Olopatadine Hydrochloride: Antihistamine & Clinical Profile

Olopatadine hydrochloride is a relatively selective histamine H1-receptor antagonist; the drug also shares many of the pharmacologic effects of mast-cell stabilizers. Efficacy of olopatadine has been established in several clinical studies, including environmental studies and conjunctival antigen challenge studies. Olopatadine ophthalmic solutions should be stored at 2-25°C. When stored as directed, the commercially available ophthalmic solutions have an expiration date of 24 months following the date of manufacture. Following topical application of olopatadine hydrochloride to the eyes, the plasma elimination half-life of the drug is about 3 hours.

Effects of Olopatadine Hydrochloride

Urticaria is a skin disease which is induced by chemical mediators, mainly histamine, released from skin mast cells by some stimulation. These chemical mediators produce flare and wheal and induce itch by stimulating sensory nerves. Oral histamine H1 receptor antagonists (antihistamines) are the first line of treatment for idiopathic urticaria and other types of urticaria. Second-generation antihistamines are commonly used, because they show lower central nervous system depression and anticholinergic effects than first-generation drugs. Each subject was given one of four kinds of treatment. We selected 3 second-generation anti-histamines, olopatadine hydrochloride (olopatadine) 5 mg, bepotastine besilate (bepotastine) 10 mg, and fexofenadine hydrochloride (fexofenadine) 60 mg, which show relatively short time to maximum concentration (Tmax). Testing for each treatment was separated by a washout interval of at least 7 days. Subjects received active or placebo treatment at 9:00 a.m. Histamine iontophoresis produced wheal and flare, which disappeared in about 40 minutes. The wheal and flare areas induced by the initial iontophoresis at 0 hour were 0.79 cm2 and 4.34 cm2 in placebo group, 1.04 cm2 and 5.13 cm2 in olopatadine hydrochloride group, 0.86 cm2 and 5.13 cm2 in bepotastine group, and 0.91 cm2 and 5.12 cm2 in fexofenadine group, respectively. Similar to wheal response, olopatadine was the only drug that showed significant suppression of flare response versus placebo at 0.5 hours and 1 hour and was significantly more effective than fexofenadine at one hour and two hours. After two hours, all three drugs significantly suppressed flare response, compared to placebo.[1]

Evaluation of three second-generation anti-histamines by means of histamine iontophoresis showed that they were similar in terms of central nervous system side effects but were different in terms of rapidness of action and efficacy. Olopatadine hydrochloride was found to be the fastest and most potent drug. When a rash recurs after remission of acute or chronic urticaria, an anti-histamine is prescribed for prompt relief of symptoms. Rapid improvement of the symptoms not only provides therapeutic benefits to patients but also improves quality of life by increasing patient's confidence in alleviating their anxiety. The data on rapidness of action seen in this study provide important information that will help us to choose a suitable anti-histamine for individual urticaria patients. Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration.

Low-dose olopatadine hydrochloride for itch in well-controlled chronic urticaria

Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines, and it is used to treat allergic disorders such as urticaria, rhinitis, and atopic dermatitis in Japan. It also has an inhibitory effect on the release of inflammatory lipid mediators, such as leukotriene and thromboxane, from human polymorphonuclear leukocytes and eosinophils. It was proven to be more potent and stable with regard to its antihistaminic effects in skin responses compared to other commonly used second-generation antihistamines in a double-blind, randomized controlled study. However, olopatadine hydrochloride has been reported to induce CNS side effects, despite being a second-generation antihistamine. It has been reported that a double dose of the prescribed drug or a change of drug was recommended for the treatment of patients with urticaria refractory to the standard dose of antihistamines. However, there have been no published reports regarding treatment strategy for well-controlled CU patients, including whether patients should be treated with the standard dose, reduced to half the dose, or whether the medication should be stopped. This study was conducted to compare the effects of olopatadine hydrochloride (10 mg, 5 mg, and 0 mg/day) for itch in well-controlled CU patients to investigate the optimal dose of olopatadine that would be convenient for CU patients.[2]

Although first-generation antihistamines have been found to be effective for relieving symptoms, they cause CNS side effects, such as sedation and psychomotor disturbances. Olopatadine hydrochloride is one of the nonsedating second-generation antihistamines, and is used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis in Japan. Its usual dose for treatment of CU is 10 mg/day. It exerts more rapid and prolonged antihistaminic effects in comparison with other second-generation antihistamines. The present study was designed to investigate the optimal dose of olopatadine hydrochloride to provide increased convenience for itch in well-controlled CU patients with fewer side effects. In addition, the present study also indicates that CU patients can be kept on medication at either 5 mg or 10 mg to achieve long-term symptom improvement. The period that the VAS itch score was maintained at less than 50 in both the 10-mg and 5-mg groups was significantly longer than that in the no-medication group. However, the difference between the 10-mg and 5-mg groups was not significant. In this study, no adverse effects including drowsiness and sedation were reported by patients in any of the three groups. However, some previous studies have described that olopatadine hydrochloride induced CNS side effects, in spite of the fact that it is a second-generation nonse-dating antihistamine. In conclusion, this study indicates that treatment with olopatadine hydrochloride at 5 mg once daily can maintain the improvement of urticarial symptoms the same as 10 mg/day with fewer CNS side effects and appears to be safe and effective for the management and prevention of CU.

Bioequivalence Study of Olopatadine Hydrochloride Tablets

Olopatadine hydrochloride, a second-generation selective histamine H1 receptor antagonist, is an effective anti-allergic agent. This study evaluated the pharmacokinetics and bioequivalence of two olopatadine hydrochloride tablet formulations in healthy Chinese subjects under fasting (n = 24) and fed (n = 24) conditions. A single-center, randomized, open-label, single-dose, two-way crossover study was conducted, in which 48 subjects were randomized to receive 5 mg of the test or reference formulation, followed by a 7-day washout period. Blood samples were collected at predefined intervals up to 24 h post-dose, and olopatadine plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. The results demonstrated no significant differences in the pharmacokinetic profiles between the test and reference formulations under fasting or fed conditions. The 90% confidence intervals (CIs) for the ratio of geometric means of Cmax, AUC0–t, and AUC0–∞ of olopatadine hydrochloride under both conditions were within the bioequivalence range of 0.80–1.25. A high-fat diet delayed olopatadine hydrochloride absorption, leading to a reduction in Cmax to approximately 60% of the fasting value and a decrease in AUC to 85%–90%. No serious adverse events occurred, and safety profiles were comparable between formulations. This research confirmed the bioequivalence and similar safety of the generic olopatadine hydrochloride tablets to the reference formulation.

References

[1]Hashimoto T, Ishii N, Hamada T, Dainichi T, Karashima T, Nakama T, Yasumoto S. Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses. Dermatol Res Pract. 2010;2010:638051. doi: 10.1155/2010/638051. Epub 2010 Sep 16. PMID: 20886023; PMCID: PMC2945667.

[2]Makino T, Takegami Y, Rehman MU, Yoshihisa Y, Ishida W, Toyomoto T, Shimizu T. Maintenance of remission with low-dose olopatadine hydrochloride for itch in well-controlled chronic urticaria. Clin Cosmet Investig Dermatol. 2012;5:141-6. doi: 10.2147/CCID.S36812. Epub 2012 Sep 19. PMID: 23055763; PMCID: PMC3459547.

[3]Lei, Yuyan et al. “Bioequivalence Study of Two Olopatadine Hydrochloride Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions.” Clinical pharmacology in drug development vol. 15,3 (2026): e1629. doi:10.1002/cpdd.1629

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