Ohtuvayre

Ohtuvayre (ensifentrine) is an inhaled, steroid-free medicine used as a maintenance (daily, ongoing) treatment for chronic obstructive pulmonary disease (COPD) in adults. It works in two ways: it helps relax and open the airways, and it reduces inflammation in the lungs.

• Ohtuvayre is used with a standard jet nebulizer.
• Ohtuvayre is a maintenance treatment, not a rescue medicine. It will not relieve sudden breathing problems, so always keep a fast-acting rescue inhaler with you.
• Ohtuvayre is taken twice a day, once in the morning and once in the evening.

Ohtuvayre belongs to a class of medicines called inhaled dual phosphodiesterase inhibitors. Specifically, it is a dual PDE3/PDE4 inhibitor, and it is the first inhaled medicine of this type approved for COPD.

Ohtuvayre (ensifentrine) received FDA approval on June 26, 2024. There is currently no generic version of Ohtuvayre.

Ohtuvayre is approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults. COPD is a long-term lung disease that includes chronic bronchitis and emphysema and causes symptoms such as breathlessness, cough, and wheezing. Ohtuvayre is used regularly to help keep the airways open. It is not used to treat sudden symptoms.

Ohtuvayre is for oral inhalation only. Do not swallow or inject it. Use Ohtuvayre only with a standard jet nebulizer that has a mouthpiece and is connected to an air compressor. Do not use Ohtuvayre until your healthcare provider has shown you how to use it correctly.

• Shake the Ohtuvayre ampule vigorously right before using it. When shaken, the liquid looks cloudy and yellow to pale yellow.
• Use 1 ampule 2 times a day, once in the morning and once in the evening.
• Do not use more than 1 ampule in a single inhalation, and do not use more than 2 ampules a day.
• Squeeze all of the contents of the ampule into the nebulizer cup, then throw the empty ampule away.
• Do not mix other medicines with Ohtuvayre in your nebulizer.
• Do not stop using Ohtuvayre even if you feel better, unless your healthcare provider tells you to, because your symptoms could get worse.
• Throw away the used ampule and any leftover medicine right after use. Because the ampules are small, they can be a choking hazard to young children.

Call your healthcare provider or get emergency care right away if your breathing problems get worse, if you need your rescue inhaler more often than usual, or if your rescue inhaler does not relieve your symptoms.

What should I do if I miss a dose?

If you miss a dose of Ohtuvayre, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and go back to your usual schedule. Do not take two doses at once.

What happens if I use too much Ohtuvayre?

If you use too much Ohtuvayre, call your healthcare provider or go to the nearest emergency room, especially if you have unusual symptoms such as a fast heartbeat, palpitations, or headache. Do not use extra doses of Ohtuvayre to relieve sudden COPD symptoms. Always keep a rescue inhaler with you for sudden symptoms, and ask your healthcare provider to prescribe one if you do not have it.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

In a drug interaction study, taking Ohtuvayre together with fluconazole (a medicine that blocks the liver enzyme CYP2C9) raised the level of ensifentrine in the blood, with about a 1.4 times higher peak level and a 1.6 times higher overall exposure. The clinical importance of this is not known. Ohtuvayre itself is not expected to change the blood levels of other medicines.

Talk to your healthcare provider about possible interactions with Ohtuvayre.

What should I tell my doctor before using Ohtuvayre?

Do not use Ohtuvayre if you have had an allergic reaction to ensifentrine or to any of the inactive ingredients in Ohtuvayre.

Before using Ohtuvayre, tell your healthcare provider about all of your medical conditions, including if you:

• Have or have had mental health problems, including depression or suicidal thoughts or behavior
• Have liver problems (Ohtuvayre is used with caution because blood levels of the medicine can be higher)
• Are pregnant or plan to become pregnant
• Are breastfeeding

Ohtuvayre has not been studied in children and should not be used in children.

Can I use Ohtuvayre while pregnant or breastfeeding?

There are no data on the use of Ohtuvayre in pregnant women, so it is not known whether it can harm an unborn baby. It is also not known whether ensifentrine passes into breast milk or how it might affect a breastfed child. Talk to your healthcare provider about the benefits and risks if you are pregnant, planning to become pregnant, or breastfeeding.

What are the common side effects of Ohtuvayre?

The most common side effects of Ohtuvayre, each reported in about 1% to 2% of people in clinical trials, are:

• Back pain
• High blood pressure (hypertension)
• Urinary tract infection (UTI)
• Diarrhea.

What are the serious side effects of Ohtuvayre?

Ohtuvayre can cause serious side effects, including:

Sudden breathing problems (paradoxical bronchospasm). Like other inhaled medicines, Ohtuvayre can cause sudden tightening of the airways, which can be life-threatening. If you have sudden breathing problems right after inhaling Ohtuvayre, use your rescue inhaler, stop using Ohtuvayre, and get medical help right away.

Mental health changes, including suicidal thoughts or behavior. Ohtuvayre has been linked to an increase in psychiatric side effects, such as trouble sleeping, anxiety, and depression. Call your healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worrying:

• Thoughts of suicide or dying, or attempting suicide
• New or worse anxiety or depression
• Trouble sleeping (insomnia)
• Acting on dangerous impulses
• Other unusual changes in behavior or mood

If you have a history of depression or suicidal thoughts or behavior, talk with your healthcare provider about the risks and benefits before starting Ohtuvayre.

Ohtuvayre should not be used to treat sudden breathing problems (it is not a rescue medicine).

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

Ohtuvayre (ensifentrine) blocks two enzymes in the lungs called phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4). These enzymes break down a cell messenger called cyclic AMP, which helps control how airway muscles relax and how the body manages inflammation.

By blocking PDE3, Ohtuvayre helps relax the airway muscles, which can ease wheezing, coughing, chest tightness, and shortness of breath. By blocking PDE4, it helps reduce inflammation in the lungs. Through this combined action, Ohtuvayre works on both the muscle tightening and the inflammation involved in COPD.

Ohtuvayre was studied in two 24-week, randomized, placebo-controlled trials called ENHANCE-1 and ENHANCE-2, which together enrolled 1,553 adults with moderate to severe COPD. Many participants were also using other COPD maintenance inhalers (such as a LAMA, a LABA, or a LABA/ICS combination) during the studies.

• Lung function: Both trials met their main goal. Compared with placebo, Ohtuvayre improved lung function (measured as FEV1, the amount of air a person can breathe out in 1 second) over the 12 hours after a dose, at week 12.
• Quality of life: In ENHANCE-1, more people taking Ohtuvayre had a meaningful improvement in COPD-related quality of life (measured by the St. George's Respiratory Questionnaire) than those on placebo, 58% compared with 46% at week 24. This quality-of-life benefit was not seen in ENHANCE-2.

Your healthcare provider can explain what these results may mean for your treatment.

The cost of Ohtuvayre depends on your insurance coverage.

• People with commercial (private) insurance who are eligible for the manufacturer's copay program may pay as little as $0 per month.
• If you do not have insurance, are underinsured, or your coverage is delayed, a patient support program may be able to help.

Ohtuvayre is available only through specialty pharmacies. For current cost-assistance options, check the official Ohtuvayre website or ask your specialty pharmacy.

What is the usual dose of Ohtuvayre?

• The recommended dose is 3 mg (one unit-dose ampule) inhaled twice daily, once in the morning and once in the evening, using a standard jet nebulizer with a mouthpiece.
• Do not use more than one ampule per inhalation or more than two ampules per day.

Kidney and liver considerations:

• No dose change is needed for mild or moderate kidney problems. Ohtuvayre has not been studied in severe kidney problems.
• Use Ohtuvayre with caution if you have liver problems, because blood levels of the medicine can be higher.

• Store Ohtuvayre at room temperature between 68°F and 77°F (20°C and 25°C). Brief exposure between 59°F and 86°F (15°C and 30°C) is allowed.
• Keep the ampules in the protective foil pouch and stand them upright. Do not store them upside down.
• Only open the foil pouch and remove an ampule right before you use it. For pouches that hold 5 ampules, put the remaining ampules back into the pouch upright. Once a foil pouch has been opened, throw away any ampules not used within 14 days.
• Protect from direct sunlight and excessive heat. Do not freeze.
• Do not use Ohtuvayre after the expiration date printed on the pouch and ampule.
• Keep Ohtuvayre and all medicines out of the reach of children.

Active ingredient: ensifentrine

Inactive ingredients: dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 20, sodium chloride, sorbitan monolaurate, and water for injection.

Each unit-dose ampule contains a 3 mg/2.5 mL aqueous suspension of ensifentrine.