Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the arteries that go from your heart to your lungs. It happens when these arteries become narrow or blocked, making it harder for blood to flow through them. This forces your heart to work harder to pump blood.
PAH is a long-term condition that can worsen over time. As the heart works harder, it may become weaker and less able to pump blood well. Many people notice symptoms such as shortness of breath, tiredness, chest pain, or swelling in the legs and ankles.
While there is no cure for PAH, your health care provider will work with you to create a treatment plan that fits your needs. Your plan may include medicines that relax or widen the blood vessels in your lungs to improve blood flow.
One option is Opsynvi, which is a pill containing the combination of two medicines: macitentan and tadalafil. Opsynvi is FDA-approved to treat adults with PAH. Macitentan helps delay the worsening (progression) of the condition and lowers the risk of hospital stays related to PAH. Tadalafil improves the ability to exercise. Opsynvi comes as an oral tablet that is taken by mouth.
If you have PAH, you may be wondering how Opsynvi works and what to expect during treatment. This article answers common questions about Opsynvi for PAH.
Is Opsynvi Right for Me?
To find out if Opsynvi is right for you, your health care provider will look at your medical history, including the type of pulmonary hypertension you have, your symptoms, and your overall health.
Pulmonary hypertension (PH) is a general term for high blood pressure in the lungs. The types of PH are grouped into five categories, called World Health Organization (WHO) Groups. Opsynvi is FDA-approved to treat adults with pulmonary arterial hypertension (PAH), which falls under WHO Group 1.
Your health care provider will also consider your symptoms and how much they affect your ability to be active. PAH symptoms are rated according to the following WHO functional classes.
- Class I: You have no symptoms with ordinary activity.
- Class II: You feel short of breath or tired during normal activity, but you feel comfortable at rest.
- Class III: Even lighter activity causes shortness of breath or tiredness, but you feel comfortable at rest.
- Class IV: You have symptoms even while resting.
Opsynvi tablets were shown to be an effective treatment for PAH in people who had WHO functional class II or III symptoms.
Opsynvi may also be used for other conditions as determined by your health care provider. Opsynvi is only approved for use in adults. It is not known if this medicine is safe or effective for children.
How Does Opsynvi Work for PAH?
Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the lungs. It happens when the pulmonary arteries (the blood vessels that go from your heart to your lungs) become narrow or blocked. This increases the pressure inside the pulmonary arteries, forcing your heart to work harder to pump blood to your lungs. Over time, the artery walls become thicker, further narrowing the space available for blood flow.
People with PAH may have too much or too little of certain natural substances in their body, including endothelin, nitric oxide, and/or prostacyclin. These substances normally help keep blood vessels relaxed and open. The goal of medicines for PAH is to balance these substances, which can help your lungs work better and allow smoother blood flow through your veins to your lungs.
Both medicines in Opsynvi work by helping relax the blood vessels in the lungs.
- Macitentan blocks endothelin-1, a substance that tightens blood vessels and worsens lung damage in people with PAH. By blocking endothelin-1, macitentan helps relax the blood vessels and lower the blood pressure in the lungs. This can help your heart pump blood better and prevent further damage.
- Tadalafil blocks an enzyme called phosphodiesterase 5 (PDE5). This enzyme normally stops some types of muscles from relaxing, including the muscles lining some types of blood vessels. By blocking PDE5, tadalafil helps relax blood vessels in the lungs. Tadalafil works on the nitric oxide pathway of PAH.
How Do I Take Opsynvi?
Opsynvi is a tablet that is taken by mouth once a day with or without food. You should swallow the tablet whole with water. Do not cut, crush, or chew the tablets. Follow your health care provider’s instructions carefully. Do not stop taking Opsynvi unless your health care provider tells you to.
How Was Opsynvi Studied for PAH?
The effect of Opsynvi on PAH was studied in a clinical trial called A DUE. To join the study, adults had to have a confirmed diagnosis of PAH. People had either never taken PAH medicine before the study (treatment-naïve) or were taking a stable dose of an endothelin receptor blocker or a PDE5 blocker (the types of medicines in Opsynvi) for at least three months before the study.
The people in the study took either Opsynvi, macitentan, or tadalafil once a day. They also took a placebo (a pill with no active medicine). Neither the people being studied nor their health care providers knew which medicines they were taking.
The main goal of the study was to see how effective and safe a single tablet with both macitentan and tadalafil was compared to the individual ingredients alone in people with PAH.
The study included 187 people with PAH. They were grouped by how much their symptoms affected daily activity, using the WHO functional class system. Most people were in Class II (51%) or Class III (49%), meaning they had mild to moderate symptoms with activity.
The following information describes the people who took part in the study:
- Their average age was 50 years.
- About 78% were women, and 22% were men.
- Most were White (62%), about 31% were Asian, about 3% were Black, and the rest were other races or not reported.
- On average, people had been diagnosed with PAH around 1.75 years before joining the study.
- About half (51%) of them had idiopathic PAH (no known cause), 5% had heritable PAH (which runs in families), 35% had PAH related to connective tissue disease, 3% had PAH linked to congenital heart disease, and 6% had PAH from other causes.
- At the start of the study, most people (53%) were not taking other PAH medicines (treatment-naïve). Of those who were taking other PAH medicines, 17% were taking an endothelin receptor blocker and 30% were taking an oral PDE5 inhibitor.
What Benefits of Opsynvi Were Seen?
