Finasteride + Tadalafil

Approved Indications:

• Benign Prostatic Hyperplasia (BPH): Treatment of lower urinary tract symptoms (LUTS) associated with BPH, such as urinary urgency, frequency, weak stream, and nocturia.
• Erectile Dysfunction (ED): Treatment of erectile dysfunction to improve the ability to achieve and maintain an erection sufficient for sexual activity.
• Concurrent BPH and ED: Management of patients presenting with both BPH symptoms and erectile dysfunction.

Off-label or Clinically Accepted Uses:

• Prevention of progression of BPH and reduction in the risk of acute urinary retention and the need for prostate surgery.
• Treatment of androgenetic alopecia (male pattern baldness) by the finasteride component (dependent on formulation and regulatory approval).

• Adults:
  One oral tablet daily containing finasteride 5 mg and tadalafil 5 mg, taken with or without food. Tablets should be swallowed whole with water.
• Duration:
  Continuous, long-term therapy is recommended for maximal benefit. Symptomatic improvement of BPH may take up to six months. Erectile function improvement can be seen within hours of tadalafil administration.
• Special Populations:
• Renal impairment: No dose adjustment required for mild to moderate impairment. Use cautiously in severe impairment.
• Hepatic impairment: Use with caution; insufficient data for dosing adjustments.
• Elderly: Same dosing applies, but monitor for adverse effects.
• Pediatric Use: Not indicated for use in children or adolescents.

Finasteride selectively inhibits the type II 5-alpha reductase enzyme, which converts testosterone into dihydrotestosterone (DHT). DHT is responsible for prostate enlargement and hair follicle miniaturization. By reducing DHT, finasteride decreases prostate size and slows hair loss.

Tadalafil is a selective phosphodiesterase type 5 (PDE5) inhibitor that prevents breakdown of cyclic guanosine monophosphate (cGMP). Elevated cGMP causes smooth muscle relaxation in the corpus cavernosum and prostate/bladder neck, facilitating erection and relieving urinary symptoms.

The combination targets hormonal pathways and smooth muscle tone to treat both BPH symptoms and erectile dysfunction effectively.

• Absorption:
  Finasteride is rapidly absorbed with peak plasma levels in 1–2 hours. Oral bioavailability is approximately 65%.
  Tadalafil reaches peak plasma concentration around 2 hours post-dose, with an oral bioavailability near 80%.
• Distribution:
  Finasteride is about 90% bound to plasma proteins. Tadalafil binds approximately 94% to plasma proteins.
• Metabolism:
  Finasteride is metabolized primarily by hepatic CYP3A4 to inactive metabolites.
  Tadalafil undergoes extensive hepatic metabolism mainly by CYP3A4.
• Elimination:
  Finasteride has a half-life of approximately 6 hours (longer in older men) and is excreted mostly in urine as metabolites.
  Tadalafil has a half-life of approximately 17.5 hours, allowing once-daily dosing, and is excreted via feces and urine.

• Pregnancy:
  Finasteride is classified as FDA Pregnancy Category X. It is contraindicated in women who are or may become pregnant due to the risk of male fetal genital abnormalities. Tadalafil is not indicated for use in women; safety data in pregnancy are lacking.
• Lactation:
  Safety during breastfeeding has not been established. Finasteride’s effect on milk excretion is unknown, and tadalafil’s excretion in breast milk is not studied. Use in nursing women is not recommended.

• Finasteride: 5-alpha reductase inhibitor
• Tadalafil: Phosphodiesterase type 5 (PDE5) inhibitor
• Combination therapy: Treatment for BPH and erectile dysfunction

• Hypersensitivity to finasteride, tadalafil, or any excipients
• Women, especially those who are or may become pregnant
• Concurrent use with nitrates (e.g., nitroglycerin) or nitric oxide donors
• Severe hepatic impairment
• Severe hypotension or unstable cardiovascular conditions
• Patients with hereditary degenerative retinal disorders (e.g., retinitis pigmentosa)

• Cardiovascular Risk: Use tadalafil cautiously in patients with cardiovascular disease. Sudden cardiac events, though rare, have been reported.
• Hypotension: Concomitant use with alpha-blockers may cause symptomatic hypotension; initiate treatment at lower doses and monitor blood pressure.
• PSA Monitoring: Finasteride lowers serum PSA levels; interpret PSA results carefully in prostate cancer screening.
• Visual and Auditory Effects: Rare cases of sudden vision loss (non-arteritic anterior ischemic optic neuropathy) and sudden hearing loss have been reported with PDE5 inhibitors; discontinue immediately if these occur.
• Priapism: Prolonged erection lasting more than 4 hours requires urgent medical attention to prevent permanent damage.
• Liver Disease: Use with caution in patients with hepatic impairment.
• Drug Interactions: CYP3A4 inhibitors or inducers can affect tadalafil metabolism.

Common Adverse Effects:

• Sexual dysfunction: decreased libido, ejaculation disorders, erectile dysfunction (paradoxical), breast tenderness or enlargement
• Headache and dizziness
• Dyspepsia and nausea
• Muscle pain and back pain (primarily with tadalafil)
• Nasal congestion and flushing

Serious/Rare Effects:

• Hypersensitivity reactions, including rash and angioedema
• Prolonged erection (priapism)
• Visual disturbances and sudden vision loss
• Sudden hearing loss
• Mood changes including depression (rare)

• Nitrates: Concurrent use with tadalafil is contraindicated due to risk of severe hypotension.
• Alpha-blockers: Combined use may cause symptomatic hypotension; monitor blood pressure closely.
• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Can increase tadalafil plasma concentration and adverse effects.
• CYP3A4 Inducers (e.g., rifampin): Can decrease tadalafil plasma concentration and reduce efficacy.
• Other PDE5 inhibitors: Should not be used concurrently.
• Finasteride: Minimal interactions; caution advised with other hormonal therapies.

• Guidelines increasingly support combination therapy with 5-alpha reductase inhibitors and PDE5 inhibitors for men with moderate to severe BPH and concomitant erectile dysfunction.
• Emphasis on cardiovascular evaluation prior to tadalafil use remains important.
• Monitoring of PSA levels continues to be necessary for men on finasteride therapy.
• No significant recent changes in dosing or safety warnings, but ongoing pharmacovigilance for rare adverse effects is advised.

• Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture, heat, and direct light.
• Keep in original packaging until use.
• Do not freeze.
• Keep out of reach of children.