Cobicistat
Pronunciation
(koe BIK i stat)
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tybost: 150 mg [contains fd&c yellow #6 aluminum lake]
Brand Names: U.S.
- Tybost
Pharmacologic Category
- Cytochrome P-450 Inhibitor
Pharmacology
Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Inhibition of CYP3A-mediated metabolism by cobicistat and increases the systemic exposure of CYP3A substrates atazanavir and darunavir.
Metabolism
Via CYP3A enzymes and to a minor extent by CYP2D6 enzymes and does not undergo glucuronidation
Excretion
Feces (86.2%), urine (8.2%)
Time to Peak
~3.5 hours
Half-Life Elimination
Terminal: ~3 to 4 hours
Protein Binding
97% to 98%
Use: Labeled Indications
HIV-1 infection: Treatment of HIV-1 infection to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents
Limitations of use: Cobicistat is not interchangeable with ritonavir to increase systemic exposure of darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data. The use of cobicistat is not recommended with darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir.
Contraindications
Concomitant use of cobicistat with atazanavir or darunavir with alfuzosin, carbamazepine, cisapride, colchicine (in patients with renal and/or hepatic impairment), dronedarone, ergot derivatives (eg, dihydroergotamine, ergotamine, methylergonovine), lovastatin, lurasidone, midazolam (oral), phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (when used for pulmonary arterial hypertension), simvastatin, St. John wort, triazolam; concomitant use of cobicistat and atazanavir with drospirenone/ethinyl estradiol, indinavir, irinotecan, or nevirapine.
Dosing: Adult
HIV-1 infection: Oral: Note: Must be administered with concomitant atazanavir or darunavir and other antiretroviral drugs. See individual agents. Cobicistat is a component (as a pharmacokinetic enhancer) of a recommended initial regimen (with elvitegravir/tenofovir [disoproxil fumarate or alafenamide]/emtricitabine) in ART-naive patients (HHS [adult] 2016).
Treatment-naive or experienced: 150 mg once daily with concomitant atazanavir
Treatment-naive or experienced with no darunavir resistance-associated substitutions: 150 mg once daily with concomitant darunavir
Dosing: Renal Impairment
When not used with concomitant tenofovir disoproxil fumarate: No dosage adjustment necessary.
When used with concomitant tenofovir disoproxil fumarate:
CrCl ≥70 mL/minute: No dosage adjustment necessary.
CrCl <70 mL/minute: Use is not recommended.
Dosing: Hepatic Impairment
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe hepatic impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Administration
Oral: Administer with food and at the same time as atazanavir or darunavir.
Dietary Considerations
Take with food
Storage
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep tightly closed. Dispense only in original container.
Drug Interactions
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. Consider therapy modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. Avoid combination
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. Avoid combination
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Avoid combination
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Consider therapy modification
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. Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Monitor therapy
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. Consider therapy modification
Amiodarone: Cobicistat may increase the serum concentration of Amiodarone. Monitor therapy
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Monitor therapy
Apixaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Consider therapy modification
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. Consider therapy modification
Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Avoid combination
Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
AtorvaSTATin: Cobicistat may increase the serum concentration of AtorvaSTATin. Management: Initiate atorvastatin at the lowest recommended dose and titrate slowly as needed while monitoring closely for evidence of atorvastatin toxicity. Atorvastatin dose should not exceed 20 mg/day with concurrent use of darunavir and cobicistat. Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Avoid combination
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. Avoid combination
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Avoid combination
Bedaquiline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit the duration of concomitant administration of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued administration is judged to outweigh the possible risks. Monitor for toxic effects of bedaquiline. Consider therapy modification
Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Monitor therapy
Bictegravir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Avoid combination
Boceprevir: Cobicistat may increase the serum concentration of Boceprevir. Management: Avoid concomitant use of boceprevir with cobicistat. US prescribing information for the combination product containing elvitegravir, cobicistat, emtricitabine, and tenofovir does not address this potential interaction. Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Monitor therapy
Bosentan: Cobicistat may increase the serum concentration of Bosentan. Management: See full drug interaction monograph for details. Consider therapy modification
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Avoid combination
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. Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP3A4 inhibitor; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor, or if a strong CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Consider therapy modification
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). Consider therapy modification
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Avoid combination
Budesonide (Nasal): Cobicistat may increase the serum concentration of Budesonide (Nasal). Management: Consider an alternative nasal corticosteroid when possible, particularly for longer-term concurrent use. If this combination must be used, monitor patients closely for evidence of systemic corticosteroid effects including adrenal suppression. Consider therapy modification
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Avoid combination
