Is it safe to advise taking Phosphodiesterase type 5 (PDE5) inhibitors as needed?

Is It Safe to Advise Taking PDE5 Inhibitors As Needed?

Yes, it is safe to advise taking PDE5 inhibitors as needed for erectile dysfunction, provided patients are properly screened for contraindications—particularly nitrate use and significant cardiovascular disease—and are counseled on proper use, timing, and potential side effects. 1

Cardiovascular Screening Before Initiation

Before prescribing PDE5 inhibitors on an as-needed basis, you must assess cardiovascular risk:

• Patients who cannot walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms require cardiology referral before treatment. 1
• PDE5 inhibitors are safe in patients with stable cardiovascular disease who can tolerate the physical demands of sexual activity. 2
• The incidence of serious adverse events with PDE5 inhibitors is less than 2%, with no significant difference between medications and placebo. 2

Absolute Contraindications

Nitrate medications are absolutely contraindicated with all PDE5 inhibitors due to potentially fatal hypotension. 3, 4

Critical timing considerations if nitrates become medically necessary:

• For sildenafil and vardenafil: Wait at least 24 hours after the last dose before administering nitrates 1
• For tadalafil: Wait at least 48 hours after the last dose before administering nitrates 1, 3, 4

Alpha-Blocker Interactions

Caution is required when combining PDE5 inhibitors with alpha-blockers due to additive blood pressure lowering effects:

• Patients should be stable on alpha-blocker therapy before initiating a PDE5 inhibitor 4, 5
• Start PDE5 inhibitors at the lowest recommended dose in patients already on alpha-blockers 4, 5
• If initiating an alpha-blocker in a patient already on an optimized PDE5 inhibitor dose, start the alpha-blocker at the lowest dose with stepwise titration 4, 5
• For BPH treatment specifically, the combination of tadalafil and alpha-blockers is not recommended; discontinue the alpha-blocker at least one day before starting daily tadalafil for BPH 4

Dosing and Administration for As-Needed Use

Starting doses for as-needed PDE5 inhibitor therapy: 2

• Tadalafil: Start at 10 mg, can titrate to 20 mg based on response 2
• Sildenafil: Typically 50 mg, adjustable to 25-100 mg 6
• Vardenafil: Typically 10 mg, adjustable to 5-20 mg 6

Onset of action varies by agent: 6

• Sildenafil: 35% of patients achieve successful intercourse within 14 minutes 6
• Vardenafil: 21% of patients within 10 minutes 6
• Tadalafil: 16% of patients within 16 minutes, but therapeutic window extends up to 36 hours due to 17.5-hour half-life 6

Renal and Hepatic Impairment Adjustments

For as-needed tadalafil use: 4

• Creatinine clearance <30 mL/min or end-stage renal disease on hemodialysis: Limit to 5 mg not more than once every 72 hours 4
• Creatinine clearance 30-50 mL/min: Start at 5 mg once daily maximum, with maximum dose of 10 mg not more than once every 48 hours 4

For hepatic impairment: 4

• Mild to moderate hepatic impairment: Do not exceed 10 mg tadalafil 4
• Severe hepatic impairment: Use is not recommended due to insufficient safety data 4

Similar dose adjustments apply to vardenafil, with a starting dose of 5 mg and maximum of 10 mg in moderate hepatic impairment (Child-Pugh B). 5

Defining Treatment Success and Failure

An adequate trial requires at least 5 separate occasions at maximum dose before declaring treatment failure, unless unacceptable side effects occur. 3

Many perceived failures are actually due to modifiable factors: 1

• Lack of adequate sexual stimulation (PDE5 inhibitors require sexual arousal to work) 1
• Incorrect timing of medication relative to sexual activity 1
• Food interactions (fatty meals reduce absorption of sildenafil and vardenafil, but not tadalafil) 6
• Heavy alcohol use 1
• Undiagnosed hormonal abnormalities (particularly testosterone deficiency) 1
• Inadequate dose titration 1

After re-education on proper use and dose optimization, many initial non-responders become responders. 1

Ongoing Monitoring Requirements

Patients on continuing PDE5 inhibitor therapy require periodic follow-up to assess: 1

• Efficacy of treatment 1
• Side effects 1
• Any significant change in health status, particularly cardiovascular health 1
• Changes in medication regimen that could create new contraindications or interactions 1

This monitoring typically occurs at the time of prescription renewal. 1

Common Side Effects

Expected side effects include: 2

• Headache 2
• Flushing (lower rates with tadalafil compared to other PDE5 inhibitors) 2
• Nasal congestion 2
• Dyspepsia 2
• Back pain and myalgia (more common with tadalafil) 2
• Visual disturbances 2

Special Considerations

Testosterone deficiency: Patients with morning total testosterone <300 ng/dL may benefit from combination therapy with testosterone replacement, which can be more effective than PDE5 inhibitors alone. 1, 3, 7

Lifestyle modifications should be addressed alongside pharmacological treatment: 1, 3

• Smoking cessation 1, 3
• Weight loss if obese 1, 3
• Increased physical activity 1, 3
• Reduction of alcohol consumption 1, 3

QT prolongation concerns: Patients with congenital QT prolongation or those taking Class IA or Class III antiarrhythmic medications should avoid vardenafil. 5

Critical Pitfalls to Avoid

• Never prescribe PDE5 inhibitors without explicitly asking about nitrate use, including sublingual nitroglycerin for angina 3, 4
• Do not declare treatment failure without ensuring the patient has had an adequate trial (at least 5 attempts at maximum dose with proper technique) 3
• Do not overlook testosterone deficiency as a contributing factor to PDE5 inhibitor non-response 7
• Avoid prescribing to patients with unstable cardiovascular disease without cardiology clearance 1