[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Immunomodulatory imide drugs (IMiDs)](https://durgical.com/en/pharmacology/classes/immunomodulatory-imide-drugs/) › Lenalidomide

# Lenalidomide

## IMiDs?

Immunomodulatory imide drugs (IMiDs)

## High alert?

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

## Pregnancy: contraindicated?

Contraindicated: it is a thalidomide analogue and caused limb defects in animal studies. It is supplied only through a programme that requires pregnancy tests and effective…

Oral thalidomide derivative that makes cereblon destroy Ikaros and Aiolos. A myeloma mainstay; teratogenic, so it is dispensed under a restricted programme.

Updated Nov 1, 2026

## Quick facts

**Group**
[Immunomodulatory imide drugs (IMiDs)](https://durgical.com/en/pharmacology/classes/immunomodulatory-imide-drugs/)

**Target**
Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase

**Used for**
Multiple myeloma · Transfusion-dependent anaemia

**Key effects**
Neutropenia and thrombocytopenia · Fatigue · Rash

**Monitor**
Pregnancy tests · Complete blood count regularly

**ATC**
L04AX04

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

◆**Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase**Lenalidomide

ⓘ The crystal shows lenalidomide in the drug-binding pocket of human cereblon, bound to its partner protein DDB1.

**Target in 3D:** Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase. PDB structure 4TZ4 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4TZ4) · Drag to rotate · pinch to zoom

Lenalidomide binds cereblon, part of a cullin-RING E3 ubiquitin ligase. The drug acts as a molecular glue: it changes cereblon's surface so the ligase grabs the transcription factors Ikaros and Aiolos (IKZF1 and IKZF3) and, in cells with deletion 5q, the kinase CK1α. These proteins are tagged with ubiquitin and destroyed by the proteasome. Myeloma cells, which depend on Ikaros and Aiolos, stop growing and die; T cells and natural killer cells become more active, and new blood vessel growth is reduced.

- Lenalidomide binds the cereblon pocket
- Cereblon now grabs Ikaros, Aiolos (and CK1α)
- These proteins are ubiquitinated and destroyed
- Myeloma cells die; T and NK cells are activated

## Indications

- Multiple myeloma: with dexamethasone, in combination regimens, and as maintenance after autologous stem cell transplant. [Multiple myeloma →](https://durgical.com/en/conditions/multiple-myeloma/)
- Transfusion-dependent anaemia in lower-risk myelodysplastic syndrome with deletion 5q. [Myelodysplastic syndromes →](https://durgical.com/en/conditions/myelodysplastic-syndromes/)
- Some B-cell lymphomas (mantle cell, follicular, marginal zone). [Non-Hodgkin lymphoma →](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)

## Adverse effects

### Common

- Neutropenia and thrombocytopenia
- Fatigue, diarrhoea or constipation, muscle cramps
- Rash, itching
- Upper respiratory infections

### Serious (rare, important)

- Embryo-fetal toxicity: limb defects in animal studies, as with thalidomide
- Deep vein thrombosis, pulmonary embolism, heart attack and stroke, especially with dexamethasone
- Second primary cancers; liver failure; severe skin reactions
- Tumour lysis syndrome and tumour flare reaction

## Contraindications

- Pregnancy
- Severe hypersensitivity (angioedema, anaphylaxis, severe skin reactions) to lenalidomide

## Key interactions

**Digoxin**
Digoxin levels rise slightly: monitored periodically.

**Erythropoiesis-stimulating agents and estrogen-containing therapies**
Add to the risk of thrombosis.

**Warfarin**
Close INR monitoring in myeloma patients also taking dexamethasone.

## What is monitored

- Pregnancy tests in women who can become pregnant, before and during treatment, as the programme requires
- Complete blood count regularly, more often at the start
- Kidney function (dosing), liver tests and thyroid function
- Signs of deep vein thrombosis or pulmonary embolism

## Administration and safety

- Dispensed only through a restricted programme with registered prescribers, pharmacies and patients.
- Capsules are not opened, broken or chewed; powder on the skin is washed off with soap and water.
- Thromboprophylaxis is chosen according to each patient's risk of clots.

## Pregnancy and breastfeeding

Contraindicated: it is a thalidomide analogue and caused limb defects in animal studies. It is supplied only through a programme that requires pregnancy tests and effective contraception in women and condoms in men.

## Nursing care

- Confirm the pregnancy test and contraception requirements are met before each dispensing.
- Teach the signs of a clot (leg swelling, chest pain, breathlessness) and of stroke, and to seek care at once.
- Check counts and creatinine; report fever, bleeding or a new rash.
- Teaching: no blood donation during treatment and for some weeks after; men use condoms even after vasectomy.

## Pharmacokinetics

**Absorption**
Oral capsules, rapidly absorbed; can be taken with or without food.

**Metabolism**
Limited: it circulates mainly unchanged.

**Elimination**
Primarily by the kidneys, unchanged: the dose is adjusted in renal impairment.

**Half-life**
About 3 hours in healthy people and 3 to 5 hours in patients (label).

## Memory aid

«LENA Loves Lysing myeLoma»: she glues Ikaros and Aiolos to cereblon. Remember the three Cs: Clots, Counts (neutropenia, thrombocytopenia) and Contraception.

## Test yourself

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

## What is the molecular target of lenalidomide?

Cereblon, the substrate receptor of the CRL4 E3 ubiquitin ligase.

## Which proteins does lenalidomide mark for destruction in myeloma cells?

The transcription factors Ikaros (IKZF1) and Aiolos (IKZF3).

## Which extra protein does lenalidomide send for destruction that matters in deletion 5q myelodysplastic syndrome?

The kinase CK1α.

## Why must kidney function be checked before lenalidomide?

It is eliminated mainly unchanged by the kidneys; the dose is adjusted when kidney function is low.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/lenalidomide/)

[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: contraindicated**
Contraindicated: it is a thalidomide analogue and caused limb defects in animal studies. It is supplied only through a programme that requires pregnancy tests and effective…

## Connections

## Related drugs 2

- [Thalidomide](https://durgical.com/en/pharmacology/thalidomide/)
- [Dexamethasone](https://durgical.com/en/pharmacology/dexamethasone/)

## Related conditions 3

- [Multiple myeloma](https://durgical.com/en/conditions/multiple-myeloma/)
- [Myelodysplastic syndromes](https://durgical.com/en/conditions/myelodysplastic-syndromes/)
- [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)

[← Back to the class: Immunomodulatory imide drugs (IMiDs)](https://durgical.com/en/pharmacology/classes/immunomodulatory-imide-drugs/)

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

Sources: [DailyMed - LENALIDOMIDE capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9943e098-20b0-dbb3-af12-7816eedd3f70) (DailyMed (U.S. National Library of Medicine), 2026); [Lenalidomide: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a608001.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [RCSB PDB - 4TZ4: Crystal Structure of Human Cereblon in Complex with DDB1 and Lenalidomide](https://www.rcsb.org/structure/4TZ4) (RCSB Protein Data Bank, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L04AX04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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