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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005148-50 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| raltegravir alone | Active Comparator | raltegravir 400 mg BID for 5 days |
|
| citalopram alone | Active Comparator | citalopram 10 mg QD for 3 days, followed by citalopram 20 mg QD for 13-14 days |
|
| raltegravir + citalopram | Experimental | raltegravir 500 mg BID and citalopram 20 mg QD for 5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| raltegravir | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| raltegravir AUC and citalopram AUC | To assess the effect of multiple dose citalopram on the steady state pharmacokinetics of raltegravir and vice versa by intrasubject comparison in healthy subjects.
| at steady state: day 5 of raltegravir treatment and day 16 or later for citalopram |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Adverse events will be scored and laboratory measurements for safety will be collected frequently from screening onwards (maximum 4 weeks before the start of the study) until the last study visit (Day 60) or longer if applicable. | up to approximately 13 weeks (from screening until the last study visit) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRCN Radboud university medical center | Nijmegen | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26375942 | Result | Blonk MI, Langemeijer CC, Colbers AP, Hoogtanders KE, van Schaik RH, Schouwenberg BJ, Burger DM. Pharmacokinetic drug-drug interaction study between raltegravir and citalopram. Antivir Ther. 2016;21(2):143-52. doi: 10.3851/IMP2993. Epub 2015 Sep 16. |
| Label | URL |
|---|---|
| Abstract 53: Pharmacokinetic drug-drug interaction study between raltegravir and citalopram in healthy volunteers. | View source |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| D015283 | Citalopram |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| citalopram |
| Drug |
|
| paper | View source |
| D011437 |
| Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |