(sarolaner, moxidectin, and pyrantel chewable tablets)
（沙罗拉纳、莫昔克丁和噻嘧啶咀嚼片）

Federal law restricts this drug to use by or on the order of a licensed veterinarian.
联邦法律限制该药物只能由有执照的兽医使用或在其指示下使用。

SIMPARICA TRIO (sarolaner, moxidectin, and pyrantel chewable tablets) is a flavored, chewable tablet for administration to dogs 8 weeks of age and older. Each tablet is formulated to provide minimum dosages of $0.54\mathrm{mg}/\mathrm{b}$$0.54\mathrm{mg}/\mathrm{b}$0.54mg//b0.54 \mathrm{mg} / \mathrm{b} ( $1.2\mathrm{mg}/\mathrm{kg}$$1.2\mathrm{mg}/\mathrm{kg}$1.2mg//kg1.2 \mathrm{mg} / \mathrm{kg} ) sarolaner, $0.011\mathrm{mg}/\mathrm{b}$$0.011\mathrm{mg}/\mathrm{b}$0.011mg//b0.011 \mathrm{mg} / \mathrm{b} ( $24\mu \mathrm{g}/\mathrm{kg}$$24\mu \mathrm{g}/\mathrm{kg}$24 mug//kg24 \mu \mathrm{~g} / \mathrm{kg} ) moxidectin, and $2.27\mathrm{mg}/\mathrm{l}/\mathrm{b}(5\mathrm{mg}/\mathrm{kg}$$2.27\mathrm{mg}/\mathrm{l}/\mathrm{b}(5\mathrm{mg}/\mathrm{kg}$2.27mg//l//b(5mg//kg2.27 \mathrm{mg} / \mathrm{l} / \mathrm{b}(5 \mathrm{mg} / \mathrm{kg} ) pyrantel (as pamoate salt).
SIMPARICA TRIO（沙罗拉纳、莫昔克丁和噻嘧啶咀嚼片）是一款调味咀嚼片，适用于 8 周龄及以上的犬只。每片配方至少包含 $0.54\mathrm{mg}/\mathrm{b}$$0.54\mathrm{mg}/\mathrm{b}$0.54mg//b0.54 \mathrm{mg} / \mathrm{b} （ $1.2\mathrm{mg}/\mathrm{kg}$$1.2\mathrm{mg}/\mathrm{kg}$1.2mg//kg1.2 \mathrm{mg} / \mathrm{kg} ）沙罗拉纳、 $0.011\mathrm{mg}/\mathrm{b}$$0.011\mathrm{mg}/\mathrm{b}$0.011mg//b0.011 \mathrm{mg} / \mathrm{b} （ $24\mu \mathrm{g}/\mathrm{kg}$$24\mu \mathrm{g}/\mathrm{kg}$24 mug//kg24 \mu \mathrm{~g} / \mathrm{kg} ）莫昔克丁和 $2.27\mathrm{mg}/\mathrm{l}/\mathrm{b}(5\mathrm{mg}/\mathrm{kg}$$2.27\mathrm{mg}/\mathrm{l}/\mathrm{b}(5\mathrm{mg}/\mathrm{kg}$2.27mg//l//b(5mg//kg2.27 \mathrm{mg} / \mathrm{l} / \mathrm{b}(5 \mathrm{mg} / \mathrm{kg} ）噻嘧啶（以双羟萘酸盐形式）。
Sarolaner is a member of the isoxazoline class of parasiticides and the chemical name is 1-(5’-((5S)-5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3’-H-spiro(azetidine-3,1’-(2) benzofuran)-1-yl)-2-(methylsulfonyl)ethanone. SIMPARICA TRIO contains the S-enantiomer of sarolaner.
Sarolaner 属于异恶唑啉类杀寄生虫药，化学名称为 1-(5'-((5S)-5-(3,5-二氯-4-氟苯基)-5-(三氟甲基)-4,5-二氢异恶唑-3-基)-3'-H-螺(氮杂环丁烷-3,1'-(2)苯并呋喃)-1-基)-2-(甲基磺酰基)乙酮。SIMPARICA TRIO 含有 Sarolaner 的 S-对映体。
Moxidectin is a semi-synthetic methoxime derivative of nemadectin which is a fermentation product of Streptomyces cyaneogriseus subspecies noncyanogenus. Moxidectin is a pentacyclic 16-membered lactone macrolide. The chemical name for moxidectin is (6R,23E,25S)-5-0-Demethyl-28-deoxy-25-[(1E)-1,3-dimethyl-1-buten-1-yl]-6,28-epoxy-23-(methoxyimino)milbemycin B.
莫昔克丁是奈玛克丁的半合成甲肟衍生物，奈玛克丁是链霉菌蓝灰亚种非氰基亚种的发酵产物。莫昔克丁是一种五环十六元内酯大环内酯。其化学名为(6R,23E,25S)-5-0-脱甲基-28-脱氧-25-[(1E)-1,3-二甲基-1-丁烯-1-基]-6,28-环氧-23-(甲氧亚氨基)米尔贝霉素 B。
Pyrantel belongs to a family classified chemically as tetrahydropyrimidines and the chemical name is (E)-1,4,5,6-Tetrahydro-1-methyl-2-[2-(2-thienyl) vinyl] pyrimidine 4,4’ methylenebis 3-hydroxy-2-naphthoate. It is a yellow, water-insoluble crystalline salt of the tetrahydropyrimidine base and pamoic acid containing 34.7% base activity.
噻嘧啶属于四氢嘧啶类化合物，化学名称为(E)-1,4,5,6-四氢-1-甲基-2-[2-(2-噻吩基)乙烯基]嘧啶 4,4'-亚甲基双 3-羟基-2-萘甲酸酯 。噻嘧啶碱与帕莫酸的结晶盐为黄色，不溶于水，碱活性为 34.7%。

