部份中文Patanase处方资料（仅供参考）
药品名称：盐酸奥洛他定鼻喷雾剂
英文名称：olopatadine hydrochloride spray
原研商品名：Patanase
化学名称：11-[(Z)-3-(二钾胺)丙烷]-6-11-二氢二苯[b.e]庚英-2-乙酸盐 
适应症：
patanase鼻喷雾剂是一种H1受体拮抗剂，对成人和6岁以上儿童的季节性过敏性鼻炎的症状缓解。
剂型及规格：
鼻喷雾剂，仅适用于鼻腔给药olopatadine hydrochloride 0.6%（665 μg/喷）。
产品特点：
本品使用后30分钟起效，作用持续12小时，疗效在统计学上较安慰剂显著。
1. DESCRIPTION 
Olopatadine Hydrochloride Nasal Spray, 665 micrograms (mcg) is a metered-spray solution for intranasal administration. Olopatadine hydrochloride, the active component of Olopatadine Hydrochloride Nasal Spray, is a white, water-soluble crystalline powder. The chemical name for olopatadine hydrochloride is (Z)-11-[3(dimethylamino) propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride. It has a molecular weight of 373.88, and its molecular formula is C21H23NO3 • HCl with the following chemical structure:
Olopatadine Hydrochloride Nasal Spray contains 0.6% w/v olopatadine (base) in a nonsterile aqueous solution with pH of approximately 3.7. After initial priming (5 sprays), each metered spray from the nasal applicator delivers 100 microliters of the aqueous solution containing 665 mcg of olopatadine hydrochloride, which is equivalent to 600 mcg of olopatadine (base) [see Dosage and Administration]. Olopatadine Hydrochloride Nasal Spray also contains benzalkonium chloride (0.01%), dibasic sodium phosphate, edetate disodium, sodium chloride, hydrochloric acid and/or sodium hydroxide (to adjust pH), and purified water.
2. INDICATIONS AND USAGE 
Seasonal Allergic Rhinitis
Olopatadine Hydrochloride Nasal Spray is indicated for the relief of the symptoms of seasonal allergic rhinitis in patients 6 years of age and older.
3. DOSAGE AND ADMINISTRATION 
Administer Olopatadine Hydrochloride Nasal Spray by the intranasal route only.
3.1 Adults and Adolescents 12 years of age and older: The recommended dosage is two sprays per nostril twice daily.
3.2 Children 6 to 11 years of age: The recommended dosage is one spray per nostril twice daily.
3.3 Administration Information
Priming: Before initial use, prime Olopatadine Hydrochloride Nasal Spray by releasing 5 sprays or until a fine mist appears. When Olopatadine Hydrochloride Nasal Spray has not been used for more than 7 days, re-prime by releasing 2 sprays. Avoid spraying Olopatadine Hydrochloride Nasal Spray into the eyes.
4. CONTRAINDICATIONS 
None.
5. MECHANISM OF ACTION 
Olopatadine is an antihistamine with selective H1-receptor antagonist activity: its principal effects are mediated via inhibition of H1 receptors. The antihistaminic activity of olopatadine has been documented in isolated tissues, animal models, and humans.
6. USE IN SPECIFIC POPULATIONS 
6.1 Usage in Pregnancy
Pregnancy Category C
No adequate and well-controlled studies in pregnant women have been conducted. Animal reproductive studies in rats and rabbits revealed treatment-related effects on fetuses or pups. Because animal studies are not always predictive of human responses, Olopatadine Hydrochloride Nasal Spray should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus.
A decrease in the number of live fetuses was observed in rabbits and rats at the oral olopatadine doses approximately 88 times and 100 times the maximum recommended human dose (MRHD) and above, respectively, for adults on a mg/m2 basis. In rats, viability and body weights of pups were reduced on day 4 post partum at the oral dose approximately 100 times the MRHD for adults on a mg/m2 basis, but no effect on viability was observed at the dose approximately 35 times the MRHD for adults on a mg/m2 basis.
6.2 Nursing Mothers
Olopatadine has been identified in the milk of nursing rats following oral administration. It is not known whether topical nasal administration could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Olopatadine Hydrochloride Nasal Spray should be used by nursing mothers only if the potential benefit to the patient outweighs the potential risks to the infant.
6.3 Pediatric Use
The safety and effectiveness of Olopatadine Hydrochloride Nasal Spray has not been established for patients under 6 years of age. The safety of olopatadine nasal spray was eva luated in 3 vehicle-controlled 2-week studies in 870 patients 6 to 11 years of age [see Adverse Reactions]. Doses studied included 1 and 2 sprays per nostril twice daily. One of these studies eva luated the safety of Olopatadine Hydrochloride Nasal Spray at doses of 1 and 2 sprays per nostril twice daily in 1188 patients, of which, 298 patients were exposed to olopatadine hydrochloride 1 spray and 297 patients were exposed to vehicle 1 spray. In this study, the incidence of epistaxis with olopatadine nasal spray treatment was 5.7%, compared to 3.2% seen in adult and adolescent studies. This study also eva luated the effectiveness of Olopatadine Nasal Spray in patients 6 through 11 years of age with seasonal allergic rhinitis.
