DESCRIPTION
Mechanism of Action
• Mechanism of action is not fully characterized.
• More potent antiproliferative immunomodulating agent than
thalidomide and lenalidomide.
• Immunomodulatory drug (IMid) that stimulates T-cell proliferation
as well as IL-2 and IFN-g production.
• Inhibition of TNF-α and IL-6 synthesis and down-modulation of cell
surface adhesion molecules similar to thalidomide.
• May exert antiangiogenic effect by inhibition of basic fibroblast
growth (bFBG) and vascular endothelial growth factor (VEGF) and
through as yet undefined mechanisms.
• Overcomes cellular drug resistance to thalidomide and lenalidomide.
Mechanism of Resistance
None characterized to date.
Absorption
Well-absorbed following oral administration, with peak plasma concentrations
at 2–3 hours post ingestion.
Distribution
Binding to plasma proteins ranges from 12%–44%. Distributed in male
semen at concentrations of approximately 67% of plasma levels after 4 days
of treatment.
Metabolism
Pomalidomide is mainly metabolized in the liver by CYP1A2 and CYP3A4
with minor effects by CYP2C19 and CYP2D6. Approximately 75% of an
administered dose is excreted in urine, primarily in the form of drug metabolites,
while 15% of an administered dose is eliminated in feces. The elimination
half-life of the drug is approximately 7.5 hours.
Indications
1. FDA-approved for the treatment of patients with multiple myeloma
who have received at least two prior therapies, including lenalidomide
and bortezomib, and who have disease progression on or
within 60 days of completion of the previous therapy.
Dosage Range
1. Recommended dose is 4 mg PO daily on days 1–21 of a 28-day cycle.
2. May be given in combination with Decadron 40 mg PO daily
on days 1, 8, 15, and 22 of a 28-day cycle.
Drug Interactions
None well characterized to date.
Special Considerations
1. Pregnancy category X. Pomalidomide is a thalidomide analog, a
known human teratogen that causes severe or life-threatening
birth defects. As such, women who are pregnant or who wish to
become pregnant should not take lenalidomide. Severe fetal malformations
can occur if even one capsule is taken by a pregnant
woman. All women should have a baseline β-human chorionic
gonadotropin (β-HCG) before starting lenalidomide therapy.
Women of reproductive age must have two negative pregnancy
tests before starting therapy: one should be 10 to 14 days before
therapy is begun, and the second should be 24 hours before
therapy. This is a black-box warning.
2. All women of childbearing potential should practice two forms of
birth control throughout therapy with pomalidomide: one highly
effective form (intrauterine device, hormonal contraception [patch,
implant, pill, injection], partner’s vasectomy, or tubal ligation) and
one additional barrier method (latex condom, diaphragm, or cervical
cap). It is strongly recommended that these precautionary measures
Cancer Chemotherapy 360 Drug Manual
P be taken 1 month before initiation of therapy, continue while on therapy,
and continue at least 1 month after therapy is discontinued.
3. Pomalidomide is only available under a special restricted distribution
program called “POMALYST REMS.” Only prescribers and pharmacists
registered with this program are able to prescribe and dispense
the drug. Pomalidomide should only be dispensed to those patients
who are registered and meet all the conditions of this program.
4. Breastfeeding while on therapy should be avoided, as it remains
unknown if pomalidomide is excreted in breast milk.
5. Men taking pomalidomide must use latex condoms for every sexual
encounter with a woman of childbearing potential, as the drug may
be present in semen.
6. Patients taking pomalidomide should not donate blood or semen
while receiving treatment, and for at least 1 month after stopping
this drug.
7. Monitor CBCs while on therapy, as pomalidomide has hematologic
toxicity.
8. Use with caution in patients with impaired renal function, as
pomalidomide and its metabolites are mainly excreted by the
kidneys. Although no formal renal dysfunction studies have been
performed, the use of pomalidomide should be avoided in patients
with a serum creatinine .3 mg/dL.
9. There is a significantly increased risk of thromboembolic complications,
including deep venous thrombosis (DVT) and pulmonary
embolism (PE). This represents a black-box warning. Prophylaxis
with low-molecular weight heparin or aspirin (325 mg PO qd) is
recommended to prevent and/or reduce this risk.
10. Smoking should be avoided while on therapy, as cigarette smoking
may reduce pomalidomide exposure secondary to CYP1A2 induction.
Toxicity 1
Potentially severe or fatal teratogenic effects.
Toxicity 2
Myelosuppression with neutropenia and thrombocytopenia that is usually
reversible.
Toxicity 3
Increased risk of thromboembolic complications, such as DVT and PE.
Toxicity 4
Nausea/vomiting, diarrhea, and constipation are most common GI side
effects.
Toxicity 5
Dizziness and confusion are the two most common neurologic side
effects.
Toxicity 6
Hypersensitivity reactions (HSRs). More likely to occur in patients with a
prior history of HSRs to thalidomide or lenalidomide.
Toxicity 7
Neuropathy observed in nearly 20% of patients, with approximately 10%
in the form of peripheral neuropathy. Usually mild with no grade 3 or higher
neuropathy reported.
SPECIFICATION
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