Usage
- Avanafil is prescribed for the treatment of erectile dysfunction (ED) in adult men.
- Pharmacological classification: Phosphodiesterase-5 (PDE5) inhibitor.
- Mechanism of action: Avanafil increases blood flow to the penis by inhibiting the PDE5 enzyme, which is responsible for the breakdown of cyclic guanosine monophosphate (cGMP). cGMP plays a crucial role in smooth muscle relaxation in the corpus cavernosum, allowing increased blood flow and facilitating erection upon sexual stimulation.
Alternate Names
- International Nonproprietary Name (INN): Avanafil
- Brand names: Stendra, Spedra
How It Works
- Pharmacodynamics: Avanafil selectively inhibits PDE5, leading to increased cGMP levels in the corpus cavernosum of the penis. This results in smooth muscle relaxation, increased blood flow, and ultimately, erection upon sexual stimulation. It does not cause an erection in the absence of sexual stimulation.
- Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, with peak plasma concentrations reached within 30-45 minutes. Food, especially high-fat meals, can delay absorption.
- Metabolism: Primarily metabolized by the CYP3A4 enzyme in the liver.
- Elimination: Mainly excreted in feces, with a smaller portion excreted in urine. The elimination half-life is approximately 6-17 hours.
- Mode of action: Avanafil competitively binds to the catalytic site of PDE5, preventing the hydrolysis of cGMP.
- Receptor binding: Specifically targets PDE5.
- Elimination pathways: Hepatic metabolism via CYP3A4, with subsequent fecal and urinary excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 100 mg orally taken approximately 15-30 minutes before sexual activity.
- The dose may be adjusted based on individual response and tolerability, ranging from 50 mg to a maximum of 200 mg per day. The lowest effective dose should be used. No more than one dose should be taken within a 24-hour period.
Children:
- Avanafil is not recommended for use in children. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment:
- Mild to moderate impairment: No dosage adjustment is usually necessary.
- Severe impairment (creatinine clearance < 30 mL/min): Avanafil is contraindicated.
- Patients with Hepatic Dysfunction:
- Mild to moderate impairment: Initiate with the lowest effective dose (50 mg) and adjust based on tolerance.
- Severe impairment (Child-Pugh Class C): Avanafil is contraindicated.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease. For patients on stable alpha-blocker therapy, the initial dose should be 50 mg.
Clinical Use Cases
Avanafil is specifically indicated for on-demand treatment of erectile dysfunction and is not intended for use in other clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be necessary based on individual efficacy, tolerability, and concomitant medications, particularly CYP3A4 inhibitors or alpha-blockers.
Side Effects
Common Side Effects:
- Headache
- Flushing
- Nasal congestion
- Back pain
Rare but Serious Side Effects:
- Priapism (prolonged and painful erection)
- Sudden vision loss or hearing loss
- Allergic reactions (rash, hives, swelling)
- Severe hypotension
Long-Term Effects: The long-term effects of avanafil are still under investigation.
Contraindications
- Concomitant use of nitrates (e.g., nitroglycerin), nitric oxide donors, or guanylate cyclase stimulators (e.g., riociguat).
- Severe hepatic or renal impairment.
- Hypersensitivity to avanafil.
- Conditions where sexual activity is inadvisable due to cardiovascular risk.
Drug Interactions
- CYP3A4 Inhibitors: Strong inhibitors (e.g., ketoconazole, ritonavir) are contraindicated. Moderate inhibitors (e.g., erythromycin) require dose reduction to a maximum of 100 mg every 48 hours or 50 mg every 24 hours.
- Alpha-blockers: Can cause additive hypotensive effects.
- Antihypertensives: May enhance blood pressure lowering.
- Alcohol: Increases risk of hypotension and other side effects.
- Grapefruit juice: Can increase avanafil levels.
- Other PDE5 Inhibitors: Concomitant use is not recommended.
Pregnancy and Breastfeeding
- Avanafil is not indicated for use in women.
- The safety of avanafil during pregnancy and breastfeeding has not been established.
Drug Profile Summary
- Mechanism of Action: PDE5 inhibitor, increases cGMP levels, leading to smooth muscle relaxation and increased penile blood flow.
- Side Effects: Headache, flushing, nasal congestion, back pain, priapism (rare), sudden vision or hearing loss (rare), allergic reactions (rare), hypotension.
- Contraindications: Nitrates, severe hepatic/renal impairment, hypersensitivity.
- Drug Interactions: CYP3A4 inhibitors, alpha-blockers, antihypertensives, alcohol.
- Pregnancy & Breastfeeding: Not indicated for use in women.
- Dosage: 100 mg (initial), 50-200 mg (adjusted), maximum once daily.
- Monitoring Parameters: Blood pressure, vision and hearing changes.
Popular Combinations
Avanafil is typically used as monotherapy. Combining it with other ED treatments is not recommended.
Precautions
- General Precautions: Assess cardiovascular status before initiating therapy.
- Specific Populations: Not for use in women, children, or patients with severe hepatic/renal impairment. Caution in patients with cardiovascular disease.
- Lifestyle Considerations: Limit alcohol intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Avanafil?
A: The initial recommended dose is 100 mg taken approximately 15-30 minutes before sexual activity. The dose can be adjusted to 50-200 mg based on individual response and tolerability, with a maximum of one dose per day.
Q2: How quickly does Avanafil work?
A: Avanafil can work as early as 15 minutes after administration, though the median time to onset is around 30 minutes.
Q3: Can Avanafil be taken with food?
A: Yes, avanafil can be taken with or without food. However, high-fat meals may delay absorption and onset of action.
Q4: What are the most common side effects of Avanafil?
A: The most common side effects include headache, flushing, nasal congestion, and back pain.
Q5: What should I do if I experience a prolonged erection (priapism)?
A: Priapism is a serious side effect. Seek immediate medical attention if an erection lasts longer than 4 hours.
Q6: Can I take Avanafil if I am taking nitrates for angina?
A: No, Avanafil is contraindicated in patients taking nitrates. The combination can cause a dangerous drop in blood pressure.
Q7: Does Avanafil interact with other medications?
A: Yes, Avanafil can interact with several medications, including CYP3A4 inhibitors and alpha-blockers. Consult with a doctor about potential drug interactions.
Q8: Can Avanafil be used by women?
A: No, Avanafil is not indicated for use in women. Its safety and efficacy in women have not been established.
Q9: How should Avanafil be stored?
A: Store avanafil at room temperature away from moisture and heat. Keep out of reach of children.
