Does Sporanox (itraconazole) cause side effects?

Sporanox (itraconazole) is an anti-fungal drug used to treat fungal infections of the toenails. It prevents growth of several types of fungi by preventing the fungi from producing the membranes that surround the fungal cells. 

Common side effects of Sporanox include

Serious side effects of Sporanox include

Drug interactions of Sporanox include cisapride, pimozide, quinidine, dofetilide, and levomethadyl, because Sporanox reduces the liver metabolism (breakdown) of these drugs, resulting in increased blood levels and side effects from the affected drugs.

HMG CoA-reductase inhibitors or "statins" such as simvastatin or lovastatin should also not be combined with Sporanox due to the risk of serious adverse effects.

Other drugs whose blood levels are increased by Sporanox include

Sporanox increases blood levels of certain calcium channel blockers, which can increase the occurrence of congestive heart failure due to Sporanox.

Sporanox increases blood levels of tacrolimus, sirolimus, and cyclosporine. It may also increase blood levels of fentanyl or prolong elimination of fentanyl, potentially leading to fatal respiratory depression.

Clarithromycin, erythromycin, indinavir, or ritonavir increase blood levels of Sporanox by reducing its elimination from the liver, resulting in increased side effects of Sporanox.

Carbamazepine, phenobarbital, phenytoin, rifampin, rifabutin, and isoniazid reduce the blood concentration of oral itraconazole, probably by increasing the elimination of itraconazole by the liver. This may reduce the effectiveness of itraconazole. Itraconazole tablets require acid from the stomach to dissolve.

Therefore, itraconazole should be administered at least two hours before taking antacids or other acid reducing medications such as cimetidine, ranitidine, or omeprazole

Sporanox has not been adequately studied in pregnant women. Cases of congenital abnormalities have been reported. Sporanox should not be used to treat nail fungal infections (onychomycosis) in pregnant patients.

Women of child bearing age undergoing treatment for fungal infections of the nails must use adequate contraception measures while receiving Sporanox and for two months after treatment. 

Sporanox is excreted in breast milk and should not be administered to nursing women or, alternatively, breastfeeding should be discontinued.

What are the important side effects of Sporanox (itraconazole)?

The most common side effects of itraconazole are:

Other important side effects include:

Less common but more serious side effects include hepatitis and congestive heart failure.

It is important to report any signs or symptoms that may suggest liver dysfunction so that the appropriate laboratory testing can be done. These signs include:

  • unusual fatigue,
  • poor appetite,
  • nausea and/or vomiting,
  • yellowing of the eyes (jaundice),
  • dark urine or
  • pale stool.

Itraconazole should not be used for treatment of onychomycosis in patients with a history of heart failure. It should be discontinued if signs and symptoms of heart failure occur. Symptoms of heart failure include

Use of calcium channel blockers may increase the risk of heart failure associated with itraconazole (see drug interactions).

Sporanox (itraconazole) side effects list for healthcare professionals

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 3: 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

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 4: 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):

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 5: 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):

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 6: 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.

What drugs interact with Sporanox (itraconazole)?

Effect Of Sporanox 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, Sporanox 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 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 Sporanox.
  • Although many of the clinicaldrug Interactions in Table 1 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with Sporanox.

Table 1 Drug Interactionswith Sporanox that Affect Concomitant Drug Concentrations

