Thalidomide

Pharmacology:

  • Non-polar glutamic acid derivative (N-phthalimido-glutarimide)
  • Pregnancy Category X
  • 50-100 mg then titrate to least effective dose 
  • Maximum of 400 mg
  • Peak plasma levels in 2-6 hrs
  • ½ life ~9 hrs
  • Metabolism mainly via non-enzymatic hydrolysis

Immunomodulatory/ anti-inflammatory

  • Inhibits tumor necrosis factor -α (tumor necrosis factor alpha) & IL-12 (interleukin 12)
  • Decreased PMN (Polymorphonuclear leukocytes) chemotaxis/ phagocytosis
  • Increased IL-4 & -5 (interleukin 4 & 5) B-cell activators + simultaneous IFN-γ (interferon-γ) inhibition

Sedative effects

  • Rapidly penetrates central nervous system, however sedative mechanism of action unclear

Neural & vascular effects

  • Unclear mechanism of action

Food & drug administration (FDA)

  • Erythema nodosum leprosum 

Off label

  • HIV (human immunodeficiency virus,) related (Kaposi sarcoma, oral stomatitis)
  • Neutrophilic (Aphthousis, Behcet’s, Pyoderma gangrenosum)
  • Lymphocytic (Lupus, Jessner’s, cutaneous lymphoid hyperplasia)
  • Vesiculobullous (erosive Lichen planus, Bullous pemphigoid, Cicatricial pemphigoid)
  • Others: Chronic graft versus host disease, prurigo nodularis, sarcoidosis, Langerhan cell histiocytosis, palmoplantar pustulosis, recurrent erythema multiforme, actinic prurigo, hydroa vacciniforme

Absolute

  • Hypersensitivity (more commonly seen with HIV (human immunodeficiency virus) patients)
  • Pregnancy/females of childbearing potential
  • Partner of a female of childbearing potential
  • Pre-existing peripheral neuropathy

Relative

  • Neuritis or other neurological disorders
  • Hepatic/renal impairment
  • Congestive heart failure, hypertension, risk of thromboembolism
  • – Hypothyroidism
  • – Constipation/ other gastrointestinal disorders

Sedation (#1)

  • Teratogenicity:
    • Even w/ a single dose  
    • Phocomelia (underdevelopment of arms/legs), ear, gastrointestinal, renal & urogenital anomalies 
  • Peripheral Neuropathy (independent of dose):
    • Distal sensory neuropathy + mild proximal motor neuropathy (sensory slowly reversible/irreversible, motor rapidly reversible)

Females & elderly at higher risk

  • Irregular menses, amenorrhea, ovarian failure
  • Hematologic: Leukopenia, thromboses (specially with antiphospholipid syndrome, multiple myeloma, corticosteroid treatment)
  • Gastrointestinal: increased appetite, constipation
  • Dermatologic: xerosis, brittle nails, pruritus, red palms, exfoliative erythroderma & toxic epidermal necrolysis (TEN)

Excess sedation with:

  • H1 antihistamines, anticholinergics, anticonvulsants, antipsychotics, antidepressants, benzodiazepines, alcohol, narcotics, barbiturates, muscle relaxants

Baseline 

  • Full neurological exam (r/o neuropathy) + Sensory nerve action potential if indicated by history or exam
  • Pregnancy test (1 month prior to initiating & a day before 1st dose)
  • Two effective contraceptive methods for both partners
  • Complete blood count, liver function tests

Follow-up

  • Neurological exam qmonthly x3 months then q1-6 months as needed
  • Sensory nerve action potential (SNAP) every 6 months
  • Pregnancy test qweekly x4 weeks then qmonthly (q2weeks if irregular menses)
  • Complete blood count qmonthly until dose stable then q2-3 months
  • Liver function tests q2-3 months