[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [CDK4/6 inhibitors](https://durgical.com/en/pharmacology/classes/cdk4-6-inhibitors/) › Palbociclib

# Palbociclib

## CDK4/6 inhibitors?

CDK4/6 inhibitors

## High alert?

An error with this medicine can cause serious harm: double checks and protocols are used.

## Pregnancy: avoid?

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…

The first CDK4/6 inhibitor: with hormone therapy it holds HR-positive, HER2-negative breast cancer in G1. Main effect: neutropenia.

Updated Nov 1, 2026

Also called: PD-0332991

## Quick facts

**Group**
[CDK4/6 inhibitors](https://durgical.com/en/pharmacology/classes/cdk4-6-inhibitors/)

**Target**
Cyclin-dependent kinases 4 and 6 (CDK4/6)

**Used for**
HR-positive · The same cancer

**Key effects**
Neutropenia and leukopenia · Infections · Fatigue

**Monitor**
Complete blood count before starting · Lung symptoms

**ATC**
L01EF01

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**Cyclin-dependent kinases 4 and 6 (CDK4/6)**Palbociclib

ⓘ The figure shows palbociclib (PD-0332991) in the ATP pocket of human CDK6, crystallised with a viral cyclin partner.

**Target in 3D:** Cyclin-dependent kinases 4 and 6 (CDK4/6). PDB structure 2EUF (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/2EUF) · Drag to rotate · pinch to zoom

Palbociclib blocks the ATP site of CDK4 and CDK6 without affecting CDK1, 2 or 5. Cyclin D–CDK4/6 can no longer phosphorylate Rb, so Rb keeps the E2F transcription factors bound and the tumour cell arrests in G1 instead of copying its DNA. Combined with an aromatase inhibitor or fulvestrant, which cut the oestrogen signal that drives cyclin D, it markedly lengthens the time before the cancer progresses.

- Cyclin D–CDK4/6 phosphorylates Rb at the G1/S checkpoint
- Palbociclib blocks the ATP site of CDK4 and CDK6
- Rb stays active and holds E2F: the cell arrests in G1
- Paired with an aromatase inhibitor or fulvestrant

## Indications

- HR-positive, HER2-negative advanced or metastatic breast cancer, with an aromatase inhibitor as initial endocrine therapy (postmenopausal women and men). [Breast cancer →](https://durgical.com/en/conditions/breast-cancer/)
- The same cancer with fulvestrant after progression on endocrine therapy. [Breast cancer →](https://durgical.com/en/conditions/breast-cancer/)

## Adverse effects

### Common

- Neutropenia and leukopenia
- Infections
- Fatigue, nausea, diarrhoea, decreased appetite
- Mouth sores (stomatitis)
- Hair thinning, dry skin, rash; anaemia and thrombocytopenia

### Serious (rare, important)

- Severe neutropenia with fever or infection
- Breathlessness, cough or chest pain from lung inflammation
- Bleeding or bruising from low platelets
- Severe skin reactions (blistering, peeling)

## Contraindications

- No absolute contraindications in the label apart from hypersensitivity; see the warnings

## Key interactions

**Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir) and grapefruit**
Raise palbociclib exposure markedly; the combination is avoided or the dose is lowered.

**Strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, enzalutamide, St John's wort)**
Lower palbociclib levels; they are avoided.

**Narrow-margin CYP3A substrates (midazolam, ciclosporin, tacrolimus, sirolimus, everolimus, fentanyl, ergotamine)**
Palbociclib raises their levels.

## What is monitored

- Complete blood count before starting and during treatment
- Signs of infection
- Lung symptoms (cough, breathlessness)

## Administration and safety

- Oral; swallowed whole, never split, crushed, chewed or opened.
- Given in cycles with a rest week in each cycle; capsules with food, tablets with or without food.
- Grapefruit, its juice and St John's wort are avoided because they change its levels.

## Pregnancy and breastfeeding

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.

## Nursing care

- Review the neutrophil count, as ordered, before treatment continues.
- Teach to report fever, chills or other signs of infection at once.
- Mouth care and soft diet for stomatitis; report nosebleeds or easy bruising.
- Confirm a negative pregnancy test before the first dose and teach contraception during treatment and afterwards.

## Pharmacokinetics

**Absorption**
Oral; capsules are taken with food, tablets with or without food.

**Metabolism**
Liver, CYP3A and the sulfotransferase SULT2A1; it also inhibits CYP3A.

**Half-life**
About 29 hours.

## Memory aid

«-ciclib = cell-cycle brake»: CDK4/6 stop, Rb stays on guard, the cell parks in G1. Palbociclib's price is paid in neutrophils.

## Test yourself

Think of the answer, then tap the question to see it.

## At which point of the cell cycle does palbociclib stop tumour cells?

At the G1 to S transition, by keeping Rb unphosphorylated.

## Which drugs is palbociclib combined with in breast cancer?

An aromatase inhibitor (such as letrozole) or fulvestrant.

## Which blood test is followed during palbociclib treatment?

The complete blood count, because neutropenia is its main toxicity.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/palbociclib/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High alert**
An error with this medicine can cause serious harm: double checks and protocols are used.

**Pregnancy: avoid**
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…

## Connections

## Related drugs 3

- [Ribociclib](https://durgical.com/en/pharmacology/ribociclib/)
- [Abemaciclib](https://durgical.com/en/pharmacology/abemaciclib/)
- [Letrozole](https://durgical.com/en/pharmacology/letrozole/)

## Related conditions 1

- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)

[← Back to the class: CDK4/6 inhibitors](https://durgical.com/en/pharmacology/classes/cdk4-6-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Palbociclib: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a615013.html) (MedlinePlus (U.S. National Library of Medicine), 2024); [Palbociclib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/palbociclib) (National Cancer Institute, 2024); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01EF01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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