Sildenafil vs. Tadalafil vs. Vardenafil (Which Is Best?)

Erectile dysfunction, or impotence, refers to the inability to acquire and maintain an erection firm enough to complete sexual intercourse. It is quite normal to have erection trouble sometimes, but when it becomes an ongoing issue, it can lead to stress, cause relationship problems, or negatively affect self-confidence. When this happens, it’s time for the best drugs for ED.

Around 5% of males will experience complete erectile dysfunction when they reach 40. When they reach 70, it increases to 15%.

Although age is a significant factor in erectile dysfunction, it can occur in some males at any age. Older men usually acquire medical conditions as they age that may affect their ability to get an erection.

What Causes Erectile Dysfunction?

Erectile dysfunction’s physical causes include (1):

• Atherosclerosis or clogged blood vessels
• Heart disease
• High blood pressure
• High cholesterol
• Obesity
• Diabetes
• Parkinson’s disease
• Metabolic syndrome
• Some prescription medications (e.g., finasteride)
• Multiple sclerosis
• Peyronie’s disease (scar tissues inside the penis)
• Sleep disorders
• Alcoholism or substance abuse
• Injuries or surgeries affecting the spinal cord or pelvic area
• Enlarged prostate or prostate cancer treatment

The brain’s role is important in triggering an erection, and it usually starts with sexual excitement. There are situations that might interfere with these sexual feelings. This can cause erectile dysfunction or even worsen it. These include:

• Stress
• Depression
• Relationship problems

The Best Drugs for ED Available

Currently, three erectile dysfunction drugs on the market are most commonly prescribed. They are Viagra (sildenafil), Cialis (tadalafil), and Levitra (vardenafil). All of these sex drugs are categorized as PDE5 inhibitors and prescribed for treating patients suffering from erectile dysfunction.

The first of the 3 is sildenafil, introduced in 1998. It’s responsible for treating more than 20 million patients in the first six years since its release on the market. It was followed by vardenafil in 2003 and then a few months later by tadalafil.

Check out BlueChew, an online portal that connects potential patients with providers for the treatment of ED. 

Sildenafil (Viagra)

Sildenafil, more commonly known as Viagra, was not intended to induce erection. In 1989, Pfizer scientists Albert Wood and Peter Dunn developed the drug to treat angina and high blood pressure. During the study, they found out that the drug also caused enhanced blood flow in the penile area, which is a requirement for male erection.

So instead of marketing it as a heart medicine, it became famous as a treatment for erectile dysfunction beginning in 1994. The rest is history, as it has become one of the best sex drugs in the world.

How Sildenafil Works

Sildenafil’s main action is suppressing the enzyme phosphodiesterase type 5 or PDE 5 (2). Its action is similar to other PDE5 inhibitors, such as tadalafil and vardenafil, which we will discuss later. Sildenafil enhances the production of guanosine monophosphate or GMP.

GMP regulates multiple cellular and tissue responses by relaxing smooth muscle cells, promoting vasodilation, and increasing blood flow to the genital area. This action applies to both men and women.

PDE5 breaks down GMP, which results in reduced blood flow. This enzyme is located in the penis corpus cavernosum, which is a spongy part that gets filled with blood during an erection.

Sildenafil inhibits PDE5 by binding to it. This action prevents the enzyme from working properly, so it can’t break down GMP. More GMP is then made available in the corpus cavernosum.

With more GMP available, the blood vessels dilate, so more blood comes in. This results in an erection.

How Effective Is Sildenafil?

So how does the vasodilation action of sildenafil translate into sexual performance? A lot of studies have been made on the efficacy of this erectile dysfunction drug.

In one study, the safety and efficacy of sildenafil were assessed vs. placebo by testing more than 11,000 men in different age groups in 48 different randomized trials (3). Most of the trials went on for three months.

The study’s starting dosage was set at 50 mg and administered an hour before the sexual activity. The dosage was adjusted by 25 or 100 mg depending on safety and efficacy. Subjects with heart problems and those taking nitrate therapy were not given additional dosage.

After the test periods, results were gathered, and they showed the significant effectiveness of sildenafil compared to the placebo. The subjects showed improvements in different areas, such as intercourse satisfaction, orgasmic function, and sexual desire.

It was also noted that Sildenafil was most effective for men aged 75 and older. The most common adverse effects were flushing and headache.

Sildenafil Dosage

Sildenafil citrate, the sex drug’s most common form, is often administered in 50 mg dosages. It’s recommended to be taken an hour before the sexual activity, although it can be anywhere from 30 minutes to 4 hours.

But some patients take double the recommended dosage for fear of losing an erection in the middle of sexual intercourse. A study made on the effects of taking 100 mg of sildenafil citrate showed that, like the 50 mg dosage, it also resulted in increased sexual satisfaction and, at the same time, reduced anxious thoughts.

Sildenafil Side Effects

Sildenafil’s common side effects include (4):

• Flushing
• Headache
• Abnormal color vision (blue tinge)
• Upset stomach
• Back pain
• Runny or stuffy nose
• Nausea
• Muscle pain
• Rash
• Dizziness

In addition to the above, there have been rare cases of stroke, heart attack, irregular heartbeat, and even death. These adverse side effects mostly happen to patients with underlying heart problems.

Tadalafil (Cialis)

Tadalafil is also a PDE5 inhibitor, just like sildenafil. Its development was initiated in 1993 by ICOS Corporation, a pharmacologic research company based in Washington. Tadalafil’s original medical name was IC351.

ICOS began clinical trials with IC351 on erectile dysfunction patients in 1995. IC351’s name was officially changed to tadalafil in 2000, and the company started marketing under the Cialis trade name.

How Tadalafil Works

Tadalafil’s action is pretty much the same when it comes to PDE5 inhibition. But these sex drugs are very different structurally, pharmacologically, and clinically.

Tadalafil can be selective for PDE5 by 9000 times more compared to other PDE families, except PDE11 (5). PDE11 can be found in the prostate and testes. The inhibition of PDE11 has not been proven to cause any health issues, particularly in testicular function or spermatogenesis.

This selectiveness level of tadalafil makes it more potent in inhibiting PDE5, which means it’s more effective even in smaller doses. It also has one major advantage over both sildenafil and vardenafil. It doesn’t cause the ‘blue tinge’ vision side effect common in patients taking the two other drugs for sex.

Sildenafil inhibits the enzyme PDE6, which is responsible for retinal phototransduction, but not tadalafil. This inhibition of PDE6 is what causes the ‘blue tinge’ vision because the blue-green color discrimination is impaired when this enzyme is suppressed.

How Effective Is Tadalafil?

Although it’s more potent than sildenafil or vardenafil gram-for-gram, the fact that it is chemically different from either PDE5 inhibitor may mean it might not be more effective. Like sildenafil, tadalafil has been the subject of many medical studies gauging its efficacy and safety (6).

In one study, more than 2000 men with an average of 56 years who were all suffering from varying levels of erectile dysfunction were given either tadalafil or a placebo random. 10 or 20 mg were given in on-demand, fixed doses in 11 randomized trials that lasted 12 weeks.

Tadalafil showed significantly better results compared with the placebo. 58 to 68% had successful intercourse attempts, and 71 to 84% showed improved erections.

The study also showed that tadalafil was still effective 36 hours after it was taken. The effectiveness of the drug was also not affected by any disease regardless of causes and severity or the subject’s age.

Tadalafil Dosage

Because of tadalafil’s potency, the recommended dosage for this sex drug is only 10 mg to be taken before sexual activity. Recommended maintenance is 5 to 20 mg daily, depending on individual tolerability and efficacy (7).

The lower dosage is also due to tadalafil’s bioavailability after the first-pass metabolism, which is at 80% compared to sildenafil’s 40% and vardenafil’s 15%. However, it is absorbed slowest compared to other PDE5 inhibitors. Tadalafil takes an average of 2 hours after administration for full concentration, while it takes only an average of 50 minutes for sildenafil and vardenafil.

