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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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 in Specific Populations
Special Populations: Children
In pediatric patients age 12 to 17 years, when used with atazanavir, both atazanavir and cobicistat exposure were higher than in adults. When used with darunavir, darunavir exposure was slightly lower than that observed in adults, while cobicistat exposure was similar. Neither of these differences were considered clinically significant.
Use: Labeled Indications
HIV-1 infection: Treatment of HIV-1 infection in adults to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents; treatment of HIV-1 infection to increase systemic exposure of atazanavir or darunavir (once-daily regimen) in pediatric patients weighing ≥35 kg or ≥40 kg, respectively, 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), lomitapide, 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.
Canadian labeling: Additional contraindications (not in US labeling): Apixaban, astemizole (not available in Canada); elbasvir/grazoprevir, ergonovine, rivaroxaban, salmeterol; terfenadine (not available in Canada)
Dosage and Administration
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: Pediatric
HIV-1 infection, treatment: Note: Cobicistat is a pharmacokinetic enhancer only and lacks antiretroviral (ARV) activity. Use in combination with ARV agents. It is not interchangeable with ritonavir (HHS [pediatric] 2019). Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary. In clinical trials, the youngest patients were 12 years of age.
Coadministered with atazanavir 300 mg once daily: Treatment-naive or treatment-experienced: Children and Adolescents ≥35 kg: Oral: 150 mg once daily.
Coadministered with darunavir 800 mg once daily: Treatment-naive or treatment-experienced with no darunavir resistance-associated substitutions: Children and Adolescents ≥40 kg: Oral: 150 mg once daily.
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
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification
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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Avoid combination
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
AtorvaSTATin: Cobicistat may increase the serum concentration of AtorvaSTATin. Management: Avoid the combined use of atorvastatin with atazanavir/cobicistat. Atorvastatin dose should not exceed 20 mg daily when combined with other cobicistat-containing regimens. Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Avoid combination
Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. 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. Consider therapy modification
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 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. 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
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Monitor therapy
Betrixaban: Cobicistat may increase the serum concentration of Betrixaban. 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
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 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. 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. Exceptions discussed in separate monographs. Consider therapy modification
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
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. Monitor therapy
Cisapride: Cobicistat may increase the serum concentration of Cisapride. Avoid combination
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification
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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Avoid combination
Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy
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. 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. 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. Consider therapy modification
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; Mirtazapine; 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 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. 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 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. 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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
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. Consider therapy modification
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Monitor therapy
Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Consider therapy modification
Edoxaban: Cobicistat may increase the serum concentration of Edoxaban. Monitor therapy
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination
Elbasvir: Cobicistat may increase the serum concentration of Elbasvir. Avoid combination
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) 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
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
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. Consider therapy modification
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. Monitor therapy
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. 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
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. Consider therapy modification
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
Erythromycin (Systemic): Cobicistat may increase the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when cobicistat is combined with atazanavir or darunavir. If combined, monitor for increased erythromycin and cobicistat effects/toxicities. Consider therapy modification
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, nonhormone-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
Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Consider therapy modification
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
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Avoid combination
Fosphenytoin-Phenytoin: May decrease the serum concentration of Cobicistat. Avoid combination
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Monitor therapy
Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. Monitor therapy
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Monitor therapy
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. Consider therapy modification
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. Consider therapy modification
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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Monitor therapy
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
Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Consider therapy modification
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 age- and weight-specific recommendations. Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. 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
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. Consider therapy modification
Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Avoid combination
Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Avoid combination
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Monitor therapy
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Monitor therapy
Levomethadone: Cobicistat may increase the serum concentration of Levomethadone. 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
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. Consider therapy modification
