Erectile dysfunction drugs, known as PDE5 inhibitors, are prescribed for treating erectile dysfunction (ED). Roughly half of all males between the ages of 40 and 70 have some degree of ED. Around 70% of people 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 some more suitable for you than others.
PDE5 inhibitors are used to overcome erectile dysfunction, also referred to as impotence. They can help males 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 by the U.S. Food and Drug Administration (FDA) for treatment of ED:
- 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, The generic versions are generally available at 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 (BPH, enlarged prostate).
PDE5 inhibitors do not work for everyone. For example, it does not work very effectively for people who have sustained damage to the blood vessels or nerves of the penis as a result of prostate surgery, cardiovascular disease, or diabetes. While PDE5 inhibitors may work at higher doses in these circumstances, other options, such as intraurethral pellet or injectable medication, may be more effective.
As a general rule, your healthcare provider will pinpoint the cause of ED before prescribing any drug. Doing so can better frame expectations.
In addition, a cardiovascular workup should be done since erectile dysfunction can be the first sign of heart issues.
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 medication that has the same effect. The combination can lead to a potentially life-threatening drop in blood pressure known as a hypotensive crisis.
Nitrate drugs include:
- Amyl nitrate
- Alkyl nitrites (“poppers”)
- Isosorbide mononitrate
- Isosorbide dinitrate
- Sodium nitroprusside
People who have 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 if you have a severe liver impairment (classified as Child-Pugh Class C).
- Levitra, Stanxyn, and Stendra are contraindicated if you are on kidney dialysis.
Viagra can be used both in these populations, at the lowest dose of 25 milligrams (mg).
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. Because they can cause side effects, the lowest effective dose is usually used.
Cialis is the only PDE5 inhibitor that can be taken as needed or in low, daily doses to achieve an erection “on demand.”
|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 healthcare provider to see if an increase in dose is safe and reasonable.
The dosages of certain PDE5 inhibitors may need to be adjusted for some people. In general, any PDE5 inhibitor is contraindicated with alpha-blockers (used for urinary issues with BPH) at higher doses.
Adjustments your healthcare provider might make for you include:
- Viagra: Decrease to 25 mg if taking alpha-blockers, and increase only under the direction of a practitioner.
- Cialis: Limit the daily intake to 10 mg for mild liver impairment, and 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 males over age 65, and increase only under the direction of a healthcare provider. Decrease to 5 mg daily, never to exceed 10 mg daily if you have mild liver impairment.
- Stendra: Decrease to 50 mg if taking alpha-blockers, and increase only under the direction of a practitioner.
How to Take and Store
Viagra is taken on an empty stomach. Others 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 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 increase the risk and/or severity of side effects.
All PDE5 inhibitors are generally well tolerated. Because they have similar mechanisms of action, they have many of the same side effects. Most of the side effects are mild to manageable, although some require terminating treatment and immediate medical attention.
Common side effects of PDE5 inhibitors include:
- 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).
There are several uncommon side effects that are especially severe and may require emergency intervention.
- 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 of people who use ED drugs. 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 of hearing in one or both ears.
The cause for the hearing loss in users of PDE5 inhibitors is unknown, and 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 on the liver and kidneys, hepatic (liver) function and renal (kidney) function may be evaluated prior to the start of treatment, especially if you are at risk of liver disease or kidney disease.
Due to the risk of vision loss, people with a family history of 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.
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)
- Minipress (prazosin)
- Norvasc (amlodipine)
- Rapaflo (silodosin)
- Remeron (mirtazapine)
- Uroxatral (alfuzosin)
Antihypertensive drug classes of concern include:
- Thiazide diuretics
- Angiotensin-converting enzyme (ACE) inhibitors
- Calcium blockers
- Angiotensin receptor blockers (ARBs)
CYP450 inhibitors of concern include:
- Crixivan (indinavir)
- Diflucan (fluconazole)
- Emend (aprepitant)
- Grapefruit juice (mainly with Cialis)
- Invirase (saquinavir)
- Lexiva (fosamprenavir)
- Nizoral (ketoconazole)
- Reyataz (atazanavir)
- Rifampin (mainly with Cialis)
- Sporanox (itraconazole)
A Word From Get Meds Info
There is no one PDE5 inhibitor that is inherently better than the others. Often, a practitioner 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 healthcare provider 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.
Gareri P, Castagna A, Francomano D, Cerminara G, De Fazio P. Erectile dysfunction in the elderly: an old widespread issue with novel treatment perspectives. Int J Endocrinol. 2014;2014:878670. doi:10.1155/2014/878670
U.S. Food and Drug Administration. Viagra (sildenafil citrate) tablets, for oral use. Revised March 2014.
U.S. Food and Drug Administration. Cialis (tadalafil) tablets, for oral use. Revised October 2011.
U.S. Food and Drug Administration. Levitra (vardenafil hydrochloride), for oral use. Revised August 2007.
U.S. Food and Drug Administration. Staxyn (vardenafil hydrochloride) orally disintegrating tablets. Revised June 2010.
U.S. Food and Drug Administration. Stendra (avanafil) tablets, for oral use. Revised April 2012.
Parsons JK, Dahm P, Köhler TS et al: Surgical management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA Guideline amendment 2020. J Urol 2020; 204: 799
Burnett AL, Nehra A, Breau RH et al: Erectile dysfunction: AUA guideline. J Urol 2018; 200: 633
Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) inhibitors In the management of erectile dysfunction. P T. 2013;38(7):407-19.
Liu B, Zhu L, Zhong J, Zeng G, Deng T. The association between phosphodiesterase type 5 inhibitor use and risk of non-arteritic anterior ischemic optic neuropathy: A systematic review and meta-analysis. Sex Med. 2018;6(3):185-92. doi:10.1016/j.esxm.2018.03.001
Barreto MA, Bahmad F. Phosphodiesterase type 5 inhibitors and sudden sensorineural hearing loss. Braz J Otorhinolaryngol. 2013;79(6):727-33. doi:10.5935/1808-8694.20130133
Tzoumas N, Farrah TE, Dhaun N, Webb DJ. Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease. Br J Pharmacol. 2019 Nov[Online ahead of print]. doi:10.1111/bph.14920
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