, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens. 5.2 potentiation of vascular insufficiency rhofade 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 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.

se reactions that occurred in at least 1% of subjects treated with rhofade 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 rhofade 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 pruritus (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.

ral 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 a dverse r eactions 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- to18-fold higher than plasma exposures after topical administration of rhofade. data human data no adequate and well-controlled trials of rhofade have been conducted in pregnant women. across all clinical trials of rhofade, 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 organogeneisis (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 organogeneisis (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 rhofade and any potential adverse effects on the breastfed child from rhofade or from the underlying maternal condition. 8.4 pediatric use safety and effectiveness of rhofade 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 rhofade (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 rhofade did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal a dverse r eactions 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- to18-fold higher than plasma exposures after topical administration of rhofade. data human data no adequate and well-controlled trials of rhofade have been conducted in pregnant women. across all clinical trials of rhofade, 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 organogeneisis (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 organogeneisis (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).

owing twice daily applications (twice the recommended frequency of application) for 28 days, the mean ± sd c max and auc 0-24hr were 68.8 ± 61.1 pg/ml and 1530 ± 922 pg*hr/ml, respectively. distribution an in vitro study demonstrated that oxymetazoline is 56.7% to 57.5% bound to human plasma proteins. metabolism in vitro studies using human liver microsomes showed that oxymetazoline was minimally metabolized, generating mono-oxygenated and dehydrogenated products of oxymetazoline. the percentage of parent drug oxymetazoline remaining was 95.9% after a 120-minute incubation with human liver microsomes. excretion the excretion of oxymetazoline following administration of rhofade has not been characterized in humans. drug i nteraction in vitro studies using human liver microsomes demonstrated that oxymetazoline up to the tested concentration of 100 nm had no inhibition on the activities of the cytochrome p450 (cyp) isoenzymes 1a2, 2b6, 2c8, 2c9, 2c19, 2d6, and 3a4/5. treatment of cultured human hepatocytes with up to 100 nm oxymetazoline did not induce cyp1a2, cyp2b6, or cyp3a4.

vitro study demonstrated that oxymetazoline is 56.7% to 57.5% bound to human plasma proteins. metabolism in vitro studies using human liver microsomes showed that oxymetazoline was minimally metabolized, generating mono-oxygenated and dehydrogenated products of oxymetazoline. the percentage of parent drug oxymetazoline remaining was 95.9% after a 120-minute incubation with human liver microsomes. excretion the excretion of oxymetazoline following administration of rhofade has not been characterized in humans. drug i nteraction in vitro studies using human liver microsomes demonstrated that oxymetazoline up to the tested concentration of 100 nm had no inhibition on the activities of the cytochrome p450 (cyp) isoenzymes 1a2, 2b6, 2c8, 2c9, 2c19, 2d6, and 3a4/5. treatment of cultured human hepatocytes with up to 100 nm oxymetazoline did not induce cyp1a2, cyp2b6, or cyp3a4.

effects on fertility or mating parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (3 times the mrhd on an auc comparison basis).

ting parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (3 times the mrhd on an auc comparison basis).

ation 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 pruritus (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.

s 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 time-point (hour) trial 1 trial 2 rhofade cream (n=222) vehicle cream (n=218) rhofade cream (n = 224) vehicle cream (n=221) 3 12% 6% 14% 7% 6 16% 8% 13% 5% 9 18% 6% 16% 9% 12 15% 6% 12% 6% * composite success is defined as the proportion of subjects achieving at least a 2-grade improvement on both cea and ssa.

dren. get medical help right away if you, a child, or anyone else swallows rhofade cream. what is rhofade cream? rhofade cream is a prescription medicine used on the skin (topical) to treat facial redness due to rosacea that does not go away (persistent) in adults. it is not known if rhofade cream is safe and effective in children under 18 years of age. before you use rhofade cream, tell your healthcare provider about all of your medical conditions, including if you: have heart, blood vessel, or blood pressure problems. call your healthcare provider or get medical help if these conditions worsen. have problems with blood circulation or have had a stroke have sjögren’s syndrome have scleroderma have raynaud’s phenomenon have thromboangiitis obliterans have narrow-angle glaucoma. call your healthcare provider or get medical help if your glaucoma worsens. have irritated skin or open sores on the face are pregnant or plan to become pregnant. it is not known if rhofade cream will harm your unborn baby. are breastfeeding. it is not known if rhofade cream passes into your breast milk. talk to your healthcare provider about the best way to feed your baby if you use rhofade cream. tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, skin products, vitamins, and herbal supplements. using rhofade cream with certain other medicines may affect each other and can cause serious side effects. how should i use rhofade cream? see the detailed instructions for use that comes with your rhofade cream tube or pump for information about how to apply rhofade cream correctly. use rhofade cream exactly as your healthcare provider tells you. do not use more rhofade cream than prescribed. rhofade cream is for use on your skin only. do not use rhofade cream in your eyes, mouth, or vagina. avoid contact with your lips and eyes. do not apply rhofade cream to irritated skin or open wounds. what are the possible side effects of rhofade cream? the most common side effects of rhofade cream include application site reactions of: • skin reactions (dermatitis) • itching • pain • worsening of rosacea pimples • redness these are not all the possible side effects of rhofade cream. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store rhofade cream? store rhofade cream at room temperature between 68°f to 77°f (20°c to 25°c). keep rhofade cream and all medicines out of the reach of children. general information about the safe and effective use of rhofade cream medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use rhofade cream for a condition for which it was not prescribed. do not give rhofade cream to other people, even if they have the same symptoms that you have. it may harm them. you can ask your pharmacist or healthcare provider for information about rhofade cream that is written for health professionals. what are the ingredients in rhofade cream? active ingredient: oxymetazoline hydrochloride 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 distributed by: allergan usa, inc. madison, nj 07940 © 2018 allergan. all rights reserved. all trademarks are the property of their respective owners. patented. see www.allergan.com/patents this patient information has been approved by the u.s. food and drug administration approved: 01/2017 v1.0ppi5300