SIMPARICA TRIO is indicated for the prevention of heartworm disease caused by Dirofilaria immitis and for the treatment and control of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and hookworm (L4, immature adult, and adult Ancylostoma caninum and adult Uncinaria stenocephala) infections. SIMPARICA TRIO kills adult fleas (Ctenocephalides felis) and is indicated for the treatment and prevention of flea infestations, the prevention of Dipylidium caninum (tapeworm) infections as a direct result of killing Ctenocephalides felis vector fleas on the treated dog, and the treatment and control of tick infestations with Amblyomma americanum (lone star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick), Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis longicornis (Asian longhorned tick) for one month in dogs and puppies 8 weeks of age and older, and weighing 2.8 pounds or greater. SIMPARICA TRIO is indicated for the prevention of Borrelia burgdorferi infections as a direct result of killing /xodes scapularis vector ticks.
SIMPARICA TRIO 适用于预防犬恶丝虫引起的心丝虫病，以及治疗和控制蛔虫（未成熟成虫、成虫犬弓首蛔虫和成虫狮弓首蛔虫）和钩虫（L4、未成熟成虫、成虫犬钩虫和成虫狭头钩虫）感染。 SIMPARICA TRIO 可杀死成年跳蚤（猫栉首蚤），用于治疗和预防跳蚤侵扰，通过杀死接受治疗的狗身上的猫栉首蚤媒介跳蚤直接预防犬复孔绦虫（绦虫）感染，以及治疗和控制蜱虫侵扰，包括美洲钝眼蜱（孤星蜱）、墨西哥湾沿岸钝眼蜱（墨西哥湾沿岸蜱）、美洲革蜱（美洲犬蜱）、肩突硬蜱（黑腿蜱）、血红扇头蜱（棕色犬蜱）和长角血蜱（亚洲长角蜱），适用于年龄 8 周及以上、体重 2.8 磅或以上的狗和幼犬，有效期为一个月。 SIMPARICA TRIO 适用于通过杀死肩胛伯氏疏螺旋体媒介蜱虫来预防伯氏疏螺旋体感染。

