Rhofade (Oxymetazoline Hydrochloride): Uses, Dosage, Side Effects & Warnings

Q: Who makes Rhofade?

Rhofade is listed by 2 labelers in the FDA NDC directory, including EPI Health, LLC, Mayne Pharma.

Uses

Oxymetazoline Hydrochloride Cream, 1% is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. Oxymetazoline Hydrochloride Cream is an alpha 1A adrenoceptor agonist indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. ( 1 )

Dosage and administration

For topical use only. Oxymetazoline Hydrochloride Cream is not for oral, ophthalmic, or intravaginal use. Apply a pea-sized amount of Oxymetazoline Hydrochloride Cream, once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. Wash hands immediately after applying Oxymetazoline Hydrochloride Cream. Not for oral, ophthalmic, or intravaginal use. ( 2 ) Prime pump bottle before initial use and discard product from first three pumps. ( 2 ) Apply a pea-sized amount once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. ( 2 ) Wash hands after application. ( 2 )

Dosage forms and strengths

Oxymetazoline Hydrochloride Cream, 1% is a white to off-white cream. Each gram of cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base. Cream, 1%. Each gram of cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

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 ) 5.1 Potential Impacts on Cardiovascular Disease Alpha-adrenergic agonists may impact blood pressure. Oxymetazoline Hydrochloride 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 Oxymetazoline Hydrochloride Cream should be used with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangitis 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 Oxymetazoline Hydrochloride 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.

Side effects

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 Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 Oxymetazoline Hydrochloride 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 Oxymetazoline Hydrochloride 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 Oxymetazoline Hydrochloride 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 Adverse Reaction Pooled Controlled Clinical Trials Oxymetazoline HCl Cream (N = 489) Vehicle Cream (N = 483) Application site dermatitis 9 (2%) 0 Worsening inflammatory lesions of rosacea 7 (1%) 1 (<1%) Application site pruritus 5 (1%) 4 (1%) Application site erythema 5 (1%) 2 (<1%) Application site pain 4 (1%) 1 (<1%) 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.

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 alpha 1 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.

Use in specific populations

8.1 Pregnancy Risk Summary There are no available data on Oxymetazoline Hydrochloride Cream use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. A literature article describing intranasal decongestant use in pregnant women identified a potential association between second-trimester exposure to oxymetazoline (with no decongestant exposure in the first trimester) and renal collecting system anomalies [see Data ] . 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 3 times and 73 times, respectively, the exposure associated with the maximum recommended human dose (MRHD) [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. Clinical Considerations Fetal/Neonatal Adverse Reactions Following repeated use of oxymetazoline hydrochloride solution nasal spray for the treatment of nasal congestion at a dose 5 times higher than recommended, one case of fetal distress was reported in a 41-week pregnant patient. The fetal distress resolved hours later, prior to the delivery of the healthy infant. The anticipated exposures for the case are 8- to 18-fold higher than plasma exposures after topical administration of Oxymetazoline Hydrochloride Cream. Data Human Data No adequate and well-controlled trials of Oxymetazoline Hydrochloride Cream have been conducted in pregnant women. Across all clinical trials of Oxymetazoline Hydrochloride Cream, two pregnancies were reported. One pregnancy resulted in the delivery of a healthy child. One pregnancy resulted in a spontaneous abortion, which was considered to be unrelated to the trial medication. A literature article summarizing the results of exploratory analyses of intranasal decongestant use during pregnancy identified a potential association between second-trimester exposure to oxymetazoline hydrochloride solution (with no decongestant exposure in the first trimester) and renal collecting system anomalies. Animal Data 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 (3 times the MRHD on an AUC 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 (73 times the MRHD on an AUC comparison basis). Maternal toxicity, such as 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 perinatal 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 (3 times the MRHD on an AUC 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 and 0.2 mg/kg/day (2 times the MRHD and 3 times the MRHD on an AUC comparison basis, respectively). Oxymetazoline hydrochloride did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (one-half of the MRHD on an AUC comparison basis). 8.2 Lactation 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 Oxymetazoline Hydrochloride Cream and any potential adverse effects on the breastfed child from Oxymetazoline Hydrochloride Cream or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of Oxymetazoline Hydrochloride Cream have not been established in pediatric patients below the age of 18 years. 8.5 Geriatric Use One hundred and ninety-three subjects aged 65 years and older received treatment with Oxymetazoline Hydrochloride Cream (n = 135) or vehicle (n = 58) in clinical trials. No overall differences in safety or effectiveness were observed between subjects ≥ 65 years of age and younger subjects, based on available data. Clinical studies of Oxymetazoline Hydrochloride Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Pregnancy

