Version July 2025
Chronic obstructive pulmonary disease, maintenance: Nebulization suspension: Oral inhalation: 3 mg twice daily.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (Child-Turcotte-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.
Moderate to severe impairment (Child-Turcotte-Pugh class B or C): There are no dosage adjustments provided in the manufacturer's labeling; however, systemic exposure increased by ~2.3-fold; use with caution.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
1% to 10%:
Cardiovascular: Hypertension (2%)
Gastrointestinal: Diarrhea (1%)
Neuromuscular & skeletal: Back pain (2%)
<1%: Nervous system: Adjustment disorder (with depressed mood), depression, major depressive disorder, suicidal tendencies
Hypersensitivity to ensifentrine or any component of the formulation.
Concerns related to adverse effects:
• Bronchospasm: Paradoxical bronchospasm that may be life threatening may occur with use of inhaled bronchodilating agents; this reaction should be distinguished from inadequate response. Discontinue immediately if paradoxical bronchospasm occurs and institute alternative therapy.
• Neuropsychiatric events: An increase in psychiatric adverse reactions (eg, anxiety, depression, insomnia, suicide attempt) have been reported. Before initiating treatment, carefully weigh the risks and benefits of treatment in patients with a history of depression and/or suicidal thoughts or behavior.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; systemic exposure is increased.
Other warnings/precautions:
• Appropriate use: Not indicated for the initial (rescue) treatment of acute episodes of bronchospasm; acute symptoms should be treated with a short-acting bronchodilator.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Inhalation:
Ohtuvayre: 3 mg/2.5 mL (2.5 mL)
No
Suspension (Ohtuvayre Inhalation)
3 mg/2.5 mL (per mL): $23.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Inhalation: Nebulization suspension: Remove ampule from sealed foil pouch immediately before use; shake vigorously to ensure complete resuspension. Squeeze and completely empty contents of the ampule into the nebulizer cup. Use with standard jet nebulizer equipped with a mouthpiece and connected to an air compressor. Do not ingest or inject contents of ampule. Do not mix with other medications; also refer to institution-specific policies.
Chronic obstructive pulmonary disease, maintenance: Maintenance treatment of chronic obstructive pulmonary disease in adults.
Substrate of BCRP, CYP2C9 (Minor), CYP2D6 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
There are no known significant interactions.
Adverse events were not observed in animal reproduction studies following administration of ensifentrine via inhalation to pregnant rats.
It is not known if ensifentrine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
FEV1, forced vital capacity, and/or other pulmonary function tests; signs/symptoms of psychiatric adverse reactions. Monitor for increased use of short-acting beta2-agonist inhalers; may be marker of a deteriorating condition.
Ensifentrine is a dual inhibitor of phosphodiesterase 3 (PDE3) and 4 (PDE4) enzymes. PDE3 primarily hydrolyzes second-messenger molecule cyclic adenosine monophosphate (cAMP) but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP). PDE4 hydrolyzes cAMP only. Inhibition results in accumulation of intracellular levels of cAMP and/or cGMP, resulting in various downstream signaling effects.
Absorption: ~90% delivered to lung upon inhalation.
Distribution: Healthy subjects: 2,700 L (apparent central), 1,820 L (peripheral volume); chronic obstructive pulmonary disease patients: 8,150 L (apparent central) and 5,490 L (peripheral volume).
Protein binding: ~90%.
Metabolism: Primary metabolic routes are oxidative (hydroxylation, O-demethylation) followed by conjugation (eg, glucuronidation); predominantly metabolized by CYP2C9 and to a lesser extent by CYP2D6.
Half-life elimination: 10.6 to 12.6 hours.
Time to peak: 0.6 to 1.5 hours.
Excretion: Feces (majority); urine (<0.3% unchanged).
Hepatic function impairment: Cmax and AUCinf increased ~2.3-fold and 2.2-fold in subjects with moderate hepatic impairment and ~1.2-fold and 2.3-fold in subjects with severe hepatic impairment.
