UPNEEQ is indicated for the treatment of acquired blepharoptosis in adults.

Instill one drop of UPNEEQ into one or both ptotic eye(s) once daily. Discard the single patient-use container immediately after dosing.

Contact lenses should be removed prior to instillation of UPNEEQ and may be reinserted 15 minutes following its administration.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications.

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1%, equivalent to 0.09% as oxymetazoline base, is formulated for topical ocular delivery as a sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution.

None. 

Accidental oral ingestion of topical intended solutions (including ophthalmic solutions and nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep UPNEEQ out of reach of children.

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% contains oxymetazoline hydrochloride, an alpha adrenoceptor agonist. UPNEEQ is an aseptically prepared, sterile, non-preserved ophthalmic solution. The chemical name is 6-tert-Butyl-3-(2-imidazolin-2-ylmethyl)-2,4- dimethylphenol monohydrochloride, and the molecular mass is 296.84. Oxymetazoline HCl is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C16H24N2O∙HCl, and its structural formula is:

Each mL of UPNEEQ (oxymetazoline hydrochloride ophthalmic solution) 0.1% contains 1 mg of oxymetazoline hydrochloride, equivalent to 0.9 mg (0.09%) of oxymetazoline free base. The ophthalmic solution contains the following inactive ingredients: calcium chloride, hydrochloric acid (used to adjust pH to 5.8 to 6.8), hypromellose, magnesium chloride, potassium chloride, sodium acetate, sodium chloride, sodium citrate, and water for injection.

UPNEEQ was evaluated for the treatment of acquired blepharoptosis in two randomized, double-masked, vehicle-controlled, parallel-group clinical efficacy trials. Both studies were randomized in an approximate 2:1 ratio of active versus vehicle. Efficacy was assessed with the Leicester Peripheral Field Test (LPFT) (primary) and photographic measurement of Marginal reflex distance 1 (MRD1). The primary efficacy endpoints were ordered in a hierarchy to compare UPNEEQ to vehicle on the mean increase from baseline (Day 1 Hour 0) in number of points seen on the top 4 rows of the LPFT in the study eye at Hour 6 on Day 1 and Hour 2 on Day 14.

In Trial 1, a total of 140 subjects were randomized 94 patients to the UPNEEQ group and 46 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 64 years. In Trial 2, a total of 164 subjects were randomized 109 patients to the UPNEEQ group and 55 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 63 years.

In both trials, each patient had a designated study eye. The increases in the number of points seen in the superior visual field in the study eye of the UPNEEQ group compared to the vehicle group were statistically significant at both time points, showing that the improvement in superior visual field was evident at the 2-hour time point and maintained at the 6-hour time point. The results from both trials on the primary endpoint are presented below.

Observed and Change from Baseline in Mean Points Seen in Superior Visual Field on LPFT in the Study Eye at Primary Efficacy Time Points (ITT Population)

CL = confidence limit; LPFT = Leicester Peripheral Field Test; ITT (intent-to-treat) – included all randomized subjects
who received at least one dose of study medication; SD = standard deviation
a p-value and 95% CI were based on ANCOVA model adjusted for baseline LFPT points.

Marginal reflex distance 1 (MRD1), showed a positive effect with UPNEEQ treatment. Greater MRD1 increases were observed for the UPNEEQ group than the vehicle group on day 1 at 6 hours post dose and on day 14 at 2 hours post dose.

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% is an aseptically prepared, sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution; 0.3 mL fill in a clear, low-density polyethylene, single patient-use container in a child-resistant foil pouch.

Storage: Store at 20°C to 25°C (68°F to 77°F). Protect from excessive heat. Keep out of reach of children.

Store single patient-use containers in the child-resistant foil pouches. Opened containers should be discarded immediately after use.

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).

When to Seek Medical Care

• Ptosis may be associated with neurologic or orbital diseases such as stroke and/or cerebral aneurysm, Horner syndrome, myasthenia gravis, external ophthalmoplegia, orbital infection and orbital masses. Consideration should be given to these conditions in the presence of ptosis with decreased levator muscle function and/or other neurologic signs [see Warnings and Precautions (5.1)].
• 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 (5.2)].
• 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 (5.3)].
• Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle glaucoma develop [see Warnings and Precautions (5.4)].

Administration Instructions
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 (2)].

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.

Administration
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 (2)].

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.

Storage Information
Instruct patients to keep the single patient-use containers in the child-resistant foil pouches until ready to use. Keep out of reach of children.