The safety of Olopatadine Nasal Spray at a dose of 1 spray per nostril twice daily was eva luated in one 2week vehicle-controlled study in 132 children ages 2 to 5 years of age with allergic rhinitis. In this trial, 66 patients ( 28 females and 38 males) were exposed to Olopatadine Nasal Spray. The racial distribution of patients receiving Olopatadine Nasal Spray was 66.7% white, 27.3% black, and 6.4% other. Two patients exposed to vehicle nasal spray discontinued due to an adverse reaction (1 patient with pneumonia and 1 patient with rhinitis) compared to no patients exposed to Olopatadine Nasal Spray. The most common (greater than 1.0%) adverse events reported were diarrhea (9.1%), epistaxis (6.1%), rhinorrhea (4.5%), bitter taste (3.0%) and wheezing (3.0%). Diarrhea was reported less frequently (< 1%) in the 6 to 11 year old age group.
The incidence of epistaxis was higher in the pediatric population (5.7% in 6 -11 year old patients and 6.1% in 2-5 year old patients) compared to the adult and adolescent population (3.2%).
6.4 Geriatric Use
Clinical studies of Olopatadine Hydrochloride Nasal Spray did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
7. WARNINGS AND PRECAUTIONS 
7.1 Local Nasal Effects
Epistaxis and Nasal Ulceration: In placebo (vehicle nasal spray)-controlled clinical trials of 2 weeks to 6 months duration, epistaxis and nasal ulcerations were reported [see Adverse Reactions].
Nasal Septal Perforation: Two placebo (vehicle nasal spray)-controlled long term (6 and 12 months) safety trials were conducted. In the 12month safety trial, patients were treated with an investigational formulation of Olopatadine Hydrochloride Nasal Spray containing povidone (not the commercially marketed formulation) or a vehicle nasal spray containing povidone. Nasal septal perforations were reported in one patient treated with the investigational formulation of Olopatadine Hydrochloride Nasal Spray and 2 patients treated with the vehicle nasal spray. In a 6-month trial with Olopatadine Hydrochloride Nasal Spray, which does not contain povidone, there were no reports of nasal septal perforation [see Adverse Reactions].
Before starting Olopatadine Hydrochloride Nasal Spray, conduct a nasal examination to ensure that patients are free of nasal disease other than allergic rhinitis. Perform nasal examinations periodically for signs of adverse effects on the nasal mucosa and consider stopping Olopatadine Hydrochloride Nasal Spray if patients develop nasal ulcerations.
7.2 Activities Requiring Mental Alertness
In clinical trials, the occurrence of somnolence has been reported in some patients taking Olopatadine Hydrochloride Nasal Spray [see Adverse Reactions]. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as driving or operating machinery after administration of Olopatadine Hydrochloride Nasal Spray. Concurrent use of Olopatadine Hydrochloride Nasal Spray with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur.
8. ADVERSE REACTIONS 
Use of Olopatadine Hydrochloride Nasal Spray has been associated with epistaxis, nasal ulceration, and somnolence.
There were 1,180 patients (Olopatadine Hydrochloride Nasal Spray, 587; vehicle nasal spray, 593) with seasonal allergic rhinitis that participated in 3 clinical trials of 2 weeks duration. Table 1 presents the most common adverse reactions (0.9% or greater in patients treated with Olopatadine Hydrochloride Nasal Spray) that occurred more frequently in patients treated with Olopatadine Hydrochloride Nasal Spray compared with vehicle nasal spray.
Table 1: Adverse Reactions Occurring at an Incidence of 0.9% or Greater in Controlled Clinical Trials of 2 Weeks Duration with Olopatadine Hydrochloride Nasal Spray in Adolescent and Adult Patients 12 Years of Age and Older with Seasonal Allergic Rhinitis.
9. OVERDOSAGE 
There have been no reported overdosages with Olopatadine Hydrochloride Nasal Spray.
Acute overdosage with this dosage form is unlikely due to the configuration of the primary container closure system. However, symptoms of antihistamine overdose may include drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in children. There is no known specific antidote to Olopatadine Hydrochloride Nasal Spray. Should overdose occur, symptomatic or supportive treatment is recommended, taking into account any concomitantly ingested medications.
10. DRUG INTERACTIONS 
Drug-drug interaction studies were not conducted for Olopatadine Hydrochloride Nasal Spray. Drug interactions with inhibitors of liver enzymes are not anticipated because olopatadine is eliminated predominantly by renal excretion. Olopatadine did not inhibit the in vitro metabolism of specific substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Based on these data, drug interactions involving P450 inhibition are not expected. Due to the modest protein binding of olopatadine (55%), drug interactions through displacement from plasma proteins are not expected.
11. PHARMACOKINETICS  
The pharmacokinetic properties of olopatadine were studied after administration by the nasal, oral, intravenous, and topical ocular routes. Olopatadine exhibited linear pharmacokinetics across the routes studied over a large dose range.
