BPH medications - 5-alpha reductase inhibitors Flashcards
What is the action of 5-alpha reductase inhibitor?
Inhibit 3-oxo-5-alpha-steroid-4-dehydrogenase
Reduce the production of dihydrotestosterone
What are the 2 main 5-alpha reductase inhibitors that you should know?
Finasteride
Dutasteride
What is the pharmacokinetic of finasteride?
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
What is the pharmacokinetic of dutasteride?
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
What are the cautions for finasteride?
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
What are the contraindications for dutasteride?
People with severe liver disease
What are the cautions for dutasteride?
People with mild-to-moderate liver disease
Monitor for adverse effects and deterioration of liver disease
What advise should you give about finasteride and dutasteride to men?
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
What is the recommended dose of finasteride?
5mg OD
What is the recommended dose of dutasteride?
500micrograms OD
What are the general and common side effects of 5-alpha reductase inhibitors?
Sexual dysfunction (e.g., decreased libido, ejaculation disorder, impotence)
Breast tenderness
Occur in the 1st year of use
What should you advise the man about the general adverse effects of 5-alpha reductase inhibitors?
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
What are the uncommon side effects of dutasteride?
Alopecia
Hypertrichosis
What are the uncommon side effects of finasteride?
Depression
Skin reactions
Suicidal thoughts
What are the frequency not known side effects of dutasteride?
Angioedema
Depression
Hypersensitivity
Skin reactions
Localised oedema
Testicular disorders
What are the frequency not known side effects of finasteride?
Angioedema
Male infertility
Palpitations
Testicular pain
After 6 months of Tx what can happen to the PSA levels for on 5-alpha reductase inhibitors?
PSA decreases by ~ 50%
What monitoring should men on 5-alpha reductase inhibitors have?
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
What are the key drug interactions for 5-alpha reductase inhibitors?
Dutasteride + CYP3A4 inhibitors e.g., itraconazole, clarithromycin, ritonavir) = increased exposure to dutasteride - consider reducing dosing frequency
Finasteride has no clinically important drug interactions