To report SUSPECTED ADVERSE REACTIONS, contact RVL Pharmaceuticals, Inc. at 1-877-482-3788 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

© 2023 RVL Pharmaceuticals, Inc. All rights reserved.
Bridgewater, New Jersey 08807
Patents 8357714, 9867808, 10799481, 10814001, 10898573, 10912765, 10940138, 11103482, 11311515, 11324722, and 11541036

Made in the U.S.A.
Manufactured for:
RVL Pharmaceuticals, Inc.
PLR-UPN-00007-7                                                                                                                                                                 
IC # 2284

UPNEEQ® (up-NEEK)
(oxymetazoline hydrochloride ophthalmic solution), 0.1%
for topical ophthalmic use

Read this Instructions for Use before you start using UPNEEQ and each time you get a refill. There
may be new information. This leaflet does not take the place of talking to your healthcare provider
about your medical condition or your treatment.

UPNEEQ single patient-use container after removal from its individual child-resistant foil pouch 

Important Information You Need to Know Before Using UPNEEQ

• UPNEEQ is for use in the eye.
• UPNEEQ can be harmful if swallowed.
• UPNEEQ is supplied as single patient-use containers individually packaged in a child-resistant foil pouch. Do not remove a single patient-use container from the child-resistant foil pouch until you are ready to use UPNEEQ.
• Wash your hands before each use to make sure you do not infect your eyes while using UPNEEQ.
• If you are using UPNEEQ with other eye (ophthalmic) medicines, you should wait at least 15 minutes between using UPNEEQ and the other medicines.
• If you wear contact lenses, remove them before using UPNEEQ. You should wait at least 15
  minutes before placing them back into your eyes.
  

Using UPNEEQ

• Do not let the tip of the UPNEEQ single patient-use container touch your eye or any other surfaces to avoid contamination or injury to your eye.
• Use 1 drop of UPNEEQ in the affected eye 1 time each day.
• Each single patient-use container of UPNEEQ will give you enough medicine to treat both eyes 1 time each day if needed.
• There is some extra UPNEEQ in each single patient-use container in case you miss getting the drop into your eye.

Storing UPNEEQ

• Store UPNEEQ at room temperature between 68°F to 77°F (20°C to 25°C).
• Store UPNEEQ single patient-use containers in the child-resistant foil pouches they come in.
• Protect UPNEEQ from excessive heat.
• Keep UPNEEQ and all medicines out of the reach of children.

Disposing of UPNEEQ

• After you have applied the daily dose of medicine, throw away (dispose of) the single patient-use container and any unused UPNEEQ.
• Do not save any unused UPNEEQ.

Follow Step 1 to Step 11 each time you use UPNEEQ:

Step 1. Remove 1 UPNEEQ child-resistant foil-pouch   from the carton.  Step 2. Make sure the single patient-use container within the foil is moved completely away from the dotted line (see Figure A). Step 3. Cut the foil along the dotted line using scissors (see Figure B).	Figure A Figure B
Step 4. Remove the single patient-use container from the foil pouch and then hold it by the long flat end (see Figure C).	Figure C
Step 5. Hold the single patient-use container upright and tap the top of the container gently to make sure that the medicine is in the bottom part of the container (see Figure D).	Figure D

Step 6. Open the single patient-use container by twisting off the tab (see Figure E). Do not let the tip of the container touch your eye or any other surfaces.	Figure E
Step 7. Tilt your head backwards. If you are not able to tilt your head, lie down. Step 8. Gently pull your lower eyelid downwards and look up (see Figure F).	Figure F
Step 9. Place the tip of the single patient-use container close to your eye, but be careful not to touch your eye with it (see Figure G). Step 10. Gently squeeze the single patient-use container and let 1 drop of UPNEEQ fall into the space between your lower eyelid and your eye (see Figure G). If a drop misses your eye, try again.	Figure G
Step 11. Repeat Step 7 to Step 10 for your other eye if instructed to do so by your healthcare provider. There is enough UPNEEQ in one container for both eyes if needed. After you have applied the daily dose of UPNEEQ, throw away the opened single patient-use container with any remaining medicine.  Be sure to keep this medicine away from children. If you use contact lenses, wait at least 15 minutes before placing them back into your eyes.

Manufactured for:
RVL Pharmaceuticals, Inc.
Bridgewater, NJ 08807
1-877-482-3788
PLR-UPN-00007-7

This Instruction for Use has been approved by the U.S. Food and Drug Administration.
Approved: August 2020

UPNEEQ 30ct Trade Carton

NDC: 73687-062-32

UPNEEQ Trade Foil Pouch

NDC: 73687-062-70

Upneeq Trade Foil Rev. 112021

UPNEEQ 45ct Trade Carton

NDC: 73687-062-45