Acenocoumarol, azole antifungals
The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk
Aliskiren/amlodipine [1], azole antifungals ---> SmPC of [1] of EMA
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.
Aliskiren/amlodipine/hydrochlorothiazide [1], azole antifungals ---> SmPC of [1] of EMA
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.
Alprazolam [1], azole antifungals ---> SmPC of [1] of eMC
Compounds that inhibit certain hepatic enzymes (particularly cytochrome P450 3A4) may increase the concentration of alprazolam and enhance its activity. Co-administration is not recommended
Amantadine, azole antifungals
The co-administration of amantadine with drugs that prolong the QT interval is contraindicated
Amlodipine, azole antifungals ---> SmPC of [amlodipine/valsartan] of EMA
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.
Amlodipine/valsartan [1], azole antifungals ---> SmPC of [1] of EMA
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.
Amlodipine/valsartan/hydrochlorothiazide [1], azole antifungals ---> SmPC of [1] of EMA
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.
Amphotericin, azole antifungals
The co-administration may induce resistance to amphotericin by antagonism of its functions
Antifungals, efavirenz/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA
Atripla is contraindicated with concomitant use of drugs that are known to prolong the QTc interval and could lead to Torsade de Pointes
Antifungals, gliquidone
The co-administration may enhance the hypoglycemic effect of gliquidone
Antifungals, miconazole
The combination of miconazol with systemic antimycotics has to be avoided due to possible enhancement of adverse effects
Antifungals, yeast
Decreased effect of yeast preparation
Apixaban [1], azole antifungals ---> SmPC of [1] of EMA
The use of apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp
Artemether, azole antifungals
The co-administration of medicinal products that prolong the interval QT is contraindicated
Artemether/lumefantrine [1], azole antifungals ---> SmPC of [1] of eMC
Artemether/lumefantrine is contraindicated in patients taking drugs that are known to prolong the QTc interval.
Atenolol/nifedipine, azole antifungals [2] ---> SmPC of [2] of eMC
Drugs known to inhibit the cytochrome P450 3A4 system when administered orally with nifedipine may substantial increase the systemic bioavailability of nifedipine due to a decreased first pass metabolism and a decreased elimination
Atorvastatin [1], azole antifungals ---> SmPC of [1] of eMC
Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Co-administration of potent CYP3A4 inhibitors should be avoided if possible.
Avapritinib [1], azole antifungals ---> SmPC of [1] of EMA
Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of avapritinib
Azole antifungals, barnidipine
The strong CYP3A4 inhibition may increase the plasma concentrations of barnidipine. Barnidipine should not be concomitantly prescribed with strong CYP3A4 inhibitors.
Azole antifungals, boceprevir [2] ---> SmPC of [2] of EMA
The inhibition of CYP3A4 and P-glycoprotein may increase the plasma concentrations of boceprevir. Caution should be exercised when boceprevir is combined with azole antifungals
Azole antifungals, brigatinib [2] ---> SmPC of [2] of EMA
The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided
Azole antifungals, bromocriptine [2] ---> SmPC of [2] of eMC
Bromocriptine is both a substrate and an inhibitor of CYP3A4. Caution should therefore be used when co-administering drugs which are strong inhibitors and/or substrates of this enzyme
Azole antifungals, brotizolam
The strong CYP3A4 inhibition may increase the plasma concentrations of brotizolam
Azole antifungals, budipine
The co-administration of budipine with drugs known to prolong QT interval is contraindicated
Azole antifungals, buprenorphine [2] ---> SmPC of [2] of EMA
CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine.
Azole antifungals, buprenorphine/naloxone [2] ---> SmPC of [2] of EMA
Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.
Azole antifungals, carbamazepine [2] ---> SmPC of [2] of eMC
Co-administration of carbamazepine with inhibitors of CYP 3A4 may result in increased carbamazepine plasma concentrations which could induce adverse reactions.
Azole antifungals, cilostazol [2] ---> SmPC of [2] of EMA
Cilostazol is extensively metabolised by CYP3A4 and CYP2C19 and to a lesser extent CYP1A2. Drugs inhibiting CYP3A4 increase the total pharmacological activity and could have the potential to enhance the undesirable effects of cilostazol.
Azole antifungals, cinitapride
The strong CYP3A4 inhibition may increase the plasma concentrations of cinitapride
Azole antifungals, cisapride
The strong CYP3A4 inhibition may increase the plasma concentrations of cisapride and prolong the QT interval. The co-administration is contraindicated
Azole antifungals, clarithromycin
Strong CYP3A4 inhibitors may increase the plasma concentrations of clarithromycin
Azole antifungals, codergocrin
The strong CYP3A4 inhibition may increase the exposition to codergocrin, which may cause a dopaminergic effect. Concomitant use should be avoided
Azole antifungals, cyclosporine [2] ---> SmPC of [2] of eMC
Inhibitors of CYP3A4 may lead to increased levels of cyclosporine.
