Ensifentrine (Monograph)

Brand name: Ohtuvayre
Drug class: Dual Phosphodiesterase Inhibitors

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

Ensifentrine is an inhibitor of phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4).

Uses for Ensifentrine

Ensifentrine has the following uses:

Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

Ensifentrine Dosage and Administration

General

Ensifentrine is available in the following dosage form(s) and strength(s):

Inhalation suspension: 3 mg/2.5 mL aqueous suspension in unit-dose ampules.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Recommended dosage is 3 mg (one ampule) twice daily, once in the morning and once in the evening, administered by oral inhalation using a standard jet nebulizer with a mouthpiece.

• See full prescribing information for administration instructions.

Related/similar drugs

Breztri Aerosphere, Anoro Ellipta, prednisone, Symbicort, Breo Ellipta, Ventolin, Ventolin HFA

Cautions for Ensifentrine

Contraindications

Ensifentrine is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.

Warnings/Precautions

Acute Episodes of Bronchospasm

Ensifentrine should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Ensifentrine has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. The safety and effectiveness of ensifentrine for relief of acute symptoms have not been established. Acute symptoms should be treated with an inhaled, short-acting bronchodilator.

Paradoxical Bronchospasm

As with other inhaled medicines, ensifentrine may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with ensifentrine, it should be treated immediately with an inhaled, short-acting bronchodilator. Ensifentrine should be discontinued immediately and alternative therapy should be instituted.

Psychiatric Events Including Suicidality

Treatment with ensifentrine is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received ensifentrine. One patient who received ensifentrine in the pooled 24-week safety population experienced a suicide-related adverse reaction (suicide attempt), and in another controlled study, one patient who received ensifentrine experienced a suicide-related adverse reaction (suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] ensifentrine 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] ensifentrine 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients (0.4%) receiving ensifentrine and no patients receiving placebo.

Before initiating treatment with ensifentrine, healthcare providers should carefully weigh the risk and benefits of treatment in patients with a history of depression and/or suicidal thoughts or behavior. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with ensifentrine if such events occur.

Specific Populations

Pregnancy

There are no available data on ensifentrine use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, administration of inhaled ensifentrine at exposures 30 times the exposure at the maximum recommended human daily inhalation dose (MRHDID) to male rats for 10 weeks prior to mating with untreated females produced increased pre- and post- implantation loss, and decreased live embryos in untreated female rats. No adverse developmental effects were observed with inhalation administration of ensifentrine to pregnant rats and rabbits during organogenesis at maternal exposures up to 79 and 9 times the exposure at MRHDID, respectively. No adverse developmental effects were observed after inhaled administration of ensifentrine to pregnant rats from the period of organogenesis through lactation at exposures up to approximately 79 times the MRHDID.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of ensifentrine in human milk, the effects on the breastfed child, or the effects on milk production. There are no data from animal studies on the presence of ensifentrine in milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ensifentrine and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of ensifentrine have not been established in pediatric patients.

Geriatric Use

There were 852 patients 65 years of age and older in the ENHANCE-1 and ENHANCE-2 studies for COPD. Of the total number of patients randomized to receive ensifentrine in these trials, 534 (55%) were 65 years of age and older, while 84 (9%) were 75 years and older. No overall differences in safety or effectiveness of ensifentrine have been observed between these patients and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

Ensifentrine systemic exposure increased by 2.3-fold in subjects with moderate or severe hepatic impairment compared with healthy subjects. Use ensifentrine with caution in patients with hepatic impairment.

Renal Impairment

No dosage adjustment in patients with mild or moderate renal impairment is required. Patients with severe renal impairment have not been evaluated.

Common Adverse Effects

Most common adverse reactions (incidence greater and equal to 1% and more common than placebo) include back pain, hypertension, urinary tract infection, and diarrhea.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Ensifentrine is a small molecule that is an inhibitor of the PDE3 and PDE4 enzymes. PDE3 primarily hydrolyzes the second-messenger molecule cyclic adenosine monophosphate (cAMP) but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP). PDE4 hydrolyzes cAMP only. Inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of cAMP and/or cGMP, resulting in various downstream signalling effects.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

• Inform patients that ensifentrine is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose. Advise patients to treat acute symptoms with an inhaled, short-acting beta₂-agonist such as albuterol. Provide patients with such medicine and instruct them in how it should be used.

• Instruct patients to seek medical attention immediately if they experience any of the following: decreasing effectiveness of inhaled, short-acting beta₂-agonists; need for more inhalations than usual of inhaled, short-acting beta₂-agonists; or significant decrease in lung function as outlined by the health care provider.

• As with other inhaled medicines, ensifentrine can cause paradoxical bronchospasm. If paradoxical bronchospasm occurs, instruct patients to discontinue ensifentrine.

• Advise patients, caregivers, and families to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider so that the risks and benefits of continuing treatment with ensifentrine may be considered.

• Instruct patients that ensifentrine should only be administered via a standard jet nebulizer. Patients should be instructed not to inject or swallow ensifentrine. Patients should be instructed not to mix other medications with ensifentrine in a nebulizer.

• Inform patients to use the contents of one ampule of ensifentrine orally inhaled twice daily, once in the morning and once in the evening. Instruct patients to vigorously shake the drug to ensure complete resuspension of the active ingredient immediately prior to use.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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