SIMPARICA TRIO is given orally once a month, at the recommended minimum dose of $0.54\mathrm{mg}/\mathrm{lb}(1.2\mathrm{mg}/\mathrm{kg})$$0.54\mathrm{mg}/\mathrm{lb}(1.2\mathrm{mg}/\mathrm{kg})$0.54mg//lb(1.2mg//kg)0.54 \mathrm{mg} / \mathrm{lb}(1.2 \mathrm{mg} / \mathrm{kg}) sarolaner, $0.011\mathrm{mg}/\mathrm{lb}(24\mu \mathrm{g}/\mathrm{kg})$$0.011\mathrm{mg}/\mathrm{lb}(24\mu \mathrm{g}/\mathrm{kg})$0.011mg//lb(24 mug//kg)0.011 \mathrm{mg} / \mathrm{lb}(24 \mu \mathrm{~g} / \mathrm{kg}) moxidectin, and $2.27\mathrm{mg}/\mathrm{lb}$$2.27\mathrm{mg}/\mathrm{lb}$2.27mg//lb2.27 \mathrm{mg} / \mathrm{lb} ( $5\mathrm{mg}/\mathrm{kg}$$5\mathrm{mg}/\mathrm{kg}$5mg//kg5 \mathrm{mg} / \mathrm{kg} ) pyrantel (as pamoate salt).
SIMPARICA TRIO 每月口服一次，推荐最低剂量为 $0.54\mathrm{mg}/\mathrm{lb}(1.2\mathrm{mg}/\mathrm{kg})$$0.54\mathrm{mg}/\mathrm{lb}(1.2\mathrm{mg}/\mathrm{kg})$0.54mg//lb(1.2mg//kg)0.54 \mathrm{mg} / \mathrm{lb}(1.2 \mathrm{mg} / \mathrm{kg}) sarolaner、 $0.011\mathrm{mg}/\mathrm{lb}(24\mu \mathrm{g}/\mathrm{kg})$$0.011\mathrm{mg}/\mathrm{lb}(24\mu \mathrm{g}/\mathrm{kg})$0.011mg//lb(24 mug//kg)0.011 \mathrm{mg} / \mathrm{lb}(24 \mu \mathrm{~g} / \mathrm{kg}) 莫昔克丁和 $2.27\mathrm{mg}/\mathrm{lb}$$2.27\mathrm{mg}/\mathrm{lb}$2.27mg//lb2.27 \mathrm{mg} / \mathrm{lb} ( $5\mathrm{mg}/\mathrm{kg}$$5\mathrm{mg}/\mathrm{kg}$5mg//kg5 \mathrm{mg} / \mathrm{kg} ) 噻嘧啶（以帕莫酸盐形式）。
Dosage Schedule  剂量表

SIMPARICA TRIO can be offered to the dog with or without food.
SIMPARICA TRIO 可以与食物一起或单独给狗食用。
Care should be taken to ensure that the dog consumes the complete dose and that part of the dose is not lost or refused. If a dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing.
应注意确保狗狗服用完整剂量，不要遗漏或拒绝服用部分剂量。如果漏服，请立即服用 SIMPARICA TRIO，并恢复每月一次的给药。

SIMPARICA TRIO should be administered at monthly intervals year-round or at least within one month of the animal’s first seasonal exposure to mosquitoes and continuing until at least 1 month after the dog’s last seasonal exposure. If a dose is missed, give SIMPARICA TRIO immediately and resume monthly dosing. When replacing a monthly heartworm preventive product, SIMPARICA TRIO should be given within one month of the last dose of the former medication.
SIMPARICA TRIO 应全年每月给药一次，或至少在犬只首次接触蚊子后一个月内给药，并持续至犬只最后一次接触蚊子后至少一个月。如果漏服一次，应立即服用 SIMPARICA TRIO，并恢复每月给药。当替代每月一次的心丝虫预防产品时，SIMPARICA TRIO 应在前一种药物最后一次给药后一个月内服用。
Flea Treatment and Prevention:
跳蚤治疗和预防：
Treatment with SIMPARICA TRIO may begin at any time of the year. SIMPARICA TRIO should be administered year-round at monthly intervals or started at least one month before fleas become active.
SIMPARICA TRIO 可在一年中的任何时候开始使用。SIMPARICA TRIO 应全年每月使用一次，或在跳蚤活跃前至少一个月开始使用。
To minimize the likelihood of flea re-infestation, it is important to treat all dogs and cats within a household with a flea control product.
为了最大限度地减少跳蚤再次感染的可能性，重要的是用跳蚤控制产品治疗家中的所有狗和猫。

Treatment with SIMPARICA TRIO may begin at any time of the year. SIMPARICA TRIO should be administered year-round at monthly intervals or started at least one month before fleas become active.
SIMPARICA TRIO 可在一年中的任何时候开始使用。SIMPARICA TRIO 应全年每月使用一次，或在跳蚤活跃前至少一个月开始使用。
SIMPARICA TRIO will only prevent $D$$D$DD. caninum infections by killing the fleas on the treated dog. Dogs may also become infected with $D$$D$DD. caninum by ingesting fleas from untreated animals, it is therefore recommended that all pets in a household are treated for fleas.
SIMPARICA TRIO 只能通过杀死已接受治疗的狗狗身上的跳蚤来预防 $D$$D$DD . caninum 感染。狗狗也可能因吞食未经治疗的宠物身上的跳蚤而感染 $D$$D$DD . caninum，因此建议家中所有宠物都进行跳蚤治疗。

