部分中文安贺拉信息资料（仅供参考）

【别  名】安贺拉；酮咯酸氨丁三醇
【外文名】Ketorolac Tromethamine,Acular
【成  分】酮咯酸氨丁三醇
【适应症】季节性过敏性结膜炎所致的眼部瘙痒及各种眼科手术后炎症。
【药 物 功 效】
1.用于中、重度疼痛(如术后、骨折、扭伤疼痛、牙痛及癌性疼痛等)的止痛。
2.本药滴眼液用于治疗眼科手术后的炎症、季节变应性结膜炎等(国外资料)。
【注意事项】
1.禁忌症
(1)对本药、阿司匹林或其它非甾体类抗炎药过敏者。
(2)鼻息肉综合征患者(国外资料)。
(3)血管性水肿患者(国外资料)。
(4)有高危出血倾向者(国外资料)。
(5)活动性消化性溃疡患者。
(6)肝肾疾病、心脏病、高血压患者。
(7)孕妇。
(8)儿童。
2.慎用尚不明确。
3.药物对妊娠的影响本药不宜用于分娩镇痛。美国药品和食品管理局(FDA)对本药的妊娠安全性分级为C级。
4.药物对哺乳的影响尚不明确。
【不良反应】
1.常见精神神经系统不良反应(如嗜睡、头晕、头痛、思维异常、抑郁、欣快、失眠)及消化道不良反应(如恶心、呕吐、腹痛、消化不良)。
2.偶见注射部位疼痛、出汗增多、皮肤瘙痒、皮下出血及紫绀。
3.其它不良反应有口干、肌肉痛、心悸、血管扩张等。
4.长期使用可引起皮疹、支气管痉挛、休克等过敏反应和肾功能不全。
5.现已有因消化道出血、术后出血、急性肾功能不全和过敏反应而致死的报道。
【国外不良反应参考】
1.血液有一例接受本药治疗关节痛复发时，引起溶血性尿毒症的报道。
2.心血管系统临床试验中，有受试者出现水肿和高血压。尚有发生心悸、晕厥、低血压和皮肤潮红的报道。
3.中枢神经系统临床试验中，有引起头痛、头晕、嗜睡、神经过敏和感觉异常的报道。但因许多患者的用药时间为大手术后的恢复期，故这些反应与本药的关系尚不明确。
4.代谢/内分泌系统有使用本药后引起高血钾和体重增加的报道。
5.消化系统本药可能引起溃疡形成、出血和穿孔，老年人大剂量使用时更易出现。也可引起恶心、消化不良、腹痛、腹泻、肝功能检测值升高等。很少引起胰腺炎。
6.泌尿生殖系统临床试验中，本药引起血尿、蛋白尿、少尿、尿潴留、多尿和尿频的发生率大于1%。肾炎、急性肾衰竭和溶血性尿毒症也有报道。
7.眼使用本药眼用制剂后，可引起一过性刺痛和烧灼感。其它眼部不良反应还有过敏反应、浅表性角膜炎、眼部刺激、角膜水肿或虹膜炎等。
8.呼吸系统本药在临床试验中有引起支气管痉挛和过敏反应的报道，出现这些症状的很多患者曾有阿司匹林过敏、哮喘和鼻息肉三联征病史。
9.其它有用药后出现听力丧失、耳鸣、头痛及引起血管性水肿的报道。还可出现注射部位疼痛。肌注后有皮肤瘙痒、烧灼感、出汗和寒战的报道，但少见。
【药物说明】
1.本药可延长出血时间，故不作为预防性镇痛药用于大手术前和术中。
2.本药若与吗啡或哌替啶合用，可减少后两者用量。
3.本药不宜长期口服用于治疗慢性疼痛。
【用法与用量】
成人
·常规剂量
·口服给药一次10mg，一日2次。剧痛时可增至一次20mg。用药时间不宜超过2日。
·肌内注射一次30-60mg，一日极量为90mg。首次注射后，可每6小时注射20-30mg。用药不宜超过3日。
·静脉注射用于重度疼痛，一次10-30mg。
·经眼给药一次1-2滴，一日3次。
·肾功能不全时剂量
推荐用低剂量。
·老年人剂量
65岁以上老人推荐用低剂量。
[国外用法用量参考]
成人
·常规剂量
·口服给药在英国，推荐一次10mg，每4-6小时1次，一日极量为40mg；在美国，建议给药持续时间不超过5日。
·肌内注射术后疼痛：初量为一次10mg，每2小时1次。必要时可将剂量调整为一次10-30mg，每4-6小时1次。一日极量为90mg；体重小于50kg者，一日极量为60mg。建议给药持续时间不超过2日，且应尽早改为口服给药。
·静脉注射术后疼痛：一次给药时间不应小于15秒，其余同肌内注射项。
·经眼给药季节变应性结膜炎所致的眼瘙痒、囊斑样水肿的局部治疗和眼科手术引起炎症的防治：使用0.5%的本药溶液。
·肾功能不全时剂量
轻度肾功能不全时，肌内注射或静脉给药的极量为一日60mg。
·老年人剂量
肌注或静脉给药的极量为一日60mg。
【禁忌】
(1)对本药、阿司匹林或其它非甾体类抗炎药过敏者。
(2)鼻息肉综合征患者(国外资料)。
(3)血管性水肿患者(国外资料)。
(4)有高危出血倾向者(国外资料)。
(5)活动性消化性溃疡患者。
(6)肝肾疾病、心脏病、高血压患者。
(7)孕妇。
(8)儿童。

ACULAR® PF is indicated for the treatment of ocular pain and photophobia.

