Idelalisib

PI3K inhibitors
PI3K inhibitors
High alert
An error with this medicine can cause serious harm: double checks and protocols are used.

Oral PI3Kδ inhibitor for relapsed CLL with rituximab. Boxed warnings: liver damage, severe diarrhoea or colitis, pneumonitis, infections, bowel perforation.

Updated Nov 1, 2026

Quick facts

Group: PI3K inhibitors
Target: PI3Kδ, catalytic subunit p110δ of phosphoinositide 3-kinase (leukocytes)
Used for: Relapsed chronic lymphocytic leukaemia
Key effects: Diarrhoea · Fever · Cough
Monitor: Liver tests frequently · Breathing symptoms
ATC: L01EM01

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

Mechanism of action

PI3Kδ, catalytic subunit p110δ of phosphoinositide 3-kinase (leukocytes)Idelalisib

The crystal structure shows idelalisib bound to the p110δ subunit of mouse PI3Kδ, whose binding site closely matches the human enzyme.

Target in 3D: PI3Kδ, catalytic subunit p110δ of phosphoinositide 3-kinase (leukocytes). PDB structure 4XE0 (RCSB PDB, public domain). View the structure at RCSB PDB

Idelalisib selectively inhibits PI3Kδ, the isoform expressed mainly in leukocytes, including normal and malignant B cells. It blocks signalling from the B-cell receptor and from the chemokine receptors CXCR4 and CXCR5, which guide B cells to the lymph nodes and bone marrow. Malignant B cells lose survival signals and protective niches, proliferate less and undergo apoptosis.

Malignant B cells depend on PI3Kδ signalling
Idelalisib blocks the PI3Kδ kinase site
B-cell receptor and CXCR4/CXCR5 signals fall
Cells leave their niches and die

Indications

Relapsed chronic lymphocytic leukaemia, with rituximab, when rituximab alone would be considered because of other illnesses. Chronic lymphocytic leukaemia →
It has been used in relapsed follicular lymphoma and small lymphocytic lymphoma after at least two prior therapies; it is not a first-line treatment. Non-Hodgkin lymphoma →

Adverse effects

Common

Diarrhoea
Fever, chills, fatigue
Cough, pneumonia
Nausea, rash
Raised liver enzymes and triglycerides, hyperglycaemia

Contraindications

History of serious allergic or skin reactions to idelalisib
Breastfeeding during therapy
Caution in liver disease and with other hepatotoxic drugs

Key interactions

CYP3A substrates (e.g. midazolam): Idelalisib inhibits CYP3A and raises their levels.
Strong CYP3A inhibitors: Raise idelalisib levels and its toxicity.
Strong CYP3A inducers (e.g. rifampicin, St John's wort): Lower idelalisib levels; avoided.
Other liver-toxic drugs: Add to the risk of hepatotoxicity; avoided.

What is monitored

Liver tests frequently
Stool frequency and abdominal pain
Breathing symptoms
Signs of infection, including cytomegalovirus
Complete blood count

Administration and safety

Oral, on a regular schedule, with or without food.
Swallowed whole; not crushed, chewed or split unless the product instructions allow it.
Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.

Pregnancy and breastfeeding

May harm the fetus; effective contraception is used during and after treatment, and breastfeeding is not done during therapy.

Nursing care

Review liver tests before refills; report jaundice or dark urine.
Ask about the number of stools and abdominal pain; severe diarrhoea is reported at once.
Ask about cough, breathlessness and fever.
Teaching: report new or worse diarrhoea, sudden severe abdominal pain, cough or rash; ask before taking St John's wort or eating grapefruit.

Pharmacokinetics

Absorption: Oral; food does not change absorption.
Metabolism: Aldehyde oxidase, CYP3A and UGT1A4; idelalisib itself inhibits CYP3A.
Half-life: About 8 hours.

Test yourself

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

Which PI3K isoform does idelalisib inhibit?

PI3Kδ, expressed mainly in leukocytes.

With which antibody is idelalisib given in relapsed CLL?

Rituximab.

What are idelalisib's boxed warnings?

Hepatotoxicity, severe diarrhoea or colitis, pneumonitis, serious infections and intestinal perforation.

Why does idelalisib raise midazolam levels?

Because idelalisib inhibits CYP3A.

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Connections

← Back to the class: PI3K 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: Idelalisib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Idelalisib - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.