Treatment with SIMPARICA TRIO can begin at any time of the year. SIMPARICA TRIO should be administered year-round at monthly intervals or started at least one month before ticks become active.
SIMPARICA TRIO 治疗可在一年中的任何时候开始。SIMPARICA TRIO 应全年每月使用一次，或在蜱虫活跃前至少一个月开始使用。

For the treatment of roundworm (immature adult and adult Toxocara canis and adult Toxascaris leonina) and hookworm (L4, immature adult, and adult Ancylostoma caninum and adult Uncinaria stenocephala) infections, SIMPARICA TRIO should be administered once as a single dose. Monthly use of SIMPARICA TRIO will control any subsequent infections.
用于治疗蛔虫（幼虫成虫、成虫犬弓首蛔虫和成虫狮弓首蛔虫）和钩虫（L4、幼虫成虫、成虫犬钩虫和成虫狭头钩虫）感染，SIMPARICA TRIO 应单剂量给药。每月使用 SIMPARICA TRIO 可控制任何后续感染。

Not for use in humans. Keep this and all drugs out of reach of children.
不可用于人体。请将本品及所有药物放在儿童接触不到的地方。
Keep SIMPARICA TRIO in a secure location out of reach of dogs, cats and other animals to prevent accidental ingestion or overdose.
将 SIMPARICA TRIO 放在狗、猫和其他动物接触不到的安全地方，以防止意外摄入或过量服用。

Sarolaner, one of the ingredients in SIMPARICA TRIO, is a member of the isoxazoline class. This class has been associated with neurologic adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders.
Sarolaner 是 SIMPARICA TRIO 的成分之一，属于异噁唑啉类药物。该类药物与神经系统不良反应有关，包括震颤、共济失调和癫痫发作。据报道，使用异噁唑啉类药物的犬只，即使没有癫痫病史的犬只，也会出现癫痫发作。有癫痫病史或神经系统疾病的犬只应谨慎使用。
Prior to administration of SIMPARICA TRIO, dogs should be tested for existing heartworm infections. Infected dogs should be treated with an adulticide to remove adult heartworms. SIMPARICA TRIO is not effective against adult $D$$D$DD. immitis.
在服用 SIMPARICA TRIO 之前，应先检测狗狗是否感染了心丝虫。感染的狗狗应使用杀成虫剂来清除心丝虫成虫。SIMPARICA TRIO 对 $D$$D$DD 心丝虫成虫无效。
The safe use of SIMPARICA TRIO has not been evaluated in breeding, pregnant, or lactating dogs.
尚未评估 SIMPARICA TRIO 对繁殖期、怀孕期或哺乳期犬的安全性。

In a field safety and effectiveness study, SIMPARICA TRIO was administered to dogs for the prevention of heartworm disease. The study included a total of 410 dogs treated once monthly for 11 treatments ( 272 treated with SIMPARICA TRIO and 138 treated with an active control). Over the 330-day study period, all observations of potential adverse reactions were recorded. The most frequent reactions reported in the SIMPARICA TRIO group are presented in the following table.
在一项安全性和有效性的实地研究中，SIMPARICA TRIO 用于犬只预防心丝虫病。该研究共纳入 410 只犬只，每月接受一次治疗，共计 11 次（其中 272 只接受 SIMPARICA TRIO 治疗，138 只接受阳性对照治疗）。在 330 天的研究期间，所有潜在不良反应的观察结果均被记录。下表列出了 SIMPARICA TRIO 组报告的最常见不良反应。
Table 1. Dogs with Adverse Reactions
表 1. 出现不良反应的狗

In a second field safety and effectiveness study, SIMPARICA TRIO was administered to 278 dogs with fleas. Adverse reactions in dogs treated with SIMPARICA TRIO included diarrhea.
在另一项现场安全性和有效性研究中，SIMPARICA TRIO 用于治疗 278 只患有跳蚤的犬只。接受 SIMPARICA TRIO 治疗的犬只出现的不良反应包括腹泻。
In a third field safety and effectiveness study, SIMPARICA TRIO was administered to 120 dogs with roundworms. Adverse reactions in dogs treated with SIMPARICA TRIO included diarrhea and vomiting.
在第三项安全性和有效性的实地研究中，SIMPARICA TRIO 用于治疗 120 只感染蛔虫的犬只。接受 SIMPARICA TRIO 治疗的犬只出现的不良反应包括腹泻和呕吐。
In one well-controlled laboratory study, one dog had a seizure 16 days after administration of SIMPARICA TRIO.
在一项控制良好的实验室研究中，一只狗在服用 SIMPARICA TRIO 16 天后出现癫痫发作。

The following adverse events are based on post-approval adverse drug experience reporting for SIMPARICA TRIO. Not all adverse events are reported to FDACVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
以下不良事件基于 SIMPARICA TRIO 上市后不良反应报告。并非所有不良事件都会报告给 FDACVM。使用这些数据并不总是能够准确地估计不良事件发生频率或与产品暴露之间的因果关系。
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
以下列出的是狗中报告的不良事件，按报告频率的降序排列：
Vomiting, diarrhea (with and without blood), seizure, lethargy, anorexia, muscle tremor, ataxia, non-specific behavioral changes, and pruritus.
呕吐、腹泻（带血或不带血）、癫痫、嗜睡、厌食、肌肉震颤、共济失调、非特异性行为改变和瘙痒。

For a copy of the Safety Data Sheet or to report adverse reactions, call Zoetis Inc. at 1-888-963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.
如需获取安全数据表 (SDS) 副本或报告不良反应，请致电 1-888-963-8471 联系硕腾公司 (Zoetis Inc.)。如需了解更多关于动物药品不良反应报告的信息，请联系 FDA，电话：1-888-FDA-VETS 或访问 www.fda.gov/reportanimalae 。

Following oral administration of SIMPARICA TRIO in Beagle dogs (13 to 15 months of age at the time of initial dosing), sarolaner and moxidectin were rapidly and well-absorbed. Following a single oral dose of SIMPARICA TRIO (sarolaner dose of $1.2\mathrm{mg}/\mathrm{kg}$$1.2\mathrm{mg}/\mathrm{kg}$1.2mg//kg1.2 \mathrm{mg} / \mathrm{kg} ), the sarolaner mean maximum plasma concentration ( ${\mathrm{C}}_{\text{max}}$${\mathrm{C}}_{\text{max }}$C_("max ")\mathrm{C}_{\text {max }} ) was $523\mathrm{ng}/\mathrm{mL}$$523\mathrm{ng}/\mathrm{mL}$523ng//mL523 \mathrm{ng} / \mathrm{mL} with a mean time to maximum concentration ( ${\mathrm{T}}_{\text{max}}$${\mathrm{T}}_{\text{max }}$T_("max ")\mathrm{T}_{\text {max }} ) of 3.5 hours and an absolute bioavailability of $88\mathrm{\%}$$88\mathrm{\%}$88%88 \%. At a moxidectin dose of $0.024\mathrm{mg}/\mathrm{kg}$$0.024\mathrm{mg}/\mathrm{kg}$0.024mg//kg0.024 \mathrm{mg} / \mathrm{kg}, the moxidectin mean ${\mathrm{C}}_{\text{max}}$${\mathrm{C}}_{\text{max }}$C_("max ")\mathrm{C}_{\text {max }} was $13.1\mathrm{ng}/\mathrm{mL}$$13.1\mathrm{ng}/\mathrm{mL}$13.1ng//mL13.1 \mathrm{ng} / \mathrm{mL} with a mean ${\mathrm{T}}_{\text{max}}$${\mathrm{T}}_{\text{max }}$T_("max ")\mathrm{T}_{\text {max }} of 2.4 hours and an absolute bioavailability of $67\mathrm{\%}$$67\mathrm{\%}$67%67 \%.
比格犬（初次给药时年龄为 13 至 15 月龄）口服 SIMPARICA TRIO 后，sarolaner 和莫昔克丁均快速且良好地吸收。单次口服 SIMPARICA TRIO（sarolaner 剂量为 $1.2\mathrm{mg}/\mathrm{kg}$$1.2\mathrm{mg}/\mathrm{kg}$1.2mg//kg1.2 \mathrm{mg} / \mathrm{kg} ）后，sarolaner 平均最大血浆浓度( ${\mathrm{C}}_{\text{max}}$${\mathrm{C}}_{\text{max }}$C_("max ")\mathrm{C}_{\text {max }} )为 $523\mathrm{ng}/\mathrm{mL}$$523\mathrm{ng}/\mathrm{mL}$523ng//mL523 \mathrm{ng} / \mathrm{mL} ，平均达峰时间( ${\mathrm{T}}_{\text{max}}$${\mathrm{T}}_{\text{max }}$T_("max ")\mathrm{T}_{\text {max }} )为 3.5 小时，绝对生物利用度为 $88\mathrm{\%}$$88\mathrm{\%}$88%88 \% 。莫昔克丁剂量为 $0.024\mathrm{mg}/\mathrm{kg}$$0.024\mathrm{mg}/\mathrm{kg}$0.024mg//kg0.024 \mathrm{mg} / \mathrm{kg} 时，莫昔克丁平均 ${\mathrm{C}}_{\text{max}}$${\mathrm{C}}_{\text{max }}$C_("max ")\mathrm{C}_{\text {max }} 为 $13.1\mathrm{ng}/\mathrm{mL}$$13.1\mathrm{ng}/\mathrm{mL}$13.1ng//mL13.1 \mathrm{ng} / \mathrm{mL} ，平均 ${\mathrm{T}}_{\text{max}}$${\mathrm{T}}_{\text{max }}$T_("max ")\mathrm{T}_{\text {max }} 为 2.4 小时，绝对生物利用度为 $67\mathrm{\%}$$67\mathrm{\%}$67%67 \% 。

