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agent, usually metronidazole or azelaic acid, for treatment of PPR. In a number of studies, combination therapy has been shown to improve global disease assess- ment and provide a quicker onset of therapeutic effect with greater reduction in lesion count. 37 Using anti-inflamma- tory doses of doxycycline lessens the possibility of photosensitivity caused by the drug; however, patients must still be counseled about possible drug interac- tions with vitamins, antacids, and other potential sources of metal ions. Other antimicrobial medications have been studied in rosacea, including mino- cycline, tetracycline, azithromycin, clar- ithromycin, and ampicillin; however, data supporting the use of these agents are limited. Azithromycin is the most common alternative agent for treatment of PPR in patients who cannot take tet- racyclines. 37 Isotretinoin Oral isotretinoin is an off-label agent for the treatment of severe, recalcitrant PPR. Its proposed mechanism of action is downregulation of TLR2. In stud- ies comparing low-dose isotretinoin (0.3 mg/kg) to placebo and doxycycline, isotretinoin was found to be superior to placebo therapy and noninferior to oral doxycycline. 38 Use of isotretinoin for 3 to 4 months is often required to achieve marked improvement. Oral isotretinoin is also used early in subtype 3, phymatous disease, when sebaceous gland hypertrophy and hyperplasia are occurring. Safety and lab monitoring are required via the iPledge program, which is also used for patients receiving isotret- inoin at higher doses to treat acne. More information about the iPledge program can be found at ipledgeprogram.com. Although doses used for rosacea are con- siderably lower than for acne, patients should be advised about dry skin and mucous membranes, as well as chapped lips. Pregnant women should not take isotretinoin due to its teratogenic- ity. Return of symptoms is likely when isotretinoin is discontinued. Continuous "microdose" isotretinoin (0.04-0.11 mg/ kg/day) has been used occasionally to control flares. 38 Beta Blockers Beta blockers have a vasoconstricting action on dermal blood vessels, which produces a therapeutic effect in erythe- ma. The primary concerns with the use of beta blockers is bradycardia and hypo- tension, although the doses used to treat erythema are lower than typical doses for cardiovascular indications. Anxiety reduction may be another advantage since anxiety may exacerbate flushing. For this purpose, carvedilol is the most frequently used beta blocker. 39 Algorithms A number of algorithms have been developed to assist health care providers in choosing treatment for patients with rosacea. In general, these algorithms classify treatment by either rosacea subtype or common symptoms. Since treatment is guided primarily by patient FIGURE 2: DRUG THERAPY FOR ROSACEA 2,40 Lifestyle measures: appropriate skincare, sunscreen (SPF >30), avoid irritants, avoid triggers Flushing Persistent erythema +/- telangiectasia Papules and pustules Generally poor response to drug therapy, depending on cause; may try alpha agonist, beta blocker, antihistamine Topical Azelaic acid Metronidazole Sulfacetamide- sulfur Ivermectin Add short-term antibiotics (tetracyclines, macrolides) Combined topical (azelaic acid) and nonantibiotic-dose doxycycline (40 mg/d) Severe cases: Initial high-dose antibiotics Low-dose oral isotretinoin (10 mg/d) Combine with topicals Azelaic acid Metronidazole Topical antibiotics Topical retinoids Nodules and plaques Oral antibiotics: (high-dose tetracyclines, macrolides) Oral isotretinoin (0.5 - 1 mg/kg/d) Intralesional corticosteroids Ocular symptoms Topical and oral antibiotics Ivermectin Isotretinoin Phymatous changes Oral Isotretinoin Oral Low-dose doxycycline Topical Azelaic acid Sulfacetamide Metronidazole Brimonidine December 2015 PharmacyTimes.org 115