)

<table width="85%" ID="Table3"><caption>Table 3: Summary of Adverse Events Reported by &#x2265;2% of Itraconazole Oral Solution Treated Patients in U.S. Clinical Trials (Total)</caption><col width="22%" align="left" valign="middle"/><col width="15%" align="center" valign="middle"/><col width="21%" align="center" valign="middle"/><col width="21%" align="center" valign="middle"/><col width="21%" align="center" valign="middle"/><thead><tr><th rowspan="2" styleCode="Lrule">Body System/ Adverse Event</th><th colspan="2" styleCode="Lrule">Itraconazole</th><th styleCode="Lrule"/><th styleCode="Lrule Rrule"/></tr><tr><th align="center" styleCode="Lrule Toprule">Total (n = 350 <footnote ID="K3318">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.</footnote>) % </th><th styleCode="Lrule Toprule">All controlled studies (n = 272) % </th><th styleCode="Lrule Toprule">Fluconazole (n = 125 <footnote ID="K3331">Of the 125 patients, 62 were treated for oropharyngeal candidiasis and 63 were treated for esophageal candidiasis. </footnote>) % </th><th styleCode="Lrule Rrule Toprule">Clotrimazole (n = 81 <footnote ID="K3337">All 81 patients were treated for oropharyngeal candidiasis.</footnote>) % </th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">11</td><td styleCode="Rrule">10</td><td styleCode="Rrule">11</td><td styleCode="Rrule">5</td></tr><tr><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">11</td><td styleCode="Rrule">10</td><td styleCode="Rrule">10</td><td styleCode="Rrule">4</td></tr><tr><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">7</td><td styleCode="Rrule">6</td><td styleCode="Rrule">8</td><td styleCode="Rrule">1</td></tr><tr><td styleCode="Lrule Rrule"> Abdominal pain</td><td styleCode="Rrule">6</td><td styleCode="Rrule">4</td><td styleCode="Rrule">7</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Constipation</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Body as a whole</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Fever</td><td styleCode="Rrule">7</td><td styleCode="Rrule">6</td><td styleCode="Rrule">8</td><td styleCode="Rrule">5</td></tr><tr><td styleCode="Lrule Rrule"> Chest pain</td><td styleCode="Rrule">3</td><td styleCode="Rrule">3</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Pain</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fatigue</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Respiratory disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Coughing</td><td styleCode="Rrule">4</td><td styleCode="Rrule">4</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Dyspnea</td><td styleCode="Rrule">2</td><td styleCode="Rrule">3</td><td styleCode="Rrule">5</td><td styleCode="Rrule">1</td></tr><tr><td styleCode="Lrule Rrule"> Pneumonia</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Sinusitis</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sputum increased</td><td styleCode="Rrule">2</td><td styleCode="Rrule">3</td><td styleCode="Rrule">3</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Skin and appendages disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Rash</td><td styleCode="Rrule">4</td><td styleCode="Rrule">5</td><td styleCode="Rrule">4</td><td styleCode="Rrule">6</td></tr><tr><td styleCode="Lrule Rrule"> Increased sweating</td><td styleCode="Rrule">3</td><td styleCode="Rrule">4</td><td styleCode="Rrule">6</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Skin disorder unspecified</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Central/peripheral nervous system</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Headache</td><td styleCode="Rrule">4</td><td styleCode="Rrule">4</td><td styleCode="Rrule">6</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dizziness</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">4</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Resistance mechanism disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pneumocystis carinii infection</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="2" styleCode="Lrule Rrule"><content styleCode="bold">Psychiatric disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Depression</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td><td styleCode="Rrule">1</td></tr></tbody></table>

<table width="80%" ID="Table4"><caption>Table 4: Postmarketing Reports of Adverse Drug Reactions</caption><colgroup><col align="left" valign="top" width="35%"/><col align="left" valign="top" width="65%"/></colgroup><tbody><tr><td><content styleCode="bold">Blood and Lymphatic System Disorders:</content></td><td>Leukopenia, neutropenia, thrombocytopenia</td></tr><tr><td><content styleCode="bold">Immune System Disorders:</content></td><td>Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema</td></tr><tr><td><content styleCode="bold">Endocrine Disorders:</content></td><td>Pseudoaldosteronism</td></tr><tr><td><content styleCode="bold">Metabolism and Nutrition Disorders:</content></td><td>Hypertriglyceridemia</td></tr><tr><td><content styleCode="bold">Nervous System Disorders:</content></td><td>Peripheral neuropathy, paresthesia, hypoesthesia, tremor</td></tr><tr><td><content styleCode="bold">Eye Disorders:</content></td><td>Visual disturbances, including vision blurred and diplopia</td></tr><tr><td><content styleCode="bold">Ear and Labyrinth Disorders:</content></td><td>Transient or permanent hearing loss</td></tr><tr><td><content styleCode="bold">Cardiac Disorders:</content></td><td>Congestive heart failure, bradycardia</td></tr><tr><td><content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders:</content></td><td>Pulmonary edema</td></tr><tr><td><content styleCode="bold">Gastrointestinal Disorders:</content></td><td>Pancreatitis</td></tr><tr><td><content styleCode="bold">Hepatobiliary Disorders</content>: </td><td>Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis, reversible increases in hepatic enzymes</td></tr><tr><td><content styleCode="bold">Skin and Subcutaneous Tissue Disorders:</content></td><td>Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity, urticaria</td></tr><tr><td><content styleCode="bold">Musculoskeletal and Connective Tissue Disorders:</content></td><td>Arthralgia</td></tr><tr><td><content styleCode="bold">Renal and Urinary Disorders:</content></td><td>Urinary incontinence, pollakiuria</td></tr><tr><td><content styleCode="bold">Reproductive System and Breast Disorders:</content></td><td>Erectile dysfunction</td></tr><tr><td><content styleCode="bold">General Disorders and Administration Site Conditions:</content></td><td>Peripheral edema</td></tr><tr><td><content styleCode="bold">Investigations:</content></td><td>Blood creatine phosphokinase increased</td></tr></tbody></table>