Following intravenous (IV) dosing of a combination solution of sarolaner and moxidectin, the sarolaner volume of distribution $\left({\mathrm{N}}_{\mathrm{ss}}\right)$$\left({\mathrm{N}}_{\mathrm{ss}}\right)$(N_(ss))\left(\mathrm{N}_{\mathrm{ss}}\right) was $2.4\mathrm{L}/\mathrm{kg}$$2.4\mathrm{L}/\mathrm{kg}$2.4L//kg2.4 \mathrm{~L} / \mathrm{kg} and systemic clearance (CL) was $6.0\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$$6.0\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$6.0mL//kg//hr6.0 \mathrm{~mL} / \mathrm{kg} / \mathrm{hr}. For moxidectin the ${\mathrm{V}}_{\mathrm{ss}}$${\mathrm{V}}_{\mathrm{ss}}$V_(ss)\mathrm{V}_{\mathrm{ss}} was $7.65\mathrm{L}/\mathrm{kg}$$7.65\mathrm{L}/\mathrm{kg}$7.65L//kg7.65 \mathrm{~L} / \mathrm{kg} and CL was $26.6\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$$26.6\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$26.6mL//kg//hr26.6 \mathrm{~mL} / \mathrm{kg} / \mathrm{hr}. The terminal half-lives were similar after oral and IV dosing for both sarolaner (12 days) and moxidectin (11 days). The primary route of elimination of both sarolaner and moxidectin is biliary excretion with minimal metabolism.
静脉注射 (IV) 沙罗拉纳和莫昔克丁的复方溶液后，沙罗拉纳的分布容积 $\left({\mathrm{N}}_{\mathrm{ss}}\right)$$\left({\mathrm{N}}_{\mathrm{ss}}\right)$(N_(ss))\left(\mathrm{N}_{\mathrm{ss}}\right) 为 $2.4\mathrm{L}/\mathrm{kg}$$2.4\mathrm{L}/\mathrm{kg}$2.4L//kg2.4 \mathrm{~L} / \mathrm{kg} ，全身清除率 (CL) 为 $6.0\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$$6.0\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$6.0mL//kg//hr6.0 \mathrm{~mL} / \mathrm{kg} / \mathrm{hr} 。莫昔克丁的 ${\mathrm{V}}_{\mathrm{ss}}$${\mathrm{V}}_{\mathrm{ss}}$V_(ss)\mathrm{V}_{\mathrm{ss}} 为 $7.65\mathrm{L}/\mathrm{kg}$$7.65\mathrm{L}/\mathrm{kg}$7.65L//kg7.65 \mathrm{~L} / \mathrm{kg} ，CL 为 $26.6\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$$26.6\mathrm{mL}/\mathrm{kg}/\mathrm{hr}$26.6mL//kg//hr26.6 \mathrm{~mL} / \mathrm{kg} / \mathrm{hr} 。沙罗拉纳（12 天）和莫昔克丁（11 天）口服和静脉给药后的终末半衰期相似。沙罗拉纳和莫昔克丁的主要消除途径均为胆汁排泄，代谢率极低。
Following an oral dose of SIMPARICA TRIO containing $5\mathrm{mg}/\mathrm{kg}$$5\mathrm{mg}/\mathrm{kg}$5mg//kg5 \mathrm{mg} / \mathrm{kg} pyrantel (as pamoate salt), pyrantel has measurable plasma concentrations, but they are low and highly variable. Pyrantel pamoate is intended to remain in the gastrointestinal tract allowing for delivery of effective concentrations to gastrointestinal nematodes.
口服含有 $5\mathrm{mg}/\mathrm{kg}$$5\mathrm{mg}/\mathrm{kg}$5mg//kg5 \mathrm{mg} / \mathrm{kg} 噻嘧啶（以双羟萘酸盐形式）的 SIMPARICA TRIO 后，噻嘧啶的血浆浓度可测量，但浓度较低且波动较大。双羟萘酸噻嘧啶旨在停留在胃肠道中，以便将有效浓度输送至胃肠道线虫。

