Included as part of the "PRECAUTIONS" Section
Potential Impacts On Cardiovascular Disease
Alpha-adrenergic agonists may impact blood pressure. UPNEEQ should be used with caution in patients with severe or unstable cardiovascular disease, orthostatic hypotension, and uncontrolled hypertension or hypotension. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens.
Potentiation Of Vascular Insufficiency
UPNEEQ should be used with caution in patients with cerebral or coronary insufficiency, or Sjogren’s syndrome. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop.
Risk Of Angle Closure Glaucoma
UPNEEQ may increase the risk of angle closure glaucoma in patients with untreated narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute angle closure glaucoma develop.
Risk Of Contamination
Patients should not touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.
Patient Counseling Information
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).
When To Seek Medical Care
- Alpha-adrenergic agonists as a class may impact blood pressure. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension or hypotension to seek medical care if their condition worsens [see WARNINGS AND PRECAUTIONS].
- Use with caution in patients with cerebral or coronary insufficiency or Sjögren’s syndrome and advise patients to seek medical care if signs and symptoms of potentiation of vascular insufficiency develop [see WARNINGS AND PRECAUTIONS].
- Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle glaucoma develop [see WARNINGS AND PRECAUTIONS].
Use With Contact Lenses
Advise patients that contact lenses should be removed prior to administration of UPNEEQ and can be re-inserted 15 minutes following administration [see DOSAGE AND ADMINISTRATION].
Use With Other Ophthalmic Drugs
If more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications.
Advise patients that the solution from one single patient-use container is to be used immediately after opening to dose one or both eye(s). The single patient-use container, including any remaining contents, should be discarded immediately after administration [see DOSAGE AND ADMINISTRATION].
Storage And Handling Instructions
Handling The Single Patient-Use Container
Advise patients not to touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.
Instruct patients to keep the foil-pouched, single patient-use containers sealed within the child-resistant zipper bag until ready to use. Keep out of reach of children.
To report SUSPECTED ADVERSE REACTIONS, contact RVL Pharmaceuticals, Inc. at 1-877-4823788 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Oxymetazoline hydrochloride was not associated with an increased incidence of neoplastic or proliferative changes in transgenic mice given oral doses of 0.5, 1.0, or 2.5 mg/kg/day oxymetazoline hydrochloride for 6 months.
Oxymetazoline hydrochloride revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo gentoxicity test (mouse micronucleus assay).
Impairment Of Fertility
Effects on fertility and early embryonic development were evaluated in rats following oral administration of 0.05, 0.1, or 0.2 mg/kg/day oxymetazoline hydrochloride prior to and during mating and through early pregnancy. Decreased number of corpora lutea and increased post-implantation losses were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (28 times the MRHOD, on a dose comparison basis). However, no treatment related effects on mating parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride.
Use In Specific Populations
There are no available data on UPNEEQ use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there were no adverse developmental effects observed after oral administration of oxymetazoline hydrochloride in pregnant rats and rabbits at systemic exposures up to 7 and 278 times the maximum recommended human ophthalmic dose (MRHOD), respectively, based on dose comparison. [see Data]. The estimated background risks of major birth defects and miscarriage for the indicated population are 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 2-4% and 15-20%, respectively.
Effects on embryo-fetal development were evaluated in rats and rabbits following oral administration of oxymetazoline hydrochloride during the period of organogenesis. Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 0.2 mg/kg/day in pregnant rats during the period of organogenesis (28 times the MRHOD, on a dose comparison basis). Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 1 mg/kg/day in pregnant rabbits during the period of organogenesis (278 times the MRHOD, on a dose comparison basis).
Maternal toxicity, including decreased maternal body weight, was produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification.
In a rat prenatal and postnatal development study, oxymetazoline hydrochloride was orally administered to pregnant rats once daily from gestation day 6 through lactation day 20. Maternal toxicity was produced at the high dose of 0.2 mg/kg/day (28 times the MRHOD, on a dose comparison basis) in pregnant rats and was associated with an increase in pup mortality and reduced pup body weights. Delayed sexual maturation was noted at 0.1 mg/kg/day (14 times the MRHOD on a dose comparison basis). Oxymetazoline hydrochloride did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (7 times the MRHOD, on a dose comparison basis).
No clinical data are available to assess the effects of oxymetazoline on the quantity or rate of breastmilk production, or to establish the level of oxymetazoline present in human breastmilk post-dose. Oxymetazoline was detected in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for UPNEEQ and any potential adverse effects on the breastfed child from UPNEEQ.
Safety and effectiveness of UPNEEQ have not been established in pediatric patients under 13 years of age.
Three hundred and fifteen subjects aged 65 years and older received treatment with UPNEEQ (n = 216) or vehicle (n = 99) in clinical trials. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects.