Pomalidomide

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pomalidomide

Structure

  • 3-amino-thalidomide
  • Amino substituted thalidomide had improved antitumor activity
  • Ability to directly inhibit both the tumor cell and vascular compartments of myeloma.

Pharmacokinetics

  • Well absorbed after oral dose
  • Peak plasma concentration – 2-3hrs
  • Metabolized by liver enzymes – CYP1A2 and CYP3A4.
  • 73% of the dose  excreted in urine and 15% in feces, as drug metabolites.
  • T1/2 – 7.5 – 9.5hrs

Indication

Multiple myeloma – in combination with dexamethasone, who have received at least two prior therapies including lenalidomide and bortezomib and have disease progression on or within 60 days of completion of the last therapy. FDA approval in Feb 2013.

Dose and administration

  • Dose – 4 mg once daily orally on Days 1-21 of 28-day cycles until disease progression.
  • Should be taken without food.
  • Available as 1, 2, 3 and 4 mg capsules in bottle containing 21 or 100 capsules.

Side effects

  • Teratogenic
  • Myelosuppression – neutropenia (40-50%) and thrombocytopenia(20-25%)
  • Thromboembolic events (5-10%)
  • GI toxicity (20-40% – all grade)
  • Dizziness and confusion (15-20% – all grade)
  • Neuropathy – (10-20%)
  • Skin rash, pruritus (10-20%)

Special Consideration

  • Precautions same as thalidomide.
  • Co-administration with strong inducers of CYP1A2, CYP3A4 or P-gp could decrease exposure and should be avoided.
  • Avoid smoking – induce CYP1A2 –reduced drug exposure.
  • Avoid in patients with a serum creatinine greater than 3.0 mg/dL.
  • Avoid in patients with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN

Dose Modification

NEUTROPENIA POMALIDOMIDE DOSE
ANC < 500

Return to >500

Interrupt drug; follow CBC weekly

Restart at 3mg/d

Each subsequent drop of ANC<500

Return to >500

Interrupt drug; follow CBC weekly

Restart at 1mg less than previous dose

 

THROMBOCYTOPENIA POMALIDOMIDE DOSE
Platelet < 25,000

Return to > 50,000

Interrupt drug; follow CBC weekly

Restart at 3mg/d

Each subsequent drop to < 25,000

Return to > 50,000

Interrupt drug; follow CBC weekly

Restart at 1mg less than previous dose

 

 

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