Tadalafil + Tamsulosin

Usage

Tadalafil + Tamsulosin is prescribed for the treatment of men with both erectile dysfunction (ED) and benign prostatic hyperplasia (BPH, enlarged prostate). It combines two medications that address these distinct conditions. Tadalafil is a phosphodiesterase-5 (PDE5) inhibitor, primarily used to treat ED, while Tamsulosin is an alpha-1 adrenergic receptor blocker, commonly used to treat BPH.

• Pharmacological Classifications:

  • Tadalafil: PDE5 inhibitor, Vasodilator
  • Tamsulosin: Alpha-1 adrenergic receptor blocker

• Mechanism of Action:

  • Tadalafil enhances the effect of nitric oxide, which relaxes smooth muscles in the penis, facilitating blood flow and enabling an erection.
  • Tamsulosin relaxes the muscles in the prostate and bladder neck, making it easier to urinate.

Alternate Names

The combination itself doesn’t have an international nonproprietary name (INN). It is generally recognized by the names of its components.

• Brand Names: Gugutams (South Korea)

How It Works

• Pharmacodynamics:

  • Tadalafil increases blood flow to the penis.
  • Tamsulosin reduces smooth muscle tone in the prostate and bladder neck.

• Pharmacokinetics:

  • Tadalafil:
    • Absorption: Rapidly absorbed after oral administration.
    • Metabolism: Primarily metabolized by CYP3A4 enzymes in the liver.
    • Elimination: Excreted primarily in feces.
  • Tamsulosin:
    • Absorption: Well absorbed after oral administration.
    • Metabolism: Extensively metabolized in the liver.
    • Elimination: Excreted mainly in urine.

• Mode of Action:

  • Tadalafil inhibits PDE5, preventing the breakdown of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation and vasodilation in the penis.
  • Tamsulosin blocks alpha-1A adrenergic receptors in the prostate, causing smooth muscle relaxation and improving urine flow.

• Receptor Binding/Enzyme Inhibition:

  • Tadalafil: PDE5 inhibition.
  • Tamsulosin: Alpha-1A adrenergic receptor blockade.

• Elimination Pathways:

  • Tadalafil: Primarily hepatic metabolism (CYP3A4) followed by fecal excretion.
  • Tamsulosin: Hepatic metabolism followed by urinary excretion.

Dosage

Standard Dosage

Adults:

The typical dosage is 5 mg of Tadalafil and 0.4 mg of Tamsulosin, taken once daily at approximately the same time, regardless of the timing of sexual activity.

Children: This combination is not recommended for use in children.

Special Cases:

• Elderly Patients: No dose adjustment is typically required for elderly patients. However, individual patient factors should be considered.
• Patients with Renal Impairment: For creatinine clearance 30 to 50 mL/min, a starting dose of 2.5 mg of Tadalafil may be considered. For creatinine clearance less than 30 mL/min or patients on hemodialysis, daily use is not recommended. Tamsulosin does not typically require dose adjustment in renal impairment.
• Patients with Hepatic Dysfunction: For mild to moderate hepatic impairment, a starting dose of 2.5 mg of Tadalafil may be considered. For severe hepatic impairment, use is not recommended. Tamsulosin does not typically require dose adjustment in mild to moderate hepatic impairment, but hasn’t been studied in severe impairment.
• Patients with Comorbid Conditions: Careful monitoring is needed in patients with cardiovascular disease.

Clinical Use Cases

The combination of Tadalafil + Tamsulosin is specifically indicated for the management of BPH and ED. Its use in the context of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is not relevant or established.

Dosage Adjustments

Dose adjustments may be needed based on individual tolerability and efficacy, as well as the presence of renal or hepatic impairment. Concomitant medication use, particularly CYP3A4 inhibitors, might require Tadalafil dose reductions.

Side Effects

Common Side Effects:

• Headache
• Dizziness
• Nasal congestion
• Dyspepsia
• Back pain
• Myalgia

Rare but Serious Side Effects:

• Priapism (prolonged erection)
• Sudden vision loss
• Sudden hearing loss
• Hypotension

Long-Term Effects:

Long-term effects are not fully characterized, but might include those associated with the individual components, like dependence on tadalafil for sexual function.

