P-glycoprotein Drug Interactions

For the most current information on this topic, please see Drug Interactions: Cytochrome P450 (CYP), P-glycoprotein, and More.

Full update June 2020

Pharmacokinetics can be affected by drug transporters (e.g., P-glycoprotein, breast cancer resistance protein [BCRP], multidrug and toxin excluders [MATEs], organic anion transporting polypeptides [OATPs]).  We are still learning about the significance of these transporters on pharmacokinetics.  Most of the available data is related to P-glycoprotein (P-gp; multidrug resistance protein 1 [MDR1]). P-gp is a drug efflux pump found in the gut, liver, kidney, blood-brain barrier, and cancer cells.¹ It pumps drugs out of cells and into the gut, bile, and/or urine for excretion.^1,6 The table below lists P-gp substrates, inhibitors, and inducers, but is not comprehensive. Inhibitors may increase levels of P-gp substrates, and inducers may decrease levels of P-gp substrates.¹ For most interactions, CYP450 enzyme inhibition or induction is also involved, and many P-glycoprotein substrates are also CYP3A4 substrates (P-gp helps prevent saturation of CYP3A4⁶), so the contribution of P-gp inhibition/induction vs CYP450 inhibition/induction can be difficult to discern.^3,17,51 Furthermore, interactions involving P-gp alone are not as often significant.⁵¹ In the table that follows, italics denote those drugs involved in a p-glycoprotein drug interaction that is clinically evident and/or is associated with a strong warning or recommendation for specific intervention (e.g., specific dose alteration, laboratory monitoring, avoidance). Keep in mind inhibition potency in patients is not well defined, and is unknown for many inhibitors. It is prudent to use any combination with potential for interaction with caution (e.g., conservative dosing, appropriate monitoring), especially those involving drugs with a narrow therapeutic index and/or potentially serious dose-dependent side effects (e.g., chemotherapy, cardiac medications, anticonvulsants). For drugs or drug combinations that are both substrates and inhibitors, the net effect is difficult to predict.

--In addition to the references cited below, product labeling was also consulted.--

 

*Denotes moderate CYP3A inhibitors. **Denotes strong CYP3A inhibitors.

NOTE: Inhibitor/inducer strength indicated if available.

Project Leader in preparation of this clinical resource (360629): Melanie Cupp, Pharm.D., BCPS

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Cite this document as follows: Clinical Resource, P-glycoprotein Drug Interactions. Pharmacist’s Letter/Prescriber’s Letter. June 2020.

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