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U.S. Department of Health and Human Services

Safety

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Sporanox (Itraconazole) Capsules

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

June 2014

Summary View

BOXED WARNING

  • Coadministration of the following drugs are contraindicated with Sporanox Capsules: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin and, in subjects with renal or hepatic impairment, colchicine. 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 torsades de pointes, a potentially fatal arrhythmia.

CONTRAINDICATIONS

Drug Interactions
  • Coadministration of a number of CYP3A4 substrates are contraindicated with Sporanox. Plasma concentrations increase for the following drugs: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin and, in subjects with renal or hepatic impairment, colchicine. This increase in drug concentrations caused by coadministration with itraconazole may increase or prolong both the pharmacologic effect 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.

WARNINGS

Cardiac Disease
  • Calcium channel blockers can have negative… Concomitant administration of Sporanox and felodipine…
Interaction potential
  • Sporanox 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.
Interchangeability
  • Sporanox (itraconazole) Capsules and Sporanox Oral Solution 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. In addition, the topical effects of mucosal exposure may be different between the two formulations. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis.

PRECAUTIONS

Information for Patients
  • …Sporanox Capsules must be swallowed whole.
  • Instruct patients that dizziness, blurred/double vision or hearing loss can sometimes occur with itraconazole. Advise patients that if they experience these events, they should not drive or use machines.

DRUG INTERACTIONS

(Entire Sections rewritten and enhanced table addition)

Geriatric Use
  • Clinical studies of Sporanox Capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. It is advised to use Sporanox Capsules in these patients only if it is determined that the potential benefit outweighs the potential risks. In general, it is recommended that the dose selection for an elderly patient should be taken into consideration, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Renal Impairment
  • …The exposure of itraconazole may be lower in some patients with renal insufficiency. Caution should be exercised … and adjusting the dose may be considered..
Hepatic Impairment
  • …It is recommended that patients with impaired hepatic function be carefully monitored when taking Sporanox. It is recommended that the prolonged elimination half-life of itraconazole observed in the single oral dose clinical trial with itraconazole capsules in cirrhotic patients be considered when deciding to initiate therapy with other medications metabolized by CYP3A4.
  • In patients with elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment with Sporanox is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk. It is recommended that liver function monitoring be done in patients with preexisting hepatic function abnormalities or those who have experienced liver toxicity with other medications

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.
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

  • Table 5: Postmarketing Reports of Adverse Drug Reactions (Minor editorial edits and addition of)
  • Investigations: Blood creatine phosphokinase increased

PATIENT INFORMATION

Never take Sporanox if you are taking any of the medicines listed below…

  • disopyramide (such as Norpace)
  • dronedarone (such as Multaq)
  • ranolazine (such as Ranexa)

are taking any of the following medicines:

  • lurasidone (such as Latuda)
  • eplerenone (such as Inspra) 
  • irinotecan (such as Camptosar)
  • colchicine (such as Colcrys) [if you also have pre-existing kidney or liver impairment]

HOW SHOULD I TAKE SPORANOX?

  • Sporanox can sometimes cause dizziness, blurred/double vision or hearing loss. If you have these symptoms, do not drive or use machines.

WHAT ARE THE POSSIBLE SIDE EFFECTS OF SPORANOX?

  • The most common side effects include: headache, and digestive system problems (such as nausea, and abdominal pain).

  

April 2012

Summary View

 

BOXED WARNING

  • Cardiac Effects and Drug Interactions:…
  • Drug interactions: Oral Midazolam, Nisoladipine, Felodipine…Triazolam…Lovastatin, Simvastatin, Ergot Alkaloids such as Dihydroergotamine, Ergometrine (Ergonovine), Ergotamine and Methylergometrine (Methylergonovine) or Methadone…
 

CONTRAINDICATIONS

  • and Clinical Pharmacology, Special Populations.
Drug Interactions:
  • Felodipine…Methadone
 

WARNINGS:

Cardiac Dysrhythmias:
  • Methadone…
 

PRECAUTIONS

Drug Interactions:
Table 1
  • Calcium Channel Blockers – felodipine…
  • Other – Methadone…
Calcium Channel blockers:
  • Nisoldipine…
  • A clinical study showed that Felodipine Exposure was increased by coadministration of Itraconazole, resulting in approximately a 6-fold increase in the AUC and an 8-fold increase in the Cmax
Other:
  • Methadone and…
  • …Methadone or…
 

PATIENT INFORMATION

Never take Sporanox if you:
Are taking any of the medicines listed below. Dangerous or even life-threatening abnormal heartbeats could result:
  • Methadone (such as Dolophine)
  • Felodipine (such as Plendil)