Itraconazole (Page 4 of 9)

Interaction Potential

Itraconazole capsules have 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 capsules and itraconazole 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

General

Itraconazole capsules should be administered after a full meal. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).

Under fasted conditions, itraconazole absorption was decreased in the presence of decreased gastric acidity. The absorption of itraconazole may be decreased with the concomitant administration of antacids or gastric acid secretion suppressors. Studies conducted under fasted conditions demonstrated that administration with 8 ounces of a non-diet cola beverage resulted in increased absorption of itraconazole in AIDS patients with relative or absolute achlorhydria. This increase relative to the effects of a full meal is unknown. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).

Hepatotoxicity

Rare cases of serious hepatotoxicity have been observed with itraconazole capsule treatment, including some cases within the first week. It is recommended that liver function monitoring be considered in all patients receiving itraconazole capsules. Treatment should be stopped immediately and liver function testing should be conducted in patients who develop signs and symptoms suggestive of liver dysfunction.

Neuropathy

If neuropathy occurs that may be attributable to itraconazole capsules, the treatment should be discontinued.

Immunocompromised Patients

In some immunocompromised patients (e.g., neutropenic, AIDS or organ transplant patients), the oral bioavailability of itraconazole capsules may be decreased. Therefore, the dose should be adjusted based on the clinical response in these patients.

Cystic Fibrosis

If a cystic fibrosis patient does not respond to itraconazole capsules, consideration should be given to switching to alternative therapy. For more information concerning the use of itraconazole in cystic fibrosis patients see the prescribing information for itraconazole oral solution.

Hearing Loss

Transient or permanent hearing loss has been reported in patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated (See BOXED WARNING: Drug Interactions, CONTRAINDICATIONS: Drug Interactions and PRECAUTIONS: Drug Interactions). The hearing loss usually resolves when treatment is stopped, but can persist in some patients.

Information for Patients

The topical effects of mucosal exposure may be different between the itraconazole capsules and oral solution. Only the oral solution has been demonstrated effective for oral and/or esophageal candidiasis. Itraconazole capsules should not be used interchangeably with itraconazole oral solution.
Instruct patients to take itraconazole capsules with a full meal. Itraconazole capsules must be swallowed whole.
Instruct patients about the signs and symptoms of congestive heart failure, and if these signs or symptoms occur during itraconazole capsule administration, they should discontinue itraconazole capsules and contact their healthcare provider immediately.
Instruct patients to stop itraconazole capsule treatment immediately and contact their healthcare provider if any signs and symptoms suggestive of liver dysfunction develop. Such signs and symptoms may include unusual fatigue, anorexia, nausea and/or vomiting, jaundice, dark urine, or pale stools.
Instruct patients to contact their physician before taking any concomitant medications with itraconazole to ensure there are no potential drug interactions.
Instruct patients that hearing loss can occur with the use of itraconazole. The hearing loss usually resolves when treatment is stopped, but can persist in some patients. Advise patients to discontinue therapy and inform their physicians if any hearing loss symptoms occur.
Instruct patients that dizziness or blurred/double vision can sometimes occur with itraconazole. Advise patients that if they experience these events, they should not drive or use machines.

Drug Interactions

Effect of Itraconazole Capsules 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, itraconazole capsules have 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 itraconazole capsules.

Although many of the clinical drug interactions in Table 1 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with itraconazole capsules.

Table 1: Drug Interactions with Itraconazole Capsules that Affect Concomitant Drug Concentrations
*
Based on clinical drug interaction information with itraconazole.
Based on 400 mg bedaquiline once daily for 2 weeks.
CYP3A4 inhibitors (including itraconazole) may increase systemic contraceptive hormone concentrations.
§
EMs: extensive metabolizers; IMs: intermediate metabolizers; PMs: poor metabolizers

Concomitant Drug Within Class

Prevention or Management

Drug Interactions with Itraconazole Capsules 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 itraconazole capsule treatment.

Analgesics

Methadone

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Fentanyl

Not recommended during and 2 weeks after itraconazole capsule treatment.

Alfentanil

Buprenorphine (IV and sublingual)

Oxycodone *

Sufentanil

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Antiarrhythmics

Disopyramide

Dofetilide

Dronedarone

Quinidine *

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Digoxin *

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Antibacterials

Bedaquiline

Concomitant itraconazole capsules not recommended for more than 2 weeks at any time during bedaquiline treatment.

Rifabutin

Not recommended 2 weeks before, during, and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment.

