部分中文IQUIX处方资料（仅供参考）
适应症
适应菌种：对本制剂敏感的葡萄球菌属、链球菌属、肺炎球菌、肠球菌属、细球菌属、莫拉氏菌属、棒状杆菌属、克雷白氏菌属、肠杆菌属、沙雷氏菌属、变形菌属、摩氏摩根菌、流感嗜血杆菌、结膜炎嗜血杆菌(科一威氏杆菌)、假单胞菌属、绿脓杆菌、嗜麦芽黄单胞菌、不动杆菌属、丙酸杆菌。
适应症
用于治疗眼睑炎、睑腺炎、泪囊炎、结膜炎、睑板腺炎、角膜炎以及用于眼科围手术期的无菌化疗法。
用法用量
一般1天3次、每次滴眼1滴，根据症状可适当增减。对角膜炎的治疗在急性期每15～30分钟滴眼1次，对严重的病例在开始30分钟内每5分钟滴眼1次，病情控制后逐渐减少滴眼次数。治疗细菌性角膜溃疡推荐使用高浓度的抗生素滴眼制剂。
不良反应
注册上市时：在共计472例中，出现不良反应的为8例(1．69％)。主要的不良反应为眼刺激感4件(O．85％)、眼瘙痒感3件(O．64％)等。
上市后使用情况调查(第7次安全性定期报告)：在共计6136例中，出现不良反应的有42例(0．68％)。
主要的不良反应为弥漫性表层角膜炎等角膜障碍12件(0．20％)、眼睑炎等9件(0．15％)、眼刺激感6件(0．10％)等。
1．严重不良反应：休克、过敏样症状：有可能引起休克、过敏样症状，应充分进行观察。当发现红斑、皮疹、呼吸困难、血压降低、眼睑浮肿等症状时应停止给药，予以妥善的处置。
2．滴眼毒性：未见眼刺激性及眼毒性。
3．抗原性：无。
药代动力学
1．血中浓度
将本品以1次2滴、一天4次给健康成人连续滴眼2周，最终滴眼1小时后的血中浓度为定量界限(O．01g／m1)以下。
2．动物的眼组织内分布(有色家兔、有色大鼠、狗)
用标记的左氧氟沙星滴眼液以1次50ul给有色家兔滴眼时，15分钟后在球结膜和睑结膜的最高浓度(Cmax)分别为1433．8ngeq／g和1058．8ng eq／g，30分钟后在角膜和房水的最高浓度(Cmax)分别为6839．5ngeq／g和842．8ngeq／g。之后随着时间的推移而减少；2小时后在含黑色素组织的虹膜、睫状体和视网膜色素上皮、脉络膜的最高浓度(Cmax)分别为11514．4ngeq／g和3269．6ng eq／g，之后缓慢消失。
此外，对有色大鼠也显示出了同样的状况。在以1次1ul、一天3次连续滴眼1周后，最终滴眼1小时后在角膜、房水和玻璃体等眼组织中的放射源浓度分别为2270．8ng eq/g、267．1ng eq／g、372．0ng eq/g。之后随着时间的推移而减少；最终滴眼1小时后在虹膜、睫状体和视网膜色素上皮、脉络膜分别为185047．6 ngeq/g、36549．6ngeq/g，之后缓慢消失。用0．3％左氧氟沙星滴眼液对比格狗以1次1滴、一天4次连续滴眼2周后，最终滴眼24小时后的眼组织内浓度为：虹膜、睫状体为39．4ug/g，脉络膜、视网膜色素上皮为12．3ug/g，眼组织中的含黑色素组织显示出了较高的分布。而向去除色素上皮的视网膜之分布却很少。
3．其他不良反应：发现不良反应时应采取停止给药等妥善的处置。
禁忌
对本品的成份、氧氟沙星及喹喏酮类抗菌制剂有过敏既往史的患者。
注意事项
1.为了防止耐药菌的出现等，原则上应确认敏感性，尽量将用药时间控制在治疗疾病所需的最少时间以内。
2.本品对甲氧苯青霉素耐药性葡萄球菌(MRSA)的有效性尚未得到证实。当MRSA所致的感染较为明显、临床症状无改善时，应尽快使用抗MRSA作用较强的药物。
3.仅用于滴眼。
4.为了防止污染药液，滴眼时应注意避免容器的前端直接接触眼部。
孕妇及哺乳期妇女用药
对孕妇或可能妊娠的妇女，只有在其治疗的有益性高于可能发生的危险性时方可给药。(对妊娠期间的安全性尚不明确)
儿童用药
根据日本可乐必妥滴眼液上市后使用情况调查的结果，在15岁以下儿童的1160例中，1岁以下的186例中未见有不良反应，在1岁至15岁用药者中出现不良反应的为4例(点状角膜炎、眼瘙痒症、接触性角膜炎、荨麻疹)
老年用药
通常，老年人的生理功能有所降低，应注意予以减量等。
药物相互作用
尚不明确。
药物过量
尚不明确
贮    藏
密封容器，避光，室温保存(1～30℃)。
Iquix(Levofloxacin Ophthalmic Solution 1.5%)
DESCRIPTION
IQUIX® (levofloxacin ophthalmic solution) 1.5% is a sterile topical ophthalmic solution. Levofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of Gram-positive and Gram-negative ocular pathogens. Levofloxacin is a fluorinated 4-quinolone containing a six-member (pyridobenzoxazine) ring from positions 1 to 8 of the basic ring structure. Levofloxacin is the pure(-)-(S)-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water at neutral pH than ofloxacin.
Chemical Name: (-)(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4 benzoxazine-6-carboxylic acid hemihydrate.
Levofloxacin (hemihydrate) is a yellowish-white crystalline powder.
Each mL of IQUIX® contains 15.36 mg of levofloxacin hemihydrate equivalent to 15 mg levofloxacin.
ContainsActive: Levofloxacin 1.5% (15 mg/mL); Inactives: glycerin and water. May also contain hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 6.5. IQUIX® solution is isotonic with an osmolality of approximately 290 mOsm/kg.
