Understanding Potential Side Effects of Upneeq

Upneeq® (oxymetazoline hydrochloride ophthalmic solution), 0.1% is a prescription eye drop used to treat acquired blepharoptosis (low-lying eyelids) in adults. In clinical trials, Upneeq was shown to be safe and effective when used as directed. [2]

The most common adverse reactions, occurring in 1 to 5% of patients, were eye inflammation, eye redness, dry eye, blurred vision, eye pain at time of use, eye irritation, and headache. [2] These are not all of the possible side effects of Upneeq. Most reactions were mild: the majority of patients who used Upneeq reported no discomfort (95.5% of patients over 6 weeks and 92.0% over 12 weeks). [5]

Because low-lying eyelids can have several underlying causes, a healthcare provider should assess your specific condition before prescribing Upneeq. Tell your doctor your medical history and all of your symptoms.

What are the most common side effects of Upneeq?

In three controlled Phase 3 clinical trials, the most common adverse reactions with Upneeq (occurring in 1 to 5% of patients) were: [2]

• Eye inflammation (punctate keratitis)
• Eye redness (conjunctival hyperemia)
• Dry eye
• Blurred vision
• Eye pain at time of use (instillation site pain)
• Eye irritation
• Headache

These are not all of the possible side effects of Upneeq. Tell your doctor about any side effect that bothers you or does not go away, and call your doctor for medical advice about side effects. [2]

Tolerability in clinical trials was high. Almost all patients (94.9%) included in the trials completed every study visit, an indication that they were comfortable enough to continue daily dosing. [5]

Are Upneeq's side effects serious? Warnings and precautions

Most side effects are mild, but there are specific warnings and precautions you and your doctor should review before starting Upneeq. [2]

Effects on blood pressure and the cardiovascular system

Upneeq is a type of medication that may affect your blood pressure. If you have heart disease, uncontrolled high or low blood pressure, or feel faint at rest or when quickly standing up, call your doctor if your symptoms get worse. [2]

Reduced blood flow and Sjogren's syndrome

Patients with reduced blood flow to the brain or heart, or patients who experience eye or mouth dryness due to an immune system disorder (Sjogren's syndrome), should use care when taking Upneeq. Call your doctor immediately if you feel your symptoms may be getting worse. [2]

Narrow-angle glaucoma

Upneeq may increase the risk of eye pressure due to fluid buildup (angle-closure glaucoma) in patients with untreated narrow-angle glaucoma. Call your doctor immediately if you feel increased pressure in your eye after using Upneeq. [2]

Preventing eye injury and contamination

Do not let the tip of the Upneeq vial touch your eye or any other surface. This can help prevent eye injury or contamination. Each Upneeq vial is for one-time use and should be discarded after being used. [2]

Does Upneeq stop working over time?

In clinical trials, patients took Upneeq once a day for 6 weeks, and there was no evidence that the effect from once-daily application decreased with continued use. [2,4] Using Upneeq more often, or using more than one drop, is not shown to increase its effectiveness. [2]

What should my doctor know before prescribing Upneeq?

Your doctor should review your full medical history before prescribing Upneeq. Tell your doctor about all medicines you take, as some may interact with Upneeq: [2]

• Alpha-adrenergic agonists. Upneeq belongs to a class of medication (alpha-adrenergic agonists) that may affect blood pressure. Use Upneeq carefully if you take an alpha-adrenergic agonist to treat heart disease or an enlarged prostate.

• Blood pressure and heart-rhythm medicines. Patients taking beta-blockers, or other medications to treat hypertension or an abnormal heartbeat, should be careful when using Upneeq.

• MAO inhibitors. Patients who use a certain class of antidepressant medication (monoamine oxidase inhibitors) should also be careful when using Upneeq, as it may affect the way your body absorbs the medication.

Upneeq side effects for specific conditions

Certain conditions call for extra care. The guidance below reflects the Upneeq Patient FAQ. Always consult your eye care professional about your specific situation. [2]

What if I have dry eye?

Dry eye is one of the most common adverse reactions reported with Upneeq (occurring in 1 to 5% of patients). If you have dry eye and are considering Upneeq, tell your doctor about any side effect that bothers you or does not go away, and consult your eye care professional with any questions. [2]

What if I have glaucoma?

Upneeq may increase the risk of eye pressure due to fluid buildup (angle-closure glaucoma) in patients with untreated narrow-angle glaucoma. Call your doctor immediately if you feel increased pressure in your eye after using Upneeq. [2]

What if I have high blood pressure?

Upneeq is a type of medication that may affect your blood pressure. If you have heart disease, uncontrolled high or low blood pressure, or feel faint at rest or when quickly standing up, call your doctor if your symptoms get worse. If you have any questions about whether Upneeq is right for you, consult your doctor. [2]

What if I have Sjogren's syndrome?

If you have Sjogren's syndrome, you should use care when taking Upneeq. Call your doctor immediately if you feel your symptoms may be getting worse. [2]

What if I have had cataract surgery or LASIK?

Patients who have had cataract or LASIK surgery are not excluded from using Upneeq. Consult your eye care provider if you have questions about using Upneeq following cataract, LASIK, or any other eye surgery. [2]

Does Upneeq change eye color?