Adverse Drug Reactions (ADR):

Clinically significant ADRs include priapism, sudden vision or hearing loss, and severe hypotension. These necessitate immediate medical attention.

Contraindications

• Hypersensitivity to tadalafil or tamsulosin
• Concomitant use of nitrates
• Severe hypotension
• Unstable angina
• Recent myocardial infarction
• Severe hepatic impairment

Drug Interactions

• Nitrates: Contraindicated, may cause severe hypotension.
• Alpha-blockers (other than Tamsulosin): Use with caution; may increase the risk of hypotension.
• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase Tadalafil levels; dose adjustments may be required.
• CYP3A4 inducers (e.g., rifampin): May decrease Tadalafil levels.
• Alcohol: May increase the risk of hypotension.

Pregnancy and Breastfeeding

Tadalafil + Tamsulosin is not intended for use in women. Tadalafil is not indicated for use in pregnant women. The safety of tamsulosin during pregnancy and breastfeeding is not established.

Drug Profile Summary

• Mechanism of Action: Tadalafil inhibits PDE5, enhancing nitric oxide’s effects; Tamsulosin blocks alpha-1A receptors, relaxing prostate smooth muscle.
• Side Effects: Headache, dizziness, nasal congestion, dyspepsia, back pain, priapism, vision/hearing changes.
• Contraindications: Nitrate use, severe hypotension, unstable angina, recent MI, severe hepatic impairment.
• Drug Interactions: Nitrates, alpha-blockers, CYP3A4 inhibitors/inducers, alcohol.
• Pregnancy & Breastfeeding: Not for use in women.
• Dosage: 5 mg Tadalafil/0.4 mg Tamsulosin once daily; adjustments may be required.
• Monitoring Parameters: Blood pressure, vision/hearing changes, signs of priapism.

Popular Combinations

This combination itself is designed to treat both ED and BPH. Other combinations may be added to address specific patient needs. For instance, Finasteride can be added for better BPH symptom control.

Precautions

• Evaluate cardiovascular status before initiating therapy.
• Patients should not take nitrates within 48 hours of taking tadalafil.
• Caution should be exercised in patients with hypotension, autonomic dysfunction, or left ventricular outflow obstruction.
• Monitor for vision and hearing changes.
• Alcohol consumption should be limited.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Tadalafil + Tamsulosin?

A: The standard recommended dosage is 5 mg tadalafil and 0.4 mg tamsulosin taken once daily, at approximately the same time each day, irrespective of sexual activity timing.

Q2: What are the common side effects of this combination?

A: Common side effects include headache, dizziness, nasal congestion, dyspepsia, and back pain.

Q3: Can patients with heart conditions take this medication?

A: Patients with certain heart conditions (e.g., unstable angina, recent MI) should not take this medication. Those with other cardiovascular conditions need careful evaluation and monitoring.

Q4: What are the serious side effects to watch out for?

A: Serious side effects include priapism (prolonged erection), sudden vision or hearing loss, and severe hypotension. Seek immediate medical attention if these occur.

Q5: Can this medication be taken with nitrates?

A: No, nitrates are contraindicated with tadalafil and this combination. Concomitant use can cause dangerous drops in blood pressure.

Q6: Are there any dietary restrictions with this medication?

A: While no specific dietary restrictions exist, limiting alcohol intake is advised due to the increased risk of hypotension. Grapefruit juice can interact with tadalafil and should be avoided.

Q7: How should dosage be adjusted for patients with kidney or liver problems?

A: Dose adjustments might be needed for patients with moderate to severe renal or hepatic impairment. Daily tadalafil is not recommended for those with severe renal impairment or severe hepatic dysfunction.

Q8: How long does the effect of this medication last?

A: Tadalafil’s effects on ED can last up to 36 hours, while tamsulosin’s effect on BPH is continuous with daily dosing.

Q9: Can this drug be used in women?

A: No, this drug is not indicated or intended for use in women.

Q10: What if a dose is missed?

A: Take the missed dose as soon as remembered, unless it’s close to the next scheduled dose. Do not double the dose.