Thalidomide
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. Even a single dose in pregnancy can cause severe birth defects, above all of the limbs, or fetal death; it is supplied only under a programme of pregnancy tests…
The sedative that caused the phocomelia disaster, now used for multiple myeloma and leprosy reactions under strict pregnancy-prevention rules.
Quick facts
- Group
- Immunomodulatory imide drugs (IMiDs)
- Target
- Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase
- Used for
- Newly diagnosed multiple myeloma
- Key effects
- Drowsiness · Constipation · Swelling of hands and feet
- Monitor
- Pregnancy tests before · Signs of thrombosis
- ATC
- L04AX02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows (S)-thalidomide in human cereblon together with a fragment of SALL4, one of the proteins the drug brings to cereblon.
Thalidomide binds cereblon and, like lenalidomide, redirects the cereblon E3 ligase to destroy proteins it normally leaves alone, including Ikaros and Aiolos in myeloma cells. It also reduces tumour necrosis factor-α and other inflammatory signals and blocks new blood vessel growth. It exists as two mirror-image forms (enantiomers) that interconvert in the body: the S form is linked to the birth defects and the R form to sedation, so giving only one form does not make it safe.
- Thalidomide binds cereblon
- Cereblon is redirected to destroy new target proteins
- Myeloma cells die; TNF-α and new vessel growth fall
- In an embryo the same effect disrupts limb development
Indications
- Newly diagnosed multiple myeloma, with dexamethasone. Multiple myeloma →
- Erythema nodosum leprosum, an inflammatory reaction of leprosy (Hansen disease): treatment and prevention of its skin lesions. Leprosy (Hansen disease) →
Adverse effects
Common
- Drowsiness, confusion, mood changes
- Constipation
- Swelling of hands and feet
- Dry skin and mouth, rash
- Tremor, dizziness
Contraindications
- Pregnancy and women who could become pregnant without the required contraception
- Hypersensitivity to thalidomide
Key interactions
- Alcohol and other sedatives
- Stronger drowsiness and other side effects.
- Dexamethasone and other chemotherapy
- Higher risk of blood clots in myeloma.
- Medicines that reduce the effect of hormonal contraceptives
- Make contraception less reliable: another method is needed.
What is monitored
- Pregnancy tests before, during and after treatment in women who can become pregnant
- Neurological examination for neuropathy at regular visits
- Signs of thrombosis; heart rate
- Blood counts in myeloma
Administration and safety
- Dispensed only through a restricted programme in which prescriber, pharmacy and every patient (including men and women who cannot become pregnant) are registered.
- Body fluids can contain the drug: carers wear gloves or wash skin that touches them.
- Usually taken at bedtime, after the evening meal, which also helps with the drowsiness.
Pregnancy and breastfeeding
Contraindicated. Even a single dose in pregnancy can cause severe birth defects, above all of the limbs, or fetal death; it is supplied only under a programme of pregnancy tests and strict contraception.
Nursing care
- Check the pregnancy-prevention requirements before each dispensing, and that two contraceptive methods are being used where required.
- Ask at every visit about numbness, tingling or burning in the hands and feet.
- Teach the signs of a clot and of slow heart rate (fainting, dizziness).
- Teaching: no blood or sperm donation during and for some weeks after treatment; men use condoms even after vasectomy; caution with alcohol, driving and machines.
Pharmacokinetics
- Absorption
- Oral capsules.
- Distribution
- Widely distributed; present in semen.
- Metabolism
- Mainly non-enzymatic hydrolysis; the two enantiomers interconvert.
- Elimination
- In the urine, as the drug and its breakdown products.
Test yourself
Think of the answer, then tap the question to see it.
Which birth defect is the hallmark of thalidomide exposure in pregnancy?
Phocomelia: severely shortened or absent limbs.
Which leprosy complication does thalidomide treat?
Erythema nodosum leprosum, an inflammatory reaction of leprosy.
Why does giving only one enantiomer of thalidomide not prevent birth defects?
The R and S forms interconvert in the body, so the teratogenic S form is formed anyway.
Which dose-limiting neurological toxicity is typical of thalidomide?
Peripheral neuropathy, which can be severe and permanent.
Connections
← Back to the class: Immunomodulatory imide drugs (IMiDs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Thalidomide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 7BQU: Cereblon in complex with SALL4 and (S)-thalidomide (RCSB Protein Data Bank, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.