Absorption:
Healthy Subjects: Olopatadine was absorbed with individual peak plasma concentrations observed between 30 minutes and 1 hour after twice daily intranasal administration of Olopatadine Hydrochloride Nasal Spray. The mean steady-state peak plasma concentration (Cmax) of olopatadine was 16.0 ± 8.99 ng/mL. Systemic exposure as indexed by area under the curve (AUC0-12) averaged 66.0 ± 26.8 ng·h/mL. The average absolute bioavailability of intranasal olopatadine is 57%. The mean accumulation ratio following multiple intranasal administration of Olopatadine Hydrochloride Nasal Spray was about 1.3.
Seasonal Allergic Rhinitis (SAR) Patients: Systemic exposure of olopatadine in SAR patients after twice daily intranasal administration of Olopatadine Hydrochloride Nasal Spray was comparable to that observed in healthy subjects. Olopatadine was absorbed with peak plasma concentrations observed between 15 minutes and 2 hours. The mean steady-state Cmax was 23.3 ± 6.2 ng/mL and AUC0-12 averaged 78.0 ± 13.9 ng·h/mL.
Distribution: The protein binding of olopatadine was moderate at approximately 55% in human serum, and independent of drug concentration over the range of 0.1 to 1000 ng/mL. Olopatadine was bound predominately to human serum albumin.
Metabolism: Olopatadine is not extensively metabolized. Based on plasma metabolite profiles following oral administration of [14C] olopatadine, at least six minor metabolites circulate in human plasma. Olopatadine accounts for 77% of peak plasma total radioactivity and all metabolites amounted to <6% combined. Two of these have been identified as the olopatadine N-oxide and N-desmethyl olopatadine. In in vitro studies with cDNA-expressed human cytochrome P450 isoenzymes (CYP) and flavin-containing monooxygenases (FMO), N-desmethyl olopatadine (Ml) formation was catalyzed mainly by CYP3A4, while olopatadine N-oxide (M3) was primarily catalyzed by FMO1 and FMO3. Olopatadine at concentrations up to 33,900 ng/mL did not inhibit the in vitro metabolism of specific substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The potential for olopatadine and its metabolites to act as inducers of CYP enzymes has not been eva luated.
Elimination: The plasma elimination half-life of olopatadine is 8 to 12 hours. Olopatadine is mainly eliminated through urinary excretion. Approximately 70% of a [14C] olopatadine hydrochloride oral dose was recovered in urine with 17% in the feces. Of the drug-related material recovered within the first 24 hours in the urine, 86% was unchanged olopatadine with the balance comprised of olopatadine N-oxide and N-desmethyl olopatadine.
Special Population:
Hepatic Impairment: No specific pharmacokinetic study examining the effect of hepatic impairment was conducted. Since metabolism of olopatadine is a minor route of elimination, no adjustment of the dosing regimen of Olopatadine Hydrochloride Nasal Spray is warranted in patients with hepatic impairment.
Renal Impairment: The mean Cmax values for olopatadine following single intranasal doses were not markedly different between healthy subjects (18.1 ng/mL) and patients with mild, moderate and severe renal impairment (range 15.5 to 21.6 ng/mL). Mean plasma AUC0-12 was two-fold higher in patients with severe impairment (creatinine clearance <30 mL/min/1.73 m2). In these patients, peak steady-state plasma concentrations of olopatadine are approximately 10-fold lower than those observed after higher 20 mg oral doses, twice daily, which were safe and well-tolerated. These findings indicate that no adjustment of the dosing regimen of Olopatadine Hydrochloride Nasal Spray is warranted in patients with renal impairment.
Gender: The mean systemic exposure (Cmax and AUC0-12) in female SAR patients following multiple administration of olopatadine was 40% and 27% higher, respectively than those values observed in male SAR patients.
Race: The effects of race on olopatadine pharmacokinetics have not been adequately investigated.
Age: The effects of age on olopatadine pharmacokinetics have not been adequately investigated.
12. HOW SUPPLIED/STORAGE AND HANDLING 
1) How Available:
a) Brand name: PATANASE, by ALCON.
b) Generic drugs: None.
2) How Supplied:
PATANASE Nasal Spray, 665 mcg is supplied in a white plastic bottle with a metered-dose manual spray pump, a white nasal applicator and a blue overcap in a box of 1 (NDC 0065-0332-30). Each trade size bottle contains 30.5 g of clear, colorless liquid and will provide 240 metered sprays. After priming [see Dosage and Administration (2)], each spray delivers a fine mist containing 665 mcg of olopatadine hydrochloride in 100 microliters of formulation through the nozzle.
Before initial use, prime PATANASE Nasal Spray by releasing 5 sprays or until a fine mist appears. After periods of non-use greater than 7 days, re-prime PATANASE Nasal Spray by releasing 2 sprays. The correct amount of medication cannot be assured before the initial priming and after 240 sprays have been used, even though the bottle is not completely empty. The nasal device should be discarded after 240 sprays (enough for 30 days of dosing) have been used.
Net content 30.5 g, 240 sprays: NDC 0065-0332-30 (trade size)
Storage: Store at 4° to 25° C ( 39° to 77° F).