Drug Profile

Vardenafil (LEVITRA, STAXYN) and tadalafil (CIALIS) join sildenafil (VIAGRA) as the second and third oral drugs, respectively, approved by the Food and Drug Administration (FDA) to treat erectile dysfunction (ED). Tadalafil was approved for daily use in 2008.[1] All three drugs work the same way: They inhibit an enzyme known as phosphodiesterase type 5 (PDE-5). Inhibition of this enzyme causes relaxation of smooth muscles and increased blood flow to the penis.

There are legitimate reasons for using ED drugs when other causes of ED have been ruled out. However, when these drugs are used for recreational purposes by men who do not need them, the risks of the drugs always outweigh the benefits.

None of these drugs is approved for use in women. They also have not been studied, and therefore should not be used, in people under 18 years of age.

Adverse effects

Heart problems

Vardenafil is unique among these three drugs in that there are precautions in the drug’s product label about a condition known as QTc interval prolongation.[2] QTc interval prolongation is an abnormality in the heart’s electrical conduction that shows up as an abnormal electrocardiogram. It can lead to fatal heart rhythm disturbances such as torsades de pointes.

Visual disturbances

There have been a number of cases of vision loss reported with the use of sildenafil and other ED drugs since 1998.

The Medical Letter on Drugs and Therapeutics (The Medical Letter) reported that in 2005 the FDA was investigating multiple reports of vision loss in men who took sildenafil. Non-arteritic ischemic optic neuropathy (NAION) — a condition in which blood flow is blocked to the optic nerve, resulting in blurred vision or loss in visual field — reportedly has occurred in some patients within hours after ingestion of sildenafil.

There have also been reports of NAION occurring in a few men taking tadalafil[3] or vardenafil.

In a study based on reports of blindness submitted to the FDA’s adverse-event reporting system, Public Citizen compared the rate of reports of NAION per million prescriptions filled in those using ED drugs with the rate in those using atorvastatin (LIPITOR) — both groups having presumed increased cardiovascular risk. For sildenafil, there were 18 times more reports of NAION per million prescriptions than for atorvastatin and, for tadalafil, 25 times more reports. Thus, it is very likely that the drugs can cause blindness in some people.

Patients who experience any visual problems while using these drugs should stop using the drugs and notify their doctors immediately.[4] (Read more in the January 2006 Worst Pills, Best Pills News.)

A study published in JAMA Ophthalmology in 2022 found that regular use of phosphodiesterase type 5 inhibitor drugs was associated with an increased risk of serious retinal detachment, retinal vascular occlusion and ischemic optic neuropathy.[5]

Seizures

In October 2006, the British Medical Journal reported a case of epileptic seizures following a high dose of oral vardenafil. After this case was submitted, a second patient experienced a partial epileptic seizure after taking oral vardenafil.[6]

Hearing loss

The FDA has received reports of cases of a sudden decrease in or loss of hearing following the use of these drugs. In some cases, the sudden hearing loss was accompanied by ringing in the ears and dizziness.[7] In most of the reports received by the FDA, those who experienced a sudden onset of hearing loss had it occur within 12 hours of using an ED drug.

A study published in May 2010 found that men who had reported hearing impairment were more than twice as likely to have used one of the three FDA-approved ED drugs. Read more in the December 2010 Worst Pills, Best Pills News.

Studies show ...

A study evaluating the use of sildenafil in men with combat-related post-traumatic stress disorder found that sildenafil did not provide an advantage over a placebo in relieving the symptoms of ED. The study also reported that the incidence of adverse effects was greater in patients using sildenafil than in patients taking a placebo.[8]

A study published in JAMA Internal Medicine in 2014 showed that patients using sildenafil may have an increased risk of melanoma. The authors of the study stated that their results show a need for further investigation.[9]

Another study published in the same journal in 2015 showed that sildenafil, vardenafil or tadalafil use was associated with a slightly increased risk of malignant melanoma.[10]

Tadalafil for benign prostatic hyperplasia

In November 2011, The Medical Letter reviewed the use of tadalafil (approved by the FDA for signs and symptoms of benign prostatic hyperplasia in men with or without ED). After reviewing the trial data, the authors of the article stated the following:

