Table 8.
Anti-infective agents categorized according to their potential risk for DDIs and QTc prolongation in combination with CDK4/6i.
| Antimicrobial therapy | Drug | CYP3A4 Substrate |
CYP3A4 Inhibitor |
CYP3A4 Inducer | Membrane transporter substrate | TdP risk | Comments |
|---|---|---|---|---|---|---|---|
| Antibiotics | |||||||
| β-lactams | – | – | – | – | Not known | Low risk of interaction with palbociclib and ribociclib. SAFE OPTIONS |
|
| Prophylactic (low dose) trimethoprim-sulfamethoxazole | – | – | – | – | Not known | ||
| Tetracyclines: Doxycycline1 Minocycline1 |
– – |
– – |
– – |
– – |
Not known Not known |
||
| Fosfomycin1 | – | – | – | – | Not known | ||
| Linezolid1 | – | – | – | – | Not known | ||
| Clindamycin | – | – | – | – | Not known | ||
| Glycopeptides: Teicoplanin1 Vancomycin1 Dalbavancin |
– – – |
– – – |
– – – |
– – – |
Not known Not known Not known |
||
| Aminoglucosides Amikacin1 Gentamicin1 |
– – |
– – |
– – |
– – |
Not known Not known |
||
| Daptomycin1 | – | – | – | – | Not known | ||
| Trimethoprim/ sulfamethoxazole |
Major (trimetho-prim) | – | – | – | Not known | Caution should be exercised | |
| Macrolides: Azithromycin |
Minor |
– |
– |
– |
known |
||
| Fluoroquinolones: Levofloxacin Moxifloxacin Norfloxacin Ofloxacin |
– – – – |
– – – – |
– – – – |
– – – – |
Known Known Possible Possible |
||
| Metronidazole | – | – | – | – | Conditional | ||
| Macrolides: Erythromycin Clarithromycin |
MajorMajor |
ModerateStrong |
– – |
gp-P– |
KnownKnown |
High risk of DDIs. Should be avoided |
|
| Rifampicin1 | – | – | Strong | OATP1B1, gp-P | Not known | ||
| Fluoroquinolones: Ciprofloxacin |
– |
Moderate-Weak |
– | OAT3, gp-P | Known | ||
| Antiherpetic | |||||||
| Acyclovir1
Famciclovir Valacyclovir |
– – – |
– – – |
– – – |
– – – |
Not known Not known Not known |
Low risk of interaction with palbociclib and ribociclib. SAFE OPTIONS |
|
| Brivudine Ganciclovir Valganciclovir |
– – – |
– – – |
– – – |
– – – |
Not knownNot known Not known |
||
| Flu | |||||||
| Oseltamivir1 | – | – | – | – | Not known | Low risk of interaction with palbociclib and ribociclib. SAFE OPTIONS |
|
| HIV, hepatitis | |||||||
| Nucleoside analog reverse transcriptase inhibitors (lamivudine, abacavir, tenofivir)Integrase inhibitors (dolutegravir, raltegravir) | –Minor (dolutegravir) | – – |
– – |
gp-P (tenofivir)gp-P (dolutegravir) | Not knownNot known | Low risk of interaction with palbociclib and ribociclib. SAFE OPTIONS |
|
| Non-nucleoside reverse transcriptase inhibitors: Nevirapine |
Major |
– |
Weak |
Not known |
Caution should be exercised | ||
| Protease inhibitors for HIV and HCV (atazanavir, darunavir, lopinavir, indinavir (usually administered in combination with ritonavir) | Major | Strong | – | gp-P (darunavir, ritonavir) | Not known | High risk; consider antiretroviral class switch | |
| Non-nucleoside reverse transcriptase inhibitors: Efavirenz |
Major |
– |
Moderate |
– |
Not known |
||
| Antifungal | |||||||
| Amphotericin B | – | – | – | – | Conditional3 | Low risk of interaction with palbociclib and ribociclib, SAFE OPTIONS | |
| Echinocandins: Caspofungin1 Anidulafungin Micafungin1 |
– Minor – |
– – – |
– – – |
– – – |
Not known Not known Not known |
||
| Amphotericin B | – | – | – | – | Conditional3 | Caution should be exercised3 | |
| FluconazoleI traconazole Isavuconazole1 Posaconazole Voriconazole |
–Major Major – Minor |
Moderate Strong Moderate Strong Strong |
– – – – – |
– – – – – |
known Conditional – Conditional Conditional |
High risk of DDIs. Should be avoided |
|
Green: Low risk of interaction with palbociclib and ribociclib, SAFE OPTIONS. Orange: Caution should be exercised. Red: High risk of DDIs. Plasmatic concentrations of the CYP3A4 substrate could be increased (or decreased) when used concomitantly with a CYP3A4 inhibitor (or inducer) moderate or strong. TdP,Torsades de pointes; gp-P, P-glycoprotein; OATP1B1, organic anion transporter polypeptide; OAT3, organic anion transporter.
Not classified risk QT. According to the source consulted (www.crediblemeds.org), the evidence available at this time did not result in a decision for it to be placed in any of the four QT risk categories.
Ribociclib can increase concentration of trimethoprim, with bone marrow toxicity.
Amphotericin B with conditional TdP risk, caution should be exercised in combination with Ribociclib.