Ensifentrine

FDA Drug Information • Also known as: Ohtuvayre

Brand Names: Ohtuvayre
Drug Class: Phosphodiesterase 3 Inhibitor [EPC], Phosphodiesterase 4 Inhibitor [EPC]
Route: RESPIRATORY (INHALATION)
Dosage Form: SUSPENSION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION OHTUVAYRE (ensifentrine) is a sterile, yellow to pale yellow aqueous inhalation suspension of ensifentrine for oral inhalation. Ensifentrine, the active component of OHTUVAYRE, is an inhibitor of phosphodiesterases 3 and 4 (PDE3 and PDE4). The chemical name for ensifentrine is N -(2-{(2 E )-9,10-dimethoxy-4-oxo-2-[(2,4,6-trimethylphenyl)imino]-6,7-dihydro-2 H -pyrimido[6,1- a ]isoquinolin-3(4 H )-yl}ethyl)urea; its structural formula is: Ensifentrine has a molecular weight of 477.56 and its empirical formula is C 26 H 31 N 5 O 4 . Ensifentrine is a yellow to pale yellow crystalline powder which is practically insoluble in water. OHTUVAYRE is supplied as 2.5 mL of sterile ensifentrine (1.2 mg/mL) suspension packaged in a unit-dose low-density polyethylene ampule overwrapped in a sealed foil pouch. Each unit-dose ampule contains 3 mg ensifentrine suspended in a pH 6.7 aqueous solution containing dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 20, sodium chloride, sorbitan monolaurate and water for injection. The ampule containing OHTUVAYRE should be shaken vigorously to ensure complete resuspension of the active ingredient immediately prior to administration by nebulization. Like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the nebulization system used, and compressor performance. Using the PARI LC Sprint® jet nebulizer attached to a PARI Vios Pro® compressor under in vitro conditions, the mean delivered dose from the mouthpiece was approximately 933 micrograms (31% of label claim) at a mean flow rate of approximately 5 liters per minute. The mean nebulization time was approximately 7 minutes. The mass median aerodynamic diameter (MMAD) of the nebulized particles/droplets using the PARI LC Sprint® jet nebulizer attached to a PARI Vios Pro® compressor (flow rate approximately 15 L per minute, nebulization time approximately 10 minutes) is 5.82 microns (geometric standard deviation =...

What Is Ensifentrine Used For?

