Thioguanine

  • 80 mg/day if normal thiopurine methyltransferase (TPMT) level (given orally but absorption incomplete/unpredictable)
  • Belong to thiopurine family, & has a mechanism of action + metabolism similar to azathioprine 
  • Pregnancy Category D
  • Thioguanine not metabolized by xanthine oxidase, so thiopurine methyltransferase (TPMT) significantly involved in clearing
  • Prodrug, converted in liver to 6-thioguanilyic acid (similar active metabolite of azathioprine), yields nucleoside analogues that produce cytotoxic effects via incorporation into DNA (deoxyribonucleic acid) during S phase of cell cycle
  • Affects primarily activated T lymphocytes
Food & drug administration (FDA)

  • Acute non-lymphocytic leukemia 

Off label

  • Psoriasis
  • Dermatitis
  • Severe atopic dermatitis
  • Connective tissue disease
  • Cutaneous-limited Lupus (very rarely used)
Absolute

  • Hypersensitivity
  • Pregnancy
  • Lactation

Relative

  • History of hepatovenular occlusive disease
  • Hematologic disorders
  • Active infection
Hematologic 

  • Myelosuppression (~50%, early sign: thrombocytopenia)

Gastrointestinal 

  • Nausea, excessive flatulence, taste changes, esophageal reflux, diarrhea
  • Hepatitis (rare) & hepatovenular occlusive disease (rare)

Metabolic

  • Hyperuricemia

Infectious 

  • Opportunistic with myelosuppression
  • Aminosalicylates (inhibit thiopurine methyltransferase (TPMT) activity) will result in more active compound
Baseline

  • History & physical exam
  • Complete blood count, chemistry profile, liver function tests, Urinalysis, tuberculin skin test (if indicated), Thiopurine methyltransferase (TPMT) level

Follow-up

  • Complete blood count, liver function tests weekly then every 2weeks as dose stabilizes. Once dose stable monthly x3 months then every 3months