Medications used for erectile dysfunction (ED) are highly effective, yet “drug interactions” can sometimes trigger unexpected side effects or serious health risks. In particular, combining ED medications with drugs for angina or high blood pressure may cause excessive drops in blood pressure. To ensure safe usage, it is essential to inform your doctor accurately about your current prescriptions and to understand the risks of drug interactions. This article provides a professional explanation of the characteristics of different ED drugs, medications that must be avoided in combination, and key points for safe administration.
1. Basics of ED Medications and Their Mechanism of Action
Most ED medications are classified as “PDE5 inhibitors (phosphodiesterase type 5 inhibitors).”
Erection occurs when sexual stimulation dilates blood vessels in the penis, allowing blood to flow into the spongy tissue known as the corpus cavernosum. Two substances play a critical role here: nitric oxide (NO) and cyclic GMP (cGMP).
Erection Mechanism
Upon sexual stimulation, NO is released from nerves.
NO acts on vascular smooth muscle, promoting cGMP production.
cGMP dilates blood vessels, increasing blood flow into the corpus cavernosum.
Accumulated blood compresses venous outflow, maintaining the erection.
However, cGMP is gradually broken down by the PDE5 enzyme, leading to the end of the erection. ED medications inhibit PDE5, preventing cGMP breakdown and sustaining vasodilation. In other words, taking these medications enhances the natural response to sexual stimulation, making it easier to maintain an erection.
Representative Drugs and Characteristics
Sildenafil (Viagra): The first approved ED drug worldwide. Effects begin 30–60 minutes after administration, lasting about 4–6 hours. Strongly influenced by food, especially high-fat meals.
Tadalafil (Cialis): Distinguished by its very long duration of action (24–36 hours), also called the “weekend pill.” Less affected by food and allows flexibility in timing sexual activity.
Vardenafil (Levitra): Rapid onset, effective in about 30 minutes. Less affected by food compared with sildenafil. Duration: approximately 5–8 hours.
Avanafil (Stendra): A newer generation ED drug with high rapidity, effective within 15–30 minutes. Considered relatively safe with fewer side effects. Duration: 6–12 hours.
Common Features and Limitations of PDE5 Inhibitors
Require sexual stimulation: They support erection but do not induce it without arousal.
Primarily improve blood flow: Effect may be limited if ED is caused by psychological or neurological factors.
Potential side effects: Headache, flushing, nasal congestion, palpitations, and visual disturbances (color perception changes) due to their systemic effects on vascular smooth muscle.
Thus, ED medications support the physiological process of erection, but their effectiveness and duration differ. Choosing the right medication depends on lifestyle, underlying conditions, and concurrent drugs.
2. Medications That Must Never Be Combined
Because PDE5 inhibitors cause vasodilation, combining them with other vasodilators can be extremely dangerous. The following drugs are considered contraindicated combinations.
(1) Nitrates (e.g., Nitroglycerin, Isosorbide)
Examples: Nitroglycerin (sublingual tablets, patches, sprays), isosorbide dinitrate (ISDN), isosorbide mononitrate (ISMN). Purpose: Treatment of angina pectoris and myocardial infarction by dilating coronary arteries and improving myocardial blood flow. Interaction Risks: Combination with ED medications can cause profound hypotension, leading to fainting, shock, myocardial ischemia, heart attack, or stroke. Clinical Note:ED medications are generally not recommended for patients with angina, requiring detailed cardiovascular assessment.
Example: Riociguat (Adempas®). Purpose: Treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Interaction Risks: Like PDE5 inhibitors, it enhances the NO–cGMP pathway, leading to extreme hypotension. Particularly dangerous in unstable cardiopulmonary patients, possibly fatal. Clinical Note: Guidelines clearly prohibit combination with ED drugs.
Why These Combinations Are Contraindicated (Common Mechanism):
Nitrates and riociguat also act on the NO–cGMP pathway.
Overlapping effects cause uncontrollable blood pressure drops.
Summary Table of Contraindicated Drugs
Drug Class
Examples
Purpose
Interaction Risks
Nitrates
Nitroglycerin, ISDN, ISMN
Angina, MI
Severe hypotension, fainting, ischemia, fatal complications
sGC stimulators
Riociguat (Adempas®)
Pulmonary hypertension
Fatal hypotension via enhanced vasodilation
In short: Nitrates and riociguat must never be combined with ED medications. Patients on these drugs cannot receive PDE5 inhibitors, and alternative treatments (psychological support, other therapies) must be considered.
3. Medications Requiring Caution When Combined
Antihypertensives: ACE inhibitors, ARBs, diuretics can generally be combined, but may cause excessive hypotension. α-blockers especially can increase risk of dizziness or fainting.
Antifungals (itraconazole, ketoconazole): Slow PDE5 inhibitor metabolism, raising blood levels and side effect risk.
HIV Protease Inhibitors: Similarly inhibit metabolism, intensifying side effects like headache, flushing, palpitations.
Antibiotics (clarithromycin, erythromycin): Prolong drug action by inhibiting metabolism, increasing risks.
4. Supplements and Alcohol
Supplements: Arginine, citrulline, and other vasodilatory supplements may amplify side effects such as headache and hypotension.
Alcohol: Small amounts are usually safe, but excessive intake may reduce effectiveness or worsen side effects (dizziness, palpitations).
5. Specific Side Effect Risks from Interactions
Hypotension leading to dizziness or fainting
Palpitations or chest pain
Worsening headache or facial flushing
Variable efficacy (too strong or too weak)
If these symptoms occur, stop the medication immediately and consult a physician.
6. Safety Checklist for Usage
Always inform your doctor of all current medications.
Do not self-prescribe over-the-counter drugs or supplements.
Start with the lowest dose and monitor your body’s response.
If uncertain, consult a urologist or specialized clinic.
Conclusion
ED medications are among the most common and effective treatment options today. PDE5 inhibitors, in particular, support the mechanism of erection and can greatly improve quality of life. However, their effectiveness comes with risks if drug interactions are ignored.
The most important point is that ED medications must never be combined with nitrates or riociguat. Such combinations can cause fatal complications from sudden hypotension. This warning is clearly stated in international guidelines and must be strictly followed.
Additionally, drugs such as antihypertensives, antifungals, HIV protease inhibitors, and certain antibiotics can alter drug levels or duration, increasing side effects. Even supplements and alcohol can influence outcomes.
Key Safety Practices:
Always disclose current medications to your doctor or pharmacist.
Avoid self-initiated use of OTC drugs or supplements.
Begin with a low dose and observe effects.
Stop use and consult a doctor if strong side effects occur.
ED is caused by multiple factors—aging, lifestyle diseases, cardiovascular conditions, stress. ED medications aim to improve symptoms but must be combined with proper health management.
With correct knowledge and medical support, ED medications can be used safely. By understanding and managing interaction risks, you can avoid side effects while improving sexual health and overall well-being.
