Viekira Pak Dose in Adults

Risk Factor C (Monitor therapy)

Abiraterone Acetate

May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors).

Alosetron

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron.

ALPRAZolam

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of ALPRAZolam.

Amiodarone

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Amiodarone. Management: Canadian labeling recommends avoiding this combination.

Antidiabetic Agents

Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents.

Apixaban

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban.

Benperidol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol.

Benzhydrocodone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased.

Bepridil

Antihepaciviral Combination Products may increase the serum concentration of Bepridil.

Betamethasone (Ophthalmic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic).

Bictegravir

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir.

Bortezomib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib.

Brentuximab Vedotin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.

Brinzolamide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide.

Budesonide (Nasal)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal).

Budesonide (Oral Inhalation)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation).

Buprenorphine

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Buprenorphine.

BuPROPion

Antihepaciviral Combination Products may decrease the serum concentration of BuPROPion.

Calcifediol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol.

Cannabidiol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol.

Cannabis

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased.

Carisoprodol

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may decrease the serum concentration of Carisoprodol.

Cinacalcet

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet.

Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Clopidogrel

May increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of dasabuvir may increase.

CloZAPine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

CloZAPine

CYP1A2 Inducers may decrease the serum concentration of CloZAPine.

Codeine

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine.

Corticosteroids (Orally Inhaled)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic).

Corticosteroids (Systemic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE.

Cyclobenzaprine

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may decrease the serum concentration of Cyclobenzaprine.

CYP2C8 Inhibitors (Moderate)

May decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors).

CYP3A4 Inhibitors (Moderate)

May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).

Deferasirox

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Deferasirox

May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors).

Dexamethasone (Ophthalmic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dexamethasone (Ophthalmic).

DiazePAM

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may decrease the serum concentration of DiazePAM.

Dienogest

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest.

Dofetilide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide.

Doxercalciferol

CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol.

Dronabinol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol.

Dutasteride

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride.

Estazolam

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam.

Estrogen Derivatives

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives.

Evogliptin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin.

Flecainide

Antihepaciviral Combination Products may increase the serum concentration of Flecainide. Management: Canadian labeling recommends avoiding this combination.

Fluvastatin

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Fluvastatin. Management: Canadian product labeling recommends use of the lowest fluvastatin dose with this combination.

Fosnetupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Fostamatinib

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib.

Galantamine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine.

Gefitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib.

Ifosfamide

CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.

Imatinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib.

Imidafenacin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin.

Lacosamide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide.

Levobupivacaine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine.

LinaGLIPtin

Antihepaciviral Combination Products may increase the serum concentration of LinaGLIPtin.

Lumefantrine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine.

MedroxyPROGESTERone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone.

MetFORMIN

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased.

Mexiletine

Antihepaciviral Combination Products may increase the serum concentration of Mexiletine.

Mirtazapine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine.

Naldemedine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine.

Nalfurafine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine.

Netupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

OLANZapine

Antihepaciviral Combination Products may decrease the serum concentration of OLANZapine.

Omeprazole

Antihepaciviral Combination Products may decrease the serum concentration of Omeprazole.

Ospemifene

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene.

Oxybutynin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin.

Parecoxib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib.

Paricalcitol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol.

Pimecrolimus

CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus.

Pitavastatin

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Pitavastatin. Management: Canadian product labeling recommends use of the lowest pitavastatin dose with this combination.

Polatuzumab Vedotin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased.

Pranlukast

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast.

Praziquantel

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel.

PrednisoLONE (Systemic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic).

PredniSONE

CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE.

Proguanil

Antihepaciviral Combination Products may decrease the serum concentration of Proguanil.

Propafenone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Propafenone

Antihepaciviral Combination Products may increase the serum concentration of Propafenone. Management: Canadian labeling recommends avoiding this combination.

QuiNIDine

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of QuiNIDine. Management: Canadian labeling recommends avoiding this combination.

Ramelteon

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon.

Repaglinide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure.

Retapamulin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations.

RomiDEPsin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin.

Sarilumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Sibutramine

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine.

Siltuximab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

SORAfenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib.

Tacrolimus (Topical)

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Tacrolimus (Topical).

Talazoparib

BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib.

Tasimelteon

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon.

Tetrahydrocannabinol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol.

Tocilizumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

TraMADol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol.

Triamcinolone (Systemic)

Antihepaciviral Combination Products may increase the serum concentration of Triamcinolone (Systemic).

Upadacitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib.

Vilanterol

May increase the serum concentration of CYP3A4 Inhibitors (Strong).

