Opsynvi

Pronunciation: op-SIN-vee
Generic name: macitentan and tadalafil
Dosage form: oral tablet
Drug class: Agents for pulmonary hypertension

Medically reviewed by Carmen Pope, BPharm. Last updated on Apr 16, 2024.

What is Opsynvi?

Opsynvi (macitentan and tadalafil) is a combination, oral, once-daily tablet for adults with pulmonary arterial hypertension (PAH, WHO Group I) of WHO functional class (FC) II-III, that works in two different ways to reduce high blood pressure in the arteries of the lungs.

Opsynvi combines macitentan, an endothelin receptor antagonist (ERA) with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor. Macitentan works by preventing the binding of endothelin (ET)-1 to ETA and ETB. Endothelin-1 is an amino acid peptide that is produced by several different cells and tissues, such as endothelial and vascular smooth muscle cells, macrophages, and the renal medulla. In disease conditions such as PAH, the local ET system is upregulated and involved in vascular hypertrophy (the thickening of the arterial wall) and organ damage. Macitentan counteracts this process and reduces the risk of clinical worsening events and hospitalization.

Tadalafil blocks the action of an enzyme known as cGMP-specific phosphodiesterase type-5 (PDE-5). This enzyme breaks down cGMP, a substance that causes smooth muscles to relax. Blocking PDE-5 for people with PAH means levels of cGMP within the smooth muscles will increase which promotes muscle relaxation and vasodilation (a widening of blood vessels), improving exercise ability.

Opsynvi was FDA-approved on 22 March 2023.

What are the side effects of Opsynvi?

Opsyni can cause serious side effects, including:

• Serious birth defects. See warnings below
• Liver problems. Your healthcare provider should do blood tests to check your liver before you start taking Opsynvi. Tell your healthcare provider if you have any of the following symptoms of liver problems during treatment.
  • nausea or vomiting
  • yellowing of your skin or whites of your eyes
  • pain in the upper right stomach
  • dark urine
  • tiredness
  • fever
  • loss of appetite
  • itching.
• Decreased blood pressure (hypotension) (temporary)
• Low red blood cell levels (anemia) can occur with Opsynvi treatment, usually during the first weeks after starting therapy. Your healthcare provider will do blood tests to check your red blood cells before starting and as needed during treatment
• Vision loss. Opsynvi can cause decreased eyesight or permanent loss of vision in 1 or both eyes, which could be a sign of NAION. There is an increased risk of NAION in people who have already had NAION in 1 eye. If you notice a sudden decrease or loss of vision in 1 or both eyes, contact your healthcare provider right away
• Hearing problems. Sudden decrease or loss of hearing, sometimes with ringing in the ears and dizziness, can happen during treatment with Opsynvi. If you notice a sudden decrease or loss of hearing, contact your healthcare provider right away
• Fluid retention. This can happen within weeks after starting Opsynvi and could lead to hospitalization. Tell your healthcare provider right away if you have any unusual weight gain, trouble breathing, or swelling of your ankles or legs. Your healthcare provider will look for the cause of any fluid retention and may stop treatment with Opsynvi
• Decreased sperm count in males and may affect the ability to father a child. Tell your healthcare provider if being able to have children is important to you
• Prolonged erection. Erections that last more than 4 hours, with or without pain, can happen during treatment with Opsynvi. Painful erections (priapism) can cause permanent damage to the penis if not treated right away. Tell your healthcare provider right away if you have an erection that lasts longer than 4 hours, with or without pain.

The most common side effects of Opsynvi affecting 10% or more people include:

• too much fluid in your body (fluid retention) and swelling caused by too much fluid (edema)
• anemia
• headache, including migraine headaches.

These are not all the possible side effects of Opsynvi. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Related/similar drugs

sildenafil, tadalafil, Adcirca, ambrisentan, Revatio, Opsumit

Warnings and serious effects

Opsynvi comes with a Boxed Warning for embryo-fetal toxicity because it can cause major birth defects. It must not be taken during pregnancy and acceptable forms of contraception should be used before initiation of treatment, during treatment, and for one month after stopping treatment. Pregnancy must be excluded before treatment initiation.

