Drug Interactions between irinotecan liposomal and Stribild
This report displays the potential drug interactions for the following 2 drugs:
- irinotecan liposomal
- Stribild (cobicistat/elvitegravir/emtricitabine/tenofovir disoproxil)
Interactions between your drugs
cobicistat irinotecan liposomal
Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil) and irinotecan liposomal
GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of irinotecan and its active metabolite, SN-38. CYP450 3A4 is the isoenzyme responsible for the metabolic conversion of irinotecan to its inactive metabolite, APC. Inhibition of APC formation results in more irinotecan metabolism to SN-38, an active and toxic metabolite. High plasma levels of irinotecan and SN-38 may increase the risk of potentially fatal toxicities such as severe diarrhea, neutropenia, sepsis, and thromboembolism. In cancer patients, coadministration of ketoconazole, a potent CYP450 3A4 inhibitor, resulted in a 100% increase in the relative exposure to SN-38 and an 87% reduction in the exposure to APC. In HIV patients with Kaposi's sarcoma, coadministration of irinotecan with lopinavir-ritonavir decreased the clearance of irinotecan by 47%, increased the AUC of SN-38 by 204%, and decreased the AUC of APC by 81%.
MANAGEMENT: Concomitant use of irinotecan with potent CYP450 3A4 inhibitors should generally be avoided. Potent CYP450 3A4 inhibitors should be discontinued for at least one week before initiation of treatment with irinotecan.
References
- (2001) "Product Information. Camptosar (irinotecan)." Pharmacia and Upjohn
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Corona G, Vaccher E, Sandron S, et al. (2008) "Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma." Clin Pharmacol Ther, 83, p. 601-6
- Cerner Multum, Inc. "Australian Product Information."
- Phansalker S, Desai AA, Bell D, et al. (2012) "High-priority drug-drug interactions for use in electronic health records." J Am Med Inform Assoc, 19, p. 735-43
- (2015) "Product Information. Onivyde (irinotecan liposomal)." Merrimack Pharmaceuticals
tenofovir cobicistat
Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil) and Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil)
MONITOR: Concomitant use of tenofovir with cobicistat may increase the risk for tenofovir-related renal adverse effects, including renal impairment, renal failure, elevated creatinine, and Fanconi syndrome. The mechanism of this interaction has not been described. Cobicistat may decrease estimated creatinine clearance via inhibition of tubular secretion of creatinine; however, renal glomerular function does not appear to be affected. When given concomitantly with cobicistat, the systemic exposure (AUC) and trough plasma concentrations (Cmin) of tenofovir was also increased by 23% and 55%, respectively. However, data are lacking to determine whether concomitant use of tenofovir with cobicistat-containing regimens is associated with a greater risk of renal complications compared with regimens that do not include cobicistat.
MANAGEMENT: Initiation of cobicistat or cobicistat-containing regimens is not recommended in patients with CrCl less than 70 mL/min if any coadministered medicine requires dose adjustment based on renal function (including tenofovir), or is nephrotoxic. If concomitant therapy is necessary, monitoring of renal function is recommended, particularly in patients with risk factors for renal impairment.
References
- (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2014) "Product Information. Tybost (cobicistat)." Gilead Sciences
emtricitabine cobicistat
Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil) and Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil)
GENERALLY AVOID: Cobicistat may increase the plasma concentrations of antiretroviral agents. The plasma concentrations of cobicistat may also be increased or reduced in the presence of antiretroviral agents. The proposed mechanism is cobicistat inhibition of the CYP450 3A4 isoenzyme, of which antiretroviral agents may be substrates, and the inhibition or induction of CYP450 3A4 by concomitant antiretroviral medications. Cobicistat is a mechanism-based inhibitor and substrate of CYP450 3A4 with no antiretroviral activity of its own. Rather, it is indicated in its capacity as a pharmacokinetic booster of CYP450 3A4 to increase the systemic exposure of some antiretroviral medications such as atazanavir, darunavir, and elvitegravir, which are substrates of this isoenzyme. Concomitant use of other antiretroviral agents with cobicistat may also increase the plasma levels and risk of side effects associated with these medicines. In contrast, concomitant use of cobicistat-boosted atazanavir or darunavir with CYP450 3A4 inducers nevirapine, etravirine, or efavirenz may reduce the plasma concentrations of cobicistat, darunavir, and atazanavir, leading to a potential loss of therapeutic effect and development of resistance to darunavir and atazanavir. Pharmacokinetic data are not available.
MANAGEMENT: Cobicistat is not intended for use with more than one antiretroviral medication that requires pharmacokinetic enhancement, such as two protease inhibitors or elvitegravir in combination with a protease inhibitor. In addition, cobicistat should not be used concomitantly with ritonavir due to their similar effects on CYP450 3A4. According to some authorities, use of the antiretroviral combinations of atazanavir-cobicistat or darunavir-cobicistat concomitantly with the CYP450 3A4 inducers efavirenz, etravirine, or nevirapine is also not recommended. Other authorities consider the administration of atazanavir-cobicistat with efavirenz or nevirapine to be contraindicated. Since dosing recommendations have only been established for a number of antiretroviral medications, product labeling and current antiretroviral treatment guidelines should be consulted.
References
- (2001) "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
- (2008) "Product Information. Intelence (etravirine)." Ortho Biotech Inc
- Cerner Multum, Inc. "Australian Product Information."
- (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences
- (2014) "Product Information. Tybost (cobicistat)." Gilead Sciences
- (2014) "Product Information. Prezcobix (cobicistat-darunavir)." Janssen Pharmaceuticals
- (2015) "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb
Drug and food interactions
elvitegravir food
Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil)
ADJUST DOSING INTERVAL: Food enhances the oral bioavailabilities of both elvitegravir and tenofovir. When a single dose of cobicistat/elvitegravir/emtricitabine/tenofovir (trade name Stribild) was given with a light meal (approximately 373 kcal; 20% fat), mean elvitegravir and tenofovir systemic exposures (AUCs) increased by 34% and 24%, respectively, relative to fasting conditions. When administered with a high-fat meal (approximately 800 kcal; 50% fat), the mean AUC of elvitegravir and tenofovir increased by 87% and 23%, respectively, relative to fasting conditions. The alterations in mean AUCs of cobicistat and emtricitabine were not clinically significant with either the light or high-fat meal.
MANAGEMENT: Cobicistat/elvitegravir/emtricitabine/tenofovir as a fixed-dose preparation should be administered once daily with food. Elvitegravir as a single-ingredient preparation should also be administered once daily with food.
References
- (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences
- (2014) "Product Information. Vitekta (elvitegravir)." Gilead Sciences
tenofovir food
Applies to: Stribild (cobicistat / elvitegravir / emtricitabine / tenofovir disoproxil)
Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.
References
- (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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