Sporanox Drug Interactions

Itraconazole is a drug with a high interaction potential. The various types of interaction and associated general recommendations are described as follows. In addition, a table is provided listing examples of drugs that may interact with itraconazole, organized per drug family for easy reference. This list of examples is not comprehensive and therefore the label of each drug that is coadministered with itraconazole should be consulted for information related to the route of metabolism, interaction pathways, potential risks, and specific actions to be taken with regards to coadministration.
Itraconazole is mainly metabolized through CYP3A4. Other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole. Coadministration of itraconazole with moderate or potent CYP3A4 inducers may decrease the bioavailability of itraconazole and hydroxy-itraconazole to such an extent that efficacy may be reduced. Coadministration with moderate or potent inhibitors of CYP3A4 may increase the bioavailability of itraconazole, which may result in increased or prolonged pharmacologic effects of itraconazole.
Capsule: Absorption of itraconazole from the capsule formulation is reduced in subjects with reduced gastric acidity. Drugs that reduce gastric acidity impair the absorption of itraconazole from itraconazole capsules. To counteract this effect it is recommended to administer itraconazole capsules with an acidic beverage (such as non-diet cola) upon coadministration with drugs that reduce gastric acidity (see Precautions).
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 (BRCP). Itraconazole can inhibit the metabolism of drugs metabolized by CYP3A4 and can inhibit the drug transport by P-glycoprotein and/or BCRP, which may result in increased plasma concentrations of these drugs and/or their active metabolite(s) when they are administered with itraconazole. These elevated plasma concentrations may increase or prolong both therapeutic and adverse effects of these drugs. For some drugs, coadministration with itraconazole may result in decreased plasma concentrations of the drug or of the active moiety of the drug. This may result in reduced efficacy of the drug.
Following cessation of medical treatment with itraconazole, plasma concentrations decrease below the detection limit within 7 to 14 days, depending on the dose and duration of treatment. In patients with hepatic cirrhosis or in subjects receiving CYP3A4 inhibitors the plasma concentrations decline slower. This is particularly important for consideration when initiating therapy with drugs whose metabolism is affected by itraconazole.
The following general recommendations apply, unless stated differently in Table 10: 'Contraindicated': Under no circumstances is the drug to be coadministered with itraconazole. This applies to: CYP3A4 substrates for which increased plasma concentrations may increase or prolong therapeutic and/or adverse effects to such an extent that a potentially serious situation may occur (see Contraindications).
'Not recommended': It is recommended that the use of the drug be avoided, unless the benefits outweigh the potentially increased risks. If coadministration cannot be avoided, clinical monitoring is recommended, and the dosage of itraconazole and/or the coadministered drug adapted as deemed necessary. When appropriate, it is recommended that plasma concentrations be measured. This applies to: Moderate or potent CYP3A4 inducers: not recommended from 2 weeks before and during treatment with itraconazole.
CYP3A4/P-gp/BCRP substrates for which increased or decreased plasma concentrations result in significant risk: not recommended during and up to 2 weeks after treatment with itraconazole.
'Use with caution': Careful monitoring is recommended when the drug is coadministered with itraconazole. Upon coadministration, it is recommended that patients be monitored closely and the dosage of itraconazole and/or the coadministered drug adapted as deemed necessary. When appropriate, it is recommended that plasma concentrations be measured. This applies to: Drugs that reduce gastric acidity (itraconazole caps only).
Moderate or potent inhibitors of CYP3A4.
CYP3A4/P-gp/BCRP substrates for which increased or decreased plasma concentrations result in a clinically relevant risk.
Examples of interacting drugs are listed in the table as follows. The drugs listed in this table are based on either drug interaction studies or case reports, or potential interactions based on the mechanism of interaction. (See Table 10a, Table 10b, Table 10c, Table 10d and Table 10e)

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Pediatric population: Interaction studies have only been performed in adults.