Allergan, Inc.
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DESCRIPTION
ACULAR® PF (ketorolac tromethamine ophthalmic solution) Preservative-Free is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) and it has the following structure:

ACULAR® PF is a racemic mixture of R-(+) and S-(-)-ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. The pKa of ketorolac is 3.5. This white to off-white crystalline substance discolors on prolonged exposure to light. The molecular weight of ketorolac tromethamine is 376.41. The osmolality of ACULAR® PF is 290 mOsml/kg.

Each ml of ACULAR® PF contains: Active: ketorolac tromethamine 0.5%. Inactives: purified water; sodium chloride; hydrochloric acid and/or sodium hydroxide to adjust the pH to 7.4.

CLINICAL PHARMACOLOGY
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory, and anti-pyretic activity. The mechanism of its action is thought to be due to its ability to inhibit prostaglandin biosynthesis. Ketorolac tromethamine given systemically does not cause pupil constriction.

One drop (0.05 mL) of ketorolac tromethamine (preserved) was instilled into one eye and one drop of vehicle into the other eye TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range 10.7 to 22.5 ng/mL) at day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hours, peak plasma levels at steady state are around 960 ng/mL.

In two double-masked, multi-centered, parallel-group studies, 340 patients who had undergone incisional refractive surgery received ACULAR® PF or its vehicle QID for up to 3 days. Significant differences favored ACULAR® PF for the treatment of ocular pain and photophobia.

Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure.

INDICATIONS AND USAGE
ACULAR® PF ophthalmic solution is indicated for the reduction of ocular pain and photophobia following incisional refractive surgery.

CONTRAINDICATIONS
ACULAR® PF ophthalmic solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation.

WARNINGS
There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory agents. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

With some nonsteroidal anti-inflammatory drugs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

PRECAUTIONS

General:
All topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Postmarketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.

Postmarketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events.

It is recommended that ACULAR® PF ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

Information for Patients:
ACULAR® PF should not be administered while wearing contact lenses.

The solution from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration. To avoid contamination, do not touch tip of unit-dose vial to eye or any other surface.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:
Ketorolac tromethamine was not carcinogenic in rats given up to 5 mg/kg/day orally for 24 months (151 times the maximum recommended human topical ophthalmic dose, on a mg/kg basis, assuming 100% absorption in humans and animals) nor in mice given 2 mg/kg/day orally for 18 months (60 times the maximum recommended human topical ophthalmic dose, on a mg/kg basis, assuming 100% absorption in humans and animals).

Ketorolac tromethamine was not mutagenic in vitro in the Ames assay or in forward mutation assays. Similarly, it did not result in an in vitro increase in unscheduled DNA synthesis or an in vivo increase in chromosome breakage in mice. However, ketorolac tromethamine did result in an increased incidence in chromosomal aberrations in Chinese hamster ovary cells.

Ketorolac tromethamine did not impair fertility when administered orally to male and female rats at doses up to 272 and 484 times the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg basis, assuming 100% absoprtion in humans and animals.

Pregnancy:

Teratogenic Effects: Pregnancy Category C. Ketorolac tromethamine, administered during organogensis, was not teratogenic in rabbits or rats at oral doses up to 109 times and 303 times the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg basis assuming 100% absorption in humans and animals. When administered to rats after Day 17 of gestation at oral doses up to 45 times the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg basis, assuming 100% absorption in humans and animals, ketorolac tromethamine resulted in dystocia and increased pup mortality. There are no adequate and well-controlled studies in pregnant women. ACULAR® PF ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects: Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ACULAR® PF ophthalmic solution during late pregnancy should be avoided.

Nursing Mothers:
Caution should be exercised when ACULAR® PF is administered to a nursing woman.

Pediatric Use:
Safety and efficacy in pediatric patients below the age of 3 years have not been established.

Geriatric Use:
No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS
The most frequent adverse events reported with the use of ketorolac tromethamine ophthalmic solutions have been transient stinging and burning on instillation. These events were reported by approximately 20% of patients participating in clinical trials.

Other adverse events occurring approximately 1 - 10% of the time during treatment with ketorolac tromethamine ophthalmic solutions included allergic reactions, corneal edema, iritis, ocular inflammation, ocular irritation, superficial keratitis, and superficial ocular infections.

Other adverse events reported rarely with the use of ketorolac tromethamine ophthalmic solutions include: corneal infiltrates, corneal ulcer, eye dryness, headaches, and visual disturbance (blurry vision).

Clinical Practice: The following events have been idientified during postmarketing use of ketorolac tromethamine ophthalmic solution 0.5% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to topical ketorolac tromethamine ophthalmic solution 0.5%, or a combination of these factors, include corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown (see PRECAUTIONS, General).

DOSAGE AND ADMINISTRATION
The recommended dose of ACULAR® PF is one drop (0.25 mg) four times a day in the operated eye as needed for pain and photophobia for up to 3 days after incisional refractive surgery.

HOW SUPPLIED
ACULAR® PF (ketorolac tromethamine ophthalmic solution) 0.5% Preservative-Free is available as a sterile solution supplied in clear, LDPE, single-use vials as follows:
 
ACULAR® PF 12 Single-Use Vials 0.4 mL each: NDC 0023-9055-04
Store ACULAR® PF at 15°C-30°C (59°F - 86°F) with protection from light.

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产地国家: 美国
所属类别: 眼科药物->治疗眼痛药物
原产地英文商品名:
ACULAR PF-0.5%drops,12ml
原产地英文药品名:
KETOROLAC TROMETHAMINE
中文参考商品译名:
安贺拉PF-0.5%滴剂，12毫升/支
中文参考药品译名:
酮咯酸氨丁三醇
生产厂家中文参考译名:
爱力根
生产厂家英文名:
Allergan　Inc.