RHOFADE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RHOFADE (RHOFADE).
Alpha-1 adrenergic receptor agonist causing vasoconstriction of dermal arterioles, reducing facial erythema.
| Metabolism | Hepatic via multiple CYP450 enzymes including CYP2D6, CYP2C19, and CYP3A4; metabolite oxymetazoline undergoes glucuronidation |
| Excretion | Renal: ~80% as unchanged drug and metabolites; fecal: ~20%. |
| Half-life | Terminal half-life: ~10 hours (range 7–13 h) after topical application; supports twice-daily dosing. |
| Protein binding | ~60–70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.15–0.25 L/kg, indicating distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Topical: ~20–30% systemic absorption based on urinary recovery; negligible oral bioavailability. |
| Onset of Action | Topical: erythema reduction begins within 30 minutes; peak effect at 3–6 hours. |
| Duration of Action | Topical: clinically significant reduction in erythema persists for 12 hours after a single application. |
Apply a pea-sized amount topically to each affected area (cheeks, chin, forehead, nose) once daily.
| Dosage form | CREAM |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy in pediatric patients under 18 years have not been established. |
| Geriatric use | No specific geriatric dose adjustment; use with caution due to potential increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RHOFADE (RHOFADE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Oxymetazoline is absorbed systemically; caution advised. Consider developmental benefits of breastfeeding vs maternal need for drug. M/P ratio unknown. |
| Teratogenic Risk | Pregnancy Category C. No adequate and well-controlled studies in pregnant women. In animal studies, topical administration of oxymetazoline (active ingredient) during organogenesis produced no evidence of fetal harm at doses up to 20 times the maximum recommended human dose (MRHD) based on AUC. However, subcutaneous administration in rats and rabbits resulted in maternal toxicity and fetal effects (reduced fetal weight, delayed ossification, increased resorptions) at doses ≥10 times MRHD. Risk cannot be ruled out; use only if potential benefit justifies risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to oxymetazoline or any component","Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy"]
| Precautions | ["Exacerbation of rosacea signs/symptoms upon discontinuation","Risk of systemic vasoconstriction and hypertension","Avoid in patients with cardiovascular disease, Raynaud's phenomenon, or orthostatic hypotension","Not for oral, ophthalmic, or intravaginal use"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate periodically due to potential systemic alpha-adrenergic effects. Observe for signs of fetal distress if used near term, as vasoconstriction may theoretically reduce uterine blood flow. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | No human data on fertility. In animal studies, no impairment of fertility was observed in rats at subcutaneous doses up to 20 times MRHD. Unlikely to have clinically significant effects on fertility at recommended topical doses. |