If you take isosorbide mononitrate once a day and you are thinking about avanafil, here is the plain-language answer: the two are not meant to be used together. Isosorbide mononitrate (often shortened to ISMN, and sold under names such as Imdur, Monoket and Ismo) is a long-acting nitrate prescribed to prevent angina. Avanafil (Stendra) is a PDE5 inhibitor prescribed for erectile dysfunction. The avanafil label bars the combination with any organic nitrate, daily or occasional.
What makes ISMN different from the nitroglycerin spray in someone’s coat pocket is its rhythm. It is a daily medicine, usually taken in the morning, that sits quietly in the background of a person’s routine. People on it tend to think of it as “part of breakfast” rather than as a heart drug with serious interactions. This article follows a typical ISMN day, hour by hour, to show where the avanafil problem arises, what a pharmacist checks, and what you can sensibly ask your cardiologist.
Please note: this is general education, not individual medical advice. Do not stop, skip or time your isosorbide mononitrate to make room for another medicine unless your cardiologist has told you to.
Quick reference card
- Drug A: Avanafil, a fast-acting PDE5 inhibitor for ED.
- Drug B: Isosorbide mononitrate, a long-acting nitrate for angina prevention.
- Status on the avanafil label: Contraindicated with any organic nitrate, whether taken regularly or intermittently.
- Main danger: A sudden, potentially severe fall in blood pressure.
- What to do: Do not combine; ask your cardiologist about alternatives for ED.
A day in the life of an ISMN prescription
To see why the interaction is hard to manage by timing alone, picture a person we will call Daniel, a composite example. Daniel is 61, has stable angina and takes a once-daily extended-release ISMN tablet. Walk through his day and note how long the drug stays active.
7:30 am: the tablet
Daniel swallows his extended-release tablet with breakfast. The tablet is designed to release the drug slowly, so its effect builds over a couple of hours and then continues for much of the day. Immediate-release versions exist, too, and they are usually taken twice a day with a gap of several hours so that the evening dose is not too late.
Midday: peak protection
During the late morning and early afternoon, nitrate levels are at their highest. Blood vessels are relaxed, and Daniel may notice a mild headache, a common side effect that often fades over days or weeks.
Evening: tapering, but not gone
By the evening, the nitrate effect is declining. Many extended-release regimens are built to leave a nitrate-free stretch overnight to prevent tolerance, which is the gradual loss of effect that occurs when the body is exposed to nitrates continuously. Daniel could easily conclude that the drug has left his system by dinner.
The tempting thought
This is where people reason, “If the medicine has worn off by the evening, avanafil will be safe at night.” The thought is understandable, but it is a plan no label supports. The nitrate-free interval is a feature of angina treatment, not an agreed safety margin for PDE5 inhibitors, and individuals clear drugs at different speeds depending on kidney and liver function, other medicines and age. Daniel’s cardiologist designed that gap for his heart. Using it as cover for a vasodilator would be an experiment on himself.
The 3 am problem
Angina is unpredictable. Some people get symptoms after exertion, some after a heavy meal, some during sexual activity itself. If Daniel experiences chest pain after taking avanafil, the standard emergency response would normally involve a nitrate. Instead, the team needs to treat him knowing that adding another vasodilator could drop his blood pressure dramatically. That is the central logic of the label’s warning.
How avanafil and ISMN stack up in the body
| Feature | Isosorbide mononitrate | Avanafil |
|---|---|---|
| Drug class | Organic nitrate (nitric oxide donor) | PDE5 inhibitor |
| Main purpose | Prevent angina attacks | Treat erectile dysfunction |
| How taken | Daily, often extended-release in the morning | As needed, around 15 to 30 minutes before sexual activity |
| Effect on cGMP | Raises production via nitric oxide | Slows breakdown of cGMP |
| Effect on blood pressure | Lowers it | Lowers it modestly |
| Label stance on the pair | Combination contraindicated | |
A useful way to picture it: nitrate is the accelerator on the “relax the vessel” pathway, while avanafil is the person holding the brake off. Neither alone is dangerous for most healthy people, but when both are active, the vessel can relax far more than intended.
