Frågedatum: 2015-08-21
RELIS database 2015; id.nr. 24555, DRUGLINE
www.svelic.se

Utredningen som riktar sig till hälso- och sjukvårdspersonal, har utformats utefter tillgänglig litteratur och resurser vid tidpunkten för utredning. Innehållet i utredningen uppdateras inte. Hälso- och sjukvårdspersonal är ansvarig för hur de använder informationen vid rådgivning eller behandling av patienter.


Does probenecid (Probecid) interact with ledipasvir and sofosbuvir (Harvoni)?



Fråga: Does probenecid (Probecid) interact with ledipasvir and sofosbuvir (Harvoni)?

Sammanfattning: We have found no studies on the interaction between probenecid and sofosbuvir/ledipasvir. The theoretical risk that the drugs interact is low, but cannot be completely excluded. The patient should be followed regarding symptoms of adverse effects of sofosbuvir/ledipasvir, as well as virological response.

Svar: We have found no literature on the interaction between the probenecid and ledipasvir/sofosbuvir, which is why the response below is based on theoretical reasoning.

Biliary excretion (to faeces) of unchanged drug is the principal route of elimination for ledipasvir and renal excretion represents only about 1% of the elimination (1). After a single oral dose of sofosbuvir approximately 80% is recovered in urine, 14% in faeces and 2.5% in exhaled air. Most of the sofosbuvir recovered in urine was present as the inactive metabolite GS-331007 (78%), while 3.5% was recovered as sofosbuvir. Thus, renal clearance is the primary route of elimination for GS-331007 (1).

Probenecid inhibits renal tubular reabsorption of some drugs and tubular secretion of other drugs (2,3). Therefore, probenecid could theoretically affect the elimination of sofosbuvir/GS-331007. Probenecid was originally developed to inhibit the tubular secretion of penicillin. This occurs by the inhibition of organic anion transporter (OAT) 1 (4). However, it has been shown that GS-331007 is not a substrate for OAT1 (5), and the mechanism behind probenecid inhibition of penicillin concentration is therefore not plausible. Other transporters may be involved, but as the interaction between probenecid and sofosbuvir has not been studied we do not know how these drugs affect each other in co-administration. Mild to moderate renal impairment resulted in less than doubling of the exposure to sofosbuvir/GS- 331007, which is below the toxicity safety margin (5).

Unfortunately, we do not currently have methods for measuring drug concentrations of probenecid, ledipasvir, or sofosbuvir in blood or urine.

Referenser: