What to Know About Erectile Dysfunction Drugs

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In This Article

Erectile dysfunction drugs, known as PDE5 inhibitors, have enhanced the sexual lives of many men since their introduction in 1998. Roughly half of all men between the ages of 40 and 70 have erectile dysfunction (ED) to some degree. Prior to the release of Viagra (sildenafil), men with ED had limited treatment options. Today, around 70% of men who take PDE5 inhibitors can maintain an erection long enough to engage in sexual intercourse.

Despite the widespread popularity of PDE5 inhibitors, there are limitations and risks associated with their use. Though the drugs all work similarly, there are differences that may make one more suitable than others for a particular person.

Uses

PDE5 inhibitors are used to overcome erectile dysfunction, also referred to as impotence. They can help men achieve and sustain an erection, especially if the underlying cause is physiological. They may even help if the cause is psychological by providing a placebo effect.

All PDE inhibitors work by blocking an enzyme known as phosphodiesterase type 5 (PDE5) in the corpus cavernosum (the spongy interior of the penis where most of the blood vessels are located). By inhibiting PDE5, nitric oxide molecules are better able to bind to muscles in the corpus cavernosum, allowing them to relax and increase the flow of blood into the penis.

There are five PDE5 inhibitors approved for the treatment of ED by the U.S. Food and Drug Administration (FDA):

  • Viagra (sildenafil) tablets, approved 1998
  • Cialis (tadalafil) tablets, approved 2003
  • Levitra (vardenafil) tablets, approved 2003
  • Staxyn (vardenafil) dissolvable tablets, approved 2010
  • Stendra (avanafil) tablets, approved 2012

In addition to the brand name versions, there are generic versions of sildenafil, tadalafil, vardenafil tablets, and vardenafil dissolvable tablets available at generally lower prices.

Some PDE5 inhibitors have other approved uses. Sildenafil, for example, is commonly prescribed to treat pulmonary hypertension (high blood pressure in the lungs), in which case it is sold under the brand name Revatio. Tadalafil is also used for this purpose as Adcirca, as well as for treating benign prostatic hyperplasia (enlarged prostate).

Before Taking

PDE5 inhibitors do not work for everyone—in particular men who have sustained damage to the blood vessels or nerves of the penis as a result of prostate surgery, cardiovascular disease, or diabetes.

As a general rule, doctors should pinpoint the cause of ED before prescribing any drug. Doing so can better frame expectations and avoid adding to the stress and self-image problems that men with ED commonly face.

Precautions and Contraindications

PDE5 inhibitors work by increasing the availability of nitric oxide in the bloodstream. For this reason, PDE5 inhibitors should never be used with any organic nitrate that has the same effect. Doing so can lead to a potentially life-threatening drop in blood pressure known as a hypotensive crisis.

Among some of the nitrate drugs of concern are:

  • Nitroglycerine
  • Amyl nitrate
  • Alkyl nitrites ("poppers")
  • Isosorbide mononitrate
  • Isosorbide dinitrate
  • Sodium nitroprusside

Men with severe liver or kidney disease also may need to avoid PDE5 inhibitors:

  • Cialis, Levitra, Staxyn (the dissolvable form of Levitra), and Stendra should never be taken by anyone with severe liver impairment (classified as Child-Pugh Class C).
  • Levitra, Stanxyn, and Stendra are contraindicated for men on kidney dialysis.

Viagra can be used both in these populations, but at the lowest dose—25 milligrams (mg).

Dosage

The dosage of ED drugs varies by the type selected. Each of the drugs has different strengths as well as different onsets and durations of action.

Cialis is the only PDE5 inhibitor that can be taken as needed or in low, daily doses to achieve an erection "on demand."

Dosing Guidelines
Drug Strength in millgrams (mg) Dose Duration of action
Viagra 25 mg, 50 mg, 100 mg (50 mg is suitable for most men) 1 hour before sex 4 to 5 hours
Cialis 2.5 mg, 5 mg, 10 mg, 20 mg (10 mg is suitable for most men) 30 to 45 minutes before sex 24 to 36 hours
Cialis (daily) 2.5 mg, 5 mg (2.5 mg is suitable for most men) Once daily, taken at the same time daily Continuous
Levitra 5 mg, 10 mg, 20 mg (10 mg is suitable for most men) 1 hour before sex 4 to 5 hours
Staxyn 10 mg 1 hour before sex 4 to 5 hours
Stendra 50 mg, 100 mg, 200 mg (100 mg is suitable for most men) 30 minutes before sex 6 to 12 hours

As a general rule, the lowest effective dose should always be used. If you are unable to achieve or sustain an erection at the prescribed dose, speak with your doctor to see if an increase in dose is safe and reasonable.

Modifications

The dosages of certain PDE5 inhibitors may need to be adjusted for some individuals. These include:

  • Viagra: Decrease to 25 mg if taking alpha-blockers and increase only under the direction of a physician.
  • Cialis: Limit the daily intake to 10 mg if you have mild liver impairment and to 5 mg if on kidney dialysis.
  • Cialis (daily): Limit to 5 mg per day if you have benign prostatic hyperplasia.
  • Levitra and Staxyn: Decrease to 5 mg for men over 65 and increase only under the direction of a physician. Decrease to 5 mg daily if you have mild liver impairment and never exceed 10 mg daily.
  • Stendra: Decrease to 50 mg if taking alpha-blockers and increase only under the direction of a physician

How to Take and Store

All PDE5 inhibitors are taken by mouth with or without food. Food does not impede the effectiveness of the drug or the onset or duration of action.