SIMPARICA TRIO contains three active pharmaceutical ingredients, sarolaner, moxidectin, and pyrantel pamoate.
SIMPARICA TRIO 含有三种活性药物成分，即 sarolaner、莫昔克丁和噻嘧啶。
Sarolaner is an acaricide and insecticide belonging to the isoxazoline group. Sarolaner inhibits the function of the neurotransmitter gamma aminobutyric acid (GABA) receptor and glutamate receptor, and works at the neuromuscular junction in insects. This results in uncontrolled neuromuscular activity leading to death in insects or acarines.
Sarolaner 是一种异噁唑啉类杀螨剂和杀虫剂。Sarolaner 抑制神经递质 γ-氨基丁酸 (GABA) 受体和谷氨酸受体的功能，作用于昆虫的神经肌肉接头。这会导致神经肌肉活动失控，最终导致昆虫或螨类死亡。
Moxidectin is an endectocide in the macrocyclic lactone class. Moxidectin acts by interfering with the chloride channel-mediated neurotransmission in the parasite. This results in paralysis and death of the parasite.
莫昔克丁是一种大环内酯类内驱虫剂。莫昔克丁通过干扰寄生虫体内氯离子通道介导的神经传递发挥作用，导致寄生虫瘫痪甚至死亡。
Pyrantel pamoate is a nematocide belonging to the tetrahydropyrimidine class. Pyrantel acts as a depolarizing, neuromuscular-blocking agent in susceptible parasites, which causes paralysis and death or expulsion of the organism.
噻嘧啶双羟萘酸酯是一种四氢嘧啶类杀线虫剂。噻嘧啶对敏感寄生虫具有去极化和神经肌肉阻断作用，可导致寄生虫麻痹、死亡或排出。

In two well-controlled laboratory studies, a single oral dose of SIMPARICA TRIO was 100% effective in preventing the development of adult $D$$D$DD. immitis in dogs inoculated with infective larvae 30 days before treatment.
在两项严格控制的实验室研究中，单次口服 SIMPARICA TRIO 可 100% 有效地预防在治疗前 30 天接种感染性幼虫的狗的成年 $D$$D$DD 犬细小炎的发展。

In a well-controlled US field study consisting of 246 dogs administered SIMPARICA TRIO and 119 administered an active control, no dogs treated with SIMPARICA TRIO tested positive for heartworm disease. All dogs treated with SIMPARICA TRIO were negative for D. immitis antigen and blood microfilariae at study completion on day 330.
在美国一项控制严格的实地研究中，246 只犬接受了 SIMPARICA TRIO 治疗，119 只犬接受了阳性对照治疗。结果显示，接受 SIMPARICA TRIO 治疗的犬均未检测出心丝虫病阳性。所有接受 SIMPARICA TRIO 治疗的犬在第 330 天（研究结束）的犬只，其犬毛滴虫抗原和血液微丝蚴检测结果均为阴性。