Azole antifungals, CYP3A4 substrates with narrow therapeutic index
Caution should be used when administering an azole antifungal (CYP3A4 inhibitor) with medicines metabolised by CYP3A4 and narrow therapeutic range
Azole antifungals, darunavir/cobicistat [2] ---> SmPC of [2] of EMA
Co-administration of REZOLSTA and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat
Azole antifungals, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA
Co-administration of Symtuza and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat
Azole antifungals, darunavir/ritonavir ---> SmPC of [darunavir] of EMA
Co-administration of darunavir and ritonavir with other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir. Co-administration with strong CYP3A4 inhibitors is not recommended and caution is warranted
Azole antifungals, delamanid [2] ---> SmPC of [2] of EMA
Treatment with delamanid should not be initiated in patients with risk factors like taking medicinal products that are known to prolong the QTc interval, unless the possible benefit is considered to outweigh the potential risks.
Azole antifungals, dienogest
The CYP3A4 inhibition may increase the plasma levels of dienogest
Azole antifungals, dihydroergotamine
Concomitant use of dihydroergotamine with strong CYP3A4 inhibitors may increase the effect of dihydroergotamine (acute ergotism and vasospastic ischemia) and is contraindicated
Azole antifungals, dihydroergotoxine
The strong CYP3A4 inhibition may increase the exposition to dihydroergotoxine, which may cause a dopaminergic effect. Concomitant use should be avoided
Azole antifungals, dihydropyridines
The azole antifungal agent, strong CYP3A4 inhibitor, may increase the plasma levels of dihydropyridine. Caution is recommended
Azole antifungals, disopyramide [2] ---> SmPC of [2] of eMC
There is evidence that phosphodiesterase Type 5 inhibitors may be potentially associated with a risk of QT prolongation. Concomitant administration of disopyramide with such drugs may potentially enhance this QT prolongation effect and is not recommended
Azole antifungals, docetaxel [2] ---> SmPC of [2] of EMA
In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism
Azole antifungals, dofetilide [2] ---> SmPC of [2] of EMA
The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated
Azole antifungals, dolutegravir [2] ---> SmPC of [2] of EMA
The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.
Azole antifungals, doxylamine
Concomitant use of doxylamine with inhibitors of cytochrome P450 should be avoided
Azole antifungals, drugs metabolised by CYP3A4
Azole antifungal, strong CYP3A4 inhibitor, may increase the plasma levels of the medicinal products metabolized by CYP3A4
Azole antifungals, drugs primarily metabolised by CYP3A4
Azole antifungal, strong CYP3A4 inhibitor, may increase the plasma levels of the medicinal products mainly metabolized by CYP3A4
Azole antifungals, drugs primarily metabolised by CYP3A4 with narrow therapeutic index
Caution should be used when administering an azole antifungal (CYP3A4 inhibitor) with medicines mainly metabolised by CYP3A4 and narrow therapeutic range
Azole antifungals, ebastine
The co-administration with CYP3A4 inhibitors may increase the plasma levels of ebastine and should be done with caution
Azole antifungals, emtricitabine/rilpivirine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA
Concomitant use of Eviplera with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). At a dose of 25 mg of rilpivirine, dose adjustment is required.
Azole antifungals, ergot derivatives
Increased risk of ergotism and concomitant use should be avoided
Azole antifungals, erlotinib [2] ---> SmPC of [2] of EMA
Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.
Azole antifungals, ethinylestradiol/chlormadinone
Active principles which inhibit hepatic microsomal enzymes may increase plasma concentrations of ethinylestradiol
Azole antifungals, felodipine ---> SmPC of [felodipine/metoprolol] of eMC
The strong CYP3A4 inhibition may increase the plasma concentrations of felodipine
Azole antifungals, felodipine/ramipril [2] ---> SmPC of [2] of eMC
The strong CYP3A4 inhibition may increase the plasma levels of felodipine. The co-administration of felodipine with strong CYP3A4 inhibitors should be avoided
Azole antifungals, fentanyl
The combination may increase the bioavailability of swallowed fentanyl and may decrease its systemic clearance
Azole antifungals, fingolimod [2] ---> SmPC of [2] of EMA
Co-administration of fingolimod with CYP3A4 inhibitors may increase the fingolimod exposure. Caution should be exercised with substances that may inhibit CYP3A4
Azole antifungals, flunitrazepam
Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded
Azole antifungals, fosphenytoin [2] ---> SmPC of [2] of eMC
Blood levels and/or effects of azole antifungals may be altered by phenytoin
Azole antifungals, imatinib [2] ---> SmPC of [2] of EMA
Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity could decrease metabolism and increase imatinib concentrations. Caution should be taken when administering imatinib with inhibitors of the CYP3A4 family.
