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Skin Therapy Letter Jul 2021The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the...
The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the presence of either (1) phymatous changes, or (2) centrofacial persistent erythema. In their absence, diagnosis can be established by presence of any two of: flushing/transient erythema, papules and pustules, telangiectases, or ocular manifestations. Management of rosacea depends on presenting feature(s), their severity, and impact. General management includes gentle skin care, sun protection, and trigger avoidance. Evidence-based treatment recommendations include topical brimonidine and oxymetazoline for persistent erythema; topical azelaic acid, ivermectin, metronidazole, minocycline and oral doxycycline, tetracycline and isotretinoin for papules and pustules; vascular lasers and light devices for telangiectases; and omega-3 fatty acids and cyclosporine ophthalmic emulsion for ocular rosacea. While surgical or laser therapy can be considered for clinically noninflamed phyma, there are no trials on their utility. Combination therapies include topical brimonidine with topical ivermectin, or topical metronidazole with oral doxycycline. Topical metronidazole, topical ivermectin, and topical azelaic acid are appropriate for maintenance therapy. In conclusion, the updated phenotype approach, based on presenting clinical features, is the foundation for current diagnosis, classification, and treatment of rosacea.
Topics: Brimonidine Tartrate; Dermatologic Agents; Doxycycline; Humans; Metronidazole; Rosacea
PubMed: 34347259
DOI: No ID Found -
Dermatology Online Journal Jul 2021Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant... (Review)
Review
BACKGROUND
Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects.
OBJECTIVE
Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF.
METHODS
Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy.
RESULTS
Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF.
CONCLUSIONS
This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.
Topics: Adult; Algorithms; Animals; Anti-Bacterial Agents; Azithromycin; Brimonidine Tartrate; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Female; Humans; Isotretinoin; Ivermectin; Metronidazole; Mice; Minocycline; Phototherapy; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Rosacea; Tetracyclines; Treatment Outcome
PubMed: 34391325
DOI: 10.5070/D327754360 -
The British Journal of Dermatology Jul 2019Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
BACKGROUND
Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
OBJECTIVES
To update our systematic review on interventions for rosacea.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence.
RESULTS
We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach.
CONCLUSIONS
For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Brimonidine Tartrate; Combined Modality Therapy; Dermatologic Agents; Dermatology; Drug Therapy, Combination; Evidence-Based Medicine; Facial Dermatoses; Humans; Intense Pulsed Light Therapy; Low-Level Light Therapy; Oxymetazoline; Randomized Controlled Trials as Topic; Rosacea; Severity of Illness Index; Treatment Outcome
PubMed: 30585305
DOI: 10.1111/bjd.17590 -
American Journal of Ophthalmology Apr 2023To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or...
PURPOSE
To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution.
DESIGN
Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.
METHODS
Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was ≥18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combination) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8.
RESULTS
There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respectively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and brimonidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyperemia.
CONCLUSIONS
The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.
Topics: Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Prospective Studies; Antihypertensive Agents; Quinoxalines; Treatment Outcome; Randomized Controlled Trials as Topic; Ocular Hypertension; Intraocular Pressure; Double-Blind Method
PubMed: 36410471
DOI: 10.1016/j.ajo.2022.11.017 -
Scientific Reports Apr 2023This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free... (Randomized Controlled Trial)
Randomized Controlled Trial
This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.
Topics: Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Quinoxalines; Glaucoma; Ocular Hypertension; Intraocular Pressure; Preservatives, Pharmaceutical; Treatment Outcome; Antihypertensive Agents; Double-Blind Method; Ophthalmic Solutions
PubMed: 37029145
DOI: 10.1038/s41598-023-31726-1 -
Frontiers in Medicine 2023To investigate the differences between 0.2 and 0.15% brimonidine tartrate eye drops for anti-mydriatic effects and the optical quality under different light conditions.
AIMS
To investigate the differences between 0.2 and 0.15% brimonidine tartrate eye drops for anti-mydriatic effects and the optical quality under different light conditions.
METHODS
This prospective study involved 80 consecutive high myopia patients undergoing implantation of a V4c ICL. The patients were randomly instilled with brimonidine 0.2 and 0.15% 2 weeks postoperatively. Visual quality, pupil center, pupil size, and refraction under different light conditions were measured before and 0.5 h after brimonidine administration. A symptom questionnaire was also evaluated.
RESULTS
There was no statistical difference in the static and dynamic pupil diameters and velocity after LS between the two groups ( > 0.05). The 0.2% group had significant changes in pupil center before and after treatment, while there was no obvious movement of the 0.15% group under all illumination condition ( > 0.05). The OSI after treatment of the 0.15% group was lower than that of 0.2% group ( = 0.012). The PVA9% and PVA100% of the 0.15% group was higher than that of 0.2% group in the dark ( = 0.009, = 0.012). The HOA RMS of the 0.15% group was lower than that of 0.2% group ( = 0.016). The QIRC score in the 0.15% group was significantly higher than that in the 0.2% group ( = 0.043).
CONCLUSION
0.15 and 0.2% brimonidine tartrate eye drops had similar anti-mydriatic ability, while 0.15% group had better visual quality than 0.2% concentration, and hardly introduced pupil shift. 0.15% brimonidine tartrate eye drops may be more suitable for patients with nocturnal glare symptoms in the early postoperative period after ICL implantation.
PubMed: 37256086
DOI: 10.3389/fmed.2023.1160414 -
International Journal of Nanomedicine 2022The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized...
BACKGROUND
The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule.
RESEARCH DESIGN AND METHODS
GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated.
RESULTS
The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution.
CONCLUSIONS
Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.
Topics: Animals; Brimonidine Tartrate; Glaucoma; Intraocular Pressure; Liposomes; Plasticizers; Rabbits
PubMed: 35782018
DOI: 10.2147/IJN.S370192 -
Pharmaceuticals (Basel, Switzerland) Jan 2023Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The...
Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.
PubMed: 36678587
DOI: 10.3390/ph16010090 -
Eye (London, England) Feb 2021To evaluate the effect of brimonidine tartrate 0.15% ophthalmic solution on pupil size under scotopic condition and upper eyelid position.
BACKGROUND
To evaluate the effect of brimonidine tartrate 0.15% ophthalmic solution on pupil size under scotopic condition and upper eyelid position.
METHODS
This study comprised 72 eyes of 36 healthy subjects. A single drop of brimonidine tartrate 0.15% ophthalmic solution was instilled in the right eye and artificial tear was instilled in the left eye. Pupil size was measured using an infra-red pupillometer under scotopic condition before and at 30 min, 2, 4, 6, 8 and 10 h after instillation. Measurement of margin reflex distance 1 (MRD1) was performed using a millimetre ruler before and after at 10 min after instillation.
RESULTS
The mean age of the subjects was 32.19 ± 11.43 years (range 10-52 years), 17 were female and 19 were male. Before brimonidine instillation, the mean pupil size was 6.09 ± 1.03 mm in the brimonidine eyes and 6.06 ± 1.04 mm in the control eyes. There was a significant decrease in mean pupil size at 30 min (4.45 ± 1.04), 2 h (4.49 ± 1.06), 4 h (4.59 ± 1.06), 6 h (4.89 ± 1.06) and 8 h (5.38 ± 1.02) after instillation compared to before in brimonidine eyes (p < 0.001 for all). There was a significant miosis continued for at least 6 h (5.95 ± 1.03) in control eyes (p < 0.001). There was no significant change in MRD1, before and after instillation both in brimonidine and control eyes.
CONCLUSIONS
Brimonidine tartrate 0.15% had a significant miosis under scotopic condition for at least 8 h after instillation and had a significant miosis on the untreated eye for at least 6 h.
Topics: Adolescent; Adult; Brimonidine Tartrate; Child; Eyelids; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Pupil; Quinoxalines; Young Adult
PubMed: 32518394
DOI: 10.1038/s41433-020-1007-9 -
BMC Anesthesiology Dec 2021To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time...
BACKGROUND
To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine.
METHODS
The median effective dose (ED) and lethal dose (LD) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD of intravenously injected brimonidine, and ED of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits.
RESULTS
Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD was 379 mg/kg. ED values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect.
CONCLUSIONS
Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, General; Animals; Brimonidine Tartrate; Dose-Response Relationship, Drug; Mice; Rabbits
PubMed: 34861822
DOI: 10.1186/s12871-021-01516-1