Ohtuvayre
(ensifentrine)Dosage & Administration
Recommended Dosage: 3 mg (one ampule) twice daily administered by oral inhalation using a standard jet nebulizer with a mouthpiece.
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Ohtuvayre Prescribing Information
OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.
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.
Administration Instructions
- Remove OHTUVAYRE unit-dose ampule from foil pouch only immediately before use.
- 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.
Inhalation suspension: 3 mg/2.5 mL (1.2 mg/mL) of sterile, yellow to pale yellow, aqueous suspension in low-density polyethylene unit-dose ampules.
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 ensifentrine at inhalation doses of up to 15 mg/kg/day (79 times the exposure at the MRHDID) during the period of organogenesis from gestation Days 6 to 17. Ensifentrine did not cause adverse effects to the fetus at exposures up to 79 times the MRHDID (on an AUC basis at a maternal inhalation dose of 15 mg/kg/day).
In an embryo-fetal development study, pregnant rabbits were administered ensifentrine at inhalation doses of up to 12 mg/kg/day (9 times the exposure at the MRHDID) during the period of organogenesis from gestation Days 6 to 19. Ensifentrine did not cause adverse effects to the fetus at maternal exposures up to 9 times the MRHDID.
In a pre- and post-natal development (PPND) study, pregnant rats were administered ensifentrine at inhalation doses of up to 19 mg/kg/day (approximately 79 times the exposure at the MRHDID) from gestation day 6 to lactation/post-partum day 24. No adverse effects were observed in the offspring exposed daily from birth (in utero) through lactation at maternal pulmonary deposited doses up to approximately 79 times the MRHDID.
Lactation
Risk Summary
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 OHTUVAYRE and any potential adverse effects on the breastfed child from OHTUVAYRE or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of OHTUVAYRE have not been established in pediatric patients.
Geriatric Use
There were 852 patients aged 65 years and older in ENHANCE-1 and ENHANCE-2 for COPD [see CLINICAL STUDIES (14)]. Of the total number of patients randomized to receive OHTUVAYRE 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 OHTUVAYRE 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 [see Clinical Pharmacology (12.3)]. Use OHTUVAYRE 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 [see Clinical Pharmacology (12.3)].
OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.
Acute Episodes of Bronchospasm
OHTUVAYRE should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. OHTUVAYRE has not been studied in the relief of acute symptoms and extra doses of OHTUVAYRE should not be used for that purpose. The safety and effectiveness of OHTUVAYRE 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, OHTUVAYRE may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with OHTUVAYRE, it should be treated immediately with an inhaled, short-acting bronchodilator. OHTUVAYRE should be discontinued immediately and alternative therapy should be instituted.
Psychiatric Events Including Suicidality
Treatment with OHTUVAYRE 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 OHTUVAYRE. One patient who received OHTUVAYRE in the pooled 24-week safety population [see Adverse Reactions (6.1)] 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%] OHTUVAYRE 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] OHTUVAYRE 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 OHTUVAYRE and no patients receiving placebo.
Before initiating treatment with OHTUVAYRE, healthcare providers should carefully weigh the risk and benefits of treatment with OHTUVAYRE 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 OHTUVAYRE if such events occur.