Drug Interactions between Adderall and Stribild

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

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.

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.