Potentially Dangerous Interactions Between Erectile Dysfunction Drugs and Other Medications

Patients taking any of the four oral prescription drugs approved by the Food and Drug Administration (FDA) for treating erectile dysfunction in men — avanafil (STENDRA),[1] sildenafil (VIAGRA),[2] tadalafil (CIALIS)[3] and vardenafil (LEVITRA, STAXYN)[4] — should be aware that all four drugs have clinically important interactions with many other prescription medications.

These erectile dysfunction drugs belong to a class of medications known as phosphodiesterase-5 (PDE5) inhibitors. They cause relaxation of muscles in the walls of blood vessels, resulting in dilation of the blood vessels (vasodilation) and increased blood flow to the penis.

Public Citizen’s Health Research Group has designated all four drugs as Limited Use.

Interactions with vasodilators[5],[6],[7],[8]

Because PDE5 inhibitors can cause mild vasodilation in blood vessels throughout the body, not just in the penis, these drugs can cause a decrease in blood pressure. Therefore, taking these drugs concomitantly with other vasodilator medications (see Table 1 below for examples) may result in a dangerous drop in blood pressure.

Table 1: Examples of Drugs That May Cause Dangerously Low Blood Pressure When Taken Concomitantly with Erectile Dysfunction Drugs

†Combination drug that contains one or more other active ingredients
*Designated as Do Not Use for all indications
**Designated as Do Not Use for hypertension, Limited Use for BPH
***Designated as Limited Use for BPH

Most importantly, the product labeling for all PDE5 inhibitors warns that patients taking any of the nitrate drugs, such as isosorbide dinitrate (BIDIL, DILATRATE-SR, ISORDIL) — which are used to dilate the blood vessels in the heart for patients with coronary artery disease — should never take these erectile dysfunction drugs. Doing so could precipitate a severe drop in blood pressure, potentially leading to a heart attack, stroke or loss of consciousness.

PDE5 inhibitors also can enhance the blood pressure-lowering effects of the six alpha blockers, which include doxazosin (CARDURA) and alfuzosin (UROXATRAL). Three alpha blockers are approved by the FDA for treatment of hypertension (high blood pressure), and five are approved for treatment of benign prostatic hypertrophy (benign enlargement of the prostate gland).[9] Use of a PDE5 inhibitor concomitantly with an alpha blocker may result in symptoms of low blood pressure, such as fainting, lightheadedness or dizziness upon sitting up or standing. For patients already using an alpha blocker, a PDE5 inhibitor should only be initiated at the lowest recommended starting dose and only if the patient has been clinically stable on alpha blocker treatment.

PDE5 inhibitors also may augment the effects of other hypertension medications, leading to low blood pressure.

Drugs that increase PDE5 inhibitor levels[10],[11],[12],[13],[14]

Like many drugs, PDE5 inhibitors are metabolized (broken down or chemically modified) by substances in the liver called enzymes. One important liver enzyme, known as CYP3A4, breaks down these drugs.

Table 2 below lists examples of drugs that are inhibitors of CYP3A4. When taken concomitantly with any of the PDE5 inhibitors, these CYP3A4-inhibiting drugs, because they decrease PDE5 inhibitor breakdown, may increase PDE5 inhibitor levels in the blood to toxic levels. The list includes antibiotics, antifungal drugs, antiviral drugs and the antidepressant nefazodone (generic only).

Signs and symptoms of PDE5 toxicity include headache, flushing, low blood pressure, fainting and priapism (a prolonged, painful erection that requires immediate medical attention if it lasts for more than four hours because it can result in penile injury).

Table 2: Examples of Drugs That Inhibit CYP3A4 and May Increase the Risk of Erectile Dysfunction Drug Toxicity

†Combination drug that contains one or more other active ingredients
*Designated as Limited Use
**Designated as Do Not Use
***Designated as Do Not Use except for serious fungal infections

What You Can Do

If you are taking any nitrate drug, you should not use a PDE5 inhibitor. If you are taking any alpha blocker or other drugs for hypertension, you should be alert for symptoms of low blood pressure when initiating treatment with any erectile dysfunction drug. If you are taking any drug listed in Table 2 and are considering treatment with a PDE5 inhibitor, speak to your doctor about starting on the lowest available dose.

These types of potentially dangerous drug interactions reinforce the importance of bringing all your drugs with you each time you visit any doctor. Because many drugs, including others not listed in this article, affect the activity of the enzyme that metabolizes PDE5 inhibitors or interact with them in other ways, you should talk to your doctor about whether any of your drugs could interact with your erectile dysfunction drug.
 

References

[1] Metuchen Pharmaceuticals. Label: avanafil (STENDRA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202276s018lbl.pdf. Accessed May 7, 2019.

[2] Pfizer Labs. Label: sildenafil (VIAGRA). December 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020895s048lbl.pdf. Accessed May 7, 2019.

[3] Eli Lilly and Company. Label: tadalafil (CIALIS). February 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf. Accessed May 7, 2019.

[4] Bayer HealthCare Pharmaceuticals. Label: vardenafil (LEVITRA). November 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a01def95-c0ef-43b9-bd9e-5565b2385ad3&type=display. Accessed May 7, 2019.

[5] Metuchen Pharmaceuticals. Label: avanafil (STENDRA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202276s018lbl.pdf. Accessed May 7, 2019.

[6] Pfizer Labs. Label: sildenafil (VIAGRA). December 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020895s048lbl.pdf. Accessed May 7, 2019.

[7] Eli Lilly and Company. Label: tadalafil (CIALIS). February 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf. Accessed May 7, 2019.

[8] Bayer HealthCare Pharmaceuticals. Label: vardenafil (LEVITRA). November 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a01def95-c0ef-43b9-bd9e-5565b2385ad3&type=display. Accessed May 7, 2019.

[9] Prostate drugs increase risks of falls, fracture. Worst Pills, Best Pills News. June 2016. /newsletters/view/1037. Accessed May 7, 2019.

[10] Metuchen Pharmaceuticals. Label: avanafil (STENDRA). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202276s018lbl.pdf . Accessed May 7, 2019.

[11] Pfizer Labs. Label: sildenafil (VIAGRA). December 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020895s048lbl.pdf. Accessed May 7, 2019.

[12] Eli Lilly and Company. Label: tadalafil (CIALIS). February 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf. Accessed May 7, 2019.

[13] Bayer HealthCare Pharmaceuticals. Label: vardenafil (LEVITRA). November 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a01def95-c0ef-43b9-bd9e-5565b2385ad3&type=display. Accessed May 7, 2019.

[14] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Accessed May 7, 2019.