Comparison of Viagra, Levitra and Cialis

Male sexual dysfunction is one of the most common health problems affecting men and is more common with increasing age. Chronic ED affects about 5% of men in their 40s and 1525% of men by the age of 65. Transient ED and inadequate erection affect as many as 50% of men between the ages of 40 and 70.

In around 95% of the cases, a satisfactory treatment can be found. Erectile dysfunction is treatable at any age, and awareness of this fact has been growing. More men have been seeking help and returning to normal sexual activity because of improved, successful treatments for erectile dysfunction.

Three PDE-5 inhibitors

Currently, there are three oral medications approved by the FDA for the treatment of erectile dysfunction: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). They block the enzyme phosphodiesterase type 5 (PDE-5) and belong to a class called phosphodiesterase (PDE) inhibitors.

Since introduction of the first PDE-5 inhibitor Viagra, there has been a fundamental change in the treatment of erectile dysfunction. Although there are a number of options available for non-surgical treatment, it is clear that oral therapy has revolutionized the treatment approach to patients with erectile dysfunction. The development of the PDE-5 inhibitors Levitra and Cialis prompts the question of whether and how these sexual medications differ in terms of their efficacy and adverse effects.

Viagra was the first and is probably the most famous of the three PDE-5 inhibitors used to treat erectile dysfunction. Viagra was approved for erectile dysfunction in March 27, 1998. Viagra is manufactured by Pfizer, Inc.

Levitra was the second PDE-5 inhibitor to come to market in the United States, and it was approved by the FDA in August 19, 2003. Levitra is manufactured by Bayer Pharmaceuticals Corporation.

Cialis was the third PDE-5 inhibitor to come to market in the United States and was approved by the FDA at the end of November 21, 2003. Cialis is manufactured by Lilly ICOS LLC.

The major advantage of these medications for sexual enhancement is that they do not cause an erection at inappropriate times, because they act only in response to sexual stimulation. If there is no sexual stimulation drug remains in the background. All three are taken orally prior to planned sexual activity, acting to increase blood flow in the penis in response to sexual stimulation. However, there are important differences between the three, differences that could influence safety, specificity, duration of action, adverse effects, and ultimately, public acceptance within this class.

Brief comparison
  Viagra (sildenafil) Levitra (vardenafil) Cialis (tadalafil)
FDA approval date March 27, 1998 August 19, 2003 November 21, 2003
Pharmaceutical Form 25mg, 50mg, 100mg tablets 2.5mg, 5mg, 10mg, 20mg tablets 5mg, 10mg, 20mg tablets
Efficacy 84% 80% 81%
Onset of action 30 minutes (effect delayed if taken with food) 25 minutes (effect delayed by fatty meal) 16-45 minutes (effect NOT delayed by food)
Recommended dose 50 mg, may be adjusted to 100 mg or 25 mg 10 mg, may be adjusted to 20 mg 10 mg, may be adjusted to 20 mg
Duration of action 4 to 5 hours 4 to 5 hours 36 hours
Food Interactions less effective if you eat a high-fat meal less effective if you eat a high-fat meal
moderate-fat meal does not reduce its effectiveness
works without regard to what you eat
Most common side effects facial flushing, headache, indigestion facial flushing, headache headache, indigestion
Less common side effects altered vision, dizziness, nasal, congestion indigestion, nausea, dizziness, nasal congestion back pain, muscle aches, nasal congestion, facial flushing, dizziness

Mechanism of action

Sildenafil, vardenafil, and tadalafil do not directly cause an erection of the penis, but they alter the body's response to sexual stimulation by enhancing the effect of the nitric oxide, a chemical that is normally released during stimulation. Nitric oxide causes relaxation of the muscles in the penis, which allows for better blood flow to the penile area.

Effectiveness

All PDE-5 inhibitors have demonstrated excellent efficacy in general and in specific populations (eg, men with diabetes mellitus or those who have undergone radical prostatectomy). Viagra, at 84%, is slightly more effective than Levitra at 80% and Cialis at 81%.

Pharmacokinetic properties

Viagra and Levitra differ only minimally in terms of their structure, while Cialis differs markedly from Viagra and Levitra in terms of its molecular structure, which is also reflected in pharmacokinetic differences.

