alcaftadine and Conjunctivitis--Allergic

To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS).. The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use.. The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Cromolyn Sodium; Dibenzazepines; Histamine Antagonists; Humans; Hyperemia; Imidazoles; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Phthalazines; Piperidines; Pruritus; Pyridines; Pyrimidinones

To assess the safety and efficacy of topical olopatadine versus placebo and other topical anti-allergic medications in treating allergic conjunctivitis.. We systematically searched the literature for randomized-controlled trials that included patients with allergic conjunctivitis, compared olopatadine versus placebo or alternative anti-allergic medications, and examined itch, conjunctival hyperemia, composite symptom or sign scores, and/or occurrence of adverse events. We assessed the safety and efficacy of topical olopatadine when compared with placebo or alternative anti-allergic medications using meta-analysis.. When compared with placebo, topical olopatadine is associated with a pooled-mean difference (MD) in ocular itch of -1.33 (p < 0.00001) and ocular hyperemia of -0.92 (p < 0.00001). When compared with other agents, olopatadine was inferior to alcaftadine on ocular itch (pooled-MD = 0.39; p < 0.00001) but comparable with epinastine and ketotifen.. Topical olopatadine is a safe and effective treatment modality for allergic conjunctivitis, whereas alcaftadine appears to be superior to olopatadine in reducing ocular itch.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Dibenzazepines; Histamine H1 Antagonists; Humans; Imidazoles; Ketotifen; Olopatadine Hydrochloride; Ophthalmic Solutions; Treatment Outcome

Alcaftadine (Lastacaft®; Allergen, Inc.) is a broad-spectrum antihistamine displaying a high affinity for histamine H1 and H2 receptors and a lower affinity for H4 receptors. It also exhibits modulatory action on immune cell recruitment and mast cell stabilizing effects. The authors reviewed all available English-language literature characterizing the efficacy, safety and pharmacokinetic profile of alcaftadine ophthalmic solution. In the studies reviewed, alcaftadine was more effective than placebo and at least as effective as olopatadine 0.01% in preventing ocular itching at 15 minutes and at 16 hours after administration. Alcaftadine 0.025% ophthalmic solution has been approved by the U.S. Food and Drug Administration for prevention of itching associated with allergic conjunctivitis in patients over 2 years of age. Comparative efficacy data of alcaftadine to other ocular antihistamine/mast cell stabilizers are limited.

Topics: Administration, Topical; Animals; Benzazepines; Conjunctivitis, Allergic; Drug Interactions; Humans; Imidazoles; Ophthalmic Solutions; Pruritus; Randomized Controlled Trials as Topic; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4

Topics: Administration, Ophthalmic; Adult; Allergens; Benzazepines; Conjunctivitis, Allergic; Cryptomeria; Double-Blind Method; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Pollen; Prospective Studies; Treatment Outcome

To compare the efficacy and safety of Alcaftadine 0.25%, Olopatadine hydrochloride 0.2%, and Bepotastine besilate 1.5% ophthalmic solutions in the treatment of allergic conjunctivitis.. This is a prospective, observer-masked, comparative study of 180 patients with mild to moderate allergic conjunctivitis, randomized into three groups of 60 patients each. Each group was assigned to be treated with one of the three treatment options namely Alcaftadine 0.25%, Olopatadine hydrochloride 0.2% and Bepotastine besilate 1.5% ophthalmic solutions. Patients were followed-up at regular intervals with relief and resolution of symptoms and signs noted using Total Ocular Scoring System (TOSS) and hyperaemia scale.. All three topical medications were effective in resolving symptoms of the patients with mild to moderate allergic conjunctivitis. Baseline mean TOSS scores for Alcaftadine group, Olopatadine group and Bepotastine besilate group were (7.68±2.32), (7.65±2.32) and (7.45±2.27) respectively as compared to the corresponding TOSS scores on 14. All three topical ophthalmic medications used in the study are safe and effective in the treatment of allergic conjunctivitis. However, Bepotastine and Alcaftadine appear to outweigh Olopatadine in resolving the symptoms of allergic conjunctivitis.

