2014年6月2日，美国FDA批准Omeros公司的眼科用药Omidria，它可在白内障手术或以人工晶体代替眼内晶状体的其它手术过程中使用。 这一结果Omeros公司期盼已久，这家公司成立20年来一直没有产品获得过FDA批准。 Omidria是一种用以保持瞳孔大小、防止术中瞳孔缩小或瞳孔收缩的散瞳剂，或称瞳孔扩张剂与一种减少术后疼的痛抗炎剂组合。该药加在灌注液中在白内障手术和其它人工晶状体置换手术过程是由，在美国每年药进行近400万次此类手术。 OMIDRIA（去氧肾上腺素和酮咯酸注射液）1％/0.3％ 美国首次批准：2014  公司:Omeros（奥麦罗制药） 适应症 OMIDRIA是一种α-肾上腺素能受体激动剂和非选择性环氧化酶抑制剂用于： 通过防止术中瞳孔缩小保持瞳孔大小 减少术后疼痛 OMIDRIA被添加到在白内障手术或人工晶状体置换用于灌溉的解决方案。 剂量与用法 OMIDRIA必须在使用前稀释。施用于接受白内障手术或眼内透镜更换，4毫升OMIDRIA患者稀释在500ml的眼用冲洗溶液。灌溉溶液是根据需要为在外科手术过程中使用。 剂型和规格 OMIDRIA是含有1％（重量）/苯肾上腺素的v和0.3％重量/在单个患者使用的管瓶V的酮咯酸的无菌溶液浓缩物。  禁忌 无。 警告和注意事项 福林的全身暴露可能引起血压升高。 不良反应 在2-24％，最常见的不良反应是眼睛发炎，后囊膜混浊，眼压升高，前房炎症。 修订日期：5/2014 Omeros announced that the FDA has approved Omidria (phenylephrine and ketorolac) injection for use during cataract surgery or intraocular lens replacement (ILR) to maintain pupil size by preventing intraoperative miosis and to reduce postoperative pain. Omidria contains phenylephrine, a mydriatic agent, and ketorolac, an anti-inflammatory agent. This combination is added to an irrigation solution used as a standard in cataract surgery and other ILR procedures. RELATED: New Supplement Supports Patients with Cataracts Omidria was evaluated in trials in which all patients received standard pupil-dilating and anesthetic agents prior to surgery. Omidria showed statistically significant and clinically meaningful improvement in the prevention of miosis and reduction of postoperative pain vs. placebo. Omidria will be available in a 1%/0.3% strength in 4- and 10- single-use 5mL vials. The product is anticipated to launch in the late summer/early fall of 2014. Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Omidria™ is added to an ophthalmic irrigation solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain. 2 DOSAGE AND ADMINISTRATION Omidria must be diluted prior to intraocular use. For administration to patients undergoing cataract surgery or intraocular lens replacement, 4 mL of Omidria is diluted in 500 mL of ophthalmic irrigation solution. Irrigation solution is to be used as needed for the surgical procedure. The storage period for the diluted product is not more than 4 hours at room temperature or 24 hours under refrigerated conditions. Do not use if the solution is colored or cloudy, or if it contains particulate matter. 3 DOSAGE FORMS AND STRENGTHS Omidria is a sterile solution concentrate containing 10.16 mg/mL (1% w/v) of phenylephrine and 2.88 mg/mL (0.3% w/v) of ketorolac in a single-patient-use vial. 4 CONTRAINDICATIONS Omidria is contraindicated in patients with a known hypersensitivity to any of its ingredients. 5 WARNINGS AND PRECAUTIONS 5.1 Elevated Blood Pressure Systemic exposure of phenylephrine can cause elevations in blood pressure. 5.2 Cross-Sensitivity or Hypersensitivity There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other non-steroidal anti-inflammatories (NSAIDs). There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac in patients who either have a known hypersensitivity to aspirin/NSAIDs or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these drugs. 6 ADVERSE REACTIONS 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. Table 1 shows frequently reported ocular adverse reactions with an incidence of ≥ 2% of subjects as seen in the combined clinical trial results from three randomized, placebo-controlled studies. Table 1: Ocular Adverse Reactions Reported by ≥ 2% of Subjects MedDRA Preferred Term Placebo (N=462) Omidria (N=459) n (%)  n (%) Ocular Events     Anterior Chamber Inflammation 102 (22%)  111 (24%) Intraocular Pressure Increased 15 (3%)  20 (4%) Posterior Capsule Opacification 16 (4%)  18 (4%) Eye Irritation 6 (1%)  9 (2%) Foreign Body Sensation in Eyes 11 (2%)  8 (2%) 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratogenic Effects: Pregnancy Category C Animal reproduction studies have not been conducted with Omidria or phenylephrine. It is also not known whether Omidria can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Omidria should be used in pregnant women only if clearly needed. Ketorolac, administered during organogenesis, was not teratogenic in rabbits or rats at oral doses of 3.6 mg/kg/day and 10 mg/kg/day, respectively. These doses produced systemic exposure that is 1150 times and 4960 times the plasma exposure (based on Cmax) at the recommended human ophthalmic dose (RHOD), respectively. When administered to rats after Day 17 of gestation at oral doses up to 1.5 mg/kg/day (740 times the plasma exposure at the RHOD), ketorolac produced dystocia and increased pup mortality. Clinical Considerations: Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Detectable ketorolac plasma concentrations are available following ocular Omidria administration [see Clinical Pharmacology (12.3)]. The use of Omidria during late pregnancy should be avoided. 8.3 Nursing Mothers Because many drugs are excreted in human milk, caution should be exercised when Omidria is administered to nursing women. 8.4 Pediatric Use Safety and effectiveness of Omidria in pediatric patients below the age of 18 years have not been established. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and adult patients. 