Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
Status:
Completed
Trial end date:
2014-04-01
Target enrollment:
Participant gender:
Summary
Depression is the most common mental health disorder among HIV-patients. Recognizing and
treating depression is important in order to improve quality of life and health outcomes in
those living with HIV. In clinical practice selective serotonin reuptake inhibitors (SSRIs)
are used most frequently in HIV patients with depressive symptoms. A complicating factor in
the concomitant use of antiretroviral agents and antidepressant therapy is the occurrence of
drug-drug interactions. Citalopram can be seen as one of the preferred SSRIs in HIV-infected
patients because citalopram has a relatively favourable drug interaction profile compared to
other SSRIs. Raltegravir is an HIV-1 integrase inhibitor and is frequently being used as
antiretroviral agent in combination with tenofovir/emtricitabine in HIV-patients. Raltegravir
has shown sustained antiretroviral activity, is generally well tolerated and has little
propensity to interact with other drugs because it does not inhibit or induce CYP450 enzymes.
Theoretically, no clinically relevant drug interaction is expected between raltegravir and
citalopram as raltegravir is not a CYP2D6 substrate and thus will not be affected by the
possible inhibition of CYP2D6 by citalopram. Raltegravir is metabolized by UGT but citalopram
is not known to influence UGT. A possible interaction may occur through inhibition of P-gp
mediated transport of raltegravir by citalopram. However, even when no drug interaction is
expected theoretically, it may be recommended to collect sufficient clinical evidence to
support this hypothesis because unexpected interactions with raltegravir have been observed
in the past. In order to be able to recommend raltegravir and citalopram concomitant use, a
pharmacokinetic study in healthy volunteers is proposed.