|Trade names||Pomalyst, Imnovid|
|Drug class||Thalidomide analog|
|Main uses||Multiple myeloma (MM), Kaposi sarcoma (KS)|
|Side effects||Tiredness, low neutrophils, low red blood cells, nausea, diarrhea, shortness of breath, fever, low platelets|
|By mouth (capsules)|
|Typical dose||4 mg OD|
|Bioavailability||73% (at least)|
|Metabolism||Liver (mostly CYP1A2- and CYP3A4-mediated; some minor contributions by CYP2C19 and CYP2D6)|
|Elimination half-life||7.5 hours|
|Excretion||Urine (73%), faeces (15%)|
|Chemical and physical data|
|Molar mass||273.248 g·mol−1|
|3D model (JSmol)|
Pomalidomide, sold under the brand name Pomalyst and Imnovid, is a medication used to treat multiple myeloma (MM) and Kaposi sarcoma (KS). For MM it is used when other treatments have failed. For KS it is used when HAART is not affected or in those who are HIV negative. It is taken by mouth.
Common side effects include tiredness, low neutrophils, low red blood cells, nausea, diarrhea, shortness of breath, fever, and low platelets. Other side effects may include liver problems, tumor lysis syndrome, blood clots, and anaphylaxis. Use in pregnancy may harm the baby. It is similar to thalidomide and works by altering the immune system.
Pomalidomide was approved for medical use in the United States and Europe in 2013. In the United Kingdom 4 weeks of treatment costs the NHS about £8,900 as of 2021. In the United States this amount costs about 20,000 USD.
To avoid embryo-fetal exposure, a "Risk Evaluation and Mitigation Strategy" (REMS) program was developed to ensure pregnancy prevention or distribution of the drug to those who are or might become pregnant. Women must produce two negative pregnancy tests and use contraception methods before beginning pomalidomide. Women must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning four weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for four weeks following discontinuation of pomalidomide therapy.[medical citation needed]
Pomalidomide is present in the semen of people receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 28 days after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Males taking pomalidomide must not donate sperm.
Mechanism of action
Pomalidomide directly inhibits angiogenesis and myeloma cell growth. This dual effect is central to its activity in myeloma, rather than other pathways such as TNF alpha inhibition, since potent TNF inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth or angiogenesis. Upregulation of interferon gamma, IL-2 and IL-10 as well as downregulation of IL-6 have been reported for pomalidomide. These changes may contribute to pomalidomide's anti-angiogenic and anti-myeloma activities.
The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994. Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma. Structure-activity studies revealed that amino substituted thalidomide had improved antitumor activity, which was due to its ability to directly inhibit both the tumor cell and vascular compartments of myeloma cancers. This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.
Phase I trial results showed tolerable side effects.
Phase III results showed significant extension of progression-free survival, and overall survival (median 11.9 months vs. 7.8 months; p = 0.0002) in patients taking pomalidomide and dexamethasone vs. dexamethasone alone.
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