10 OVERDOSAGE Systemic overdosage of phenylephrine may cause a rise in blood pressure. It may also cause headache, anxiety, nausea, vomiting, and ventricular arrhythmias. Supportive care is recommended. 11 DESCRIPTION Omidria is a sterile aqueous solution concentrate containing the α1-adrenergic receptor agonist phenylephrine HCl and the nonsteroidal anti-inflammatory ketorolac tromethamine. The descriptions and structural formulae are: Phenylephrine Hydrochloride Drug Substance: Common Name:  phenylephrine hydrochloride Chemical Name:  (‑)‑m‑Hydroxy‑α‑[(methylamino)methyl]benzyl alcohol hydrochloride Molecular Formula:              C9H13NO2 · HCl Molecular Weight:  203.67 g/mole Figure 1: Chemical Structure for Phenylephrine HCl Ketorolac Tromethamine Drug Substance: Common Name:  ketorolac tromethamine Chemical Name: (±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) Molecular Formula:            C15H13NO3 · C4H11NO3 Molecular Weight: 376.40 g/mole Figure 2: Chemical Structure for Ketorolac Tromethamin Omidria is a clear, colorless, sterile solution concentrate with a pH of approximately 6.3. Each vial of Omidria contains: Actives: phenylephrine hydrochloride 12.4 mg/mL equivalent to 10.16 mg/mL of phenylephrine and ketorolac tromethamine 4.24 mg/mL equivalent to 2.88 mg/mL of ketorolac. Inactives: citric acid monohydrate; sodium citrate dihydrate; water for injection; may include sodium hydroxide and/or hydrochloric acid for pH adjustment. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The two active pharmaceutical ingredients (API) in Omidria, phenylephrine and ketorolac, act to maintain pupil size by preventing intraoperative miosis, and reducing postoperative pain. Phenylephrine is an α1-adrenergic receptor agonist and, in the eye, acts as a mydriatic agent by contracting the radial muscle of the iris. Ketorolac is a nonsteroidal anti-inflammatory that inhibits both cyclooxygenase enzymes (COX-1 and COX-2), resulting in a decrease in tissue concentrations of prostaglandins to reduce pain due to surgical trauma. Ketorolac, by inhibiting prostaglandin synthesis secondary to ocular surgical insult or direct mechanical stimulation of the iris, also prevents surgically induced miosis. 12.3 Pharmacokinetics In a pharmacokinetic study eva luating Omidria, systemic exposure to both phenylephrine and ketorolac was low or undetectable. A single-dose of Omidria as part of the irrigation solution was administered in 14 patients during lens replacement surgery. The volume of irrigation solution used during surgery ranged between 150 mL to 300 mL (median 212.5 mL). Detectable phenylephrine plasma concentrations were observed in one of 14 subjects (range 1.2 to 1.4 ng/mL) during the first two hours after the initiation of Omidria administration. The observed phenylephrine plasma concentrations could not be distinguished from the preoperative administration of phenylephrine 2.5% ophthalmic solution prior to exposure to Omidria. Ketorolac plasma concentrations were detected in 10 of 14 subjects (range 1.0 to 4.2 ng/mL) during the first 8 hours after the initiation of Omidria administration. The maximum ketorolac concentration was 15 ng/mL at 24 hours after the initiation of Omidria administration, which may have been due to application of postoperative ketorolac ophthalmic solution. 14 CLINICAL STUDIES The efficacy and safety of Omidria were eva luated in two Phase 3, randomized, multicenter, double-masked, placebo-controlled clinical trials in 808 adult subjects undergoing cataract surgery or intraocular lens replacement. Subjects were randomized to either Omidria or placebo. Subjects were treated with preoperative topical mydriatic and anesthetic agents. Pupil diameter was measured throughout the surgical procedure. Postoperative pain was eva luated by self-administered 0-100 mm visual analog scales (VAS). Mydriasis was maintained in the Omidria-treated groups while the placebo-treated groups experienced progressive constriction. Figure 3: Intraoperative Pupil Diameter (mm) Change-from-Baseline At the end of cortical clean-up, 23% of placebo-treated subjects and 4% of Omidria-treated subjects had a pupil diameter less than 6 mm (p < 0.01). Pain during the initial 10-12 hours postoperatively was statistically significantly less in the Omidria-treated groups than in the placebo-treated groups. Figure 4: Postoperative Mean Visual Analog Scale (VAS) Scores for Pain During the 10-12 hours postoperatively, 26% of Omidria-treated subjects reported no pain (VAS = 0 at all timepoints) while 17% of placebo-treated subjects reported no pain (p < 0.01). 16 HOW SUPPLIED/STORAGE AND HANDLING Omidria is supplied as a sterile solution concentrate in a clear, 5-mL glass, single-patient-use vial containing 4 mL of sterile solution. Omidria is supplied in a multi-pack containing: 4 single-patient-use vials: NDC 62225-600-04 or 10 single-patient-use vials: NDC 62225-600-10 Storage: Store at 20˚ to 25˚C (68˚ to 77˚F). Protect from light. Drug Name(s) OMIDRIA FDA Application No. (NDA) 205388 Active Ingredient(s) KETOROLAC TROMETHAMINE; PHENYLEPHRINE HYDROCHLORIDE Company OMEROS Original Approval or Tentative Approval Date May 30, 2014 Chemical Type 4  New combination Review Classification S  Standard review drug