1 INDICATIONS AND USAGE OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. OHTUVAYRE is a phosphodiesterase 3 (PDE3) inhibitor and phosphodiesterase 4 (PDE4) inhibitor indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dosage of OHTUVAYRE is 3 mg (one unit-dose ampule) twice daily, once in the morning and once in the evening, administered by oral inhalation using a standard jet nebulizer with a mouthpiece. Recommended Dosage : 3 mg (one ampule) twice daily administered by oral inhalation using a standard jet nebulizer with a mouthpiece. ( 2 ) See full prescribing information for administration instructions. ( 2 ) Administration Instructions Remove OHTUVAYRE unit-dose ampule from foil pouch only immediately before use. For pouches of 5 ampules, remove one ampule and place the remaining ampules back into the pouch until next use. Once the foil pouch is opened, discard ampules if not used within 14 days. Shake OHTUVAYRE ampule vigorously. Squeeze and completely empty contents of the ampule into the nebulizer cup for administration of OHTUVAYRE by oral inhalation. Discard ampule with any residual content. Administer OHTUVAYRE by oral inhalation using a standard jet nebulizer equipped with a mouthpiece, connected to an air compressor [see Instructions for Use ] . Drug Compatibility Compatibility of OHTUVAYRE mixed with other drugs has not been established. OHTUVAYRE should not be physically mixed with other drugs or added to solutions containing other drugs.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Paradoxical Bronchospasm [see Warnings and Precautions (5.2) ] Psychiatric Events Including Suicidality [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence greater and equal to 1% and more common than placebo) include back pain, hypertension, urinary tract infection, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Verona Pharma at 888-672-0371 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OHTUVAYRE was based on the pooled safety population from two randomized, double-blind, placebo-controlled trials (ENHANCE-1 and ENHANCE-2) for 24 weeks, and a 48-week cohort that assessed safety in ENHANCE-1. In these trials, a total of 975 patients received 3 mg of OHTUVAYRE twice daily administered by oral inhalation using a standard jet nebulizer [see Clinical Studies (14) ] . The safety population included all patients who were randomized and received at least one dose of OHTUVAYRE or placebo. Adverse reactions that occurred at an incidence greater than or equal to 1% in OHTUVAYRE and were more common than placebo in the pooled population are provided in Table 1. The proportion of patients who discontinued treatment due to adverse reactions was 7.6% for the OHTUVAYRE-treated patients and 8.2% for placebo-treated patients. Table 1. Adverse Reactions with OHTUVAYRE with incidence ≥ 1% and More Common than Placebo in Patients with COPD in the Pooled 24-Week Safety Population (ENHANCE-1 and ENHANCE-2) Adverse Reaction OHTUVAYRE N=975 n (%) Placebo N=574 n (%) Back pain 18 (1.8%) 6 (1.0%) Hypertension 17 (1.7%) 5 (0.9%) Urinary tract infection 13 (1.3%) 6 (1.0%) Diarrhea 10 (1.0%) 4 (0.7%) Adverse Reactions in the 48-Week Cohort In the 48-week cohort of ENHANCE-1, 369 patients were enrolled to be treated with 3 mg OHTUVAYRE (N=280) or placebo (N=89) twice daily for 48 weeks [see Clinical Studies (14) ] . The adverse reactions reported in the 48-week cohort were consistent with those observed in the pooled 24-week safety population.

Contraindications

4 CONTRAINDICATIONS OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product. OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on OHTUVAYRE 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. (see Data ) . 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. Data Animal Data In a male fertility study, ensifentrine was administered to male rats at inhalation doses of 2, 6, and 16 mg/kg/day (4, 13, and 30 times the exposure at the MRHDID) for 10 weeks prior to mating to untreated females. Adverse effects at 16 mg/kg/day (30 times the exposure at the MRHDID) on reproductive performance included increased pre- and post- implantation loss, and decreased live embryos per litter in untreated females. No developmental toxicity was observed in rats at 6 mg/kg/day (13 times the exposure at the MRHDID). In an embryo-fetal development study, pregnant rats were administered...

Overdosage

10 OVERDOSAGE An overdosage of OHTUVAYRE may lead to signs and symptoms such as headache, tachycardia, and palpitations. Treatment of overdosage consists of temporary interruption of OHTUVAYRE along with appropriate symptomatic and/or supportive therapy.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING OHTUVAYRE (ensifentrine) 3 mg/2.5 mL inhalation suspension is a sterile aqueous suspension in a unit-dose low-density polyethylene ampule. OHTUVAYRE is supplied as: Carton of 60: 60 pouches of 1 unit-dose ampule (NDC 83034-003-60) Carton of 60: 12 pouches of 5 unit-dose ampules (NDC 83034-003-65) Ampules are overwrapped in a sealed foil pouch. The ampule containing OHTUVAYRE should be shaken vigorously to ensure complete resuspension of the active ingredient immediately prior to use. The used ampule and any residual content should be discarded after use. Store OHTUVAYRE in the protective foil pouch. Only remove an ampule from foil pouch immediately before use. For pouches of 5 ampules, remove one ampule and place the remaining ampules back into the foil pouch until next use. Once the foil pouch is opened, discard ampules if not used within 14 days. Store at controlled room temperature (68°F to 77°F [20°C to 25°C], excursions permitted from 59ºF to 86ºF [15ºC to 30ºC]) [See USP Controlled Room Temperature], maintaining the orientation indicated on the carton. Protect from direct sunlight and excessive heat. Do not freeze.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.