Vindesine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine.

Vinorelbine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine.

Vitamin K Antagonists (eg, warfarin)

Antihepaciviral NS5B RNA Polymerase Inhibitors may diminish the anticoagulant effect of Vitamin K Antagonists.

Risk Factor D (Consider therapy modification)

Abemaciclib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily.

Alcohol (Ethyl)

May diminish the therapeutic effect of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Management: Avoid alcohol consumption within 4 hours of taking the extended release ombitasvir/paritaprevir/ritonavir/dasabuvir product. This interaction does not apply to the immediate-release ombitasvir/paritaprevir/ritonavir/dasabuvir product.

Alfentanil

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Alfentanil. Management: Monitor for increased anesthetic and respiratory depressant effects of alfentanil if these agents are combined. Consider using lower initial doses of alfentanil or an alternative anesthetic. Canadian labeling recommends avoidance of this combination.

Alitretinoin (Systemic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor.

Almotriptan

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function.

Alpelisib

BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions.

AmLODIPine

Antihepaciviral Combination Products may increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated.

ARIPiprazole

CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details.

ARIPiprazole Lauroxil

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments.

Atazanavir

May increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the paritaprevir component may increase significantly. Management: These agents can be combined if the atazanavir dose is 300 mg daily, atazanavir is administered in the morning at the same time as the ombitasvir/paritaprevir/ritonavir/dasabuvir combination product, and atazanavir is given without additional ritonavir.

Bedaquiline

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline. Exceptions discussed in separate monographs.

Brexpiprazole

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer.

Brigatinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg).

Budesonide (Topical)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased.

BusPIRone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors.

Cabazitaxel

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose.

Cabozantinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details.

Candesartan

Antihepaciviral Combination Products may increase the serum concentration of Candesartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the candesartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination.

Cariprazine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details.

Ceritinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: If such combinations cannot be avoided, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Exceptions discussed in separate monographs.

Cilostazol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4.

Cladribine

BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration.

Clarithromycin

Antihepaciviral Combination Products may increase the serum concentration of Clarithromycin. Management: Avoid clarithromycin doses greater than 1000 mg/day when used with an antihepaciviral combination product. Further dose reductions may be needed in patients with impaired renal function. Consider an alternative antimicrobial for any non-MAC infection.

Copanlisib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities.

Crizotinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors whenever possible. If combined use cannot be avoided, decrease the crizotinib dose to 250 mg daily. Exceptions are discussed in separate monographs.

CycloSPORINE (Systemic)

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of CycloSPORINE (Systemic). Management: Reduce cyclosporine dose 80% when initiating therapy with ombitasvir/paritaprevir/ritonavir/dasabuvir and monitor cyclosporine blood levels closely.

CYP3A4 Inhibitors (Strong)

May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).

CYP3A4 Substrates (High risk with Inhibitors)

CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); AmLODIPine; Benzhydrocodone; Buprenorphine; Gefitinib; HYDROcodone; Mirtazapine; Praziquantel; Telithromycin; Vinorelbine.

Daclatasvir

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat.

Darunavir

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may decrease the serum concentration of Darunavir. Management: Avoid combination in treatment experienced patients with darunavir resistance substitution(s) or no baseline resistance information. In treatment naive patients or those with no darunavir resistance, darunavir 800 mg daily (without ritonavir) can be used.

Dasatinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, dasatinib dose reductions are recommended. See full monograph for details. Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Deflazacort

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor.

Delamanid

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Exceptions discussed separately.

DOCEtaxel

CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities.

DOXOrubicin (Conventional)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.

Drospirenone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors.

Duvelisib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor.

Eliglustat

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details.

Eluxadoline

Antihepaciviral Combination Products may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with antihepaciviral combination products. Monitor patients for increased eluxadoline effects/toxicities.

Encorafenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and strong CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose. See monograph for details.

Entrectinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Entrectinib. Management: Avoid strong CYP3A4 inhibitors during treatment with entrectinib. Reduce dose to 100 mg/day if combination cannot be avoided in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters. No alternative dosing provided for others.

Erdafitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly.

Erlotinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements).

Eszopiclone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression).

Etizolam

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely.

Fedratinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated.

FentaNYL

CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary.

Fesoterodine

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors.

Fluticasone (Oral Inhalation)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely.

Fosamprenavir

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Management: Use of ritonavir-boosted fosamprenavir with ombitasvir/paritaprevir/ritonavir/dasabuvir is not recommended. Consider a reduced dose of fosamprenavir 1400 mg once daily (unboosted) when used with ombitasvir/paritaprevir/ritonavir/dasabuvir.

Gilteritinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. If the combination cannot be avoided, monitor more closely for evidence of gilteritinib toxicities.

Glasdegib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib.

GuanFACINE

CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.

HYDROcodone

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of HYDROcodone. Management: Reduce the hydrocodone dose by 50% during concurrent use of ombitasvir, paritaprevir, ritonavir, and dasabuvir; monitor closely for both analgesic effectiveness and for signs of toxicity or withdrawal.

Iloperidone

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor.

Ivacaftor

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations.

Ivosidenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs.

Ixabepilone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone.

Ketoconazole (Systemic

Antihepaciviral Combination Products may increase the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Antihepaciviral Combination Products. Specifically, ketoconazole may increase serum concentrations of paritaprevir. Management: Limit the dose of ketoconazole to 200 mg per day in patients taking antihepaciviral combination products. Additionally, monitor for increased ketoconazole effects/toxicities and for increased paritaprevir effects/toxicities.

Larotrectinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor half-life.

Levomilnacipran

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors.

Losartan

Antihepaciviral Combination Products may increase the serum concentration of Losartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the losartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination.

Manidipine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required.

Maraviroc

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min.

Meperidine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Management: Consider reducing meperidine dose if concomitant use with strong CYP3A4 inhibitors is required. Monitor for signs and symptoms of respiratory depression and sedation when these agents are combined.

MethylPREDNISolone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects.

Midostaurin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Exceptions are discussed in separate monographs.

MiFEPRIStone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or indication.

MiFEPRIStone

May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors). Management: Use CYP2C8 substrates at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment.

MiFEPRIStone

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.

Mirodenafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination.

Nilotinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Exceptions discussed in separate monograph.

Olaparib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 100 mg twice daily.

OxyCODONE

CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased.

Panobinostat

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor.

Pexidartinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg/day to 200 mg/day.

Pimavanserin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors.

Piperaquine

CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Management: Avoid concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. If the combination cannot be avoided, frequent ECG monitoring is recommended due to the risk for QTc prolongation. Exceptions are discussed separately.

PONATinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor.

Pravastatin

Antihepaciviral Combination Products may increase the serum concentration of Pravastatin. Management: Limit the pravastatin dose to a maximum of 40 mg per day when used with antihepaciviral combination products and monitor patients for evidence of pravastatin toxicities (eg, myopathy).

QUEtiapine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of regular dose after starting strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Exceptions discussed separately.

Reboxetine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine.

Ribociclib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily. Exceptions are discussed in separate monographs.

Riociguat

Antihepaciviral Combination Products may increase the serum concentration of Riociguat. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times daily. Patients receiving such a combination should also be monitored closely for signs or symptoms of hypotension.

Rosuvastatin

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Rosuvastatin. Management: Limit the rosuvastatin dose to a maximum of 10 mg per day when used with the ombitasvir/paritaprevir/ritonavir/dasabuvir combination product. Canadian labeling recommends limiting the rosuvastatin dose to 5 mg per day.

Ruxolitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details.

SAXagliptin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Saxagliptin U.S. product labeling recommends limiting saxagliptin adult dose to 2.5 mg/day when used with a strong CYP3A4 inhibitor. Monitor for increased saxagliptin levels/effects. A similar recommendation is not made in the Canadian product labeling.

Sildenafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours.

Solifenacin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit solifenacin doses to 5 mg daily when combined with strong CYP3A4 inhibitors.

Stiripentol

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.

SUFentanil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression).

SUNItinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose decreases are recommended, and vary by indication. See full monograph for details.

Tadalafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving strong CYP3A4 inhibitors may vary based on indication and/or international labeling. Consult appropriate product labeling.

Temsirolimus

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors whenever possible. If combined, decrease temsirolimus dose to 12.5 mg per week and monitor patients for increased temsirolimus effects and toxicities.

Tezacaftor

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor. Management: When combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor alone should be administered.

Thiotepa

CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy.

Tofacitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full monograph for details.

Tolterodine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor.

Toremifene

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Exceptions are discussed in separate monograph.

TraZODone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors.

Valbenazine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors.

Valsartan

Antihepaciviral Combination Products may increase the serum concentration of Valsartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the valsartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination.

Vardenafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. See full drug interaction monograph for details.

Vemurafenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. Consider use of an alternative that is not a strong inhibitor of CYP3A4 as clinically appropriate. Exceptions are discussed in separate monographs.

