dutasteride/ tamsulosin

Action and Spectrum

Actions and Spectrum: 

dutasteride and tamsulosin are two medications commonly used to treat benign prostatic hyperplasia, a non-cancerous prostate gland enlargement. They are often prescribed in a single combination pill for managing BPH symptoms. dutasteride is a medication that belongs to a class of drugs known as 5-alpha-reductase inhibitors.

It works by typically inhibiting the enzyme 5-alpha-reductase, which transforms testosterone into dihydrotestosterone. It is a hormone that contributes to the growth of the prostate gland. By blocking the transformation of testosterone into DHT, dutasteride helps reduce the prostate’s size and alleviate BPH symptoms such as urinary hesitancy, weak urine flow, and frequent urination. 

tamsulosin, on the other hand, is classified as an alpha-1 blocker or alpha-1 adrenergic antagonist. It works by selectively relaxing the smooth muscles in the prostate gland and also the bladder neck, which helps to improve urine flow and relieve urinary symptoms associated with BPH. tamsulosin specifically targets the alpha-1 adrenergic receptors in these tissues, leading to smooth muscle relaxation and decreased resistance to urine flow. 

Combined in a combination pill, dutasteride and tamsulosin can provide complementary effects for treating BPH. dutasteride helps to shrink the prostate gland over time, while tamsulosin provides more immediate relief by relaxing the smooth muscles, allowing for better urine flow. This combination approach is often prescribed for men with moderate to severe BPH symptoms and an enlarged prostate. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Impotence (1.1-5.4%) 

Breast disorders (≤1.1%) 

Ejaculation disorders (1.6-7.8%) 

Decreased libido (≤4.5%) 

Dizziness (≤1.1%) 

<1% 

Dizziness 

Breast disorders 

Cardiac failure 

Decreased libido 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

dutasteride: 

• Hypersensitivity: Individuals with known hypersensitivity or allergy to dutasteride or its components should not take this medication. 
• Pregnancy and Women of Childbearing Potential: dutasteride is contraindicated for use in women, particularly those who are pregnant or may become pregnant. dutasteride can be generally absorbed through the skin and might cause harm to a developing fetus. 

tamsulosin: 

• Hypersensitivity: Individuals with known hypersensitivity or allergy to tamsulosin or its components should avoid taking this medication. 
• Severe Liver Impairment: tamsulosin is contraindicated in patients with severe liver impairment. The medication is primarily eliminated through the liver, and severe liver dysfunction may affect its metabolism and clearance. 

Caution 

dutasteride: 

• Prostate-Specific Antigen (PSA) Testing: dutasteride can lower levels of PSA, a marker used in prostate cancer screening. This can affect the accuracy of PSA tests, potentially masking the presence of prostate cancer. Healthcare professionals should consider this when interpreting PSA test results in individuals taking dutasteride. 
• Increased Risk of High-Grade Prostate Cancer: Although dutasteride can reduce the risk of developing low-grade prostate cancer, evidence suggests an increased risk of developing a more aggressive form of the disease (high-grade prostate cancer) in some individuals. A healthcare professional should carefully assess the benefits and risks of dutasteride treatment. 
• Breast Changes: dutasteride may cause breast enlargement, tenderness, or other changes in breast tissue. Individuals experiencing such changes should notify their healthcare provider. 
• Concomitant Use with Other Medications: dutasteride may interact with other medications, including those that inhibit or induce drug-metabolizing enzymes. To avoid potential drug interactions, you must inform your healthcare professional about all your medications. 

tamsulosin: 

• Orthostatic Hypotension: tamsulosin may cause a drop in blood pressure, leading to dizziness, lightheadedness, or fainting upon standing up. Use caution when getting up from a sitting/lying position, especially at the beginning of treatment or when increasing the dosage. 
• Intraoperative Floppy Iris Syndrome (IFIS): tamsulosin has been associated with intraoperative floppy iris syndrome, which can complicate cataract surgery. Inform your eye surgeon about your tamsulosin use before any eye surgery. 
• Hepatic Impairment: tamsulosin should be used cautiously in individuals with liver impairment. Dosage adjustments may be necessary, as the liver primarily eliminates tamsulosin. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: X 

US FDA pregnancy category: X 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

dutasteride and tamsulosin have distinct pharmacological actions. dutasteride is a 5-alpha-reductase inhibitor that selectively inhibits the transformation of testosterone into dihydrotestosterone (DHT) by blocking the activity of the enzyme 5-alpha-reductase. By reducing DHT levels, dutasteride helps shrink the prostate gland in benign prostatic hyperplasia (BPH) and alleviates associated urinary symptoms.

On the other hand, tamsulosin is an alpha-1 adrenergic antagonist that selectively blocks alpha-1 adrenergic receptors in smooth muscles of the prostate gland and bladder neck. tamsulosin improves urine flow and relieves urinary symptoms by relaxing these smooth muscles. When combined, dutasteride and tamsulosin provide complementary effects, with dutasteride reducing prostate size over time and tamsulosin providing immediate relief by relaxing smooth muscles, ultimately managing BPH symptoms effectively. 