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. Consider therapy modification
Buprenorphine: Cobicistat may increase the serum concentration of Buprenorphine. Monitor therapy
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. Consider therapy modification
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. Consider therapy modification
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. Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Monitor therapy
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Monitor therapy
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
CarBAMazepine: May decrease the serum concentration of Cobicistat. Avoid combination
Cariprazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details. Consider therapy modification
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. Avoid combination
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. Consider therapy modification
Cisapride: Cobicistat may increase the serum concentration of Cisapride. Avoid combination
Clarithromycin: May increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Clarithromycin. Management: Consider alternative antibiotics. Reduce clarithromycin dose by 50% in patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir with estimated creatinine clearance 50 to 60 mL/min. Closely monitor for clarithromycin toxicity. Consider therapy modification
ClonazePAM: Cobicistat may increase the serum concentration of ClonazePAM. Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Avoid combination
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. Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Avoid combination
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. Consider therapy modification
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). Monitor therapy
Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Avoid combination
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of CycloSPORINE (Systemic). Consider therapy modification
CYP2D6 Substrates (High risk with Inhibitors): Cobicistat may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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. Consider therapy modification
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; Praziquantel; Telithromycin; Vinorelbine. Consider therapy modification
Dabigatran Etexilate: Cobicistat may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Avoid combination
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. Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Avoid combination
Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided; consider reducing dasatinib dose if a strong CYP3A4 inhibitor must be used. If using dasatinib 70 mg/day or 100 mg/day, consider reduction to 20 mg/day; if using dasatinib 140 mg/day, consider reduction to 40 mg/day. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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. Consider therapy modification
Delamanid: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase electrocardiogram (ECG) monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors because the risk for QTc interval prolongation may be increased. Continue frequent ECG assessments throughout the full delamanid treatment period. Consider therapy modification
Dexamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dexamethasone (Ophthalmic). Monitor therapy
Dexamethasone (Systemic): May decrease the serum concentration of Cobicistat. Dexamethasone (Systemic) may also counteract the boosting effects of Cobicistat on some agents. Management: Consider an alternative corticosteroid. Monitor patients receiving this combination closely for evidence of diminished response to the antiviral regimen. Consider therapy modification
Digoxin: Cobicistat may increase the serum concentration of Digoxin. Monitor therapy
Dihydroergotamine: Cobicistat may increase the serum concentration of Dihydroergotamine. Avoid combination
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. Consider therapy modification
Dofetilide: Cobicistat may increase the serum concentration of Dofetilide. Monitor therapy
Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Avoid combination
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy
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. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Monitor therapy
Elbasvir: Cobicistat may increase the serum concentration of Elbasvir. Avoid combination
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination
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. Consider therapy modification
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. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Avoid combination
Ergotamine: Cobicistat may increase the serum concentration of Ergotamine. Avoid combination
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). Consider therapy modification
Estazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam. Monitor therapy
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. Monitor therapy
Estrogen Derivatives (Contraceptive): Cobicistat may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider an alternative, non-hormone-based contraceptive in patients receiving cobicistat-containing products. Consider therapy modification
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). Consider therapy modification
Ethosuximide: Cobicistat may increase the serum concentration of Ethosuximide. Monitor therapy
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. Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Avoid combination
Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Monitor therapy
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. Consider therapy modification
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. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Avoid combination
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Avoid combination
Fluticasone (Oral Inhalation): Cobicistat may increase the serum concentration of Fluticasone (Oral Inhalation). Avoid combination
Fluvastatin: Cobicistat may increase the serum concentration of Fluvastatin. Monitor therapy
Fosamprenavir: Cobicistat may increase the serum concentration of Fosamprenavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Avoid combination
Fosphenytoin-Phenytoin: May decrease the serum concentration of Cobicistat. Avoid combination
