Dutasteride

+ 8 more variants

As the body adjusts to the medication, or as treatment continues beyond the six-month mark, patients may experience:

• Gynecomastia: This refers to breast enlargement or breast tenderness in men. Because Dutasteride blocks the conversion of testosterone to DHT, more testosterone may be converted into estrogen (estradiol), leading to breast tissue growth. This occurs in about 1-2% of men.
• Dizziness: Particularly when Dutasteride is used in combination with alpha-blockers like tamsulosin, which can cause orthostatic hypotension (a drop in blood pressure when standing up).

• Testicular Pain and Swelling: Some men report localized discomfort in the scrotum.
• Depression and Anxiety: While not definitively linked in all studies, some patients report mood changes or a 'brain fog' sensation, which some clinicians attribute to the reduction of neurosteroids that are also metabolites of the 5-alpha reductase pathway.
• Allergic Reactions: Skin rash, itching, or hives.

> Warning: Stop taking Dutasteride and call your doctor immediately if you experience any of the following serious symptoms:

• Angioedema: Swelling of the face, lips, tongue, or throat, which can cause difficulty breathing or swallowing. This is a sign of a severe allergic reaction.
• Breast Changes: While mild tenderness is a known side effect, any lumps, nipple discharge, or persistent pain should be evaluated immediately to rule out male breast cancer.
• Severe Skin Reactions: Peeling skin or widespread redness.
• Signs of High-Grade Prostate Cancer: While Dutasteride reduces the risk of low-grade prostate cancer, some studies (like the REDUCE trial) suggested a potential increase in the detection of high-grade (more aggressive) prostate cancer. Regular screening and PSA monitoring are mandatory.

One of the most discussed aspects of 5-alpha reductase inhibitors is the potential for persistent side effects. In some men, sexual side effects (such as decreased libido or erectile dysfunction) have been reported to persist even after the medication has been discontinued. This phenomenon is sometimes referred to in patient communities as 'Post-Finasteride Syndrome,' though it can apply to Dutasteride as well. However, the medical community continues to study the prevalence and causality of these long-term effects. Additionally, long-term use will lead to a sustained 50% reduction in Prostate-Specific Antigen (PSA) levels, which must be accounted for during cancer screenings.

No FDA black box warnings currently exist for Dutasteride. However, the FDA has issued a Safety Communication regarding the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer) when taking 5-ARIs. This is not a black box warning but a significant safety precaution that all prescribing physicians must discuss with their patients.

Report any unusual symptoms or changes in sexual function to your healthcare provider. Early intervention can often help manage side effects through dose timing or the addition of other supportive therapies.

Healthcare providers will typically require the following monitoring:

• Digital Rectal Examination (DRE): Performed before starting therapy and periodically thereafter to check for prostate abnormalities.
• PSA Levels: A baseline PSA should be established before starting treatment. Follow-up PSA tests are usually conducted at 3 to 6 months to establish a new 'nadir' (lowest point) and then annually.
• Liver Function Tests (LFTs): Since the drug is metabolized by the liver, patients with pre-existing liver conditions may need periodic enzyme checks.

Dutasteride generally does not affect the ability to drive or operate machinery. However, if taken in combination with an alpha-blocker (like tamsulosin), patients may experience dizziness or fainting (syncope) upon standing, especially after the first dose. Caution is advised until the patient knows how the combination affects them.

There is no known direct interaction between alcohol and Dutasteride. However, alcohol can exacerbate urinary symptoms and contribute to dizziness, especially if the patient is also taking alpha-blockers. Moderate consumption is generally considered acceptable, but patients should consult their doctor.

Stopping Dutasteride will lead to a gradual increase in DHT levels. Over several months, the prostate gland may return to its pre-treatment size, and urinary symptoms may recur. There is no known 'withdrawal syndrome,' but the benefits of the drug are lost upon discontinuation. Always consult a physician before stopping long-term BPH therapy.

> Important: Discuss all your medical conditions, especially any history of liver disease or prostate cancer, with your healthcare provider before starting Dutasteride.

• Calcium Channel Blockers: Verapamil and Diltiazem are moderate inhibitors of CYP3A4. Long-term co-administration may increase Dutasteride levels.
• Alpha-Blockers: While frequently used together (e.g., Tamsulosin), this combination increases the risk of orthostatic hypotension (dizziness upon standing). The mechanism is pharmacodynamic synergy in relaxing smooth muscle and lowering blood pressure.
• Cimetidine: A weak CYP3A4 inhibitor that may slightly increase Dutasteride exposure.