Eight things your pharmacist is checking
When ISMN and avanafil appear on the same profile, or when you mention ISMN during a consultation, the pharmacist usually follows a mental checklist. Here it is made visible.
1. Is the nitrate current?
They look at the date of the last fill. A prescription filled a month ago that has been refilled on schedule is almost certainly active. Gaps raise a gentle question about whether you have stopped, and why.
2. Is it truly isosorbide mononitrate?
Brand names confuse people. Imdur, Monoket and Ismo all contain ISMN. Combination products and generics add further names. The pharmacist reads the active ingredient rather than relying on the brand you recall.
3. Are there other nitrates around?
People occasionally hold both a daily nitrate and a rescue spray. Both count. Our companion guides on avanafil and nitroglycerin and avanafil and isosorbide dinitrate explain these relatives in detail.
4. Who prescribed what?
A cardiologist may prescribe ISMN while a urologist or telehealth service prescribes avanafil. Neither prescriber automatically sees the other’s record. The pharmacist is often the only person looking at both lists.
5. Does the patient know avanafil is a PDE5 inhibitor?
Some people take sildenafil or tadalafil in the past and do not link the new brand to the same family. The pharmacist reminds you that the class warning is shared.
6. Other blood-pressure factors
Alpha-blockers for the prostate, antihypertensives, diuretics and alcohol all matter. Dehydration, for example after illness or hot weather, makes low blood pressure more likely; our article on hot weather and erectile dysfunction touches on how heat and fluid loss affect circulation.
7. Liver, kidney and age
Avanafil is not recommended in severe hepatic impairment, and some kidney problems alter how drugs are handled. These details affect dosing decisions even when a nitrate is not involved.
8. The ED itself
Erectile dysfunction in a person with angina may be driven by the same vascular disease. A pharmacist will usually recommend that this is discussed with the doctor rather than treated in isolation.
Three types of ISMN patient, three different conversations
The long-term stable patient
This person has taken ISMN for years with no recent episodes. They often feel well and wonder whether the nitrate is still needed. The right step is a review with the cardiologist, who may confirm continued need, adjust therapy or consider other angina medicines. It is not a decision to make at the pharmacy counter.
The post-stent or post-heart-attack patient
Someone recently treated for a cardiac event faces additional cautions. The avanafil label notes that people with recent heart attack, stroke or other serious cardiovascular conditions were not included in its trials and that sexual activity may itself be inadvisable. The cardiologist’s clearance for exertion comes first.
The person who was prescribed ISMN for something other than classic angina
Nitrates are sometimes used in other circumstances, for example in certain heart-failure regimens or oesophageal spasm in specialist care. The interaction logic does not depend on why the nitrate was given. Tell the pharmacist the reason if you know it, because it affects how they advise you to approach your cardiologist.
What if a doctor says you can stop ISMN?
Sometimes a cardiologist reviews the whole picture and decides a nitrate is no longer required. If that happens, the decision should be documented, and the doctor can then talk through whether avanafil is appropriate given your cardiovascular status. Two cautions apply. First, the avanafil label focuses on the nitrate itself; the clinician will also consider your general heart health. Second, stopping a nitrate abruptly without medical guidance can cause symptoms to return, so supervision matters.
If angina continues, there are other drug families to discuss, each with trade-offs for sexual function. Beta-blockers, for instance, are sometimes blamed for ED, a topic explored in our article asking whether metoprolol causes erectile dysfunction. Calcium channel blockers carry their own considerations; see our piece on amlodipine and erectile dysfunction.
Alternatives to explore with your care team
- Non-oral ED treatments: Vacuum devices, alprostadil injections or urethral inserts act locally and do not use the PDE5 pathway.
- Hormone testing: Low testosterone can contribute to ED and is treatable in some cases.
- Psychological support: Anxiety about heart health or about sex after a cardiac event is common and responds to counselling. Our guide to beating psychological erectile dysfunction offers practical ideas.
