Tamoxifen

Question 1

How does tamoxifen work?

Answer 1

It prevents cell proliferation by blocking the Estrogen receptor

Question 2

Class of drug and indication:

Answer 2

Selective estrogen receptor modulator (SERM) for breast cancer

Question 3

What enzyme metabolizes Tamoxifen?

Answer 3

It is a prodrug and needs to be converted into active form: Endoxifen by CYP2D6

Question 4

Which enzyme and factors are also involved in activating Tamoxifen?

Answer 4

CYP3A4/5 and environmental factors: SSRIs (Fluoxetine, Paroxetine)

Question 5

Amount of clinical use, where is the CYP2D gene located?

Answer 5

25-30% of all drugs given clinically,

located on Chromosome 22q13.1

Question 6

In which population is IM an PM more common?

Answer 6

IM: East asian and African

PM: European

Question 7

What is the consequence of poor metabolism alleles?

Answer 7

PM -> less Endoxifen -> therapy failure

the active metabolite is 100x more active

Question 8

Which enzymes may also influence the level of Endoxifen?

Answer 8

CYP2C9 and UDP glucuronosyltransferase (UGT)

Question 9

Which drugs can inhibit CYP2D6?

Answer 9

SSRIs are prescribed in combination with cancer therapy,
Paroxetine (greatest), Venlafaxine, and Fluoxetine (strong) are known of inhibiting

Question 10

How can you monitor the function of tamoxifen?

Answer 10

Monitor of Endoxifen level