Pharmacodynamics: 

Mechanism of action: The action of dutasteride and tamsulosin differs due to their distinct pharmacological properties: 

dutasteride is a 5-alpha-reductase inhibitor. It works by selectively inhibiting the enzyme 5-alpha-reductase, specifically the type II and type III isoenzymes. This enzyme converts testosterone, a male sex hormone, into dihydrotestosterone (DHT). DHT is a more potent and active form of testosterone that promotes the growth and enlargement of the prostate gland in individuals with benign prostatic hyperplasia (BPH). By inhibiting 5-alpha-reductase, dutasteride reduces the levels of DHT in the prostate gland, thereby shrinking the glandular tissue, relieving the obstruction of the urethra, and improving urinary symptoms associated with BPH. 

tamsulosin belongs to a class of medications known as alpha-1 adrenergic antagonists or alpha-blockers. It selectively blocks alpha-1 adrenergic receptors, primarily of the alpha-1A and alpha-1D subtypes, found in the smooth muscle cells of the prostate gland, bladder, neck, and urethra. By blocking these receptors, tamsulosin inhibits the binding of norepinephrine, a neurotransmitter, to the receptor sites, leading to the relaxation of smooth muscle in these tissues. This relaxation reduces the resistance to urine flow, dilates the urinary passage, and improves urinary symptoms such as weak urine flow, urinary hesitancy, and frequent urination associated with BPH. 

Combination Therapy (dutasteride/tamsulosin): The combination therapy of dutasteride and tamsulosin is often prescribed to individuals with moderate to severe BPH symptoms and an enlarged prostate. By using both medications, the combination approach provides complementary effects. dutasteride helps to reduce the size of the prostate gland over time by inhibiting the conversion of testosterone to DHT. tamsulosin provides immediate relief by relaxing the smooth muscle in the prostate, bladder, neck, and urethra, allowing for improved urine flow. This combined action addresses the prostate gland’s underlying enlargement and the relief of urinary symptoms. 

Pharmacokinetics: 

Absorption 

dutasteride is well absorbed after oral administration. Food intake does not significantly affect its absorption. Peak plasma concentrations are typically reached within 2 to 3 hours after ingestion. 

tamsulosin is well absorbed after oral administration, with peak plasma concentrations occurring approximately 4 to 6 hours after ingestion. The bioavailability of tamsulosin is relatively low (approximately 30%) due to first-pass metabolism. 

Distribution 

dutasteride is extensively bound to plasma proteins (approximately 99.5%). It has a large volume of distribution, suggesting it can distribute widely throughout the body, including the prostate gland. 

tamsulosin is extensively bound to plasma proteins, primarily to alpha-1 acid glycoprotein. It exhibits a moderate volume of distribution, indicating distribution throughout the body. 

Metabolism 

dutasteride undergoes extensive hepatic metabolism via the cytochrome P450 enzyme system, primarily CYP3A4 and CYP3A5. The metabolites of dutasteride are mainly formed through hydroxylation and oxidation processes. 

tamsulosin undergoes extensive hepatic metabolism through several pathways, including oxidation and conjugation, primarily mediated by cytochrome P450 enzymes, mainly CYP3A4. The metabolites formed are pharmacologically inactive. 

Elimination and Excretion 

dutasteride and its metabolites are mainly excreted in feces (approximately 66%) through biliary elimination. A smaller fraction is excreted in urine (approximately 5%). 

tamsulosin and its metabolites are primarily excreted in urine (approximately 75%) as unchanged drugs and metabolites. Only a tiny fraction is excreted in feces (approximately 10%). 

Adminstartion

Administration: 

Oral administration 

dutasteride and tamsulosin can be administered orally as capsules or tablets. The specific dosing instructions and frequency may vary depending on the formulation and the individual’s medical condition.  

dutasteride: 

• Dosage: The typical recommended dose of dutasteride for treating benign prostatic hyperplasia (BPH) is 0.5 mg taken orally once a day. 
• Timing: dutasteride can be taken with or without food. It’s essential to take it consistently at the same time each day to maintain steady levels in the body. 
• Swallowing: Swallow the dutasteride capsule whole with a glass of water. Do not crush, chew, or open the capsule, which may affect the medication’s release and effectiveness. 

tamsulosin: 

• Dosage: The typical recommended dose of tamsulosin for BPH is 0.4 mg orally once daily. 
• Timing: tamsulosin should be taken approximately 30 minutes after the same meal each day to enhance absorption and reduce the potential for postural hypotension. 
• Swallowing: Swallow the tamsulosin capsule whole with a glass of water. Do not crush, chew, or open the capsule, which may affect the medication’s release and effectiveness. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dutasteride/ tamsulosin 

Pronounced: [ doo-TAS-ter-ide-and-tam-soo-LOE-sin ] 

Why do we use dutasteride/ tamsulosin? 

dutasteride and tamsulosin are commonly used to treat benign prostatic hyperplasia (BPH), a non-cancerous prostate gland enlargement. While they can be used individually, they are often prescribed together in a single combination pill due to their complementary effects. 

• Benign Prostatic Hyperplasia (BPH): The combination of dutasteride and tamsulosin is often prescribed for moderate to severe BPH symptoms and an enlarged prostate. dutasteride helps to shrink the prostate gland over time, while tamsulosin provides more immediate relief by relaxing the smooth muscles and improving urine flow.