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Monitor therapy
Glecaprevir and Pibrentasvir: Cobicistat may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy
Grazoprevir: Cobicistat may increase the serum concentration of Grazoprevir. Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Avoid combination
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Monitor therapy
HydrOXYzine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HydrOXYzine. Management: This combination is specifically contraindicated in some non-U.S. labeling. Consider therapy modification
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. Avoid combination
Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Monitor therapy
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
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. Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Monitor therapy
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. Avoid combination
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. Avoid combination
Itraconazole: May increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Itraconazole. Management: Limit itraconazole to a maximum adult dose of 200 mg/day in patients treated with the elvitegravir/cobicistat/emtricitabine/tenofovir combination product. Dosing recommendations for other cobicistat-containing products are not available. Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Avoid combination
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. Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Consider therapy modification
Ketoconazole (Systemic): May increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Ketoconazole (Systemic). Management: Limit ketoconazole to a maximum adult dose of 200 mg/day in patients being treated with the elvitegravir/cobicistat/emtricitabine/tenofovir combination product. Dosing recommendations for other cobicistat-containing products are not available. Consider therapy modification
Lacosamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Monitor therapy
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. Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Avoid combination
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Monitor therapy
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. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Avoid combination
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Avoid combination
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid combination
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Avoid combination
Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Consider therapy modification
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. Consider therapy modification
Methadone: Cobicistat may increase the serum concentration of Methadone. Management: No increased monitoring appears necessary if the cobicistat regimen also contains elvitegravir. Monitor therapy
Methylergonovine: Cobicistat may increase the serum concentration of Methylergonovine. Avoid combination
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. Consider therapy modification
Midazolam: Cobicistat may increase the serum concentration of Midazolam. Management: Oral midazolam use is contraindicated with cobicistat-containing products. IV midazolam should be used with caution, close monitoring, and consideration of lower IV midazolam doses. Avoid combination
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. Consider therapy modification
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. Consider therapy modification
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. Consider therapy modification
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. Consider therapy modification
Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Avoid combination
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Avoid combination
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid combination
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. Consider therapy modification
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy
OXcarbazepine: May decrease the serum concentration of Cobicistat. Management: Consider an alternative antiepileptic when possible. Consider therapy modification
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Monitor therapy
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. Consider therapy modification
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Avoid combination
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. Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy
PHENobarbital: May decrease the serum concentration of Cobicistat. Avoid combination
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination
Piperaquine: CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Management: Avoid the concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. If this combination cannot be avoided, frequent ECG monitoring is recommended due to the increased risk for QTc prolongation. Consider therapy modification
Pitavastatin: Cobicistat may increase the serum concentration of Pitavastatin. Monitor therapy
Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification
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. Consider therapy modification
Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. Monitor therapy
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Monitor therapy
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Monitor therapy
PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Monitor therapy
Primidone: May decrease the serum concentration of Cobicistat. Avoid combination
Progestins (Contraceptive): Cobicistat may increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, non-hormone-based contraceptive in patients receiving cobicistat-containing products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. Consider therapy modification
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce the quetiapine dose to one sixth of the regular dose following strong CYP3A4 inhibitor initiation. In patients receiving strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and up-titrate as needed. Consider therapy modification
QuiNIDine: Cobicistat may increase the serum concentration of QuiNIDine. Monitor therapy
Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Avoid combination