For men who dislike or are unable to swallow pills, Staxyn tablets offer an attractive alternative. The pills have a sweet, peppermint flavor and dissolve quickly when placed on the tongue.

PDE5 inhibitors are stored safely at or around 77°F (25°C). Short-term exposure to temperatures of 59° F to 86°F (15° C to 30°C) won't harm the drug, but never store them in your glove compartment or in direct sunlight. It is best to store the drugs in their original containers or blister-packs until use. Never use expired drugs.

Never take more than the maximum recommended dose or take two different PDE5 inhibitors to "boost" their effects. This will only serve to increase the risk and/or severity of side effects.

Side Effects

All PDE5 inhibitors are generally well tolerated. Because they have similar mechanisms of actions, they have many of the same side effects. Most of the side effects are mild to manageable, although some require the termination of treatment and immediate medical attention.

Common

Common side effects of PDE5 inhibitors include:

  • Headache
  • Dizziness
  • Flushing
  • Upset stomach
  • Nasal congestion
  • Muscle aches
  • Nausea (mainly with Viagra and Levitra)
  • Back pain (mainly with Cialis, Staxyn, and Stendra)
  • Bluish visual disturbances (mainly with Viagra)

The incidence and severity of side effects tend to increase with the dose. If taken in excess, PDE5 inhibitors can cause a rapid drop in blood pressure and syncope (fainting). For this reason the lowest effective dose should always be used.

Severe

There are several uncommon side effects that are especially severe and may require emergency intervention. Among them:

  • Priapism (persistent and painful erections) are a common concern with all ED drugs. If an erection lasts longer than four hours, seek urgent care.
  • Sudden vision loss may be related to a condition known as non-arteritic anterior ischemic optic neuropathy ("eye stroke"), a condition that has been known to affect a small number or ED drug users. Emergency care is necessary in the case of a sudden loss of vision in one or both eyes.
  • Sudden hearing loss has been noted as a possible side effect of PDE5 inhibitors. Seek medical attention if there is a sudden decrease or loss in hearing in one or both ears.

The cause for the hearing loss in users of PDE5 inhibitors is as of yet unknown, although Viagra appears to pose the greatest risk.

Warnings and Interactions

PDE5 inhibitors are primarily excreted in feces and, to a lesser degree, in urine. Because of their possible impact of the liver and kidneys, efforts should be made to evaluate their hepatic (liver) function and renal (kidney) function prior to the start of treatment. This is especially true for people diagnosed with or at risk of liver disease or kidney disease.

Due to the risk of vision loss, men with hereditary eye diseases (such as color blindness, corneal dystrophy, or retinoblastoma) and those with a prior history of eye stroke should not take PDE5 inhibitors.

Drug-Drug Interactions

Even beyond contraindicated organic nitrates, there is an extensive list of medications and substances that may interact with PDE5 inhibitors.

Among these, alpha-blockers and antihypertensive drugs need to be used with extreme caution due to the risk of severe hypotension. If the doses are not separated by 24 hours (or 48 hours with Cialis ), a severe hypotensive event may occur. Guanylate cyclase stimulators (nitric oxide receptors) pose similar risks.

Even alcohol can cause a transient drop in blood pressure if taken with a PDE5 inhibitor. This is especially true with Cialis (in part because the drug remains in the system for far longer than the other ED drugs).

Drugs classified as cytochrome 450 (CYP450) inhibitors pose different concerns. CYP450 is an enzyme the body uses to metabolize many drugs. Certain CYP450 inhibitors can increase the concentration of PDE5 inhibitors in the blood by as much as 11-fold (and, with it, risk of side effects), while others decrease concentrations (and, with it, the efficacy of the drug). Many antibiotics and HIV drugs are strong CYP inhibitors.

Alpha-blockers of concern include:

  • Antisedan (atipamezole)
  • Cardura (doxazosin)
  • Dibenzyline (phenoxybenzamine)
  • Flomax (tamsulosin)
  • Hytrin (terazosin)
  • Idazoxan
  • Minipress (prazosin)
  • Norvasc (amlodipine)
  • Phentolamine
  • Rapaflo (silodosin)
  • Remeron (mirtazapine)
  • Tolazoline
  • Trazadone
  • Uroxatral (alfuzosin)
  • Yohimbine

Antihypertensive drug classes of concern include:

  • Thiazide diuretics
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Calcium blockers
  • Beta-blockers
  • Angiotensin receptor blockers (ARBs)

CYP450 inhibitors of concern include:

  • Clarithromycin
  • Crixivan (indinavir)
  • Diflucan (fluconazole)
  • Diltiazem
  • Emend (aprepitant)
  • Erythromycin
  • Grapefruit juice (mainly with Cialis)
  • Invirase (saquinavir)
  • Lexiva (fosamprenavir)
  • Nizoral (ketoconazole)
  • Reyataz (atazanavir)
  • Rifampin (mainly with Cialis)
  • Ritonavir
  • Sporanox (itraconazole)
  • Telithromycin
  • Verapamil

A Word From Verywell

There is no one PDE5 inhibitor that is inherently "better" than the others. Often, a doctor will prescribe Viagra to first-time users, in part because of name recognition and cost. But, the simple truth is that others may work just as well, if not better, and offer fewer side effects. You often won't know until you try several out.

When discussing with your doctor which drug to use, be sure they know about any liver or kidney problems you have, what drugs you are taking (both prescription or over-the-counter), and if you've been diagnosed with an eye or cardiovascular disease.

The more a healthcare provider knows about your health, the more likely they will be to find the drug and dose that is just right for you.

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