Sporanox Oral Solution

>10%

Nausea (11%)

1-10%

Rash (9%)

Vomiting (5%)

Edema (4%)

Headache (4%)

Abnormal liver function test results (3%)

Diarrhea (3%)

Fever (3%)

Hypertension (3%)

Pruritus (3%)

Fatigue (2-3%)

Abdominal pain (2%)

Dizziness (2%)

Hypertriglyceridemia (2%)

Hypokalemia (2%)

Albuminuria (1%)

Anorexia (1%)

Decreased libido (1%)

Hepatitis (1%)

Malaise (1%)

Postmarketing Reports

Blood and Lymphatic System Disorders: Leukopenia, neutropenia, thrombocytopenia

Immune System Disorders: Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema

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

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: Peripheral edema

Mechanism of Action

Triazole antifungal agent; inhibits cytochrome P450-dependent synthesis of ergosterol, which in turn inhibits cell-membrane formation

Absorption

Peak plasma time: Oral solution with fasting, 2.2 hr; capsule with food, 5 hr

Peak plasma concentration: Oral solution with fasting, 544 ng/mL; capsule with food, 302 ng/mL

Distribution

Protein bound: 99.8%

Vd: 796 L or 10 L/kg

Metabolism

Metabolized by hepatic enzyme CYP3A4

Enzymes inhibited: CYP3A4

Elimination

Half-life: 64±32 hr

Excretion: Urine, feces

Avoid taking antacids or stomach acid reducers (Tagamet, Pepcid, Axid, Zantac, and others) within 1 hour before or 2 hours after you take itraconazole. These medications can make it harder for your body to absorb itraconazole.

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.

SPORANOX® 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 SPORANOX® use should be reassessed. (See WARNINGS: Hepatic Effects and PRECAUTIONS: Hepatotoxicity and PATIENT INFORMATION .)

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 2 below lists adverse events reported by at least 2% of patients treated with SPORANOX® Oral Solution in U.S. clinical trials. Data on patients receiving comparator agents in these trials are included for comparison.

Table 2: Summary of Adverse Events Reported by ≥ 2% of SPORANOX® Treated Patients in U.S. Clinical Trials (Total)

Adverse events reported by less than 2% of patients in U.S. clinical trials with SPORANOX® 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 SPORANOX® Oral Solution or received Amphotericin B reported the following adverse events in the itraconazole intravenous/SPORANOX® Oral Solution treatment arm which are not listed above in the subsection “Adverse Events Reported in Oropharnyngeal 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, tremor, and pulmonary infiltration.

In addition, the following adverse drug reactions were reported in patients who participated in SPORANOX® 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 SPORANOX® 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, gammaglutamyltransferase 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 SPORANOX® Oral Solution clinical trials: mucosal inflammation.

Post-marketing Experience

Adverse drug reactions that have been first identified during post-marketing experience with SPORANOX® (all formulations) are listed in the table 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 3: Postmarketing Reports of Adverse Drug Reactions

There is limited information on the use of SPORANOX® 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 post-marketing experience. A causal relationship with SPORANOX® has not been established. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: DRUG INTERACTIONS for more information.)

Read the entire FDA prescribing information for Sporanox Oral Solution (Itraconazole Oral Solution)