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通用名：alcaftadine
中文名：阿卡他定滴眼液
英文化学名：6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-Imidazo[2,1-b](3)benzazepine-3-carboxaldehyde
CAS号： 147084-10-4
分子式： C19H21N3O
分子量： 307.3949
结构式：
2010年7月28日,美国食品药物监督管理局(FDA)批准新分子实体药物阿卡他定(Alcaftadine)滴眼液上市,商品名Lastacaft,用于预防过敏性结膜炎引起的瘙痒。Lastacaft现已获准用于2岁以上儿童患者。
阿卡他定属组胺H1-受体拮抗剂和肥大细胞稳定剂，能抑制肥大细胞释放组胺并阻止组胺作用。从而减轻过敏反应。但阿卡他定滴眼液不能用于角膜接触镜相关的刺激症状的治疗。
阿卡他定推荐剂量方案是每日每眼滴1滴药液，最常见眼副反应(总发生率<4％)是眼刺激、眼发红、眼痒及滴眼时的烧灼感和(或)针刺感；最常见非眼副反应(总发生率<3％)包括鼻咽炎、头痛和流感样症状。阿卡他定不可用于治疗隐形眼镜相关刺激，但佩戴隐形眼镜的变应性结膜炎患者仍可使用阿卡他定治疗，只不过滴眼时间应至少在佩戴隐形眼镜前10min。
LASTACAFT - alcaftadine solution
Vistakon Pharmaceuticals, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use LASTACAFT™ safely and effectively. See full prescribing information for LASTACAFT™.
LASTACAFT™ (alcaftadine ophthalmic solution)
Initial U.S. Approval: 2010
INDICATIONS AND USAGE
LASTACAFT™ is a H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis (1)
DOSAGE AND ADMINISTRATION
Instill one drop in each eye once daily. (2)
DOSAGE FORMS AND STRENGTHS
Ophthalmic solution containing alcaftadine, 0.25% (2.5 mg/mL) (3)
WARNINGS AND PRECAUTIONS
To minimize the risk of contamination, do not touch dropper tip to any surface. Keep bottle tightly closed when not in use. (5.1)
LASTACAFT™ should not be used to treat contact lens-related irritation. (5.2)
Remove contact lenses prior to instillation of LASTACAFT™. (5.2)
ADVERSE REACTIONS
The most common ocular adverse reactions, occurring in < 4% of LASTACAFT™-treated eyes, were eye irritation, burning and/or stinging on instillation, eye redness, and eye pruritus. (6.1)
The most common non-ocular adverse reactions, occurring in < 3% of subjects with LASTACAFT™-treated eyes, were nasopharyngitis, headache and influenza (6.2)
See 17 for PATIENT COUNSELING INFORMATION
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
LASTACAFT™ is a H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis.
2 DOSAGE AND ADMINISTRATION
Instill one drop in each eye once daily.
3 DOSAGE FORMS AND STRENGTHS
Topical ophthalmic solution containing alcaftadine, 0.25% (2.5 mg/mL).
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Contamination of Tip and Solution
To minimize contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.
5.2 Contact Lens Use
Patients should be advised not to wear a contact lens if their eye is red. LASTACAFT™ should not be used to treat contact lens-related irritation.
LASTACAFT™ should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of LASTACAFT™. The preservative in LASTACAFT™, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of LASTACAFT™.
5.3 Topical Ophthalmic Use Only
LASTACAFT™ is for topical ophthalmic use only.
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
6.1 Ocular Adverse Reactions
The most frequent ocular adverse reactions, occurring in < 4% of LASTACAFT™-treated eyes, were eye irritation, burning and/or stinging upon instillation, eye redness and eye pruritus.
6.2 Non-ocular Adverse Reactions
The most frequent non-ocular adverse reactions, occurring in < 3% of subjects with LASTACAFT™-treated eyes, were nasopharyngitis, headache and influenza. Some of these events were similar to the underlying disease being studied.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B. Reproduction studies performed in rats and rabbits revealed no evidence of impaired female reproduction or harm to the fetus due to alcaftadine. Oral doses in rats and rabbits of 20 and 80 mg/kg/day, respectively, produced plasma exposure levels approximately 200 and 9000 times the plasma exposure at the recommended human ocular dose. There are however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LASTACAFT™ is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients below the age of 2 years have not been established.