Medications that contain ERAs, such as Opsynvi, can cause liver toxicity and liver failure. Your healthcare provider will monitor your liver function and total bilirubin regularly during treatment and before you start treatment.

Opsynvi may cause low blood pressure. Be careful when going from sitting or lying down to standing.
May cause fluid retention that requires treatment. If fluid collects in your lungs (pulmonary edema) then your healthcare provider should discontinue treatment.

Seek emergency help if you develop sudden vision loss. Opsynvi has been associated with non-arteritic ischemic optic neuropathy (NAION) (a sudden loss of blood flow to the optic nerve) and may be permanent.

Should not be used with certain other medications, such as nitrates and other PDE5 inhibitors, such as sildenafil, vardenafil, avanafil, and other products that contain tadalafil.

May decrease hemoglobin levels and sperm counts. There is a risk of prolonged erections with Opsynvi and patients should seek emergency treatment if an erection lasts for more than 4 hours.

For all female patients, Opsynvi is only available through a restricted program called the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS). Males can receive Opsynvi without taking part in this program.

It is not known if Opsynvi is safe and effective in children.

Before taking

Do not take Opsynvi if you are allergic to macitentan, tadalafil, Opsynvi, or any of the inactive ingredients in the medication.

Before taking Opsynvi, tell your healthcare provider about all of your medical conditions, including if you:

• have low blood pressure
• have anemia
• have heart problems including heart attack or heart failure
• have pulmonary veno-occlusive disease (PVOD)
• have any eye problems, including NAION or an inherited eye disorder called retinitis pigmentosa
• have hearing problems such as ringing in the ears, dizziness, or loss of hearing
• have a deformed penis shape or Peyronie’s disease or have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia. These conditions increase your risk of getting a prolonged erection
• have kidney problems or get dialysis
• take any medicines called nitrates or guanylate cyclase (GC) stimulators
• are pregnant, plan to become pregnant, or become pregnant during treatment
• are breastfeeding or plan to breastfeed
• wish to protect your fertility
• plan to have unprotected sex.

Females can only receive Opsynvi through a restricted program called the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS). If you are a female who can get pregnant, you must talk to your healthcare provider, understand the benefits and risks of Opsynvi, and agree to all of the instructions in the Macitentan-Containing Products REMS.

Males can receive Opsynvi without taking part in the Macitentan-Containing Products REMS.

Pregnancy

Opsynvi can cause serious birth defects if taken during pregnancy. People who can become pregnant must not be pregnant when they start taking Opsynvi, or become pregnant during treatment or for 1 month after stopping treatment.

People who can become pregnant should have a negative pregnancy test before starting treatment with Opsynvi, each month during treatment, and 1 month after stopping Opsynvi. Talk to your healthcare provider about your menstrual cycle. Your healthcare provider will decide when to do the pregnancy test and will order a pregnancy test for you depending on your menstrual cycle.

People who can become pregnant are people who:

• have entered puberty, even if they have not started their menstrual period
• have a uterus,
• and have not gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed.

People who cannot become pregnant are people who:

• have not yet entered puberty, or
• do not have a uterus, or
• have gone through menopause
• are infertile for other medical reasons and this infertility is permanent and cannot be reversed.

People who can become pregnant should use 2 acceptable methods of birth control before starting treatment with Opsynvi, during treatment, and for 1 month after stopping Opsynvi because the medicine may still be in your body.

If you have had a tubal sterilization, have a progesterone implant, or have an intrauterine device (IUD), these methods can be used alone, and no other form of birth control is needed.

Talk with your healthcare provider or gynecologist (a healthcare provider who specializes in female reproduction) to find out about options for acceptable birth control that you may use to prevent pregnancy during treatment with Opsynvi. Also, see the prescribing information for a list of acceptable birth control options.
Tell your healthcare provider right away if you miss a menstrual period or you think you might be pregnant.

