Risk Factor C (Monitor therapy)

Abacavir

Protease Inhibitors may decrease the serum concentration of Abacavir.

Alosetron

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

AmLODIPine

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

Antidiabetic Agents

Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.

Artesunate

Ritonavir may decrease serum concentrations of the active metabolite(s) of Artesunate.

Atovaquone

Ritonavir may decrease the serum concentration of Atovaquone.

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.

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.

Brentuximab Vedotin

P-glycoprotein/ABCB1 Inhibitors 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

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

BuPROPion

Ritonavir may decrease the serum concentration of BuPROPion. Mixed effects on concentrations of the active hydroxybupropion metabolite have been reported. Management: Monitor for decreased bupropion effects. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving ritonavir.

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.

Cat's Claw

May increase the serum concentration of Ritonavir.

Celiprolol

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.

Cinacalcet

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

Clopidogrel

Ritonavir may diminish the antiplatelet effect of Clopidogrel. Ritonavir may decrease serum concentrations of the active metabolite(s) of Clopidogrel.

Clorazepate

Ritonavir may increase the serum concentration of Clorazepate.

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.

Cyclophosphamide

Protease Inhibitors may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased.

CYP2B6 Substrates (High risk with Inducers)

CYP2B6 Inducers (Moderate) may decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers).

CYP3A4 Inducers (Moderate)

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

Darolutamide

Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Darolutamide.

Dexamethasone (Ophthalmic)

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

DiazePAM

Ritonavir may increase 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

Ritonavir may increase the serum concentration of Dronabinol.

Dutasteride

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

Efavirenz

May enhance the adverse/toxic effect of Ritonavir. Efavirenz may increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of Efavirenz.

Enfuvirtide

Protease Inhibitors may increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors.

Estazolam

Ritonavir may increase the serum concentration of Estazolam.

Estriol (Systemic)

Ritonavir may decrease the serum concentration of Estriol (Systemic).

Estriol (Topical)

Ritonavir may decrease the serum concentration of Estriol (Topical).

Estrogen Derivatives

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

Evogliptin

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

Flurazepam

Ritonavir may increase the serum concentration of Flurazepam.

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.

HYDROcodone

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

Idelalisib

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

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.

Levomethadone

Ritonavir may decrease the serum concentration of Levomethadone.

LinaGLIPtin

Ritonavir 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.

Methadone

Ritonavir may decrease the serum concentration of Methadone.

Mirtazapine

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

Naldemedine

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

Naldemedine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.

Nalfurafine

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

Nintedanib

Combined Inhibitors of CYP3A4 and P-glycoprotein may increase the serum concentration of Nintedanib.

OLANZapine

Ritonavir may decrease the serum concentration of OLANZapine.

Orlistat

May decrease the serum concentration of Antiretroviral Agents.

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.

P-glycoprotein/ABCB1 Inhibitors

May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).

P-glycoprotein/ABCB1 Substrates

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide.

Pimecrolimus

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

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.

Posaconazole

May increase the serum concentration of Ritonavir.

Pranlukast

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

Praziquantel

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

PredniSONE

Ritonavir may increase the serum concentration of PredniSONE.

Proguanil

Ritonavir may decrease the serum concentration of Proguanil.

Prucalopride

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.

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.

RifAXIMin

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.

Rilpivirine

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

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)

Protease Inhibitors may decrease the metabolism of Tacrolimus (Topical).

Talazoparib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.

Tasimelteon

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

Tegaserod

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod.

Telithromycin

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

Tetrahydrocannabinol

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

Tetrahydrocannabinol and Cannabidiol

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

Theophylline Derivatives

Ritonavir may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline.

Thyroid Products

Ritonavir may diminish the therapeutic effect of Thyroid Products.

Tocilizumab

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

TraMADol

Ritonavir may decrease serum concentrations of the active metabolite(s) of TraMADol. Ritonavir may increase the serum concentration of TraMADol.

Triamcinolone (Systemic)

Ritonavir may enhance the adverse/toxic effect of Triamcinolone (Systemic). Specifically, risks of developing iatrogenic Cushing syndrome and secondary adrenal insufficiency may be increased. Ritonavir may increase the serum concentration of Triamcinolone (Systemic).

Tricyclic Antidepressants

Protease Inhibitors may increase the serum concentration of Tricyclic Antidepressants.

Upadacitinib

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

Valproate Products

Protease Inhibitors may decrease the serum concentration of Valproate Products.

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.

Warfarin

Ritonavir may decrease the serum concentration of Warfarin.

Zidovudine

Protease Inhibitors may decrease the serum concentration of Zidovudine.

Zolpidem

Ritonavir may increase the serum concentration of Zolpidem.

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.

Afatinib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. Iif used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.

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.

ALPRAZolam

CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Management: Consider using an alternative agent that is less likely to interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor.

Apixaban

Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated.