Concomitant Drug Within Class Prevention or Management
Drug Interactions with Sporanox 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 Sporanox treatment.
Analgesics
Methadone Contraindicated during and 2 weeks after Sporanox treatment.
Fentanyl Not recommended during and 2 weeks after Sporanox treatment.
Alfentanil
Buprenorphine (IV and sublingual)
Oxycodonea
Sufentanil
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Antiarrhythmics
Disopyramide
Dofetilide
Dronedarone
Quinidinea
Contraindicated during and 2 weeks after Sporanox treatment.
Digoxina Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Antibacterials
Bedaquilineb Concomitant Sporanox not recommended for more than 2 weeks at any time during bedaquiline treatment.
Rifabutin Not recommended 2 weeks before, during, and 2 weeks after Sporanox 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 Sporanox treatment.
Apixaban
Rivaroxaban
Vorapaxar
Not recommended during and 2 weeks after Sporanox 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 Sporanox treatment. See also Table 2.
Antidiabetic Drug
Repaglinidea
Saxagliptin
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Antihelminthics, Antifungals and Antiprotozoals
Isavuconazonium Contraindicated during and 2 weeks after Sporanox treatment.
Praziquantel Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Artemether-lumefantrine
Quininea
Monitor for adverse reactions.
Antimigraine Drugs
Ergot alkaloids (e.g., dihydroergotamine, ergotamine) Contraindicated during and 2 weeks after Sporanox treatment.
Eletriptan Monitor for adverse reactions. Concomitant drug dose reduction may be necessary
Antineoplastics
Irinotecan Contraindicated during and 2 weeks after Sporanox treatment.
Axitinib
Bosutinib
Cabazitaxel
Cabozantinib
Ceritinib
Cobimetiniba
Crizotinib
Dabrafenib
Dasatinib
Docetaxel
Ibrutinib
Lapatinib
Nilotinib
Olapariba
Pazopanib
Sunitinib
Trabectedin
Trastuzumabemtansine
Vinca alkaloids
Not recommended during and 2 weeks after Sporanox treatment.
Bortezomib
Brentuximabvedotin
Busulfana
Erlotinib
Gefitiniba
Idelalisib
Imatinib
Ixabepilone
Nintedanib
Panobinostat
Ponatinib
Ruxolitinib
Sonidegib
Vandetaniba
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For idelalisib, see also Table 2.
Antipsychotics, Anxiolytics and Hypnotics    
Alprazolama
Aripiprazolea
Buspironea
Cariprazine
Diazepama
Haloperidola
Midazolam (IV)a
Quetiapine
Ramelteon
Risperidonea
Suvorexant
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Zopiclonea Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Lurasidone
Midazolam (oral)a
Pimozide
Triazolama
Contraindicated during and 2 weeks after Sporanox treatment.
Antivirals
Simeprevir Not recommended during and 2 weeks after Sporanox treatment.
Daclatasvir
Indinavira
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 Sporanox treatment.

Monitor for adverse reactions.
Monitor for adverse reactions.

Beta Blockers
Nadolola Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Calcium Channel Blockers
Felodipinea
Nisoldipine
Contraindicated during and 2 weeks after Sporanox 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 Sporanox treatment.
Aliskirena
Riociguat
Sildenafil (for pulmonary hypertension)
Tadalafil (for pulmonary hypertension)
Not recommended during and 2 weeks after Sporanox 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 Contraindicated during and 2 weeks after Sporanox treatment.
Gastrointestinal Drugs
Cisapride
Naloxegol
Contraindicated during and 2 weeks after Sporanox treatment.
Aprepitant
Loperamidea
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Netupitant Monitor for adverse reactions.
Immunosuppressants
Everolimus
Sirolimus
Temsirolimus (IV)
Not recommended during and 2 weeks after Sporanox treatment.
Budesonide (inhalation)a
Budesonide (noninhalation)
Ciclesonide (inhalation)
Cyclosporine (IV)a Cyclosporine (non-IV)
Dexamethasonea
Fluticasone (inhalation)a
Fluticasone (nasal)
Methylprednisolonea
Tacrolimus (IV)a
Tacrolimus (oral)
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Lipid-Lowering Drugs
Lomitapide
Lovastatina
Simvastatina
Contraindicated during and 2 weeks after Sporanox treatment.
Atorvastatina Monitor for drug adverse reactions. Concomitant drug dose reduction may be necessary.
Respiratory Drugs
Salmeterol Not recommended during and 2 weeks after Sporanox treatment.
SSRIs, Tricyclics and Related Antidepressants
Venlafaxine Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Urologic Drugs
Avanafil Contraindicated during and 2 weeks after Sporanox treatment.
Fesoterodine Patients with moderate to severe renal or hepatic impairment: Contraindicated during and 2 weeks after Sporanox treatment.
Other patients: Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Solifenacin Patients with severe renal or moderate to severe hepatic impairment: Contraindicated during and 2 weeks after Sporanox treatment.
Other patients: Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Darifenacin
Vardenafil
Not recommended during and 2 weeks after Sporanox treatment.
Dutasteride
Oxybutynina
Sildenafil (for erectile dysfunction)
Tadalafil (for erectile dysfunction and benign prostatic hyperplasia)
Tolterodine
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For sildenafil and tadalafil, see also Cardiovascular Drugs above.
Miscellaneous Drugs and Other Substances
Colchicine Patients with renal or hepatic impairment: Contraindicated during and 2 weeks after Sporanox treatment.
Other patients: Not recommended during and 2 weeks after Sporanox treatment.
Eliglustat CYP2D6 EMsc taking a strong or moderate CYP2D6 inhibitor, CYP2D6 IMsc, or CYP2D6 PMsc: Contraindicated during and 2 weeks after Sporanox treatment.
CYP2D6 EMsc not taking a strong or moderate CYP2D6 inhibitor: Monitor for adverse reactions. Eliglustat dose reduction may be necessary.
Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after Sporanox treatment.
Alitretinoin (oral)
Cabergoline
Cannabinoids
Cinacalcet
Galantamine
Ivacaftor
Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
Vasopressin Receptor Antagonists
Conivaptan
Tolvaptan
Not recommended during and 2 weeks after Sporanox treatment.
Drug Interactions with Sporanox that Decrease Concomitant Drug Concentrations and May Reduce Efficacy of the Concomitant Drug
Antineoplastics
Regorafenib Not recommended during and 2 weeks after Sporanox treatment.
Gastrointestinal Drugs
Saccharomyces boulardii Not recommended during and 2 weeks after Sporanox treatment.
Nonsteroidal Anti-Inflammatory Drugs
Meloxicama Concomitant drug dose increase may be necessary.
*CYP3A4 inhibitors (including itraconazole) may increase systemic contraceptive hormone concentrations.
a Based on clinical drug interaction information with itraconazole.
b Based on 400 mg bedaquiline once daily for 2 weeks.
c EMs: extensive metabolizers; IMs: intermediate metabolizers, PMs: poor metabolizers