Azole antifungals, isradipine [2] ---> SmPC of [2] of eMC
Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors
Azole antifungals, ivabradine [2] ---> SmPC of [2] of EMA
The concomitant use of ivabradine and potent CYP3A4 inhibitors increases plasma concentrations of ivabradine (may be associated with the risk of excessive bradycardia). The concomitant use of ivabradine with these medicinal products is contraindicated
Azole antifungals, lumefantrine
The co-administration of medicinal products that prolong the interval QT is contraindicated
Azole antifungals, methadone [2] ---> SmPC of [2] of eMC
Methadone clearance is decreased when co-administered with drugs which inhibit CYP3A4 activity, since the metabolism of methadone is mediated by the CYP3A4 isoenzyme.
Azole antifungals, methylergometrine
The strong CYP3A4 inhibition may increase the plasma concentrations of methylergometrine. The concomitant use should be avoided
Azole antifungals, methysergide [2] ---> SmPC of [2] of eMC
The concomitant use of cytochrome P450 3A (CYP3A) inhibitors, since this can result in an elevated exposure to methysergide and ergot toxicity (vasospasm and ischemia of the extremities and other tissues).
Azole antifungals, metildigoxin
Increased plasma levels of metildigoxin
Azole antifungals, midazolam [2] ---> SmPC of [2] of EMA
Midazolam is metabolized by CYP3A4. Inhibitors of CYP3A4 have the potential to increase the plasma concentrations and, subsequently, the effects of midazolam thus requiring dose adjustments accordingly.
Azole antifungals, mirtazapine [2] ---> SmPC of [2] of eMC
The strong CYP3A4 inhibition may increase the plasma concentrations of mirtazapine
Azole antifungals, naftidrofuryl
The strong CYP3A4 inhibition may increase plasma concentrations of naftidrofuryl
Azole antifungals, nifedipine [2] ---> SmPC of [2] of eMC
Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.
Azole antifungals, nilvadipine
The strong CYP3A4 inhibition may increase the plasma concentrations of nilvadipine. Caution is recommended
Azole antifungals, nimodipine [2] ---> SmPC of [2] of eMC
Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.
Azole antifungals, nisoldipine
The co-administration of nisoldipine with medicinal products that inhibit the cytochrome P450 3A4-system may increase the bioavailability of nisoldipine. Concomitant use is contraindicated
Azole antifungals, nitrendipine
The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine. Caution is recommended
Azole antifungals, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.
Azole antifungals, oral anticoagulants
The co-administration may enhance the anticoagulant effect and increase the bleeding risk
Azole antifungals, oxybutynine [2] ---> SmPC of [2] of EMA
As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.
Azole antifungals, paclitaxel [2] ---> SmPC of [2] of EMA
The strong CYP3A4 inhibition may increase the plasma concentrations of paclitaxel
Azole antifungals, pancuronium
Possible enhancement of pancuronium effect and the intensity of neuromuscular block
Azole antifungals, perphenazine
Concomitant use of perphenazine with drugs inhibiting the metabolism of perphenazine is not recommended.
Azole antifungals, phenprocoumon
The co-administration may enhance the anticoagulant effect and increase the bleeding risk
Azole antifungals, pimozide [2] ---> SmPC of [2] of eMC
Potent inhibitors of the CYP3A4 will inhibit the metabolism of pimozide, resulting in markedly elevated pimozide plasma levels. Concomitant use of pimozide with drugs known to be inhibitors of cytochrome CYP3A4 is contraindicated
Azole antifungals, piperaquine ---> SmPC of [piperaquine/artenimol] of EMA
The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval
Azole antifungals, piperaquine/artenimol [2] ---> SmPC of [2] of EMA
The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval
Azole antifungals, prasugrel [2] ---> SmPC of [2] of EMA
CYP3A inhibitors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.