Venetoclax

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: This combination is contraindicated during venetoclax initiation and ramp-up in patients with CLL/SLL. Reduced venetoclax doses are required during ramp-up for patients with AML, and reduced doses are required for all patients during maintenance therapy.

Vilazodone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor.

Voriconazole

Antihepaciviral Combination Products may decrease the serum concentration of Voriconazole. Management: Concurrent use of voriconazole with antihepaciviral combination products should be avoided unless the patient-specific benefit/risk ratio justifies the use of voriconazole. Decreased efficacy of voriconazole is possible.

Zopiclone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined.

Zuclopenthixol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity.

Risk Factor X (Avoid combination)

Acalabrutinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib.

Ado-Trastuzumab Emtansine

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component.

Alfuzosin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin.

Aprepitant

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant.

Astemizole

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Asunaprevir

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir.

Asunaprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir.

AtorvaSTATin

Antihepaciviral Combination Products may increase the serum concentration of AtorvaSTATin.

Avanafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil.

Axitinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended.

Barnidipine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine.

Blonanserin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin.

Bosutinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib.

Bromocriptine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine.

Budesonide (Systemic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic).

Cisapride

Antihepaciviral Combination Products may increase the serum concentration of Cisapride.

Cobimetinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib.

Colchicine

Antihepaciviral Combination Products may increase the serum concentration of Colchicine.

Conivaptan

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan.

Conivaptan

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

CYP2C8 Inhibitors (Strong)

May increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the serum concentrations of dasabuvir may increase significantly.

CYP3A4 Inducers (Moderate)

May decrease the serum concentration of Antihepaciviral Combination Products.

CYP3A4 Inducers (Strong)

May decrease the serum concentration of Antihepaciviral Combination Products.

Dabrafenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib.

Dapoxetine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine.

Domperidone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Dronedarone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Elagolix

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix.

Eletriptan

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan.

Eplerenone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone.

Ergot Derivatives

Antihepaciviral Combination Products may increase the serum concentration of Ergot Derivatives. Exceptions: Cabergoline; Nicergoline; Pergolide.

Ethinyl Estradiol

May enhance the hepatotoxic effect of Antihepaciviral Combination Products. Management: Use of ethinyl estradiol must be discontinued prior to use of this combination; ethinyl estradiol can be restarted 2 weeks after cessation of the antihepaciviral combination product.

Everolimus

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus.

Everolimus

Antihepaciviral Combination Products may increase the serum concentration of Everolimus.

Flibanserin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin.

Fluticasone (Nasal)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal).

Fosaprepitant

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant.

Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Grazoprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir.

Halofantrine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Ibrutinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued.

Idelalisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Irinotecan Products

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products.

Isavuconazonium Sulfate

CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4.

Ivabradine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine.

Lapatinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor.

Lefamulin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4.

Lercanidipine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine.

Lomitapide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide.

Lopinavir

May increase the serum concentration of Antihepaciviral Combination Products. Specifically, the serum concentrations of the paritaprevir component may increase significantly.

Lovastatin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin.

Lurasidone

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone.

Macitentan

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan.

Midazolam

Antihepaciviral Combination Products may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with antihepaciviral combination products. When used with intravenous midazolam, monitor for increased midazolam effects (eg, sedation, respiratory depression) and consider using a reduced midazolam dose.

Naloxegol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol.

Neratinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib.

NiMODipine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine.

Nisoldipine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine.

Palbociclib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib.

PAZOPanib

BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib.

Pimozide

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide.

QuiNINE

Antihepaciviral Combination Products may increase the serum concentration of QuiNINE.

Radotinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib.

Ranolazine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine.

Red Yeast Rice

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased.

Regorafenib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib.

Revefenacin

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin.

Rilpivirine

Antihepaciviral Combination Products may increase the serum concentration of Rilpivirine.

Rupatadine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine.

Salmeterol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol.

Silodosin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin.

Simeprevir

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.

Simvastatin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin.

Sirolimus

Antihepaciviral Combination Products may increase the serum concentration of Sirolimus.

Sonidegib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib.

Suvorexant

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant.

Tacrolimus (Systemic)

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir may increase the serum concentration of Tacrolimus (Systemic).

Tamsulosin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.

Terfenadine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Tetrahydrocannabinol and Cannabidiol

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol.

Ticagrelor

CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor.

Tolvaptan

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan.

Topotecan

BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan.

Trabectedin

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin.

Triazolam

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam.

Udenafil

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil.

Ulipristal

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity.

VinCRIStine (Liposomal)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal).

Vinflunine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine.

Vorapaxar

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar.

Voxilaprevir

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir.