SPORANOX SIDE EFFECTS
- Generic Name: itraconazole capsules
- Brand Name: Sporanox
- Drug Class: Antifungals, Systemic
SIDE EFFECTS
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.
Adverse Events In The Treatment Of Systemic Fungal Infections
Adverse event data 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). The table lists adverse events reported by at least 1% of patients.
Table 1: Clinical Trials of Systemic Fungal Infections: Adverse Events Occurring with an Incidence of Greater than or Equal to 1%
| Body System/Adverse Event | 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* | 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 |
| * Rash tends to occur more frequently in immunocompromised patients receiving immunosuppressive medications. | |
Adverse events infrequently reported in all studies included constipation, gastritis, depression, insomnia, tinnitus, menstrual disorder, adrenal insufficiency, gynecomastia, and male breast pain.
Adverse Events Reported In Toenail Onychomycosis Clinical Trials
Patients in these trials were on a continuous dosing regimen of 200 mg once daily for 12 consecutive weeks.
The following adverse events led to temporary or permanent discontinuation of therapy.
Table 2: Clinical Trials of Onychomycosis of the Toenail: Adverse Events Leading to Temporary or Permanent Discontinuation of Therapy
| Adverse Event | Incidence (%) Itraconazole (N=112) |
| Elevated Liver Enzymes (greater than twice the upper limit of normal) | 4 |
| Gastrointestinal Disorders | 4 |
| Rash | 3 |
| Hypertension | 2 |
| Orthostatic Hypotension | 1 |
| Headache | 1 |
| Malaise | 1 |
| Myalgia | 1 |
| Vasculitis | 1 |
| Vertigo | 1 |
The following adverse events occurred with an incidence of greater than or equal to 1% (N=112): headache: 10%; rhinitis: 9%; upper respiratory tract infection: 8%; sinusitis, injury: 7%; diarrhea, dyspepsia, flatulence, abdominal pain, dizziness, rash: 4%; cystitis, urinary tract infection, liver function abnormality, myalgia, nausea: 3%; appetite increased, constipation, gastritis, gastroenteritis, pharyngitis, asthenia, fever, pain, tremor, herpes zoster, abnormal dreaming: 2%.
Adverse Events Reported In Fingernail Onychomycosis Clinical Trials
Patients in these trials were on a pulse regimen consisting of two 1-week treatment periods of 200 mg twice daily, separated by a 3-week period without drug.
The following adverse events led to temporary or permanent discontinuation of therapy.
Table 3: Clinical Trials of Onychomycosis of the Fingernail: Adverse Events Leading to Temporary or Permanent Discontinuation of Therapy
| Adverse Event | Incidence (%) Itraconazole (N=37) |
| Rash/Pruritus | 3 |
| Hypertriglyceridemia | 3 |
The following adverse events occurred with an incidence of greater than or equal to 1% (N=37): headache: 8%; pruritus, nausea, rhinitis: 5%; rash, bursitis, anxiety, depression, constipation, abdominal pain, dyspepsia, ulcerative stomatitis, gingivitis, hypertriglyceridemia, sinusitis, fatigue, malaise, pain, injury: 3%.
Adverse Events Reported From Other Clinical Trials
In addition, the following adverse drug reaction was reported in patients who participated in SPORANOX® Capsules clinical trials: Hepatobiliary Disorders: hyperbilirubinemia.
The following is a list of additional adverse drug reactions associated with itraconazole that have been reported in clinical trials of SPORANOX® Oral Solution and itraconazole IV excluding the adverse reaction term “Injection site inflammation” which is specific to the injection route of administration:
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, gamma-glutamyltransferase 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: rash erythematous, hyperhidrosis;
Vascular Disorders: hypotension
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 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 |
| 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 Conditions: | |
| Investigations: | Blood creatine phosphokinase increased |
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.
SRC: NLM .