ARIPiprazole

May enhance the adverse/toxic effect of Ritonavir. The risk of metabolic disturbances (e.g. hyperglycemia, weight gain, hyperlipidemia) may be increased. Ritonavir may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph. Aripiprazole dose adjustment may not be required when used as adjunctive therapy for major depressive disorder.

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.

AtorvaSTATin

Protease Inhibitors may increase the serum concentration of AtorvaSTATin. Management: See full monograph for recommended dose limits. Avoid atorvastatin with tipranavir/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.

Betrixaban

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor.

Bilastine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors.

Bosentan

Ritonavir may increase the serum concentration of Bosentan. Management: Use bosentan 62.5 mg daily or every other day in adult patients who have been on ritonavir for at least 10 days. Temporarily stop bosentan (for at least 36 hrs) before starting ritonavir; wait until at least 10 days on ritonavir before restarting.

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.

Calcium Channel Blockers (Nondihydropyridine)

Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If used, monitor for CCB toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Saquinavir, tipranavir, and darunavir/cobicistat use with bepridil is contraindicated.

Canagliflozin

Ritonavir may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2.

CarBAMazepine

May increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine.

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

Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration.

Clarithromycin

Protease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxyclarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors. Management: Saquinavir is contraindicated with clarithromycin. Avoid clarithromycin adult doses over 1000 mg/day with a protease inhibitor. Further dose reductions may be needed with impaired renal function. Consider alternative antimicrobial for a non-MAC infection.

Colchicine

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details.

Colchicine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details.

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)

Ritonavir may increase the serum concentration of CycloSPORINE (Systemic). Management: Consider empiric cyclosporine dose reductions and monitor cyclosporine serum concentrations closely if ritonavir is initiated.

CYP3A4 Inducers (Strong)

May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.

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.

Dabigatran Etexilate

P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling.

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.

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.

Deferasirox

Ritonavir may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing.

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.

Delavirdine

Protease Inhibitors may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Protease Inhibitors.

Digoxin

Ritonavir may increase the serum concentration of Digoxin.

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.

DOXOrubicin (Conventional)

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein 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.

Edoxaban

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation.

Elagolix

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months.

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

Ritonavir may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with ritonavir and 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.

Enzalutamide

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.

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).

Estrogen Derivatives (Contraceptive)

Protease Inhibitors may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use oral contraceptives containing at least 35mcg ethinyl estradiol with atazanavir/ritonavir, or no more than 30mcg in patients receiving atazanavir alone. Use of an alternative, non-hormonal contraceptive is recommended with other protease inhibitors.

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.

Etravirine

Ritonavir may decrease the serum concentration of Etravirine. Management: Avoid concomitant use of etravirine with antiviral doses of ritonavir; use with ritonavir-boosted fosamprenavir or with ritonavir-boosted tipranavir is also not recommended.

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.

Fosphenytoin

May decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Fosphenytoin.

Garlic

May decrease the serum concentration of Protease Inhibitors. Management: Concurrent use of garlic supplements with protease inhibitors is not recommended. If this combination is used, monitor closely for altered serum concentrations/effects of protease inhibitors, and particularly for signs/symptoms of therapeutic failure.

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.

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.

Itraconazole

Ritonavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving ritonavir.

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)

Ritonavir may increase the serum concentration of Ketoconazole (Systemic). Management: Limit the adult maximum ketoconazole dose to 200 mg/day in patients receiving ritonavir.

LamoTRIgine

Ritonavir may decrease the serum concentration of LamoTRIgine.

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.

Lorlatinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily.

Lorlatinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.

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.

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.

Mitotane

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.

Nefazodone

Protease Inhibitors may increase the serum concentration of Nefazodone. Management: Consider alternatives to, or reduced doses of, nefazodone in patients treated with HIV protease inhibitors. Monitor patients receiving these combinations closely for toxic effects of nefazodone.

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.

Phenytoin

May decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Phenytoin.

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.

PrednisoLONE (Systemic)

Ritonavir may increase the serum concentration of PrednisoLONE (Systemic). Management: Consider prednisolone dose reductions in patients receiving ritonavir and monitor for increased adverse effects with concomitant use.

Protease Inhibitors

May increase the serum concentration of other Protease Inhibitors. Management: Atazanavir--indinavir combination contraindicated. Tipranavir/ritonavir or atazanavir/ritonavir not recommended with other protease inhibitors (PI). Darunavir/cobicistat not recommended with PI that require boosting.Other combos may require dose changes.

QUEtiapine

Ritonavir may increase the serum concentration of QUEtiapine. Management: The ritonavir Canadian labeling states this combination should not be used. U.S. labeling recommends using an alternative when possible; if the combination must be used, quetiapine dose reductions are needed.

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.

Rifabutin

Ritonavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Ritonavir may increase the serum concentration of Rifabutin. Management: Ritonavir US prescribing information recommends reducing rifabutin doses by at least 75%. Refer to drug interaction monographs addressing concomitantly administered protease inhibitors for dosing recommendations specific to ritonavir-boosted regimens.