CLINICAL PHARMACOLOGY
PharmacokineticsLevofloxacin concentration in plasma was measured in 14 healthy adult volunteers during a 16-day course of treatment with IQUIX® solution. The dosing schedule was 1-2 drops per eye once in the morning on Days 1 and 16; 1-2 drops per eye every two hours Days 2 through 8; and 1-2 drops per eye every four hours Days 9 through 15. The mean levofloxacin concentration in plasma 1 hour postdose ranged from 3.13 ng/mL on Day 1 to 10.4 ng/mL on Day 16. Maximum mean levofloxacin concentrations increased from 3.22 ng/mL on Day 1 to 10.9 ng/mL on Day 16, which is more than 400 times lower than those reported after standard oral doses of levofloxacin.
Levofloxacin concentration in tears was measured in 100 healthy adult volunteers at various time points following instillation of 2 drops of IQUIX® solution. Mean tear concentration measured 15 minutes after instillation was 757 µg/mL.
MicrobiologyLevofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair, and recombination.
Levofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms and is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from β-Iactam antibiotics and aminoglycosides, and therefore may be active against bacteria resistant to β-Iactarn antibiotics and aminoglycosides. Additionally, β-Iactam antibiotics and aminoglycosides may be active against bacteria resistant to levofloxacin. Resistance to levofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 to 10-10).
Levofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:
Efficacy for this organism was studied in fewer than 10 infections.
The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of levofloxacin in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials.
These organisms are considered susceptible when eva luated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of corneal ulcer. Levofloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2 µg/mL or less (systemic susceptible breakpoint) against most (≥90%) strains of the following ocular pathogens:
Clinical StudiesIn two randomized, double-masked, multicenter controlled clinical trials of 280 patients with positive cultures, subjects were dosed with IQUIX® or ofloxacin 0.3% ophthalmic solution. Dosing occurred on Days 1 through 3 every two hours while awake and 4 and 6 hours after retiring. Dosing occurred on Day 4 through treatment completion 4 times daily while awake. Clinical cure was defined as complete re-epithelialization and no progression of the infiltrate for two consecutive visits. The IQUIX® treated subjects had an approximately equal mean clinical cure rate of 80% (73% to 87%) compared to 84% (82% to 86%) for the subjects treated with ofloxacin 0.3% ophthalmic solution.