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. Consider therapy modification
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Avoid combination
Lumacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumacaftor and Ivacaftor. Management: When initiating or resuming lumacaftor/ivacaftor after a therapy interruption of 7 days or more, reduce the lumacaftor/ivacaftor dose to 1 tablet daily or 1 packet of oral granules every other day for the first week, and then resume the standard dose. Consider therapy modification
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. 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
Meperidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Monitor therapy
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. Exceptions are discussed in separate monographs. 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 900 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
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. Monitor therapy
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. 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. Consider therapy modification
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
Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg/day to 200 mg/day. Consider therapy modification
PHENobarbital: May decrease the serum concentration of Cobicistat. Avoid combination
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. 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 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. Consider therapy modification
Pitavastatin: Cobicistat may increase the serum concentration of Pitavastatin. Monitor therapy
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. Monitor therapy
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
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, nonhormone-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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
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. 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
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination
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. Consider therapy modification
Rifabutin: Cobicistat may increase the serum concentration of Rifabutin. Management: Reduce rifabutin dose. Clinical guidelines recommend administering rifabutin 150 mg daily or 300 mg 3 times per week when used with cobicistat. Cobicistat labeling recommends decreasing the rifabutin dose to 150 mg every other day. 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
Rosuvastatin: Cobicistat may increase the serum concentration of Rosuvastatin. Management: Rosuvastatin dose should not exceed 10 mg/day with concurrent use of atazanavir and cobicistat or 20 mg/day with concurrent use of darunavir and cobicistat. Consider therapy modification
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: 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. Consider therapy modification
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. Monitor therapy
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
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. 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
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. 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
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy
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
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. 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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor and Ivacaftor. 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. Consider therapy modification
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. 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: 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. 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. Avoid combination
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. Consider therapy modification
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
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. Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Avoid combination
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. 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
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Monitor therapy
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. 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. Consider therapy modification
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. Consider therapy modification
Vilanterol: May increase the serum concentration of CYP3A4 Inhibitors (Strong). Monitor 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. 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
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. Consider therapy modification
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination
Warfarin: Cobicistat may increase the serum concentration of Warfarin. Monitor therapy
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. Consider therapy modification
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.
>10%: Hepatic: Hyperbilirubinemia (grades 3/4: 73%)
1% to 10%:
Cardiovascular: Increased serum creatine kinase (grades 3/4: 8%)
Central nervous system: Headache (2%), abnormal dreams (<2%), depression (<2%), fatigue (<2%), insomnia (<2%)
Dermatologic: Skin rash (5%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (grades 3/4: 4%), glycosuria (grades 3/4: 3%), hyperglycemia (grades 3/4: 2%), Fanconi's syndrome (<2%)
Gastrointestinal: Increased serum lipase (grades 3/4: 7%), increased serum amylase (grades 3/4: 4%), diarrhea (2%), nausea (2%), upper abdominal pain (<2%), vomiting (<2%)
Genitourinary: Hematuria (grades 3/4: 6%), proximal tubular nephropathy (2%)
Hematologic & oncologic: Decreased neutrophils (grades 3/4: 3%)
Hepatic: Increased serum alanine aminotransferase (grades 3/4: 6%), jaundice (6%), increased serum aspartate aminotransferase (grades 3/4: 4%)
Neuromuscular & skeletal: Rhabdomyolysis (<2%)
Ophthalmic: Scleral icterus (4%)
Renal: Nephrolithiasis (<2%), renal disease (<2%)
Frequency not defined:
Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides
Renal: 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
Pregnancy Considerations
Cobicistat has low placental transfer.
An increased risk of teratogenic effects has not been observed based on information collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and 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 for use in pregnant females living with HIV who are antiretroviral-naive, who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive. Cobicistat exposure is decreased in pregnancy. Use of cobicistat boosted atazanavir, darunavir, or elvitegravir in pregnancy is not recommended; patients who become pregnant during therapy should consider changing to a more effective, recommended regimen. If cobicistat is continued in a pregnant patient who is virally suppressed, monitor the viral load more frequently (eg, monthly during the second and third trimesters).
In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2019).
Patient Education
What is this drug used for?
- It is used to help the action of some other drugs used to treat HIV (atazanavir or darunavir).
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
- Yellow skin or eyes
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