• Grapefruit and Grapefruit Juice: Grapefruit is a known inhibitor of CYP3A4 in the gut wall. While the interaction with Dutasteride has not been specifically quantified, it is theoretically possible that large amounts of grapefruit juice could increase the drug's absorption and blood levels. Patients are often advised to maintain consistent dietary habits.
• High-Fat Meals: Can delay the time it takes to reach peak concentration (Tmax) but do not affect the total amount of drug absorbed (AUC). No restrictions are necessary.

• St. John's Wort: This herbal supplement is a potent inducer of CYP3A4. It may increase the metabolism of Dutasteride, potentially reducing its efficacy in shrinking the prostate and managing BPH symptoms.
• Saw Palmetto: Many men take Saw Palmetto for prostate health. Since Saw Palmetto is also thought to have mild 5-alpha reductase inhibitory properties, taking it with Dutasteride may result in additive effects. However, clinical data on this combination is limited, and most urologists recommend stopping herbal prostate supplements when starting prescription 5-ARIs.

• PSA (Prostate-Specific Antigen): This is the most significant interaction. Dutasteride will reduce PSA levels by roughly 50%. This must be communicated to any healthcare provider interpreting a PSA test to avoid missing a potential prostate cancer diagnosis.
• Testosterone Levels: Dutasteride may cause a slight increase in total serum testosterone levels (usually 10-20%) because the testosterone is not being converted to DHT. This is generally within the normal physiological range.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter vitamins.

• Hepatic Impairment: Because Dutasteride is cleared almost exclusively by the liver and has a 5-week half-life, patients with moderate to severe liver disease may accumulate the drug to unsafe levels. Use in this population requires vigilant monitoring.
• High-Grade Prostate Cancer History: While not an absolute contraindication, men with a history of or high risk for aggressive prostate cancer must have a thorough discussion with their urologist, as 5-ARIs may influence the detection and progression of high-grade disease.
• Obstructive Uropathy: Patients with very large residual urine volumes or severely impaired urinary flow may not be ideal candidates for Dutasteride as monotherapy, as the drug takes months to work. These patients may require immediate surgical intervention instead.

There is a potential for cross-sensitivity between Dutasteride and finasteride (Proscar, Propecia). Both drugs share a similar 4-azasteroid structure. If a patient has experienced a severe allergic reaction (such as anaphylaxis or Stevens-Johnson Syndrome) to finasteride, they should not be prescribed Dutasteride.

> Important: Your healthcare provider will evaluate your complete medical history, including liver function and previous drug allergies, before prescribing Dutasteride.

A significant portion of patients taking Dutasteride are over the age of 65, as BPH is a condition of aging. Clinical trials have included thousands of subjects in this age bracket. No overall differences in safety or effectiveness have been observed between these patients and younger adult men. However, elderly patients are more likely to be taking multiple medications (polypharmacy), increasing the risk of CYP3A4-mediated drug interactions. Additionally, when used with alpha-blockers, the risk of falls due to orthostatic hypotension is higher in the geriatric population.

No dosage adjustment is required for patients with renal impairment. Less than 0.1% of a 0.5 mg dose of Dutasteride is recovered in human urine. Studies in patients with chronic renal failure have not shown a need for dose modification, though general medical caution is always warranted in patients with end-stage renal disease.

The liver is the primary organ responsible for the metabolism and clearance of Dutasteride. In patients with hepatic impairment, the half-life of the drug may be even longer than the standard 5 weeks, leading to higher steady-state concentrations. There are no specific guidelines for dose reduction (as the capsule is a fixed 0.5 mg dose), but the drug should be used with caution in patients with Child-Pugh Class A, B, or C liver disease.

> Important: Special populations, particularly those with liver disease or those at risk of pregnancy exposure, require individualized medical assessment and strict adherence to safety protocols.

|---|---|

| Bioavailability | ~60% (40% to 94%) |

| Protein Binding | >99% (Albumin and Alpha-1 acid glycoprotein) |

| Half-life | ~5 weeks (at steady state) |

| Tmax | 1 to 3 hours |

| Metabolism | Hepatic (CYP3A4 and CYP3A5) |

| Excretion | Fecal (40% as metabolites, 5% unchanged); Renal (<0.1%) |

• Molecular Formula: C27H30F6N2O2
• Molecular Weight: 528.5 g/mol
• Solubility: Insoluble in water; soluble in ethanol, methanol, and polyethylene glycol 400.
• Description: Dutasteride is a white to pale yellow powder. The softgel capsules contain the drug dissolved in a mixture of mono-diglycerides of caprylic/capric acid and butylated hydroxytoluene.

Dutasteride is classified as a 5-alpha reductase inhibitor (5-ARI). It is therapeutically categorized as a benign prostatic hyperplasia (BPH) agent. Related medications include finasteride (Proscar), though Dutasteride's dual-isoenzyme inhibition distinguishes it within the class.