Effect Of Other Drugs On Sporanox

  • Itraconazole is mainly metabolized through CYP3A4. Other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole.
  • Some concomitant drugs have the potential to interact with Sporanox resulting in either increased or sometimes decreased concentrations of Sporanox. Increased concentrations may increase the risk of adverse reactions associated with Sporanox.
  • Decreased concentrations may reduce Sporanox efficacy.
  • Table 2 lists examples of drugs that may affect itraconazole concentrations, but 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 Sporanox.
  • Although many of the clinical drug Interactionsin Table 2 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with Sporanox.

Table 2. Drug Interactions with Other Drugs that Affect Sporanox Concentrations

Concomitant Drug Within Class Prevention or Management
Drug Interactions with Other Drugs that Increase Sporanox Concentrations and May Increase Risk of Adverse Reactions Associated with Sporanox
Antibacterials
Ciprofloxacina
Erythromycina
Clarithromycina
Monitor for adverse reactions. Sporanox dose reduction may be necessary.
Antineoplastics
Idelalisib Monitor for adverse reactions. Sporanox dose reduction may be necessary. See also Table 1.
Antivirals
Cobicistat
Darunavir (ritonavir-boosted)
Elvitegravir (ritonavir-boosted)
Fosamprenavir (ritonavir-boosted)
Indinavira
Ombitasvir/ Paritaprevir/ Ritonavir with or without Dasabuvir
Ritonavir
Saquinavir
Monitor for adverse reactions. Sporanox dose reduction may be necessary. For, cobicistat, elvitegravir, indinavir, ombitasvir/ paritaprevir/ ritonavir with or without dasabuvir, ritonavir, and saquinavir, see also Table 1.
Calcium Channel Blockers
Diltiazem Monitor for adverse reactions. Sporanox dose reduction may be necessary. See also Table 1.
Drug Interactions with Other Drugs that Decrease Sporanox Concentrations and May Reduce Efficacy of Sporanox
Antibacterials
Isoniazid
Rifampicina
Not recommended 2 weeks before and during Sporanox treatment.
Rifabutina Not recommended 2 weeks before, during, and 2 weeks after Sporanox treatment. See also Table 1.
Anticonvulsants
Phenobarbital
Phenytoina
Not recommended 2 weeks before and during Sporanox treatment.
Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after Sporanox treatment. See also Table 1.
Antivirals
Efavirenza
Nevirapinea
Not recommended 2 weeks before and during Sporanox treatment.
Gastrointestinal Drugs
Drugs that reduce gastric acidity e.g. acid neutralizing medicines such as aluminum hydroxide, or acid secretion suppressors such as H2-receptor antagonists and proton pump inhibitors. Use with caution. Administer acid neutralizing medicines at least 2 hours before or 2 hours after the intake of Sporanox capsules
Miscellaneous Drugs and Other Substances
Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after Sporanox treatment.
a Based on clinical drug interaction information with itraconazole.

Pediatric Population

  • Interaction studies have only been performed in adults.

Summary

Sporanox (itraconazole) is an anti-fungal drug used to treat fungal infections of the toenails. It prevents growth of several types of fungi by preventing the fungi from producing the membranes that surround the fungal cells. Common side effects of Sporanox include nausea, vomiting, diarrhea, rash, fluid retention (edema), fatigue, and dizziness. Sporanox should not be used to treat nail fungal infections (onychomycosis) in pregnant patients. Sporanox is excreted in breast milk and should not be administered to nursing women or, alternatively, breastfeeding should be discontinued.

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Medically Reviewed on 10/2/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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