Azole antifungals, prazepam
The strong CYP3A4 inhibition may increase the plasma concentrations of prazepam. Caution is recommended
Azole antifungals, prednisolone
Medicinal products that inhibit the hepatic metabolism of prednisolone may enhance the corticoid effect
Azole antifungals, quetiapine [2] ---> SmPC of [2] of eMC
The strong CYP3A4 inhibition may increase the plasma concentrations of quetiapine. Concomitant use of quetiapine with CYP3A4 inhibitors is contraindicated.
Azole antifungals, quinine
Quinine is metabolised via hepatic oxidative cytochrome P450, predominantly by CYP3A4. There is the potential for increased quinine toxicity with concurrent use of potent CYP3A4 inhibitors
Azole antifungals, reboxetine [2] ---> SmPC of [2] of eMC
The CYP3A4 inhibition may increase the plasma levels of reboxetine (narrow therapeutic margin and primarily metabolised by the CYP3A4). Reboxetine should not be given together with drugs known to inhibit CYP3A4
Azole antifungals, rifampicin [2] ---> SmPC of [2] of eMC
Rifampicin is a potent inducer of certain cytochrome P-450 enzymes. Coadministration of rifampicin with drugs that are also metabolised through these cytochrome P-450 enzymes may accelerate the metabolism and reduce the activity of these other drugs.
Azole antifungals, rilpivirine [2] ---> SmPC of [2] of EMA
Not studied. Concomitant use of rilpivirine with azole antifungal agents (inhibition of CYP3A enzymes) may cause an increase in the plasma concentrations of rilpivirine. No dose adjustment is required.
Azole antifungals, riociguat [2] ---> SmPC of [2] of EMA
Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended
Azole antifungals, rivaroxaban [2] ---> SmPC of [2] of EMA
Co-administration of rivaroxaban with strong inhibitors of both CYP3A4 and P-gp may lead to an increased bleeding risk. The use of rivaroxaban with inhibitors of both CYP3A4 and P-gp is not recommended
Azole antifungals, sertindole
The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels
Azole antifungals, statins
The co-administration increases the risk of myopathy and on occasions has resulted in rhabdomyolysis with renal dysfunction secondary to myoglobinuria
Azole antifungals, stiripentol [2] ---> SmPC of [2] of EMA
The impact of azole antifungals on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known
Azole antifungals, tacrolimus [2] ---> SmPC of [2] of EMA
Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.
Azole antifungals, telithromycin [2] ---> SmPC of [2] of EMA
Due to a potential to increase the QT interval, telithromycin (contraindicated in patients with severe renal or hepatic insufficiency) should be used with care in patients concomitantly treated with potent CYP 3A4 inhibitors
Azole antifungals, temsirolimus [2] ---> SmPC of [2] of EMA
Strong CYP3A4 inhibitors may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.
Azole antifungals, terfenadine
The strong CYP3A4 inhibition may increase the terfenadine plasma levels and prolong the QT interval (risk of life-threatening arrythmias). The combination is contraindicated
Azole antifungals, thiotepa [2] ---> SmPC of [2] of EMA
Thiotepa appears to be metabolised via CYP2B6 and CYP3A4. Co-administration with inhibitors of CYP2B6 or CYP3A4 may increase the plasma concentrations of thiotepa and potentially decrease the concentrations of the active metabolite TEPA.
Azole antifungals, tolbutamide
Increased hypoglycaemic effects have occurred or might be expected
Azole antifungals, tolterodine [2] ---> SmPC of [2] of eMC
Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage
Azole antifungals, toremifene [2] ---> SmPC of [2] of EMA
Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.
Azole antifungals, triazolam
The strong CYP3A4 inhibition may increase the plasma concentrations of triazolam. Concomitant use of triazolam with this azole antifungal is not recommended
Azole antifungals, tricyclic antidepressant
Possible increase of plasma levels and toxicity of tricyclic antidepressant
Azole antifungals, trofosfamide
The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity
Azole antifungals, verapamil [2] ---> SmPC of [2] of eMC
Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.
Azole antifungals, vinca alkaloids
The strong CYP3A4 inhibition may increase the plasma concentrations of vinca alkaloid
Azole antifungals, warfarin [2] ---> SmPC of [2] of eMC
Azole antifungals potentiate the effect of warfarin
Azole antifungals, zolpidem
CYP3A4 inhibitors may increase the effect of zolpidem
Azole antifungals, zopiclone [2] ---> SmPC of [2] of eMC
Since zopiclone is metabolised by the cytochrome P450 (CYP) 3A4, plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors
Clotrimazole, polyene antifungals
Clotrimazole decreases the efficacy of amphotericin and other polyene antibiotics
Miconazole, polyene antifungals
Miconazole with polyene antimycotics, e.g. amphotericin B, may have an antagonic effect