INDICATIONS AND USAGE
IQUIX® solution is indicated for the treatment of corneal ulcer caused by susceptible strains of the following bacteria:
Efficacy for this organism was studied in fewer than 10 infections.
CONTRAINDICATIONS
IQUIX® solution is contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication.
WARNINGS
NOT FOR INJECTION.
IQUIX® solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
In patients receiving systemic quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
PRECAUTIONS
GeneralAs with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, induding fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.
Patients should be advised not to wear contact lenses if they have signs and symptoms of corneal ulcer.
Information for PatientsAvoid contaminating the applicator tip with material from the eye, fingers or other source.
Systemic quinolones have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.
Drug InteractionsSpecific drug interaction studies have not been conducted with IQUIX®. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving systemic cyclosporine concomitantly.
Carcinogenesis, Mutagenesis, Impairment of FertilityIn a long term carcinogenicity study in rats, levofloxacin exhibited no carcinogenic or tumorigenic potential following daily dietary administration for 2 years; the highest dose (100 mg/kg/day) was 100 times the highest recommended human ophthalmic dose.
Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay (S. typhimurium and E. coli), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the in vivo mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and in vitro sister chromatid exchange (CHL/IU cell line) assays.
Levofloxacin caused no impairment of fertility or reproduction in rats at oral doses as high as 360 mg/kg/day, corresponding to 400 times the highest recommended human ophthalmic dose.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Levofloxacin at oral doses of 810 mg/kg/day in rats, which corresponds to approximately 1000 times the highest recommended human ophthalmic dose, caused decreased fetal body weight and increased fetal mortality.
No teratogenic effect was observed when rabbits were dosed orally as high as 50 mg/kg/day, which corresponds to approximately 60 times the highest recommended maximum human ophthalmic dose, or when dosed intravenously as high as 25 mg/kg/day, corresponding to approximately 30 times the highest recommended human ophthalmic dose.
There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing MothersLevofloxacin has not been measured in human milk. Based upon data from ofloxacin, it can be presumed that levofloxacin is excreted in human milk. Caution should be exercised when IQUIX® is administered to a nursing mother.
Pediatric UseSafety and effectiveness in children below the age of six years have not been established. Oral administration of systemic quinolones has been shown to cause arthropathy in immature animals. There is no evidence that the ophthalmic administration of levofloxacin has any effect on weight bearing joints.
Geriatric UseNo overall differences in safety or effectiveness have been observed between elderly and other adult patients.
ADVERSE REACTIONS
The most frequently reported adverse events in the overall study population were headache and a taste disturbance following instillation. These events occurred in approximately 8–10% of patients.
Adverse events occurring in approximately 1–2% of patients included decreased/blurred vision, diarrhea, dyspepsia, fever, infection, instillation site irritation/discomfort, ocular infection, nausea, ocular pain/discomfort, and throat irritation.
Other reported ocular reactions occurring in less than 1% of patients included chemosis, corneal erosion, corneal ulcer, diplopia, floaters, hyperemia, lid edema, and lid erythema.
DOSAGE AND ADMINISTRATION
Days 1 through 3Instill one to two drops in the affected eye(s) every 30 minutes to 2 hours while awake and approximately 4 and 6 hours after retiring.
Day 4 through treatment completionInstill one to two drops in the affected eye(s) every 1 to 4 hours while awake.
HOW SUPPLIED
IQUIX® (levofloxacin ophthalmic solution) 1.5% is supplied in a white, low density polyethylene bottle with a controlled dropper tip and a tan, high density polyethylene cap in the following size:
5 mL fill in 5 cc container– NDC 68669-145-05
StorageStore at 15° – 25°C (59°– 77°F).
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=067EA8EC-99A3-4A0B-9116-4FFD6160B24B