  • Viagra: 25 mg, 50 mg 100 mg tablets
    • Onset of action: 30 minutes (effect delayed if taken with food)
    • Duration of action: 4 to 5 hours
  • Levitra: 2.5 mg, 5 mg, 10 mg, 20 mg tablets
    • Onset of action: 25 minutes (effect delayed by fatty meal)
    • Duration of action: 4 to 5 hours
  • Cialis: 5 mg, 10 mg, 20 mg tablets
    • Onset of action: 16-45 minutes (effect NOT delayed by food)
    • Duration of action: 36 hours

Viagra does not work as well as it would otherwise if you eat a high-fat meal around the time you take it. Viagra should be taken on an empty stomach. Levitra may be slightly less effective if you eat a high-fat meal, but a moderate-fat meal does not reduce its effectiveness. Cialis works without regard to what you eat.

Viagra and Levitra have similar half-lives, and onset and duration of action. Cialis has a slower onset of action and longer duration of action, which is attributed to its longer half-life.

Men who wish for spontaneity may opt for Cialis, which may allow for successful intercourse up to 36 hours postdose, even though it takes longer to reach peak effect. The considerably longer duration of effect for Cialis will likely allow less frequent dosing and greater impulsiveness between partners, but also could potentially prolong adverse effects.

PDE-5 inhibitors are primarily excreted via the fecal route with varying percentages eliminated renally.

Dosage

The recommended dose for Viagra is 50 mg, and the physician may adjust this dose to 100 mg or 25 mg, depending on the patient.

The recommended dose for either Levitra or Cialis is 10 mg, and the physician may adjust this dose to 20 mg if 10 mg is insufficient. A lower dose of 5 mg is available for men who take other medicines or have conditions that may decrease the body's ability to use the drug. Levitra is also available in a 2.5 mg dose.

None of these PDE-5 inhibitors should be used more than once a day.

Side effects

Most common side effects:

  • Viagra: headache, epistaxis, flushing, indigestion, dizziness, nasal congestion, abnormal vision
  • Levitra: headache, flushing, indigestion, nausea, dizziness, nasal congestion
  • Cialis: headache, indigestion, back pain

PDE-5 inhibitors are generally well tolerated. Side effects include headache, flushing, dyspepsia, and nasal congestion.

Visual abnormalities are encountered with Viagra, but are less likely with Levitra and unlikely with Cialis. Flushing and dyspepsia that are associated with Viagra and Levitra are less common with Cialis. Back pain and muscle aches (myalgia) may occur with Cialis, but are unusual with either Viagra or Levitra. Side effects of Cialis tend to last longer, but are less marked than with the other drugs.

Precautions and contraindications

All PDE-5 inhibitors are absolutely contraindicated in persons who take organic nitrates, because they induce vasodilation.

The FDA no longer considers concomitant use of alpha-blockers a contraindication to use of PDE-5 inhibitors. However, persons on alpha-blockers must be on a stable dose of alpha-blocker prior to using a PDE-5 inhibitor.

Since both Viagra and Levitra have moderate vasodilatory and hypotensive effects, they should not be given in the presence of marked arterial or orthostatic hypotension, and should only be administered with caution in aortic stenosis or hypertrophic obstructive cardiomyopathy.

Men who have had a heart attack or stroke within the past 6 months and those with certain medical conditions (e.g., uncontrolled high blood pressure, severe low blood pressure or liver disease, unstable angina) that make sexual activity inadvisable should not take Cialis. Dosages of the drug should be limited in patients with kidney or liver disorders.

Conclusions

The differences between the 3 drugs are not great. All appear to be effective and safe. Levitra has less side effects compared to Viagra and lasts about the same time as Viagra in the body. Cialis has few side effects and lasts longer in the body to increase spontaneity than either Levitra or Viagra and there is no reduction in absorption when Cialis is taken with food. However, the longer half-life imposes increased risk for drug interactions.

References & Resources

  • 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.
  • 2. Doggrell SA. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin Pharmacother. 2005 Jan;6(1):75-84.

Published: May 05, 2007
Last updated: May 16, 2011

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