8.5 Geriatric Use
No overall differences in safety or effectiveness were observed between elderly and younger subjects.
11 DESCRIPTION
LASTACAFT™ is a sterile, topically administered H1 receptor antagonist containing alcaftadine for ophthalmic use.
Alcaftadine is a white to yellow powder with an empirical formula of C19H21N3O and a molecular weight of 307.39.
Contains:
Active: alcaftadine 0.25% (2.5 mg/mL)
Preservative: benzalkonium chloride 0.005%
Inactives: edetate disodium, monobasic sodium phosphate, purified water, sodium chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH)
Chemical Name: 6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b] [3] benzazepine-3-carboxaldehyde
Structural Formula:
The drug product has a pH of approximately 7 and an osmolality of approximately 290 mOsm/kg.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Alcaftadine is a H1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.
12.3 Pharmacokinetics
Absorption
Following bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by 3 hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately 3 ng/mL and occurred at 1 hour after dosing. Plasma concentrations of the carboxylic acid metabolite were below the lower limit of quantification (100 pg/mL) by 12 hours after dosing. There was no indication of systemic accumulation or changes in plasma exposure of alcaftadine or the active metabolite following daily topical ocular administration.
Distribution
The protein binding of alcaftadine and the active metabolite are 39.2% and 62.7%, respectively.
Metabolism
The metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite.
Excretion
The elimination half-life of the carboxylic acid metabolite is approximately 2 hours following topical ocular administration. Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.
In vitro studies showed that neither alcaftadine nor the carboxylic acid metabolite substantially inhibited reactions catalyzed by major CYP450 enzymes.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Alcaftadine was not mutagenic or genotoxic in the Ames test, the mouse lymphoma assay or the mouse micronucleus assay.
Alcaftadine was found to have no effect on fertility of male and female rats at oral doses up to 20 mg/kg/day (approximately 200 times the plasma exposure at the recommended human ocular dose).
14 CLINICAL STUDIES
Clinical efficacy was evaluated in conjunctival allergen challenge (CAC) studies. LASTACAFT™ was more effective than its vehicle in preventing ocular itching in patients with allergic conjunctivitis induced by an ocular allergen challenge, both at 3 minutes post-dosing and at 16 hours post-dosing of LASTACAFT™.
The safety of LASTACAFT™ was evaluated in a randomized clinical study of 909 subjects over a period of 6 weeks.
16 HOW SUPPLIED/STORAGE AND HANDLING
LASTACAFT™ (alcaftadine ophthalmic solution) 0.25% is supplied in an opaque, white low-density polyethylene bottle with a white polypropylene cap.
3 mL fill in 5 mL bottle (NDC 68669-412-03)
Storage: Store at 15-25°C (59-77°F)
17 PATIENT COUNSELING INFORMATION
17.1 Sterility of Dropper Tip
Patients should be advised to not touch dropper tip to any surface, as this may contaminate the contents.
17.2 Concomitant Use of Contact Lenses
Patients should be advised not to wear a contact lens if their eye is red. Patients should be advised that LASTACAFT™ should not be used to treat contact lens-related irritation. Patients should also be advised to remove contact lenses prior to instillation of LASTACAFT™. The preservative in LASTACAFT™, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of LASTACAFT™.
17.3 Topical Ophthalmic Use only
For topical ophthalmic administration only.
Manufactured for Vistakon Pharmaceuticals, LLC
Jacksonville, FL 32256 USA
PRINCIPAL DISPLAY PANEL - 3 mL Bottle Carton
NDC 68669-412-03
LASTACAFT™
(alcaftadine ophthalmic
solution) 0.25%
3 mL
Sterile
VISTAKON® PHARMACEUTICALS, LLC | 