Topics: Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Humans; Imidazoles; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Treatment Outcome

With increasing environmental pollution, the incidence of allergic conjunctivitis is increasing. Newer anti-allergic medications with combined anti-histaminic and mast cell stabilization action can help reducing the use of topical steroids for milder form of disease. There is no study directly comparing olopatadine (0.1%), bepotastine (1.5%), and alcaftadine (0.25%) for mild to moderate allergic conjunctivitis cases. Hence, we decided to methodically study the efficacy of three topical medications.. Prospective, observer-masked clinical trial enrolled 45 patients with 15 patients in each of the three groups. Patients with mild to moderate allergic conjunctivitis were sequentially assigned to respective groups, and relief of symptoms and signs were noted upto 1-month follow-up.. All three topical medications faired almost equally in resolving symptoms of the patients with mild to moderate allergic conjunctivitis, and most of them reported complete relief after 1 week of use of medication. Few cases with limbal or palpebral papillae reported symptomatic relief after use of medication, but the resolution of these signs was not noted in all three groups.. We concluded similar efficacy of three medications in relieving symptoms and inefficacy in regressing palpebral and limbal papillae in cases of allergic conjunctivitis.

Topics: Adolescent; Adult; Anti-Allergic Agents; Benzazepines; Child; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Imidazoles; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Single-Blind Method; Treatment Outcome; Young Adult

Topics: Adult; Benzazepines; Cedrus; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Imidazoles; Incidence; Japan; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Pollen; Retrospective Studies; Seasons; Treatment Outcome

The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated.. Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score<1) and zero itch (itch score=0) was also assessed.. A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P=0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P=0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P<0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P=0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported.. Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated.

Topics: Adult; Allergens; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Drug Monitoring; Female; Humans; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Patient Outcome Assessment; Pruritus

The purpose of this study was to evaluate the safety and clinical efficacy of alcaftadine 0.25% ophthalmic solution, a new topical anti-allergic agent for the prevention of the signs and symptoms of allergic conjunctivitis induced by conjunctival allergen challenge (CAC).. This two-arm, double-masked, multi-center, placebo-controlled Phase III study (NCT00889330) enrolled healthy volunteers (N = 58) with a history of allergic conjunctivitis. Subjects ≥10 years of age with a reproducible, positive reaction to a CAC were randomized to receive either one drop of alcaftadine 0.25% ophthalmic solution bilaterally or vehicle bilaterally. After 16 hours (Visit 3) and 15 minutes (Visit 4), a CAC was performed and ocular and nasal symptoms of allergy were graded over a 20-minute period. Clinical and statistical significance were evaluated.. The primary endpoints were ocular itching and conjunctival redness. The secondary endpoints were all other signs and symptoms of allergic conjunctivitis. Visual acuity, slit lamp biomicroscopy and adverse event reporting were the predetermined safety measures.. Alcaftadine was effective in the prevention of ocular itching based on both clinically relevant and statistically significant differences compared with vehicle (placebo). Alcaftadine significantly reduced conjunctival redness, and almost all other allergic signs and symptoms at both 15 minutes and 16 hours after drug administration. No significant safety issues were reported. Between-group differences in ocular itching were higher 16 hours after drug administration than at 15 minutes after drug administration.. With an onset of action within 3 minutes and a duration of action of at least 16 hours, the statistically and clinically significant effect of alcaftadine 0.25% on itching make it an important addition to therapy for ocular allergy. Additional studies are warranted to better understand the mechanisms affording a fast onset and prolonged duration of action.

Topics: Adult; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine Antagonists; Humans; Imidazoles; Male; Middle Aged; Ophthalmic Solutions; Osmolar Concentration; Placebos; Pruritus; Time Factors; Treatment Outcome; Young Adult

