Adempas Has Some Dangerous Drug Interactions — Here's What You Need to Know

Adempas (Riociguat) is an effective medication for pulmonary hypertension, but it comes with some of the most serious drug interactions of any PH medication. Some combinations aren't just inadvisable — they're life-threatening.

Whether you're just starting Adempas or have been on it for a while, this guide covers every major interaction you should know about: which medications are absolutely off-limits, which ones require caution, and what to tell your doctor about everything you take — including supplements and over-the-counter products.

How Drug Interactions Work With Adempas

Adempas works by stimulating an enzyme called soluble guanylate cyclase (sGC), which increases levels of a molecule called cGMP in your blood vessels. cGMP tells the blood vessels to relax, which lowers blood pressure — especially in the pulmonary arteries. For a full explanation, see how Adempas works.

Drug interactions with Adempas generally fall into three categories:

1. Medications that also increase cGMP — combining them with Adempas can cause a dangerous drop in blood pressure
2. Medications that change how your body processes Adempas — making blood levels too high (increasing side effects) or too low (reducing effectiveness)
3. Substances that affect absorption — preventing Adempas from getting into your bloodstream properly

Contraindicated Medications — Never Take With Adempas

These combinations are absolutely prohibited. Taking any of these with Adempas can cause severe, potentially fatal consequences.

Nitrates and Nitric Oxide Donors

This is the most dangerous combination. Nitrates increase cGMP through a similar pathway as Adempas. Together, cGMP levels can spike to dangerous levels, causing severe, life-threatening hypotension (low blood pressure).

Medications to avoid include:

• Nitroglycerin (Nitrostat, Nitro-Dur, Minitran) — including sublingual tablets, patches, and sprays
• Isosorbide mononitrate (Imdur, Monoket)
• Isosorbide dinitrate (Isordil, BiDil component)
• Sodium nitroprusside (Nitropress) — an IV medication used in hospitals
• Amyl nitrite ("poppers") — sometimes used recreationally

This includes all forms of nitrates — oral, topical patches, sprays, and IV. If you're prescribed a nitrate for chest pain (angina) or heart failure, your doctor must find an alternative before starting Adempas.

PDE-5 Inhibitors

PDE-5 inhibitors also increase cGMP — by preventing its breakdown. Combining them with Adempas (which increases cGMP production) can lead to dangerous hypotension.

Medications to avoid include:

• Sildenafil (Viagra for erectile dysfunction, Revatio for PAH)
• Tadalafil (Cialis for erectile dysfunction, Adcirca for PAH)
• Vardenafil (Levitra, Staxyn)
• Avanafil (Stendra)

This is especially important for PAH patients because Sildenafil (Revatio) and Tadalafil (Adcirca) are commonly used to treat pulmonary hypertension. If you're switching from one of these to Adempas, there must be an appropriate washout period. Your doctor will manage this transition carefully.

It also means that erectile dysfunction medications are off-limits while taking Adempas. Talk to your doctor about alternative approaches for ED.

Major Interactions — Use With Caution

These medications don't require absolute avoidance but need careful monitoring or dose adjustments:

Strong CYP and P-gp Inhibitors

Adempas is broken down in your body by multiple enzyme systems, including CYP1A1, CYP3A4, CYP2C8, and CYP2J2, and is also transported by P-glycoprotein (P-gp) and BCRP (breast cancer resistance protein). Medications that strongly inhibit these systems can increase Adempas blood levels, raising the risk of side effects — especially low blood pressure.

Medications that may increase Adempas levels:

• Ketoconazole and Itraconazole (antifungal medications) — strong CYP3A4 and P-gp inhibitors. Ketoconazole increased Adempas blood levels by approximately 150% in studies
• Ritonavir (HIV protease inhibitor, also used as a pharmacokinetic booster) — strong CYP3A4 inhibitor
• Clarithromycin (antibiotic) — CYP3A4 inhibitor

If you must take one of these medications, your doctor may start Adempas at a lower dose and monitor you more closely.

Strong CYP Inducers

On the flip side, medications that speed up the enzymes that break down Adempas can decrease its blood levels, making it less effective.

Medications that may decrease Adempas levels:

• Rifampin (Rifadin) — a tuberculosis medication and one of the most potent CYP inducers. It can reduce Adempas blood levels by approximately 50%
• Phenytoin (Dilantin) — an anti-seizure medication
• Carbamazepine (Tegretol) — another anti-seizure medication
• St. John's Wort — an herbal supplement (more on this below)
• Phenobarbital — a barbiturate used for seizures

If you take any of these, your doctor needs to know — your Adempas dose may need to be higher, or an alternative medication may be considered.

Antacids (Aluminum and Magnesium Hydroxide)

Antacids that contain aluminum hydroxide or magnesium hydroxide (like Maalox or Mylanta) can reduce Adempas absorption when taken at the same time. If you need an antacid, take it at least 1 hour before or 2 hours after your Adempas dose.

Proton pump inhibitors (like omeprazole/Prilosec) and H2 blockers (like famotidine/Pepcid) do not appear to have the same interaction and are generally considered safe to use with Adempas.

Supplements and Over-the-Counter Products to Watch

St. John's Wort

This popular herbal supplement for mood is a potent CYP enzyme inducer. It can significantly reduce Adempas blood levels, making the medication less effective. Avoid St. John's Wort while taking Adempas.

Nitric Oxide Supplements (L-Arginine, Beet Root)

Supplements marketed as "nitric oxide boosters" — including L-Arginine and beetroot extract — may theoretically interact with the same pathway as Adempas. While there's limited clinical data on this specific interaction, it's worth discussing with your doctor. The concern is that additional nitric oxide could amplify the blood pressure-lowering effect of Adempas.

NSAIDs (Ibuprofen, Naproxen)

While not a direct interaction with Adempas, NSAIDs can affect kidney function and blood pressure. Since Adempas already lowers blood pressure, adding NSAIDs may complicate blood pressure management. Use acetaminophen (Tylenol) for pain when possible, and discuss NSAID use with your doctor.

Herbal Blood Thinners

Supplements like fish oil, garlic, ginkgo biloba, and vitamin E have mild blood-thinning effects. Since Adempas is associated with an increased risk of bleeding, combining these supplements may add to that risk — especially if you're also on an anticoagulant.

Food and Drink Interactions

Smoking (Tobacco)

This is a significant interaction. Smoking induces CYP1A1, one of the enzymes that breaks down Adempas. Smokers have 50-60% lower Adempas blood levels compared to non-smokers. This means:

• If you smoke, your doctor may need to prescribe a higher dose of Adempas
• If you quit smoking while on Adempas, your blood levels will increase — potentially causing side effects like low blood pressure. Tell your doctor immediately if you quit smoking so they can adjust your dose
• If you start smoking while on Adempas, your levels will decrease and the medication may become less effective

Grapefruit

Grapefruit and grapefruit juice inhibit CYP3A4, which can increase Adempas blood levels. While the effect may be modest, it's worth mentioning to your doctor if you regularly consume grapefruit.

Alcohol

Alcohol isn't a direct drug interaction, but it can lower blood pressure on its own. Since Adempas already lowers blood pressure, drinking alcohol may increase your risk of dizziness, lightheadedness, and fainting. Use caution and limit alcohol consumption.

What to Tell Your Doctor

Before starting Adempas — and at every follow-up appointment — make sure your doctor has a complete picture of everything you take:

• All prescription medications — especially nitrates, PDE-5 inhibitors, antifungals, HIV medications, and antibiotics
• Over-the-counter medications — including antacids, pain relievers, and cold medicines
• Supplements and herbal products — especially St. John's Wort, nitric oxide boosters, and herbal blood thinners
• Smoking status — and any changes in smoking habits during treatment
• Recreational substances — including amyl nitrite ("poppers"), which is a nitrate and absolutely contraindicated

Don't start, stop, or change the dose of any medication or supplement without talking to your PH specialist first. Even seemingly harmless changes can affect how Adempas works in your body.

Final Thoughts

Adempas has some of the most critical drug interactions of any pulmonary hypertension medication. The contraindications with nitrates and PDE-5 inhibitors are absolute — these combinations can be fatal. Other interactions with CYP inhibitors, CYP inducers, and antacids require awareness and communication with your doctor.

The key takeaway: keep your doctor informed about everything you take, including supplements, OTC products, and lifestyle factors like smoking. Your PH specialist is your partner in making sure Adempas works safely and effectively for you.

For more information about Adempas, read our guides on what Adempas is, side effects to watch for, and how to save money on your prescription. Need help finding a pharmacy? Medfinder can help.