This slower absorption, however, also means that tadalafil remains inside the patient’s system longer than other PDE5 inhibitors. Tadalafil’s effects can be felt for as long as 36 hours compared to 8 hours for sildenafil or vardenafil.

Tadalafil Side Effects

Tadalafil’s common side effects include (8):

• Upset stomach
• Headache
• Muscle pain
• Back pain
• Flushing
• Stuffy nose
• Dizziness

In very rare cases, tadalafil may cause sudden decreased vision and even permanent blindness in both eyes or just one. This medical issue is more likely to happen to patients with conditions like diabetes, heart disease, other eye problems, high cholesterol, and high blood pressure or those over 50 years old.

Severe allergic reactions to tadalafil are very rare.

Vardenafil (Levitra)

Vardenafil is the last of the three PDE5 inhibitors on this list, and like Sildenafil and tadalafil, this sex drug also works similarly – inhibits PDE5 to allow vasodilation. Its chemical structure is closer to Sildenafil than to tadalafil.

Vardenafil was first marketed by a partnership between Schering-Plough, GlaxoSmithKline, and Bayer Pharmaceuticals in 2005 under the name Levitra. Currently, it’s also marketed under the names Vivanza and Staxyn.

How Vardenafil Works

The method of action of vardenafil is similar to that of sildenafil or tadalafil (9). Like tadalafil, this drug also doesn’t inhibit the enzyme PDE6, so the occurrence of the “blue tinge” vision is very rare.

Like sildenafil, the effects of vardenafil can be felt in 15 to 30 minutes. It also lasts in the system for 8 hours.

Also, vardenafil is the most potent and PDE5-specific of all three inhibitors.

How Effective Is Vardenafil?

So how potent is vardenafil? (10) A study was made on an international scale with more than 70,000 subjects aged more than or equal to 18 years, all suffering from mild to severe erectile dysfunction.

Subjects attended a physician visit and followed up with two more consultations. Data was acquired via patient diaries and physician interviews. Patient data were gathered from 47 countries in different parts of the world, including Latin America, Asia Pacific, Europe, and the rest of the world. The information included the severity of erectile dysfunction, body mass index or BMI, and existing medical conditions such as cardiovascular diseases, lipid metabolism disorder, diabetes, and hypertension.

The result was overwhelming, with more than 90% of the subjects saying they were “satisfied” or “very satisfied” with the effects of vardenafil. The drug was also highly tolerated, and adverse incidence was low. This makes vardenafil seemingly the best drug for ED.

Vardenafil Dosage

The initial dosage of vardenafil is recommended at 10 mg once daily or as needed (11). The drug has to be taken one hour before the sexual activity. This dosage can be increased by 20 mg or reduced to 5 mg depending on tolerability and efficacy, with a maximum of 20 mg daily.

The recommended dosage is 5 mg per day for patients undergoing stable alpha-blocker therapy.

Vardenafil Side Effects

Vardenafil’s common side effects include:

• Flushing
• Headache
• Dizziness
• Stuffy or runny nose
• Back pain
• Heartburn
• Nausea

In very rare cases, vardenafil may also cause sudden vision or hearing loss, chest pain, and irregular heartbeat. This is common in patients with underlying cardiovascular conditions.

Best Drugs for ED FAQ

Which One Is the Best Drug for ED?

Each one of the available sex drugs (Sildenafil, Tadalafil, Vardenafil) has its own advantages over the others.

Sildenafil has been around for a long time now, which means it may be the cheapest and most available option.

Tadalafil might be potent, but it takes an average of 2 hours for the drug to take full effect. The upside to the slow absorption rate is that the drug remains in the system for up to 36 hours, and so are the erection benefits.

Vardenafil is considered the most expensive of the lot but is also the most potent and safest as far as the studies are concerned.

These three are the best drugs for ED available on the market, but the choice depends on the budget and need. As with other medications, it’s best to consult the doctor before taking a drug to treat erectile dysfunction.