- Lifestyle changes: Regular activity, a heart-friendly diet, weight management, no smoking and limited alcohol benefit both heart and erections. Foods are discussed in our breakfast ideas for erectile dysfunction article.
- Review of other medicines: Some non-heart drugs also affect erections, and swapping them can help.
Be careful with herbal and “natural” products. Many promise better blood flow, and some do lower blood pressure. Treat them as active substances and tell your pharmacist about them; our overview of natural alternatives to Stendra discusses what evidence exists and where caution is needed.
Immediate-release versus extended-release: why the formulation matters
ISMN is dispensed in two main styles, and knowing which one you have helps both you and the pharmacist.
- Extended-release tablets are taken once daily, usually on waking. They must be swallowed whole, because crushing or chewing destroys the release mechanism and delivers a large amount of drug at once. A crushed tablet is a bigger risk for sudden low blood pressure.
- Immediate-release tablets are typically taken twice daily, with the second dose several hours after the first rather than at bedtime. That spacing is intentional and creates the daily nitrate-free period.
Neither style makes avanafil acceptable. What the difference does change is how long the vessels are exposed to the nitrate and how predictable the exposure window is. With extended-release tablets, effects can linger beyond what patients expect. Combined with variation in kidney function and age, it becomes clear why no “gap hours” table can be responsibly offered in a blog post.
Why the nitrate-free interval exists, and why it is not a loophole
If the body is exposed to a nitrate all day, every day, the blood vessels gradually stop responding as strongly. Doctors call this tolerance. To keep the drug effective, the schedule leaves part of the day without it. Researchers have also described a rebound effect in which angina can worsen if a nitrate is withdrawn abruptly, which is another reason schedules are set by clinicians.
Now consider what a PDE5 inhibitor does in that interval. Avanafil does not need a nitrate to lower blood pressure slightly; it simply amplifies whatever nitric oxide signalling is already present. During the nitrate-free interval, blood vessels are also in a state of recovering sensitivity. The practical effect of adding avanafil at that moment has never been established as safe in labelling, so the sensible reading is that the interval is for the heart’s benefit and nothing more.
Other items on a medicine list that change the picture
Even before the nitrate issue is resolved, a pharmacist may notice other combinations that increase the chance of low blood pressure or higher avanafil levels. A few common ones:
- Alpha-blockers such as tamsulosin or doxazosin. The avanafil label advises that patients be stable on the alpha-blocker first and that avanafil start at 50 mg. For more detail, read our article on avanafil and tamsulosin.
- Other blood-pressure drugs, including ACE inhibitors, ARBs, diuretics and calcium channel blockers.
- Strong CYP3A4 inhibitors such as ketoconazole, ritonavir and clarithromycin, which can raise avanafil exposure.
- Riociguat or vericiguat, used for lung and heart conditions, which are contraindicated with PDE5 inhibitors. See avanafil and riociguat.
- Other ED drugs, such as sildenafil or tadalafil. Stacking PDE5 inhibitors is not recommended; our article on taking Viagra and Cialis together explains why.
How to talk to your cardiologist about ED without embarrassment
Cardiologists see erectile dysfunction in their patients all the time. Raising it is not awkward for them, and it may help them understand your overall vascular health. A few scripts that work:
- “I have been having trouble with erections. Could it be related to my heart condition or my medicines?”
- “I take isosorbide mononitrate daily. Are there ED options that are compatible with it?”
- “Is my heart stable enough for sexual activity, and how would I know if it is not?”
- “Is there a way to change my angina treatment so a PDE5 inhibitor becomes possible, or should I focus on other ED treatments?”
Write the answers down, or ask for them in the after-visit summary, so your pharmacist can add them to your profile.
