PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - 30 g Tube Carton

NDC 71403-003-30

Rhofade®
(oxymetazoline
hydrochloride) cream, 1%*

*Each gram of RHOFADE® cream contains 10 mg
of oxymetazoline hydrochloride, equivalent to
8.8 mg of oxymetazoline free base

For Topical Use Only
Keep Out of Reach of Children

EPIHEALTH
Advancing Dermatology

Rx only
30 g

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WARNINGS AND PRECAUTIONS SECTION

Highlight: * 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. (5.1)

• Use with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangiitis obliterans, scleroderma, or Sjögren's syndrome and advise patients to seek medical care if signs and symptoms of potentiation of vascular insufficiency develop. (5.2)
• Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle glaucoma develop. (5.3)

5 WARNINGS AND PRECAUTIONS

5.1 Potential Impacts on Cardiovascular Disease

Alpha-adrenergic agonists may impact blood pressure. RHOFADE cream should be used with caution in patients with severe or unstable or uncontrolled 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.

5.2 Potentiation of Vascular Insufficiency

RHOFADE cream should be used with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangiitis obliterans, scleroderma, or Sjögren's syndrome. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop.

5.3 Risk of Angle Closure Glaucoma

RHOFADE cream may increase the risk of angle closure glaucoma in patients with narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute angle closure glaucoma develop.

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DRUG INTERACTIONS SECTION

7 DRUG INTERACTIONS

7.1 Anti-hypertensives/Cardiac Glycosides

Alpha-adrenergic agonists, as a class, may impact blood pressure. Caution in using drugs such as beta-blockers, anti-hypertensives and/or cardiac glycosides is advised.

Caution should also be exercised in patients receiving alpha1 adrenergic receptor antagonists such as in the treatment of cardiovascular disease, benign prostatic hypertrophy, or Raynaud's disease.

7.2 Monoamine Oxidase Inhibitors

Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

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ADVERSE REACTIONS SECTION

Highlight: Most common adverse reactions (incidence ≥ 1%) are application site dermatitis, worsening inflammatory lesions of rosacea, application site pruritis, application site erythema, and application site pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact EPI Health, LLC at 1-800-499-4468 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 489 subjects with persistent facial erythema associated with rosacea were treated with RHOFADE cream once daily for 4 weeks in 3 controlled clinical trials. An additional 440 subjects with persistent facial erythema associated with rosacea were also treated with RHOFADE cream once daily for up to one year in a long-term (open-label) clinical trial. Adverse reactions that occurred in at least 1% of subjects treated with RHOFADE cream through 4 weeks of treatment are presented in Table 1 below.

Table 1: Adverse Reactions Reported by ≥ 1% of Subjects through 4 Weeks of Treatment in Controlled Clinical Trials

In the long-term (open-label) clinical trial, the rates of adverse reactions over a one-year treatment period were as follows: worsening inflammatory lesions of rosacea (3%), application site dermatitis (3%), application site pruritis (2%), application site pain (2%), and application site erythema (2%). Subjects with persistent erythema along with inflammatory lesions were allowed to use additional therapy for the inflammatory lesions of rosacea.

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

RHOFADE cream was evaluated for the treatment of persistent erythema associated with rosacea in two identical, randomized, double-blind, vehicle- controlled, parallel-group clinical trials. The trials enrolled 885 subjects aged 18 years and older. Overall, 90% of subjects were Caucasian and 79% were female. Subjects applied either RHOFADE cream or vehicle once daily for 29 days.

Disease severity was graded by the clinician using a 5-point clinician erythema assessment (CEA) scale and by the subject on a similar 5-point subject self-assessment (SSA) scale, on which subjects scored either "moderate" or "severe" on both scales.

CEA and SSA were measured over a 12-hour period at equally-spaced timepoints (hours 3, 6, 9, and 12) post dose on Days 1, 15, and 29. The primary efficacy endpoint was defined as the proportion of subjects with at least a 2-grade reduction in erythema (improvement) from baseline (pre-dose on Day 1) on both the CEA and SSA measured at hours 3, 6, 9, and 12 on Day 29. The results from both trials on the composite endpoint for Day 29 are presented in Table 2.

Table 2: Proportion of Subjects Achieving Composite Success* on Day 29

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INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

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

Important Administration Instructions

Advise patients of the following:

• RHOFADE cream is for topical use only.
• RHOFADE cream pumps require priming before initial use and discard product from the first three pumps.
• Do not apply RHOFADE cream to irritated skin or open wounds.
• Avoid contact with the eyes and lips.
• Wash hands immediately after application.
• Keep RHOFADE cream out of reach of children.

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

RHOFADE® (oxymetazoline hydrochloride) cream, 1%, is a white to off-white cream. The product is available in a laminated tube and an airless pump polypropylene bottle in the following packaging configurations, each with a child-resistant closure:

Storage: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30ºC (59°F-86ºF) [see USP Controlled Room Temperature].

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