Breastfeeding

It is not known if Opsynvi passes into your breastmilk. Do not breastfeed during treatment. Talk to your healthcare provider about the best way to feed your baby if you take Opsynvi.

Fertility

Opsynvi may decrease sperm counts in males and affect their ability to father a child. Tell your healthcare provider if being able to have children is important to you.

Unprotected sex

Do not have unprotected sex. Talk to your healthcare provider or pharmacist right away if you have unprotected sex or if you think your birth control has failed. Your healthcare provider may talk with you about using emergency birth control.

How should I take Opsynvi?

Opsynvi will be mailed to you by a specialty pharmacy. Your healthcare provider will give you complete details.
Take it exactly as your healthcare provider tells you to take it. Do not stop taking it unless your healthcare provider tells you.

• Take Opsynvi with or without food.
• Do not cut, crush, or chew the tablets.

Opsynvi dosage

Your healthcare provider will determine the right dosage for you.

The recommended starting dose of Opsynvi is one 10 mg/20 mg tablet taken orally once daily with or without food for one week.

• If tolerated, the dosage can be increased to one 10 mg/40 mg tablet taken orally once daily with or without food as the maintenance dose.

For patients transitioning from PDE5 inhibitor monotherapy or PDE5 inhibitor and ERA therapy in combination the recommended dose is one 10 mg/40 mg tablet taken orally once daily.

What should I avoid while taking Opsynvi?

Do not have more than 4 alcohol-containing drinks in a short period during treatment with Opsynvi. Drinking too much alcohol can increase your chances of getting low blood pressure, increased heart rate, dizziness, and headaches.

Avoid standing quickly, when seated or lying down. Opsynvi can lower your blood pressure and standing up too quickly may make you feel faint or dizzy.

What happens if I miss a dose?

If you miss a dose of Opsynvi, take it as soon as you remember that day. Take the next dose at your regular time.

Do not take 2 doses at the same time to make up for a missed dose.

What happens if I miss a dose?

If you miss a dose of Opsynvi, take it as soon as you remember that day. Take the next dose at your regular time. Do not take 2 doses at the same time to make up for a missed dose.

What happens if I overdose?

If you take too much Opsynvi, call your healthcare provider or go to the nearest hospital emergency room right away.

What other drugs will affect Opsynvi?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Opsynvi with other medicines may affect the way it and the other medicines work, and may increase your risk of side effects. Do not start any new medicine until you check with your healthcare provider.

• Especially tell your healthcare provider if you take:
• nitrate medicines
• antiseizure medicines
• blood pressure medicines
• HIV medicines
• medicines used to treat infection
• medicines used to treat PAH or heart problems
• antifungal medicines
• erectile dysfunction medicines.

Avoid concomitant use with other medications that affect certain enzyme pathways (such as strong CYP3A4 inducers/inhibitors and moderate dual or combined CYP3A4 and CYP2C9 inhibitors). Ask your healthcare provider or pharmacist if you are not sure if you take medications that fall into this category.

Know the medicines you take. Keep a list and show it to your healthcare provider or pharmacist when you get a new medicine.

Storage

Store Opsynvi tablets at room temperature between 68°F to 77°F (20°C to 25°C) in the original package that it comes in to protect from moisture. Do not discard or eat the desiccant.

Keep out of the reach of children.

Opsynvi ingredients

Active ingredients: macitentan and tadalafil

Inactive ingredients: tablet core: hydroxypropyl cellulose, hydroxypropyl cellulose (low substituted), lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 80, povidone, sodium starch glycolate, sodium lauryl sulfate. 10 mg/20 mg

Film-coating: hydroxypropyl methylcellulose, iron oxide red, iron oxide yellow, lactose monohydrate, talc, titanium dioxide, triacetin. 10 mg/40 mg film-coating: hydroxypropyl methylcellulose, lactose monohydrate, talc, titanium dioxide, triacetin.

Manufacturer

Actelion Pharmaceuticals US, Inc., a Janssen Pharmaceutical Company.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer