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.

Apixaban

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

Atovaquone

May decrease the serum concentration of Indinavir.

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.

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.

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.

Cinacalcet

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

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.

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.

CYP3A4 Inducers (Moderate)

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

Deferasirox

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

DexAMETHasone (Ophthalmic)

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

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.

Enfortumab Vedotin

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

Enfuvirtide

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

Estrogen Derivatives

The serum concentration of oestrogen derivatives may rise in response to strong CYP3A4 inhibitors.

Etravirine

Evogliptin

Evogliptin's serum levels may rise in response to CYP3A4 Inhibitors (Strong).

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.

Histamine H2 Receptor Antagonists

Indinavir's serum concentration can drop.

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.

Levamlodipine

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

Levobupivacaine

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

Lumefantrine

Lumefantrine's serum levels may rise when taken with CYP3A4 Inhibitors (Strong).

MedroxyPROGESTERone

The blood concentration of medroxyPROGESTERone may rise in response to CYP3A4 Inhibitors (Strong).

Meperidine

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

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.

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.).

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.

Pranlukast

Pranlukast's serum levels may rise in response to CYP3A4 Inhibitors (Strong).

Praziquantel

Praziquantel's serum levels may rise in response to CYP3A4 Inhibitors (Strong).

PrednisoLONE (Systemic)

PrednisoLONE serum levels may rise in response to strong CYP3A4 inhibitors (Systemic).

PredniSONE

PredniSONE's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong).

Propafenone

Propafenone serum levels may rise after taking CYP3A4 Inhibitors (Strong). Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.

Proton Pump Inhibitors

Indinavir's serum concentration can drop.

QuiNIDine

Indinavir may increase the serum concentration of QuiNIDine.

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.

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).

Tasimelteon

Tasimelteon's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong).

Telithromycin

Telithromycin's serum levels may rise in response to CYP3A4 Inhibitors (Strong).

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.

Tocilizumab

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

TraMADol

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

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.

Venlafaxine

May decrease the serum concentration of Indinavir.

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.

Zidovudine

Protease Inhibitors may decrease the serum concentration of Zidovudine.

Zolpidem

CYP3A4 Inhibitors (Strong) 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.

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.

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.

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.

Bosentan

The serum levels of bosentan may rise when indinavir is used. The serum concentration of Indinavir may drop while taking bosentan. Treatment: Begin or adjust bosentan at 62.5 mg once daily or every other day (depending on tolerability) in patients receiving indinavir (see ritonavir for dosing if that agent is used). Watch out for any potential changes in indinavir's response as well.

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.

CarBAMazepine

Protease inhibitors may have a faster metabolism. The metabolism of CarBAMazepine may be slowed down by protease inhibitors.

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.

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.

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)

Protease Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Protease Inhibitors.

CycloSPORINE (Systemic)

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

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.

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.

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.

Didanosine

Indinavir's serum concentration can drop. Treatment: Formulations of didanosine that contain a buffer should be given at least an hour apart from indinavir.

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

It's possible that CYP3A4 Inhibitors (Strong) will raise Duvelisib's serum levels. Treatment: If duvelisib is used with a potent CYP3A4 inhibitor, lower the dose to 15 mg twice daily.

Efavirenz

Indinavir's serum concentration can drop. Treatment: It is unknown how indinavir should be dose-adjusted when combined with efavirenz. Indinavir doses that are higher and unboosted are probably not the best course of action. Consider using an indinavir regimen that is enhanced by ritonavir.

Elagolix

The serum levels of Elagolix may rise when using CYP3A4 Inhibitors (Strong). Usage of elagolix 200 mg twice day together with a potent CYP3A4 inhibitor for more than one month is the recommended course of treatment.

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.

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).

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

Fedratinib's serum levels may rise when taken with CYP3A4 Inhibitors (Strong). Management: When feasible, take into account alternatives. Fedratinib dosage should be reduced if combined to 200 mg daily. Increase fedratinib dosage to 400 mg/day as tolerated when the inhibitor is withdrawn, starting at 300 mg/day for the first two weeks.

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.

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.

