• Thalidomide tragedy – A serious adverse effect:
    • In the 1960s, drug as a sedative & anti-emetic drug for morning sickness.
    • Banned due to teratogenic effects (phocomelia).
    • Re-introduced & marketed recently for anticancer drug in multiple myeloma & melanoma.
    • Due to its anti-cancer properties, immunomodulatory & anti-angiogenic characteristics.
  • Two enantiomers of thalidomide (R & S) are present.
    • Both are inter-convertible within body.
    • Hence, racemic mixture is used.

Drug groups:

1. Immunomodulatory derivatives of thalidomide are called IMiDs.

  • Eg: Lenalidomide.
    • More potent & non-teratogenic derivative.
    • Approved as first-line therapy for multiple myeloma, combined with dexamethasone & bortezomib.
    • Approved recently for mantle cell lymphoma.
    • Also used for myelodysplastic syndrome.
  • Adverse effect: 
    • Can cause peripheral sensory neuropathy.

2. SelCIDs (Selective Cytokine Inhibitory Drugs):

  • Thalidomide analogs. 
  • Are phosphodiesterase-4 (PDE-4) inhibitors with potent anti-TNFα activity.
  • Eg: Pomalidomide – Newer thalidomide analog.
    • Has anti-angiogenic & immunomodulatory properties.
    • Indicated for treatment of relapsed & refractory multiple myeloma.
  • MOA: 
    • Directly inhibits both tumor cell & vascular compartments of myeloma cancers.
    • This dual activity of pomalidomide is more efficacious than thalidomide in vitro & in vivo.

Major actions:

  • Inhibition of angiogenesis
  • Inhibition of TNF- a
  • Increased IL-10 production
  • Reduces phagocytosis
  • Alteration of adhesion molecule expression
  • Enhance cell-mediated immunity via interactions with T- cells.


  • Multiple myelomas at initial diagnosis
  • In solid tumors like AIDS-related Kaposi’s sarcoma
  • Relapsed/refractory cases of multiple myeloma
  • Erythema nodosum leprosum – Provides dramatic relief; Daily dosage: 200-300 mg
  • DOC – For steroid-resistant cases
  • Skin manifestations of SLE
  • AIDS-related aphthous ulcers
  • AIDS-related wasting syndrome
  • Prevention of graft versus host disease (GVHD) after transplantation
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Crohn’s disease
  • Behcet’s syndrome
  • In steroid-resistant type 2 lepra reaction.

Adverse effects:

  • Teratogenicity
  • Peripheral neuropathy
  • Sedation & constipation in cancer patients.
  • Rash
  • Hypothyroidism
  • Increased risk of DVT
  • Congenital abnormalities: 
    • Phocomelia (defect in development of long bones)
    • Polydactyly
    • Syndactyly
    • External ear defects (from agenesis to pre-auricular tags)
    • Mobius syndrome – 
      • Rare congenital condition of facial paralysis & inability to move laterally.
      • Resulting in IV & VII CN paralysis & abnormalities in gut musculature.

Exam Important


  • Thalidomide tragedy is a serious adverse effect happened in the 1960s, on using the drug as a sedative & anti-emetic drug for morning sickness.
  • Thalidomide was banned due to teratogenic effects (phocomelia).
  • Thalidomide has been re-introduced & marketed recently for anticancer drug in multiple myeloma & melanoma.
  • Though thalidomide has teratogenic effects, it also possesses anti-cancer properties, immunomodulatory & anti-angiogenic characteristics. 
  • Thalidomide acts by inhibiting angiogenesis.
  • Two enantiomers of thalidomide (R & S), are inter-convertible within body.
  • Thalidomide are indicated for multiple myelomas at initial diagnosis,its relapsed/refractory states, erythema nodosum leprosum & skin manifestations of SLE.
  • Thalidomide is used in steroid-resistant type-2 lepra reaction.
  • Daily dosage of thalidomide for controlling ENL is 200-300 mg.
  • Major adverse effects of thalidomide includes, teratogenicity, peripheral neuropathy, sedation & constipation in cancer patients.
  • Thalidomide causes congenital abnormalities particularly phocomelia (defect in development of long bones).
  • Immunomodulatory derivatives of thalidomide are called IMiDs.
  • Lenalidomide is an ImiD’s, which is more potent & non-teratogenic derivative.
  • Lenalidomide is approved as first-line therapy for multiple myeloma, combined with dexamethasone & bortezomib.
  • Lenalidomide is approved recently for mantle cell lymphoma.
  • Lenalidomide can cause peripheral sensory neuropathy.
  • Sel CID’s are Selective Cytokine Inhibitory Drugs.
  • Sel CID’s are thalidomide analogs.
  • Sel CID’s are phosphodiesterase-4 (PDE-4) inhibitors with potent anti-TNFα activity.
  • Pomalidomide is a SelCIDs (Selective Cytokine Inhibitory Drugs).
  • Pomalidomide is used for treatment of relapsed & refractory multiple myeloma.
  • Pomalidomide acts by directly inhibiting both tumor cell & vascular compartments of myeloma cancers.
  • Pomalidomide is more efficacious than thalidomide.


Don’t Forget to Solve all the previous Year Question asked on THALIDOMIDE

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