8.1 Pregnancy Risk Summary There are no available data on Oxymetazoline Hydrochloride Cream use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. A literature article describing intranasal decongestant use in pregnant women identified a potential association between second-trimester exposure to oxymetazoline (with no decongestant exposure in the first trimester) and renal collecting system anomalies [see Data ] . 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 3 times and 73 times, respectively, the exposure associated with the maximum recommended human dose (MRHD) [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. Clinical Considerations Fetal/Neonatal Adverse Reactions Following repeated use of oxymetazoline hydrochloride solution nasal spray for the treatment of nasal congestion at a dose 5 times higher than recommended, one case of fetal distress was reported in a 41-week pregnant patient. The fetal distress resolved hours later, prior to the delivery of the healthy infant. The anticipated exposures for the case are 8- to 18-fold higher than plasma exposures after topical administration of Oxymetazoline Hydrochloride Cream. Data Human Data No adequate and well-controlled trials of Oxymetazoline Hydrochloride Cream have been conducted in pregnant women. Across all clinical trials of Oxymetazoline Hydrochloride Cream, two pregnancies were reported. One pregnancy resulted in the delivery of a healthy child. One pregnancy resulted in a spontaneous abortion, which was considered to be unrelated to the trial medication. A literature article summarizing the results of exploratory analyses of intranasal decongestant use during pregnancy identified a potential association between second-trimester exposure to oxymetazoline hydrochloride solution (with no decongestant exposure in the first trimester) and renal collecting system anomalies. Animal Data 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 (3 times the MRHD on an AUC 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 (73 times the MRHD on an AUC comparison basis). Maternal toxicity, such as 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 perinatal 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 (3 times the MRHD on an AUC 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 and 0.2 mg/kg/day (2 times the MRHD and 3 times the MRHD on an AUC comparison basis, respectively). Oxymetazoline hydrochloride did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (one-half of the MRHD on an AUC comparison basis).

Pediatric use

8.4 Pediatric Use Safety and effectiveness of Oxymetazoline Hydrochloride Cream have not been established in pediatric patients below the age of 18 years.

Geriatric use

8.5 Geriatric Use One hundred and ninety-three subjects aged 65 years and older received treatment with Oxymetazoline Hydrochloride Cream (n = 135) or vehicle (n = 58) in clinical trials. No overall differences in safety or effectiveness were observed between subjects ≥ 65 years of age and younger subjects, based on available data. Clinical studies of Oxymetazoline Hydrochloride Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Overdosage

Oxymetazoline Hydrochloride Cream is not for oral use. If oral ingestion occurs, seek medical advice. Monitor patient closely and administer appropriate supportive measures as necessary. Accidental ingestion of topical solutions (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 Oxymetazoline Hydrochloride Cream out of reach of children.

Description

Oxymetazoline Hydrochloride Cream, 1% contains oxymetazoline hydrochloride, an alpha 1A adrenoceptor agonist. Oxymetazoline Hydrochloride Cream is a white to off-white cream. It has a chemical name of 3-[(4,5-Dihydro1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)- 2,4-dimethyl-phenol hydrochloride and a molecular weight of 296.8. It 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 C 16 H 25 ClN 2 O and its structural formula is: Each gram of Oxymetazoline Hydrochloride Cream, 1% contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base. The cream contains the following inactive ingredients: sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water. Chemical Structure

Mechanism of action

12.1 Mechanism of Action Oxymetazoline is an alpha 1A adrenoceptor agonist. Oxymetazoline acts as a vasoconstrictor.

How supplied

Oxymetazoline Hydrochloride Cream, 1%, is a white to off-white cream. The product is available in a laminated tube in the following packaging configuration, each with a child-resistant closure: NDC 68308-766-30 30 gram tube 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].

Storage

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].

Patient 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: Oxymetazoline Hydrochloride Cream is for topical use only. Do not apply Oxymetazoline Hydrochloride Cream to irritated skin or open wounds. Avoid contact with the eyes and lips. Wash hands immediately after application. Keep Oxymetazoline Hydrochloride Cream out of reach of children.

Active ingredients

Oxymetazoline Hydrochloride in 3 products

Rhofade NDC products (3)

NDC	Strength & form	Labeler	Type
71403-003	Oxymetazoline Hydrochloride 1 g/100g Cream	EPI Health, LLC	NDA
51862-765	Oxymetazoline Hydrochloride 10 mg/g Cream	Mayne Pharma	NDA
68308-766	Oxymetazoline Hydrochloride 10 mg/g Cream	Mayne Pharma	NDA

Frequently asked questions

What is Rhofade used for?

Oxymetazoline Hydrochloride Cream, 1% is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. Oxymetazoline Hydrochloride Cream is an alpha 1A adrenoceptor agonist indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. ( 1 )

What are the side effects of Rhofade?

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 Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are… See the full label for the complete list.

Who makes Rhofade?

Rhofade is listed by 2 labelers in the FDA NDC directory, including EPI Health, LLC, Mayne Pharma.