Usage
- Tadalafil is prescribed for the treatment of erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH).
- Pharmacological Classification: Phosphodiesterase-5 (PDE5) inhibitor.
- Mechanism of Action: Tadalafil inhibits PDE5, an enzyme that breaks down cyclic guanosine monophosphate (cGMP). In ED, this leads to increased cGMP levels in the smooth muscle of the corpus cavernosum, promoting vasodilation and facilitating erection upon sexual stimulation. In PAH, the same mechanism leads to vasodilation in the pulmonary arteries, reducing pulmonary vascular resistance and improving blood flow.
Alternate Names
- International and regional variations: None specifically mentioned.
- Brand Names: Cialis®, Adcirca®, Alyq™.
How It Works
- Pharmacodynamics: Tadalafil’s primary effect is smooth muscle relaxation, achieved through PDE5 inhibition and subsequent increase in cGMP. This results in vasodilation in specific tissues, including the corpus cavernosum in the penis and pulmonary vasculature.
- Pharmacokinetics:
- Absorption: Tadalafil is readily absorbed after oral administration, reaching peak plasma concentrations within 2 hours. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized by CYP3A4 in the liver.
- Elimination: Excreted mainly in the feces and to a lesser extent in urine. The elimination half-life is approximately 17.5 hours, allowing for a longer duration of action compared to other PDE5 inhibitors.
- Mode of Action: Tadalafil binds to and inhibits PDE5, preventing the degradation of cGMP, which sustains smooth muscle relaxation and vasodilation.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Tadalafil specifically inhibits PDE5. It does not directly bind to receptors or modulate neurotransmitters in the same way that some other drugs do.
- Elimination Pathways: Predominantly hepatic metabolism via CYP3A4, followed by excretion primarily through feces and to a lesser extent in urine.
Dosage
Standard Dosage
Adults:
- ED (as needed): 10 mg orally, taken 30 minutes before anticipated sexual activity. The dose may be adjusted to 5 mg or 20 mg based on individual response. Maximum once per day.
- ED (daily): 2.5 mg or 5 mg orally once a day, taken at approximately the same time, regardless of sexual activity.
- BPH/ED and BPH: 5 mg orally once a day, taken at approximately the same time.
- PAH: 40 mg orally once a day (may be initiated at 20 mg in elderly patients).
Children:
- Tadalafil is not recommended for use in children under 18 years of age.
Special Cases:
- Elderly Patients: May require lower starting doses, particularly for PAH (20 mg once daily). Dose adjustments should be made based on individual tolerability.
- Patients with Renal Impairment:
- Mild to moderate impairment: No dose adjustment necessary.
- Severe impairment: 10 mg maximum dose for on-demand use. Daily dosing is not recommended.
- Patients with Hepatic Dysfunction:
- Mild to moderate impairment: No dose adjustment necessary.
- Severe impairment: 10 mg maximum dose. Careful benefit-risk assessment is required. Daily dosing not evaluated.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, diabetes, and other conditions. Dosage adjustments may be necessary.
Clinical Use Cases
Tadalafil is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Adjust dosage based on individual patient response and tolerability.
- Consider renal/hepatic function, comorbid conditions, and concomitant medications.
- Genetic polymorphisms affecting drug metabolism may influence dosage requirements, but specific guidelines are not universally established.
Side Effects
Common Side Effects:
Headache, dyspepsia, back pain, myalgia, flushing, nasal congestion, dizziness.
Rare but Serious Side Effects:
Priapism (prolonged erection), sudden vision loss, sudden hearing loss, allergic reactions (including angioedema and hives), severe hypotension.
Long-Term Effects:
Limited data on long-term effects, but potential for cardiovascular complications with chronic use.
Adverse Drug Reactions (ADR):
As mentioned under “Rare but Serious Side Effects,” any occurrence of priapism, sudden vision or hearing loss, severe allergic reactions, or significant hypotension requires urgent medical intervention.
Contraindications
- Hypersensitivity to tadalafil.
- Concomitant use of nitrates.
- Use of guanylate cyclase stimulators (e.g., riociguat).
- Recent history of myocardial infarction or stroke.
- Unstable angina.
- Severe hypotension.
Drug Interactions
- Nitrates: Can cause severe hypotension.
- Alpha-blockers: May lead to additive hypotensive effects.
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): Increase tadalafil plasma concentrations.
- CYP3A4 inducers (e.g., rifampin): Decrease tadalafil plasma concentrations.
- Alcohol: May increase risk of hypotension and dizziness.
- Grapefruit juice: May increase tadalafil exposure.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (PAH). Not indicated for ED/BPH in women.
- Fetal Risks/Teratogenicity: Limited data available. Use only if clearly needed for PAH.
- Breastfeeding: Excretion in breast milk unknown. Not recommended.
Drug Profile Summary
- Mechanism of Action: PDE5 inhibitor leading to smooth muscle relaxation and vasodilation.
- Side Effects: Headache, dyspepsia, back pain, myalgia, flushing, nasal congestion. Rare but serious: priapism, vision/hearing loss, allergic reactions, hypotension.
- Contraindications: Hypersensitivity, nitrates, guanylate cyclase stimulators, recent MI or stroke, unstable angina, severe hypotension.
- Drug Interactions: Nitrates, alpha-blockers, CYP3A4 inhibitors/inducers, alcohol, grapefruit juice.
- Pregnancy & Breastfeeding: Category B (PAH). Not recommended during breastfeeding.
- Dosage: ED (as needed): 10 mg; ED (daily): 2.5-5 mg; BPH: 5 mg; PAH: 40 mg. Adjustments needed for renal/hepatic impairment.
- Monitoring Parameters: Blood pressure, heart rate, vision, hearing.
Popular Combinations
- Tadalafil is sometimes used in combination with alpha-blockers (e.g., tamsulosin) for the management of BPH and ED. However, careful blood pressure monitoring is crucial.
Precautions
- Evaluate for underlying causes of ED/BPH.
- Assess cardiovascular status before initiating therapy.
- Caution in patients with renal/hepatic impairment.
- Monitor for vision and hearing changes.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tadalafil IP?
A: The dosage depends on the indication: ED (as needed) – 10 mg (adjustable 5-20 mg); ED (daily) – 2.5-5 mg; BPH – 5 mg; PAH – 40 mg (may start at 20 mg in elderly).
Q2: How long does it take for Tadalafil to work?
A: Typically starts to work within 30-60 minutes for ED.
Q3: What are the common side effects of Tadalafil?
A: Headache, back pain, dyspepsia, myalgia, flushing, nasal congestion.
Q4: Can Tadalafil be taken with nitrates?
A: No, Tadalafil is contraindicated with nitrates due to the risk of severe hypotension.
Q5: How long does the effect of Tadalafil last?
A: Up to 36 hours.
Q6: Is Tadalafil safe for patients with heart problems?
A: Use with caution in patients with heart problems. Consult a cardiologist before starting tadalafil if you have a heart condition.
Q7: Can Tadalafil be taken daily?
A: Yes, lower doses (2.5-5 mg) can be taken daily for ED or BPH.
Q8: What should I do if I experience a prolonged erection (priapism) while taking Tadalafil?
A: Seek immediate medical attention as priapism can cause permanent damage.
Q9: Does Tadalafil cure ED?
A: No, Tadalafil does not cure ED. It helps achieve an erection when sexually stimulated.
Q10: How should Tadalafil be stored?
A: Store at room temperature away from moisture and heat.