Istradefylline

The blood levels of istradefylline may increase after taking CYP3A4 Inhibitors (Strong). When taken with potent CYP3A4 inhibitors, the maximum daily dose of istradefylline should be limited to 20 mg, and istradefylline effects and toxicities should be well monitored.

Itraconazole

Indinavir's serum concentration can rise. Itraconazole's serum levels may rise as a result of indinavir. When taking itraconazole, reduce the standard adult dose of indinavir to 600 mg every 8 hours. Keep an eye out for any increased systemic effects of itraconazole, especially harmful or toxic ones.

Ivacaftor

Ivacaftor's serum levels may rise in response to strong CYP3A4 inhibitors. Management: Ivacaftor dose reductions are necessary; for product-specific advice, refer to the entire monograph information.

Ivosidenib

Ivosidenib's serum levels may rise in response to CYP3A4 Inhibitors (Strong). Management: Whenever possible, avoid taking ivosidenib with a potent CYP3A4 inhibitor. Ivosidenib dosage should be decreased to 250 mg once daily when combination use is necessary. Medications that are specifically mentioned as exceptions are covered in further detail in their own drug interaction monographs.

Ixabepilone

Ixabepilone's serum levels may rise in response to CYP3A4 Inhibitors (Strong).

Ketoconazole (Systemic)

Indinavir's serum concentration can rise. Ketoconazole's serum levels may rise in response to indinavir (Systemic). When given with ketoconazole, the standard adult dose of indinavir should be decreased to 600 mg every 8 hours. Keep an eye out for any increased systemic effects, including harmful or toxic ones,

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.

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 900 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.

Nevirapine

May decrease the serum concentration of Indinavir. Management: Increased indinavir doses may be needed when used with nevirapine; however, specific dosing guidelines have not been established.

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.

PAZOPanib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. 

Pexidartinib

Pexidartinib's serum levels may rise when taken with CYP3A4 Inhibitors (Strong). Management: If at all feasible, avoid taking pexidartinib with potent CYP3A4 inhibitors. Pexidartinib dosage should be decreased if concomitant use cannot be avoided. Reduce daily doses of 800 mg or 600 mg to 200 mg twice day. Reduce 400 mg/day doses 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.

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

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.

Rifabutin

Indinavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Indinavir. Indinavir may increase the serum concentration of Rifabutin.

Rifapentine

Indinavir's serum concentration can drop. Management: Because of the potential for lower indinavir concentrations, decreased efficacy, and the emergence of resistance, you should think about avoiding the combination of indinavir and rifapentine whenever you can. Keep an eye out for indinavir treatment failure if coupled.

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: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors.

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)

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

Tacrolimus (Systemic)

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor clinical tacrolimus response closely and frequently monitor tacrolimus serum concentrations with concurrent use of any strong CYP3A4 inhibitor. Tacrolimus dose reductions and/or prolongation of the dosing interval will likely be required.

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

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.

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.

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.

Voxelotor

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inhibitors. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily.

Zanubrutinib

CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details.

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.

ALPRAZolam

Indinavir may increase the serum concentration of ALPRAZolam.

Amiodarone

Indinavir may increase the serum concentration of Amiodarone.

Aprepitant

The serum concentration of aprepitant may rise in response to CYP3A4 Inhibitors (Strong).

Astemizole

Astemizole's serum concentration may rise in response to CYP3A4 Inhibitors (Strong). Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.

Asunaprevir

Asunaprevir's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong).

Atazanavir

Could make Indinavir's harmful or hazardous effects worse. Atazanavir's harmful or hazardous effects may be exacerbated by indinavir.

Avanafil

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

Avapritinib

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

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.

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.

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.

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.

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.

Lasmiditan

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Lefamulin

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

Lemborexant

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

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.

Lumateperone

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

Lurasidone

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

Macitentan

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

Midazolam

Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with all protease inhibitors. IV midazolam contraindicated with f 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.

Pimozide

Protease Inhibitors may increase the serum concentration of Pimozide.

Pimozide

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

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 Indinavir.

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.

Tipranavir

May decrease the serum concentration of Protease Inhibitors.

Tolvaptan

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

Trabectedin

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

Triazolam

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

Ubrogepant

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

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.