Riociguat

Protease Inhibitors may increase the serum concentration of Riociguat. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times a day (for adults). Patients receiving such a combination should also be monitored extra closely for signs or symptoms of hypotension.

Rosuvastatin

Protease Inhibitors may increase the serum concentration of Rosuvastatin. Management: Start at the lowest rosuvastatin dose and monitor for toxicity. See full drug interaction monograph for details.

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

Protease Inhibitors may increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension.

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.

Sirolimus

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus. Management: Consider avoiding concurrent use of sirolimus with strong CYP3A4 inhibitors in order to minimize the risk for sirolimus toxicity. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated.

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.

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.

Tacrolimus (Systemic)

Ritonavir may increase the serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose reductions may be needed with concurrent ritonavir. Monitor tacrolimus concentrations closely to determine dose; doses of tacrolimus 0.5 mg to 1 mg every week may be adequate.

Tadalafil

Ritonavir may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving ritonavir may vary based on indication and/or international labeling. Consult appropriate product labeling.

Temsirolimus

Protease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.

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.

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.

Velpatasvir

Ritonavir may decrease the serum concentration of Velpatasvir. Ritonavir may increase the serum concentration of Velpatasvir.

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.

Venetoclax

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors.

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.

VinBLAStine

Ritonavir may increase the serum concentration of VinBLAStine. Management: Monitor closely for signs and symptoms of vinblastine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use.

VinCRIStine

Ritonavir may increase the serum concentration of VinCRIStine. Management: Monitor closely for signs and symptoms of vincristine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use.

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.

Alfuzosin

Protease Inhibitors may increase the serum concentration of Alfuzosin.

Amiodarone

Ritonavir may increase the serum concentration of Amiodarone. Management: Ritonavir US prescribing information lists this combination as contraindicated. Amiodarone use should be avoided with lopinavir/ritonavir, but if the combination must be used, monitor closely for increased amiodarone serum concentrations and effects.

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.

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

Protease Inhibitors may increase the serum concentration of Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Clobetasone

Ritonavir may increase the serum concentration of Clobetasone.

Cobicistat

May enhance the therapeutic effect of Ritonavir. Specifically, cobicistat and ritonavir have overlapping effects on the CYP3A4-mediated metabolism of other drugs.

Cobimetinib

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

Conivaptan

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

Dabrafenib

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

Dapoxetine

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

Disulfiram

Ritonavir may enhance the adverse/toxic effect of Disulfiram. Specifically, the combination of ritonavir oral solution, which contains 43% alcohol, may result in a disulfiramalcohol reaction if combined.

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.

Eletriptan

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

Eplerenone

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

Ergot Derivatives

Protease Inhibitors may increase the serum concentration of Ergot Derivatives. Exceptions: Cabergoline; Nicergoline; Pergolide.

Everolimus

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

Flecainide

Ritonavir may increase the serum concentration of Flecainide.

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

Ritonavir may increase the serum concentration of Fusidic Acid (Systemic). Fusidic Acid (Systemic) may increase the serum concentration of Ritonavir.

Glecaprevir and Pibrentasvir

Ritonavir may increase the serum concentration of Glecaprevir and Pibrentasvir.

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.

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.

Lovastatin

Protease Inhibitors may increase the serum concentration of Lovastatin.

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.

Meptazinol

Ritonavir may increase the serum concentration of Meptazinol.

MetroNIDAZOLE (Systemic)

Ritonavir may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Specifically, the combination of ritonavir oral solution or ritonavir soft gelatin capsule, both of which contain alcohol, and metronidazole may result in a disulfiram-like reaction.

Midazolam

Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with all protease inhibitors. IV midazolam contraindicated with fosamprenavir and nelfinavir; other protease inhibitors recommend caution, close monitoring, and consideration of lower IV midazolam doses with concurrent use.

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

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.

Pimozide

Protease Inhibitors may increase the serum concentration of Pimozide.

Pimozide

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

Propafenone

Ritonavir may increase the serum concentration of Propafenone.

QuiNIDine

Ritonavir may increase the serum concentration of QuiNIDine.

QuiNINE

Ritonavir may decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. QuiNINE may increase the serum concentration of Ritonavir. Ritonavir 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.

RifAMPin

May decrease the serum concentration of Ritonavir.

Rivaroxaban

Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban.

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.

Simeprevir

Protease Inhibitors may increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Protease Inhibitors.

Simvastatin

Protease Inhibitors may increase the serum concentration of Simvastatin.

Simvastatin

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

Sonidegib

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

St John's Wort

May increase the metabolism of Protease Inhibitors.

Suvorexant

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

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.

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

P-glycoprotein/ABCB1 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).

VinCRIStine (Liposomal)

P-glycoprotein/ABCB1 Inhibitors 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.

Voriconazole

Ritonavir may decrease the serum concentration of Voriconazole. Management: Concurrent voriconazole and high-dose ritonavir (adult doses of 400 mg every 12 hrs or greater) is contraindicated. Voriconazole with lower-dose ritonavir should be avoided unless benefits outweigh risk of inadequate voriconazole concentrations.