Can Palbociclib Cause Liver Injury?
Yes, palbociclib (Ibrance) can cause liver injury, though it is relatively uncommon compared to other adverse effects such as neutropenia. The risk appears to be higher in patients with pre-existing hepatic impairment, particularly moderate to severe cases.
Mechanism and Metabolism
Palbociclib undergoes extensive hepatic metabolism in humans, which explains its potential for liver effects:
- According to the FDA drug label, palbociclib is primarily metabolized in the liver through oxidation and sulfonation pathways 1
- Only 2.3% of the drug is excreted unchanged in feces and 6.9% in urine, confirming its high rate of hepatic metabolism 1
- CYP3A and SULT2A1 enzymes are mainly involved in palbociclib metabolism 1
Risk Factors for Liver Injury
The risk of palbociclib-induced hepatotoxicity increases with:
- Pre-existing moderate to severe hepatic impairment (Child-Pugh class B or C)
- Palbociclib unbound AUCINF increases by 34% in moderate and 77% in severe hepatic impairment 1
- Palbociclib unbound Cmax increases by 38% in moderate and 72% in severe hepatic impairment 1
Clinical Evidence of Hepatotoxicity
Several case reports document palbociclib-associated liver injury:
- A case of severe acute drug-induced hepatitis in a 61-year-old female with metastatic breast cancer treated with palbociclib and letrozole 2
- This patient improved dramatically after discontinuation of palbociclib and treatment with N-acetylcysteine 2
Safety in Mild Hepatic Impairment
Recent evidence suggests palbociclib is generally safe in patients with mild hepatic impairment:
- A 2025 multicenter retrospective study of 478 female patients found that those with mild hepatic impairment (n=205) did not have an increased risk of developing grade 3/4 neutropenia compared to patients with normal hepatic function 3
- Progression-free survival was also not significantly different between both groups 3
Cross-Reactivity with Other CDK4/6 Inhibitors
There appears to be differential hepatotoxicity among CDK4/6 inhibitors:
- A case report describes successful treatment with palbociclib after abemaciclib-induced severe hepatotoxicity (grade 4) 4
- Another case report documents successful switching to palbociclib after ribociclib-induced grade 3 hepatotoxicity 5
Monitoring Recommendations
For patients on palbociclib:
- Regular monitoring of liver function tests is recommended, especially in patients with pre-existing liver disease
- Particular attention should be paid to patients with moderate to severe hepatic impairment
- Dose adjustments may be necessary based on the degree of hepatic impairment
Management of Suspected Hepatotoxicity
If liver injury is suspected:
- Consider temporary interruption or discontinuation of palbociclib
- Evaluate for other potential causes of liver injury
- N-acetylcysteine may be beneficial in cases of severe hepatotoxicity, as suggested by one case report 2
- Consider switching to an alternative CDK4/6 inhibitor if appropriate, as cross-reactivity is not universal
In conclusion, while palbociclib can cause liver injury, it appears to be relatively uncommon, with most cases being manageable through dose adjustment or temporary discontinuation. Patients with pre-existing moderate to severe hepatic impairment are at higher risk and require closer monitoring.