In this report, we characterize the in vitro pharmacokinetic properties of a new antihistamine, alcaftadine. In addition, we report results from phase 1 studies of several ophthalmic formulations of alcaftadine and examine the pharmacokinetic properties of one formulation in detail.. In vitro pharmacology employed a human liver microsome assay combined with index substrates or inhibitors for specific cytochromes. Metabolic fate of (14)C-alcaftadine was determined by high-performance liquid chromatography-based separation of parent compound from metabolites. Plasma protein binding was determined by equilibrium dialysis using (3)H-labeled alcaftadine and (3)H-labeled alcaftadine carboxylic acid metabolite. Relative tolerability (comfort) of 4 concentrations and 3 formulations of alcaftadine ophthalmic solution was assessed in 2 double-masked, randomized, placebo-controlled, contralateral studies in which formulations were compared to Tears Naturale II (placebo) in normal adult subjects. Data analysis focused on the mean differences in subject-reported drop comfort scores (within each dose level, at each time point) and compared the study-treatment eye with the placebo eye. Pharmacokinetics of alcaftadine 0.25% ophthalmic solution were determined in an open-label, single-center study after a single bilateral dose and after 7 days of once-a-day bilateral doses in healthy subjects 18-55 years old.. Alcaftadine is not significantly metabolized by microsomal cytochromes, but it is rapidly converted to the carboxylic acid metabolite by one or more cytosolic enzymes. Neither the parent compound nor its carboxylic acid metabolite displayed significant plasma protein binding. Over a range of formulations and concentrations (0.05%-0.5%), alcaftadine was well tolerated and subjects reported little or no discomfort or taste perversion in any treatment group. Pharmacokinetic studies showed that both the parent compound and the carboxylic acid metabolite reach peak serum levels within minutes of administration and fall below detectable levels within 3 h of dosing.. Based upon pharmacokinetic and phase 1 studies, the novel antihistamine alcaftadine is an appropriate drug for use as an ophthalmic formulation for prevention and treatment of ocular allergic conditions such as allergic conjunctivitis (alcaftadine ophthalmic solution 0.25% was recently approved for use by the FDA). Topical administration of alcaftadine 0.25% ophthalmic solution was well tolerated and had an acceptable safety profile.

Topics: Adolescent; Adult; Benzazepines; Chemistry, Pharmaceutical; Conjunctivitis, Allergic; Cytochrome P-450 Enzyme Inhibitors; Female; Histamine Antagonists; Humans; Imidazoles; Male; Microsomes, Liver; Middle Aged; Protein Binding

Topics: Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Histamine H1 Antagonists; Humans; Imidazoles; Ophthalmic Solutions

To report the first case of allergic contact dermatitis (ACD) associated with alcaftadine 0.25% ophthalmic solution.. The patient was a 51-year-old woman with no previous history of side effects to ophthalmic antihistamine agents. She had been prescribed alcaftadine 0.25% for allergic conjunctivitis. On first application of the medication, she did not experience any cutaneous reaction. One day later, after the second alcaftadine 0.25% application, both eyelids became swollen, and erythematous changes were evident. On slit-lamp examination, conjunctival injection was noted in the absence of conjunctival swelling or any other findings. Fundus examination was unremarkable. To evaluate the cause of ACD, a patch test was performed and 48 h later was noted to be positive for alcaftadine 0.25%. Based on the positive patch test, the patient was diagnosed with ACD caused by alcaftadine 0.25%. After 9 days of treatment, the swelling and erythema completely resolved.. Although there have been no previous reports of alcaftadine 0.25%-associated ACD, it should be suspected in patients with swelling and erythematous change of both eyes after using alcaftadine 0.25%.

Topics: Administration, Oral; Benzazepines; Conjunctivitis, Allergic; Dermatitis, Allergic Contact; Female; Glucocorticoids; Histamine H1 Antagonists; Humans; Imidazoles; Methylprednisolone; Middle Aged; Ophthalmic Solutions; Orbit; Tomography, X-Ray Computed

Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.. Studies employed a modified conjunctival allergen challenge model. Sensitized mice were challenged with topical allergen with or without drug treatments. Treatment groups were assayed for acute-phase (15 minutes) and delayed-phase (24 hours) responses. Groups were scored for allergy symptoms (redness, itch, tearing, and edema) and for conjunctival mast cell numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.. Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase. In contrast, alcaftadine-treated animals had significantly lower conjunctival eosinophil infiltration than either controls or olopatadine-treated animals. Allergen challenge caused a significant decrease in expression of the junctional protein, ZO-1, and this decrease was prevented by alcaftadine but not by olopatadine.. Alcaftadine displays therapeutic properties beyond its antihistamine action. These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

Topics: Animals; Anti-Allergic Agents; Benzazepines; Conjunctiva; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Eosinophils; Epithelium; Gene Expression Regulation; Imidazoles; Membrane Proteins; Mice; Mice, Inbred BALB C; Olopatadine Hydrochloride; Phosphoproteins; Tight Junctions; Time Factors; Zonula Occludens-1 Protein

Topics: Benzazepines; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Imidazoles; Pruritus