Warning signs that need urgent help
If you took avanafil and ISMN within the same day, or you are unsure whether you did, watch for these symptoms and seek emergency help without delay:
- Light-headedness or fainting, especially when standing
- Chest pain, pressure or tightness
- Rapid, pounding or irregular heartbeat
- Shortness of breath
- Sudden vision changes or severe headache
- Cold, clammy skin or confusion
Lie flat with the legs raised while waiting for help, and tell responders the name, dose and time of every medicine taken. Do not take extra nitrate unless emergency clinicians instruct you to do so, because the combination is the very thing under concern.
A simple record you can keep
Many interaction near-misses happen because information sits in the wrong place. A one-page medicine summary solves much of the problem. Include:
- Every prescription, with strength and the reason it was prescribed
- Over-the-counter products, supplements and herbal items
- Allergies and past reactions
- The names and numbers of your prescribers and your pharmacy
- A line such as “Takes isosorbide mononitrate. Do not give PDE5 inhibitors.”
Keep a copy on your phone and one in your wallet. If you ever need urgent care, that single sheet speaks for you.
Practical safeguards while your plan is being sorted out
Sometimes the cardiology appointment is weeks away, and the question of ED treatment feels urgent. In that gap, a few safeguards reduce risk without requiring you to guess at timing.
Keep avanafil out of reach until you have clearance
If you already hold a supply from an earlier prescription, from a partner, or from an online order, store it separately and do not use it while ISMN is part of your regimen. Medicines shared between people are a frequent source of accidental interactions, because the person sharing may not know your heart history.
Do not rely on how you feel
People often judge a medicine’s safety by whether they feel unwell afterwards. Blood-pressure drops can be abrupt and may not be preceded by warning symptoms. A good day with ISMN says nothing about how a vasodilator will behave on top of it.
Ask the pharmacist to add a note to your file
Most pharmacy systems let staff record an alert such as “on daily nitrate; avoid PDE5 inhibitors.” If you use more than one pharmacy, consolidating to a single one makes that safeguard far more reliable.
Be wary of products that do not list ingredients clearly
Some supplements marketed for sexual performance have been found to contain hidden PDE5 inhibitor ingredients. Someone on a nitrate who takes such a product could be exposed without knowing. Choose products from reputable sources, and read our overview of the best sex pills for men with an eye on ingredient transparency.
Check the date and storage of your nitrate
Nitrates that have degraded may not work as intended, which can tempt people into taking extra doses. Keep tablets in their original container, away from heat and moisture, and replace them according to the label. Reliable angina control is part of reducing the number of times you might need emergency treatment.
Frequently asked questions
Is isosorbide mononitrate the same as nitroglycerin?
They are different molecules in the same drug class. Both release nitric oxide and both are subject to the avanafil contraindication.
Can I take avanafil at night if my ISMN is taken in the morning?
The label gives no such allowance for patients who use nitrates regularly. Individual clearance varies, and an unplanned angina episode would still raise the dilemma. Ask your cardiologist before considering any arrangement.
What if I already took both by mistake?
Sit or lie down, monitor for symptoms and contact emergency services if you feel unwell. Even if you feel fine, call your pharmacist or a poison-control service the same day.
Does ISMN cause erectile dysfunction itself?
Nitrates are not typically blamed for ED, but the heart condition they treat often is associated with it. Other cardiac drugs may play a role, so a medication review can be worthwhile.
Is there an ED drug that is safe with ISMN?
Oral PDE5 inhibitors as a class share the nitrate warning. Non-PDE5 approaches, chosen with a urologist and cardiologist, are the usual route. Our general comparison of ED drugs explains how the pills differ, though none overrides the nitrate rule.
Could a lower dose of avanafil, such as 50 mg, be safe with a nitrate?
The 50 mg strength is discussed in the label for people taking alpha-blockers or certain interacting drugs, not as a way around the nitrate contraindication.
Related reading on PinkViva
To understand how avanafil behaves relative to other medicines, see Stendra versus Viagra and avanafil versus vardenafil. The wider PinkViva blog collects more guides on sexual health and medicines.
References and trusted sources
This content is for general information and does not replace advice from a licensed healthcare professional. Medicine labels are updated regularly, so confirm details with your pharmacist.