The PDE-5 inhibitor tadalafil (Cialis) might be helpful in relieving some urinary symptoms associated with benign prostatic hyperplasia. However, the mechanism of action is not clear, improvements in urinary flow rates have been limited and participants in double-blind trials may have known whether they were taking the active drug or a placebo. There is no evidence that tadalafil is as effective for this indication as an alpha1 blocker, which costs much less.[11]

What users should know

Alpha-blocker contraindications

In general, vardenafil, tadalafil and sildenafil should not be used in combination with the alpha-blocker family of drugs, which are used to treat high blood pressure and enlarged prostate. These drugs include alfuzosin (UROXATRAL), doxazosin (CARDURA), prazosin (MINIPRESS), tamsulosin (FLOMAX) and terazosin (HYTRIN). Using alpha-blockers with any of the three ED drugs can cause dangerously low blood pressure that could lead to a stroke or heart attack. (Read more about ED drugs and alpha-blockers in the June 2009 Worst Pills, Best Pills News.)

The product label for ED drugs is less cautious than Public Citizen thinks is appropriate. The label for tadalafil says not to take the drug with alpha-blockers other than tamsulosin,[12] and the label for sildenafil says that the drug should not be taken in a dose greater than 25 milligrams at the same time (within four hours) as a dose of any alpha-blocker.[13] We advise consumers to be more cautious than this and avoid ED drugs if they are taking an alpha-blocker. (Click here to read about other interactions between drugs for ED and other medications.)

Heart warnings

Men with congenital QT prolongation and those taking drugs for heart rhythm disturbances  — such as amiodarone (CORDARONE), procainamide (PROCANBID), quinidine (DURAQUIN, QUINAGLUTE DURA-TABS, QUINIDEX) and sotalol (BETAPACE) — should not take vardenafil.

Caution with certain conditions

People with any of the following medical conditions should be cautious when using vardenafil, tadalafil and sildenafil (or should not use the drugs at all) because of the potential for adverse effects:

• Heart problems such as angina, heart failure, irregular heartbeats or a heart attack (Ask your doctor if it is safe for you to have sexual activity.)
• Low blood pressure or high blood pressure that is not controlled
• Stroke
• Liver problems
• Kidney problems or dialysis
• Retinitis pigmentosa (a rare genetic [hereditary] eye disease) 
• Stomach ulcers
• Bleeding problems, deformed penis shape or Peyronie’s disease
• Erection that has lasted more than four hours
• Blood cell problems such as sickle-cell anemia, multiple myeloma or leukemia

Regulatory actions surrounding ED drugs

2005: In July, the FDA updated the labeling for tadalafil, vardenafil and sildenafil to reflect a small number of post-marketing reports of sudden vision loss, attributed to NAION. The label advises patients to stop taking these medicines and call a doctor or health care provider right away if they experience sudden decreased vision or vision loss in one or both eyes.[14]

On Oct. 20, Public Citizen filed a petition with the FDA to add black-box warnings to the product labels for the ED drugs sildenafil, tadalafil and vardenafil. The warnings would alert prescribers to the possibility of irreversible vision loss with the use of these drugs. The petition also urged the FDA to require that a Medication Guide be distributed by pharmacists with each new and refill prescription for these drugs to warn consumers about the possibility of irreversible blindness.[4]

2007: In October, the FDA revised the labeling of sildenafil, tadalafil and vardenafil to include the potential risk of sudden hearing loss. This revision came after the FDA received reports of cases of a sudden decrease in or loss of hearing following the use of these drugs. In these cases, sudden hearing loss was sometimes accompanied by ringing in the ears and dizziness.[7]

2008: The FDA reported 29 cases of a sudden decrease in hearing or hearing loss associated with the use of sildenafil, tadalafil and vardenafil. The agency also admitted that sudden hearing loss had been reported in a few patients in clinical trials of these drugs, making a causal relationship more likely. The drug label was revised to include this information. Health care professionals should advise their patients to seek medical attention if they experience any sudden loss in hearing.[15]

2011: In a Nov. 22 letter, the FDA denied Public Citizen’s 2005 petition to add to the product labels of ED drugs black-box warnings alerting patients and health care professionals of the risk of irreversible blindness.