No. There is no evidence from clinical trials that Upneeq affects eye color or skin pigmentation. The active ingredient, oxymetazoline, has been well studied and is known to primarily act on a muscle of the eyelid. [2]

How to use Upneeq safely and reduce the chance of side effects

• Contact lenses. Remove contact lenses before using Upneeq and wait at least 15 minutes before placing them back in your eyes. [2]

• Other eye drops. If you use Upneeq with other eye (ophthalmic) medicines, wait at least 15 minutes between using Upneeq and the other medicines. [2]

• One drop, once daily. Use one drop in each affected eye, once a day. There is no evidence that using it more often, or using more than one drop, increases effectiveness. [2]

• Single use only. After you apply the daily dose, throw away the single patient-use container and any unused Upneeq. Do not save unused solution. [2]

• Avoid contamination. Do not let the tip of the vial touch your eye or any other surface. [2]

When should I contact my doctor?

Contact your doctor if you have any side effect that bothers you or does not go away, and for medical advice about side effects. Seek care promptly if you have heart or blood pressure symptoms that worsen, or if you feel increased pressure in your eye after using Upneeq. [2]

To report side effects or product complaints, contact RVL Pharmaceuticals at 1-877-482-3788. You may also report side effects to the FDA by calling 1-800-FDA-1088 or visit www.fda.gov/medwatch.

IMPORTANT SAFETY INFORMATION

(Preserve the current MLR-approved ISI block from the Prescribing Information. The language below reflects PM-US-UPN-1029 and must be reconciled against the latest approved ISI before publication.)

What is UPNEEQ?

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% is a prescription eyedrop used to treat acquired blepharoptosis (low-lying lids) in adults.

What warnings and precautions are associated with UPNEEQ?

• Low-lying lids may be related to conditions such as stroke and/or brain aneurysm, Horner syndrome, myasthenia gravis, loss of the ability to move eye muscles, eye infection and eye tumors. Tell your doctor if you have any of these conditions.

• UPNEEQ is a type of medication that may affect your blood pressure. If you have heart disease, uncontrolled high or low blood pressure, or feel faint at rest or when quickly standing up, you should call your doctor if your symptoms get worse.

• Patients with reduced blood flow to the brain or heart, or patients who experience eye or mouth dryness due to an immune system disorder (Sjogren's syndrome), should use care when taking UPNEEQ. Call your doctor immediately if you feel your symptoms may be getting worse.

• UPNEEQ may increase the risk of eye pressure due to fluid buildup (angle-closure glaucoma) in patients with untreated narrow-angle glaucoma. Call your doctor immediately if you feel increased pressure in your eye after using UPNEEQ.

• Do not let the tip of the UPNEEQ vial touch your eye or any other surface. This can help prevent eye injury or contamination. Each UPNEEQ vial is for one-time use and should be discarded after being used.

What are the most common side effects of UPNEEQ?

The most common adverse reactions with UPNEEQ (occurring in 1-5% of patients) were eye inflammation, eye redness, dry eye, blurred vision, eye pain at time of use, eye irritation, and headache. These are not all of the possible side effects of UPNEEQ. Tell your doctor if you have any side effect that bothers you or does not go away. Call your doctor for medical advice about side effects.

What should my doctor know about before prescribing me UPNEEQ?

• Your doctor should review your full medical history before prescribing UPNEEQ.

• UPNEEQ belongs to a class of medication (alpha-adrenergic agonists) that may affect your blood pressure. Use UPNEEQ carefully if you currently take an alpha-adrenergic agonist medication to treat heart disease or an enlarged prostate. Patients taking beta-blockers, or other medications to treat hypertension or an abnormal heartbeat, should also be careful when using UPNEEQ.

• Patients who use a certain class of antidepressant medication (monoamine oxidase inhibitors) should also be careful when using UPNEEQ, as it may affect the way your body absorbs the medication.

To report side effects or product complaints, contact RVL Pharmaceuticals at 1-877-482-3788. You may also report side effects to the FDA by calling 1-800-FDA-1088 or visit www.fda.gov/medwatch. This is a summary of the most important safety information for UPNEEQ. For more in-depth safety information, please review the full Prescribing Information for UPNEEQ.

Please see accompanying full Prescribing Information and Patient Information.

Resources List

1. Finsterer J. Ptosis: causes, presentation, and management. Aesthetic Plast Surg. 2003;27(3):193-204.

2. Upneeq (oxymetazoline hydrochloride ophthalmic solution), 0.1%. Prescribing Information. RVL Pharmaceuticals, Inc. 2021.

3. Bacharach J, Wirta DL, Smyth-Medina R, et al. Rapid and sustained eyelid elevation in acquired blepharoptosis with oxymetazoline 0.1%: randomized phase 3 trial results. Clin Ophthalmol. 2021;15:2743-2751.

4. Slonim CB, Foster S, Jaros M, et al. Association of oxymetazoline hydrochloride, 0.1%, solution administration with visual field in acquired ptosis: a pooled analysis of 2 randomized clinical trials. JAMA Ophthalmol. 2020;138(11):1168-1175.

5. Wirta DL, Korenfeld MS, Foster S, et al. Safety of once-daily oxymetazoline HCl ophthalmic solution, 0.1% in patients with acquired blepharoptosis: results from four randomized, double-masked clinical trials. Clin Ophthalmol. 2021;15:4035-4048.