Apixaban

Rivaroxaban

Vorapaxar

Not recommended during and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment. See also Table 2.

Antidiabetic Drugs

Repaglinide *

Saxagliptin

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Antihelminthics, Antifungals and Antiprotozoals

Isavuconazonium

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Praziquantel

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Artemether-lumefantrine

Quinine *

Monitor for adverse reactions.

Antimigraine Drugs

Ergot alkaloids (e.g., dihydroergotamine, ergotamine)

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Eletriptan

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Antineoplastics

Irinotecan

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Axitinib

Bosutinib

Cabazitaxel

Cabozantinib

Ceritinib

Cobimetinib *

Crizotinib

Dabrafenib

Dasatinib

Docetaxel

Ibrutinib

Lapatinib

Nilotinib

Olaparib *

Pazopanib

Sunitinib

Trabectedin

Trastuzumab-emtansine

Vinca alkaloids

Not recommended during and 2 weeks after itraconazole capsule treatment.

Bortezomib Brentuximab-vedotin

Busulfan *

Erlotinib

Gefitinib *

Idelalisib

Imatinib

Ixabepilone

Nintedanib

Panobinostat

Ponatinib

Ruxolitinib

Sonidegib

Vandetanib *

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For idelalisib, see also Table 2.

Antipsychotics, Anxiolytics and Hypnotics

Alprazolam * Aripiprazole * Buspirone *

Cariprazine Diazepam * Haloperidol *

Midazolam (IV)* Quetiapine

Ramelteon

Risperidone *

Suvorexant

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Zopiclone *

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Lurasidone

Midazolam (oral)*

Pimozide

Triazolam *

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Antivirals

Simeprevir

Not recommended during and 2 weeks after itraconazole capsule treatment.

Daclatasvir

Indinavir *

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)*

Monitor for adverse reactions. See also Table 2.

Elbasvir/grazoprevir

Glecaprevir/pibrentasvir

Tenofovir disoproxil fumarate

Not recommended during and 2 weeks after itraconazole capsule treatment.

Monitor for adverse reactions.

Monitor for adverse reactions.

Beta Blockers

Nadolol *

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Calcium Channel Blockers

Felodipine *

Nisoldipine

Contraindicated during and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment.

Aliskiren *

Riociguat

Sildenafil (for pulmonary hypertension)

Tadalafil (for pulmonary hypertension)

Not recommended during and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment.

Gastrointestinal Drugs

Cisapride

Naloxegol

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Aprepitant

Loperamide *

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 itraconazole capsule treatment.

Budesonide (inhalation)*

Budesonide (non-inhalation)

Ciclesonide (inhalation)

Cyclosporine (IV)*

Cyclosporine (non-IV)

Dexamethasonea

Fluticasone (inhalation)*

Fluticasone (nasal)

Methylprednisolone *

Tacrolimus (IV)*

Tacrolimus (oral)

Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Lipid-Lowering Drugs

Lomitapide

Lovastatin *

Simvastatin *

Contraindicated during and 2 weeks after itraconazole capsule treatment.

Atorvastatin *

Monitor for drug adverse reactions. Concomitant drug dose reduction may be necessary.

Respiratory Drugs

Salmeterol

Not recommended during and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment.

Fesoterodine

Patients with moderate to severe renal or hepatic impairment: Contraindicated during and 2 weeks after itraconazole capsule 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 itraconazole capsule treatment.

Other patients: Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

Darifenacin

Vardenafil

Not recommended during and 2 weeks after itraconazole capsule treatment.

Dutasteride

Oxybutynin *

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 itraconazole capsule treatment.

Other patients: Not recommended during and 2 weeks after itraconazole capsule treatment.

Eliglustat

CYP2D6 EMs § taking a strong or moderate CYP2D6 inhibitor, CYP2D6 IMs §, or CYP2D6 PMs §: Contraindicated during and 2 weeks after itraconazole capsule treatment.

CYP2D6 EMs § 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 itraconazole capsule 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 itraconazole capsule treatment.

Drug Interactions with Itraconazole Capsules that Decrease Concomitant Drug Concentrations and May Reduce Efficacy of the Concomitant Drug

Antineoplastics

Regorafenib

Not recommended during and 2 weeks after itraconazole capsule treatment.

Gastrointestinal Drugs

Sacchromyces boulardii

Not recommended during and 2 weeks after itraconazole capsule treatment.

Nonsteroidal Anti-Inflammatory Drugs

Meloxicam *

Concomitant drug dose increase may be necessary.

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