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ITRACONAZOLE
DIR Classification
Classification:Moderate-DIR concern
Severity Score:3
Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF
- BOXED WARNING
- Congestive Heart Failure
- TOLSURA can cause or exacerbate congestive heart failure (CHF). When itraconazole was administered intravenously to healthy human volunteers and dogs, negative inotropic effects were seen. If signs or symptoms of congestive heart failure occur or worsen during administration of TOLSURA, reassess the benefit and risk of continuing treatment [see WARNINGS AND PRECAUTIONS (5.1) and ADVERSE REACTIONS (6.1)].
- [Drug Interactions]
- Co-administration of certain drugs that are metabolized by human CYP3A4 enzymes are contraindicated with TOLSURA because plasma concentrations of such drugs are increased, which may also increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs [see CONTRAINDICATIONS (4.1) and DRUG INTERACTIONS (7.1)]
- Co-administration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and
- Co-administration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors.
- Increased plasma concentrations of some of these drugs caused by co-administration with TOLSURA can lead to QT prolongation and/or ventricular tachyarrhythmias, including occurrences of torsades de pointes, a potentially fatal arrhythmia [see CONTRAINDICATIONS (4.1), WARNINGS AND PRECAUTIONS (5.4) and DRUG INTERACTIONS (7.1)].
- DRUG INTERACTIONS
- Effect of TOLSURA 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 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 4 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.
- CONTRAINDICATIONS
- Drug Interactions
- Increased plasma concentrations of some of these drugs due to co-administration of TOLSURA can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia [see DRUG INTERACTIONS (7.1)].
Postmarketing Surveillance
Contingency Table:
Current Drug
Other Drugs
Rhabdomyolysis
81
42831
Other ADRs
6949
14110330
Odds Ratio = 3.841
Drug Property Information
ATC Code(s):
- J02AC02 - itraconazole
- J02AC - Triazole derivatives
- J02A - ANTIMYCOTICS FOR SYSTEMIC USE
- J02 - ANTIMYCOTICS FOR SYSTEMIC USE
- J - ANTIINFECTIVES FOR SYSTEMIC USE
Active Ingredient:itraconazole
Active Ingredient UNII:304NUG5GF4
Drugbank ID:DB01167
PubChem Compound:55283
CAS Number:84625-61-6
Dosage Form(s):tablet
Route(s) Of Administrator:oral
Daily Dose:
- 200.0 mg/day J02AC02
Chemical Structure: 
SMILE Code:
CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5CO[C@](O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl
CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5CO[C@](O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl
Reference
COHORT STUDY:
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