Table 17.
Antidepressants categorized according to their safety as concomitant treatment with palbociclib and ribociclib.
| Antidepressants | CYP3A4 Substrate |
CYP3A4 Inhibitor |
CYP3A4 Inducer | Membrane transporter substrate | TdP risk | Comments |
|---|---|---|---|---|---|---|
| Duloxetine1 | – | – | – | – | Not known | Low risk of interaction with palbociclib and ribociclib SAFE OPTIONS |
| Desvenlafaxine Vortioxetine2 |
Minor Minor |
– – |
– – |
– – |
Not known Not known |
|
| Paroxetine1 | – | – | – | – | Conditional | Caution should be exercised in combination with ribociclib or palbociclib |
| Sertraline1
Fluoxetine1,3 |
Minor Minor |
– – |
– – |
– – |
Conditional Conditional |
|
| Trazodone | Major | – | – | – | Conditional | High risk of DDIs. Should be avoided the combination with ribociclib or palbociclib |
| Mirtazapine Venlafaxine |
Major Major |
– – |
– – |
– – |
Possible Possible |
|
| Citalopram Escitalopram |
Major, NTI Major, NTI |
– – |
– – |
– – |
Known Known |
Green: Low risk of interaction with palbociclib and ribociclib, SAFE OPTIONS. Orange: Caution should be exercised. Red: High risk: Plasmatic concentrations of the substrate could be increased when used concomitantly with a CYP3A4 inhibitor, such as palbociclib (weak) or ribociclib (moderate-potent). Risk of increased toxicity. NTI, narrow therapeutic index; SPC, Summary of Product Characteristics; TdP, torsades de pointes.
Fluoxetine and paroxetine are strong CYP2D6 inhibitors; duloxetine is moderate CYP2D6 inhibitors; and sertraline is a weak CYP2D6 inhibitor. Concomitant use with tamoxifen should be avoided.
Controversial data. The Summary of Product Characteristics[105] and other authors [106] categorize Vortioxetine as a major substrate of CYP2D6 and a minor substrate of CYP3A4. For Uptodate® [107], vortioxetine is a major substrate for CYP2D6 and CYP3A4.
Fluoxetine has a longer half-life.