The main goal (primary endpoint) of the A DUE study was to compare the effect of Opsynvi on pulmonary vascular resistance (PVR) with that of macitentan and tadalafil taken alone. PVR is the resistance that blood flow has as it flows through the blood vessels in the lungs and to the upper left chamber of your heart. PVR is a way to measure how severe PAH is.
A total of 108 people took Opsynvi, 35 people took macitentan alone, and 44 people took tadalafil alone. The study lasted 16 weeks.
The study found that people who took Opsynvi had a 45% decrease in PVR compared to a 23% decrease in those who took macitentan. People who took Opsynvi had a 44% decrease in PVR compared to a 22% decrease in those who took tadalafil. This means that Opsynvi had a 29% greater decline in PVR compared to macitentan alone, and a 28% greater decrease in PVR compared to tadalafil.
The PVR-lowering effects of Opsynvi were seen across different ages, sexes, races, countries of origin, and baseline WHO functional classes. The effects were seen both in people who were treatment-naïve and those who had been taking an endothelin receptor blocker or PDE5 blocker before the study started.
Your results may differ from what was seen in clinical studies.
Talk with your health care team about the plan to monitor how well your PAH treatment plan is working.
What Are the Side Effects of Opsynvi, and How Can I Manage Them?
The most common side effects seen with Opsynvi include headache, too much fluid in your body (fluid retention), and low levels of red blood cells (anemia).
To help prevent headaches or migraine, be sure to get enough sleep at night, exercise regularly, eat regular meals, drink plenty of water, and limit stress.
Fluid retention (edema) can happen with Opsynvi and may be serious. It can happen within weeks of starting Opsynvi. Weigh yourself every day and tell your health care provider if you have unusual weight gain or swelling in your ankles, legs, belly, or other areas.
Opsynvi can cause low red blood cell counts (anemia). This is more common during the first weeks of starting Opsynvi. Anemia can make you feel more tired than usual or cause shortness of breath. If your red blood cells are very low, you may need a blood transfusion. Your health care provider will have you do blood tests before you start and while you are taking Opsynvi. Keep all appointments for blood tests and tell your health care provider if you have any new or bothersome symptoms.
Opsynvi can cause low blood pressure. Make sure you stand up slowly and use support if needed. If you feel dizzy or faint, sit or lie down. Call your health care provider if you have low blood pressure or dizziness that does not improve or gets worse.
Opsynvi may cause liver problems. You will need a blood test to check for liver problems before you start treatment. If you get liver problems during treatment, you may need to have blood tests more often. If you notice symptoms of liver problems, such as nausea or vomiting, loss of appetite, pain or tenderness in your right upper stomach area (abdomen), feeling very tired, yellowing of your skin or whites of your eyes, dark pee, fever, or itching, tell your health care provider right away.
Do not take Opsynvi if you are pregnant, as it can cause harm to a fetus. Talk to your health care provider if you are pregnant, planning to get pregnant, or become pregnant while using Opsynvi. If you can get pregnant, you should use effective birth control while taking Opsynvi and for at least one month after your last dose. Talk with your health care provider about what birth control is a good choice for you. You should also have a negative pregnancy test before starting Opsynvi. Tell your health care provider right away if you have unprotected sex or if you think your birth control has not worked. If this happens, you may need to use emergency contraception.
Opsynvi may lower sperm count. Talk to your health care provider if this is an important concern for you.
These are not all of the possible side effects of Opsynvi. Talk with your health care provider if you are having symptoms that bother you. If you experience anything that you think may be caused by Opsynvi, you can also report side effects to the FDA at 800-FDA-1088 (800-332-1088).
What Type of Drug Interactions Can Happen?
Many other medicines can interact with Opsynvi. Do not start any new medicine until you check with your health care provider.
Medicines called nitrates should never be taken with Opsynvi, whether you use the nitrate as needed or regularly. Nitrate medicines include nitroglycerin (Nitro-Dur, NitroMist, Nitrostat, and others), isosorbide dinitrate (Isordil), or isosorbide mononitrate. Taking any nitrate within 48 hours of your last dose of Opsynvi can make your blood pressure drop too low.
You should also not take Opsynvi with any medicine known as a guanylate cyclase (GC) stimulator. GC stimulators include riociguat (Adempas) and vericiguat (Verquvo). Taking these medicines with Opsynvi can make your blood pressure drop too low.
Many medicines can increase or decrease the blood levels of Opsynvi, which could increase your risk for side effects or make Opsynvi not work as well. These medicines are called cytochrome CYP3A4 and CYP2C9 inducers and inhibitors. Some examples include rifampin(a medicine used to treat certain bacterial infections) and fluconazole (a medicine used to treat fungal infections).
Tell your health care provider about all the prescription and over-the-counter medicines and supplements you are taking. Your health care provider can tell you if you are taking a medicine or supplement that could affect CYP3A or CYP2C9 or interact with Opsynvi.
How Can I Get Opsynvi? Can I Get It at Any Pharmacy?
Opsynvi requires a prescription from a health care provider. It is a specialty medicine. Your local pharmacy may not carry it. Instead, your health care provider will likely send your prescription to be filled by a specialty pharmacy. The specialty pharmacy will make arrangements to ship the medicine to your home.
Is There Any Cost Assistance Available?
There is a patient support program offered by the drugmaker that may help you afford Opsynvi. Your health care provider can help you get started. You can find out more at www.opsynvi.com/patient-support or by calling 866-228-3546.
