What is the recommended initial dosing for erectile dysfunction (ED) medication, specifically phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) or tadalafil (Cialis), in a patient starting treatment, considering potential interactions with other medications and underlying medical conditions like diabetes, hypertension, and cardiovascular disease?

ED Medication Initial Dosing

Start with sildenafil 50 mg or tadalafil 10 mg taken as needed, approximately 1 hour before sexual activity, with dose titration based on efficacy and tolerability after at least 5 attempts at each dose level. 1, 2

Critical Pre-Treatment Safety Assessment

Before prescribing any PDE5 inhibitor, you must:

• Verify the patient is not taking nitrates in any form (oral, sublingual, transdermal, or recreational)—this is an absolute contraindication due to potentially fatal hypotension 3, 4
• Assess cardiovascular risk: Ask if the patient can walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms 3
  • If unable to perform this level of activity, refer to cardiology before prescribing 3
  • Low-risk patients (controlled hypertension, mild stable angina, successful revascularization, uncomplicated past MI, CHF NYHA class I) can safely receive PDE5 inhibitors 4
• Screen for medications that interact with CYP3A4: ritonavir, saquinavir, ketoconazole, erythromycin, cimetidine—these require lower starting doses 5, 2

Specific Starting Doses by Medication

Sildenafil (Viagra)

• Standard starting dose: 50 mg taken approximately 1 hour before sexual activity 5, 2
• Titrate to 100 mg if 50 mg is inadequate, or reduce to 25 mg if side effects are problematic 5, 2
• Maximum frequency: once daily 2
• Special populations requiring 25 mg start: severe hepatic impairment, severe renal impairment (CrCl <30), or concurrent CYP3A4 inhibitors 5, 2
• Duration of action: approximately 4 hours 6, 7
• Food interaction: Avoid taking with large/fatty meals as this delays absorption 5

Tadalafil (Cialis)

• As-needed dosing: Start with 10 mg taken prior to anticipated sexual activity 1
• Titrate to 20 mg or reduce to 5 mg based on response 1
• Maximum frequency: once daily 1
• Daily dosing alternative: 2.5 mg once daily, can increase to 5 mg daily 1
  • Daily dosing eliminates need to time medication with sexual activity, preferred for couples wanting spontaneity 4
• Duration of action: up to 36 hours 1, 7
• No food interaction: Can be taken without regard to meals 1
• Renal impairment adjustments 1:
  • CrCl 30-50 mL/min: Start 5 mg as-needed (max 10 mg every 48 hours), or 2.5 mg daily
  • CrCl <30 or hemodialysis: Max 5 mg every 72 hours; daily dosing not recommended
• Hepatic impairment: Max 10 mg once daily for mild-moderate (Child-Pugh A or B); contraindicated in severe (Child-Pugh C) 1

Key Pharmacologic Difference

Tadalafil does NOT show dose-dependent improvement between 5 mg, 10 mg, and 20 mg—unlike sildenafil where higher doses show greater efficacy 4. Choose between tadalafil 10 mg and 20 mg based primarily on tolerability, not expecting dramatically better results at higher doses 4.

Defining an Adequate Trial Before Declaring Failure

An adequate trial requires at least 5 separate attempts at the maximum tolerated dose before concluding the medication is ineffective 3, 4. Many apparent failures result from:

• Lack of sexual stimulation (PDE5 inhibitors require arousal to work) 3, 5
• Improper timing: Taking too early or too late relative to sexual activity 4, 5
• Heavy alcohol use: Impairs erectile function and reduces medication efficacy 4
• Taking sildenafil/vardenafil with fatty meals: Delays absorption 5, 7
• Inadequate dose: Not titrating to maximum before giving up 4, 5

Special Population Considerations

Diabetes, Cardiovascular Disease, Post-Prostatectomy

• These patients have more severe baseline ED and may respond less robustly to PDE5 inhibitors 4, 5, 8
• Still effective, but may require maximum doses and realistic expectation-setting 4, 2

Testosterone Deficiency

• If testosterone <300 ng/dL, consider combination therapy: PDE5 inhibitor plus testosterone replacement is more effective than either alone 4, 5
• Testosterone alone is NOT effective monotherapy for ED 4
• Check total testosterone, free testosterone, and SHBG before declaring PDE5 inhibitor failure 4

Concurrent Alpha-Blockers

• Use caution with alpha-blockers (except tamsulosin) due to additive hypotensive effects 9
• Start with lowest doses of both medications 9

Common Adverse Effects and Management

All PDE5 inhibitors share similar side effect profiles 2, 6:

• Headache, flushing, nasal congestion, dyspepsia (most common, transient, mild-to-moderate) 5, 2
• Tadalafil has lower rates of flushing and dyspepsia compared to sildenafil 4
• Sildenafil causes more visual disturbances than tadalafil 10
• Back pain and myalgia more common with tadalafil 4

Switching Medications After Failure

If the first PDE5 inhibitor fails after an adequate trial (5 attempts at maximum dose), switch to a different PDE5 inhibitor 3. Before switching, verify:

• Adequate sexual stimulation was present 4
• Proper timing and frequency of dosing 4
• No heavy alcohol use 4
• No unaddressed hormonal abnormalities 4
• No relationship issues interfering with sexual activity 4

Emergency Nitrate Protocol

If a patient on PDE5 inhibitors requires emergency nitrate administration 4:

• Wait 24 hours after sildenafil before giving nitrates 4, 5
• Wait 48 hours after tadalafil before giving nitrates 4
• Administer only under close medical supervision with continuous monitoring 4

Ongoing Management

Periodic follow-up should assess 4, 5:

• Treatment effectiveness and patient satisfaction
• Side effects and tolerability
• Changes in cardiovascular health or new cardiovascular symptoms
• New medications (especially nitrates, alpha-blockers, CYP3A4 inhibitors)
• Continued absence of nitrate use