BPH medications - 5-alpha reductase inhibitors

Question 1

What is the action of 5-alpha reductase inhibitor?

Answer 1

Inhibit 3-oxo-5-alpha-steroid-4-dehydrogenase

Reduce the production of dihydrotestosterone

Question 2

What are the 2 main 5-alpha reductase inhibitors that you should know?

Answer 2

Finasteride

Dutasteride

Question 3

What is the pharmacokinetic of finasteride?

Answer 3

Oral bioavailability = 65%

Protein binding = 90% (plasma proteins)

Half-life = 6 hours (range 3-16 hours)

Metabolism = hepatic - CYP3A4

Excretion = 32-46% kidney via urine, 51-64% in faeces

Question 4

What is the pharmacokinetic of dutasteride?

Answer 4

Oral bioavailability = 60% (range = 40-94%)

Protein binding = 99% bound to albumin, 96.6% bound to α-1 acid glycoprotein

Half-life = 5 weeks

Metabolism = hepatic - CYP3A4 + CYP3A5

Excretion = <1% kidney via urine, 2-90% in faeces, 1-15% excreted as the unchanged parent compound

Question 5

What are the cautions for finasteride?

Answer 5

People with large residual urine and/or heavily decreased urinary flow to avoid obstructive complications - possibility of surgery should be an option

No data on finasteride in people with liver disease, but advised to use it as you would dutasteride in people with severe liver disease = avoid

Question 6

What are the contraindications for dutasteride?

Answer 6

People with severe liver disease

Question 7

What are the cautions for dutasteride?

Answer 7

People with mild-to-moderate liver disease

Monitor for adverse effects and deterioration of liver disease

Question 8

What advise should you give about finasteride and dutasteride to men?

Answer 8

Finasteride and dutasteride can be absorbed through the skin and excreted in semen

Women should not handle crushed or broken tablets of finasteride/leaking capsules of dutasteride if they are pregnant or may be pregnant

Use condom is his sexual partner is pregnant or likely to become pregnant

Question 9

What is the recommended dose of finasteride?

Answer 9

5mg OD

Question 10

What is the recommended dose of dutasteride?

Answer 10

500micrograms OD

Question 11

What are the general and common side effects of 5-alpha reductase inhibitors?

Answer 11

Sexual dysfunction (e.g., decreased libido, ejaculation disorder, impotence)

Breast tenderness

Occur in the 1st year of use

Question 12

What should you advise the man about the general adverse effects of 5-alpha reductase inhibitors?

Answer 12

Sexual dysfunction tends to improve with duration of Tx

Promptly report any changes in their breast tissue e.g., lumps, pain, or nipple discharge - cases of breast cancer have rarely been reported

Question 13

What are the uncommon side effects of dutasteride?

Answer 13

Alopecia

Hypertrichosis

Question 14

What are the uncommon side effects of finasteride?

Answer 14

Depression

Skin reactions

Suicidal thoughts

Question 15

What are the frequency not known side effects of dutasteride?

Answer 15

Angioedema

Depression

Hypersensitivity

Skin reactions

Localised oedema

Testicular disorders

Question 16

What are the frequency not known side effects of finasteride?

Answer 16

Angioedema

Male infertility

Palpitations

Testicular pain

Question 17

After 6 months of Tx what can happen to the PSA levels for on 5-alpha reductase inhibitors?

Answer 17

PSA decreases by ~ 50%

Question 18

What monitoring should men on 5-alpha reductase inhibitors have?

Answer 18

Baseline PSA after 6 months of Tx

Monitor PSA values regularly thereafter

Any confirmed increase from lowest PSA level while on a 5-alpha reductase inhibitor may signal the presence of prostate cancer or noncompliance to Tx and should be carefully evaluated even if those values are still within the normal range for people not taking a 5-alpha reductase inhibitor

DRE + other tests for prostate cancer before starting 5-alpha reductase inhibitor Tx

Question 19

What are the key drug interactions for 5-alpha reductase inhibitors?

Answer 19

Dutasteride + CYP3A4 inhibitors e.g., itraconazole, clarithromycin, ritonavir) = increased exposure to dutasteride - consider reducing dosing frequency

Finasteride has no clinically important drug interactions