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Avoid combination
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Consider therapy modification
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. Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Avoid combination
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. Monitor therapy
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. Monitor therapy
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. Consider therapy modification
RifAMPin: May decrease the serum concentration of Cobicistat. Avoid combination
Rifapentine: May decrease the serum concentration of Cobicistat. Avoid combination
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Monitor therapy
Riociguat: Cobicistat may increase the serum concentration of Riociguat. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times a day. Patients receiving such a combination should also be monitored extra closely for signs or symptoms of hypotension. Consider therapy modification
Ritonavir: Cobicistat may enhance the therapeutic effect of Ritonavir. Specifically, cobicistat and ritonavir have overlapping effects on the CYP3A4-mediated metabolism of other drugs. Avoid combination
Rivaroxaban: Cobicistat may increase the serum concentration of Rivaroxaban. Avoid combination
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. Avoid combination
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Avoid combination
Saquinavir: Cobicistat may increase the serum concentration of Saquinavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Avoid combination
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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. Consider therapy modification
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. Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Avoid combination
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. Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Avoid combination
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Monitor therapy
St John's Wort: May decrease the serum concentration of Cobicistat. Avoid combination
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). Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Avoid combination
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. Consider therapy modification
Tadalafil: Cobicistat may increase the serum concentration of Tadalafil. Management: Recommendations for use of tadalafil in patients also receiving cobicistat vary by tadalafil indication and country. See full drug interaction monograph for details. Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Monitor therapy
Telaprevir: Cobicistat may increase the serum concentration of Telaprevir. Management: Avoid concomitant use of telaprevir with cobicistat. This warning does not apply to use of the combination product containing elvitegravir, cobicistat, emtricitabine, and tenofovir. Avoid combination
Telithromycin: May increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Telithromycin. Management: Seek alternatives to telithromycin. US prescribing information for the combination product containing elvitegravir, cobicistat, emtricitabine, and tenofovir does not address this potential interaction. Consider therapy modification
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. Consider therapy modification
Tenofovir Products: Cobicistat may enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy
Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tezacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor. Management: When combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor (100 mg/150 mg) should be administered in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. Consider therapy modification
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. Avoid combination
Tipranavir: Cobicistat may increase the serum concentration of Tipranavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Reduce the adult dose of tofacitinib to 5 mg daily in patients receiving strong CYP3A4 inhibitors. Consider therapy modification
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. Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Consider therapy modification
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy
Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Avoid combination
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. Avoid combination
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. Consider therapy modification
Vardenafil: Cobicistat may increase the serum concentration of Vardenafil. Management: Recommendations regarding use of vardenafil with cobicistat-containing products vary by vardenafil product and by country. See full drug interaction monograph for details. Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: These combinations are contraindicated during venetoclax initiation and ramp-up. In patients receiving steady venetoclax doses after completing ramp-up, reduce the venetoclax by at least 75% if strong CYP3A4 inhibitor use cannot be avoided. Consider therapy modification
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. Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Monitor therapy
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Avoid combination
Voriconazole: May increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Voriconazole. Management: Careful consideration of the risk/benefit ratio for voriconazole use is recommended prior to its use in patients who are being treated with cobicistat-containing products. Consider therapy modification
Voxilaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination
Warfarin: Cobicistat may increase the serum concentration of Warfarin. Monitor therapy
Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Monitor therapy
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. Consider therapy modification
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. Consider therapy modification
Test Interactions
May inhibit tubular secretion of creatinine without affecting actual renal glomerular function. Patients who experience a confirmed increase in serum creatinine >0.4 mg/dL from baseline should have renal function monitored closely.
Adverse Reactions
All adverse reactions are from trials using cobicistat coadministered with atazanavir, emtricitabine + tenofovir unless otherwise noted.
Frequency not always defined.
Central nervous system: Headache (2%), abnormal dreams (<2%), depression (<2%), fatigue (<2%), insomnia (<2%)
Dermatologic: Skin rash (5%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (>5 x ULN: 4%), glycosuria (3%), Fanconi's syndrome (<2%), increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides
Gastrointestinal: Increased serum amylase (>2 x ULN: 4% to 7%), diarrhea (2%), nausea (2%), upper abdominal pain (<2%), vomiting (<2%)
Genitourinary: Hematuria (6%), proximal tubular nephropathy (2%)
Hepatic: Hyperbilirubinemia (>2.5 x ULN: 73%), increased serum ALT (>5 x ULN: 6%), jaundice (6%), increased serum AST (>5 x ULN: 4%)
Neuromuscular & skeletal: Increased creatine phosphokinase (8%), rhabdomyolysis (<2%)
Ophthalmic: Scleral icterus (4%)
Renal: Nephrolithiasis (<2%), renal disease (<2%), decreased creatinine clearance (no effect on renal glomerular function in patients with normal renal function), increased serum creatinine, renal insufficiency
Warnings/Precautions
Concerns related to adverse effects:
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Renal toxicity: When used with concomitant tenofovir disoproxil fumarate, may cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy. In patients receiving concomitant tenofovir disoproxil fumarate, assess creatinine clearance, urine glucose, and urine protein prior to and periodically during treatment; assess serum phosphorus in patients with or at risk for renal impairment. Do not initiate therapy in combination with tenofovir disoproxil fumarate in patients with CrCl <70 mL/minute.
Concurrent drug therapy issues:
• Appropriate use: Use with HIV-1 protease inhibitors other than atazanavir or darunavir administered once daily is not recommended; use with more than one antiretroviral that requires pharmacokinetic enhancement (eg, two protease inhibitors or elvitegravir in combination with a protease inhibitor); darunavir 600 mg twice daily; darunavir in combination with efavirenz, etravirine, or nevirapine; atazanavir in combination with etravirine; or atazanavir in combination with efavirenz in treatment-experienced patients is not recommended.
• Concurrent therapy: Avoid concurrent use with other cobicistat-containing products or ritonavir-containing products.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions. Cobicistat and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications. Consult drug interactions database and contraindications section for more detailed information.
Other warning/precautions:
• False elevations in serum creatinine: May inhibit tubular secretion of creatinine without affecting actual renal glomerular function; use caution when interpreting serum creatinine values in patients with medical conditions or receiving drugs needing to be monitored with estimated creatinine clearance (CrCl). Patients who experience a confirmed increase in serum creatinine >0.4 mg/dL from baseline should have renal function monitored closely. Assess estimated CrCl prior to initiating therapy; consider alternative medications that do not require dosage adjustments in patients with renal impairment.
Monitoring Parameters
CBC with differential, reticulocyte count, CD4 count, HIV RNA plasma levels, and serum creatinine at baseline and when clinically indicated during therapy; when coadministered with tenofovir disoproxil fumarate, serum creatinine, urine glucose and urine protein prior to initiation and as clinically indicated during therapy; assess serum phosphorus in patients with or at risk for renal impairment. Patients who experience a confirmed increase in serum creatinine >0.4 mg/dL from baseline should have renal function monitored closely. Testing for HBV is recommended prior to the initiation of antiretroviral therapy.
Pregnancy Considerations
Cobicistat has low placental transfer. Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk. Maternal antiretroviral therapy (ART) may increase the risk of preterm delivery, although available information is conflicting possibly due to variability of maternal factors (disease severity; gestational age at initiation of therapy); however, maternal antiretroviral medication should not be withheld due to concerns of preterm birth. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services (HHS) Perinatal HIV Guidelines do not recommend cobicistat as initial therapy in antiretroviral-naive pregnant females. Cobicistat exposure is decreased in pregnancy; however, pharmacokinetic data are insufficient to make dosing recommendations. Use of a preferred agent is recommended until more data on cobicistat are available. In general, ART is recommended for all pregnant females with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a female who has never received antiretroviral therapy, ART should begin as soon as possible after diagnosis. Females who become pregnant on a stable ART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in nonpregnant adults; ART should be continued postpartum for all females living with HIV.
Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for HIV-infected females and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2017).
Patient Education
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain) or jaundice (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
Further information
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