In a well-controlled laboratory study, SIMPARICA TRIO began to kill fleas at 4 hours and demonstrated 100% effectiveness at 8 hours after initial administration. After weekly re-infestations, SIMPARICA TRIO reduced the number of live fleas by $\ge 97.8\mathrm{\%}$$\ge 97.8\mathrm{\%}$>= 97.8%\geq 97.8 \% within 12 hours of infestation for 28 days.
在一项严格控制的实验室研究中，SIMPARICA TRIO 在首次使用后 4 小时开始杀死跳蚤，并在 8 小时后显示出 100% 的有效性。在每周再次感染后，SIMPARICA TRIO 在感染后 12 小时内将活跳蚤数量减少了 $\ge 97.8\mathrm{\%}$$\ge 97.8\mathrm{\%}$>= 97.8%\geq 97.8 \% ，持续 28 天。
In a separate well-controlled laboratory study, SIMPARICA TRIO demonstrated 100% effectiveness against adult fleas within 24 hours following treatment and maintained $\ge 99.7\mathrm{\%}$$\ge 99.7\mathrm{\%}$>= 99.7%\geq 99.7 \% effectiveness against weekly re-infestations for 35 days.
在另一项严格控制的实验室研究中，SIMPARICA TRIO 在治疗后 24 小时内显示出对抗成年跳蚤的 100% 有效性，并在 35 天内保持对每周再次感染的 $\ge 99.7\mathrm{\%}$$\ge 99.7\mathrm{\%}$>= 99.7%\geq 99.7 \% 有效性。
In a study to explore flea egg production and viability, SIMPARICA TRIO killed fleas before they could lay eggs for 35 days.
在一项探索跳蚤卵的产量和生存能力的研究中，SIMPARICA TRIO 在跳蚤产卵 35 天内将其杀死。
In a well-controlled 60-day US field study conducted in dogs with existing flea infestations of varying severity, the effectiveness of SIMPARICA TRIO against fleas on Day 30 and 60 visits was $99.0\mathrm{\%}$$99.0\mathrm{\%}$99.0%99.0 \% and $99.7\mathrm{\%}$$99.7\mathrm{\%}$99.7%99.7 \%, respectively, compared to baseline. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating fleas.
在美国一项为期 60 天、控制良好的田间研究中，受跳蚤侵扰程度各异的犬只进行了一项控制良好的田间研究。结果表明，SIMPARICA TRIO 在第 30 天和第 60 天的灭蚤效果与基线相比分别为 $99.0\mathrm{\%}$$99.0\mathrm{\%}$99.0%99.0 \% 和 $99.7\mathrm{\%}$$99.7\mathrm{\%}$99.7%99.7 \% 。有跳蚤过敏性皮炎症状的犬只在清除跳蚤后，红斑、丘疹、鳞屑、脱发、皮炎/脓性皮炎和瘙痒症状均有所改善。

In two well-controlled laboratory studies, a single oral dose of SIMPARICA TRIO was $\ge 92.1\mathrm{\%}$$\ge 92.1\mathrm{\%}$>= 92.1%\geq 92.1 \% effective in preventing Dipylidium caninum infections in dogs after multiple infestations with Dipylidium caninum-infected C. felis fleas for one month.
在两项严格控制的实验室研究中，在狗多次感染犬复孔绦虫感染的猫复孔绦虫跳蚤一个月后，单次口服剂量 SIMPARICA TRIO 可有效预防犬复孔绦虫感染。 $\ge 92.1\mathrm{\%}$$\ge 92.1\mathrm{\%}$>= 92.1%\geq 92.1 \%

In a well-controlled laboratory study, SIMPARICA TRIO began to kill existing I scapularis within 8 hours, SIMPARICA TRIO reduced the number of live ticks by $\ge 94.2\mathrm{\%}$$\ge 94.2\mathrm{\%}$>= 94.2%\geq 94.2 \% within 24 hours of infestation for 28 days.
在一项严格控制的实验室研究中，SIMPARICA TRIO 在 8 小时内开始杀死现有的肩胛带蜱，SIMPARICA TRIO 在感染后 24 小时内将活蜱数量减少了 $\ge 94.2\mathrm{\%}$$\ge 94.2\mathrm{\%}$>= 94.2%\geq 94.2 \% ，持续了 28 天。
In well-controlled laboratory studies, SIMPARICA TRIO demonstrated $\ge 98.9\mathrm{\%}$$\ge 98.9\mathrm{\%}$>= 98.9%\geq 98.9 \% effectiveness against an existing infestation of Amblyomma maculatum, Ixodes scapularis, Rhipicephalus sanguineus, Dermacentor variabilis, and Haemaphysalis longicornis 48 hours post-administration and maintained $\ge 90.4\mathrm{\%}$$\ge 90.4\mathrm{\%}$>= 90.4%\geq 90.4 \% effectiveness 48 hours after re-infestation for at least 28 days. Against Amblyomma americanum, SIMPARICA TRIO demonstrated $\ge 99.4\mathrm{\%}$$\ge 99.4\mathrm{\%}$>= 99.4%\geq 99.4 \% effectiveness 72 hours after treatment of existing infestations, and maintained $\ge 98.4\mathrm{\%}$$\ge 98.4\mathrm{\%}$>= 98.4%\geq 98.4 \% effectiveness 72 hours after re-infestation for at least 28 days. In two separate, well-controlled laboratory studies, SIMPARICA TRIO was effective at preventing Borrelia burgdorferi infections after dogs were infested with /xodes scapularis vector ticks 28 days post-treatment.
在严格控制的实验室研究中，SIMPARICA TRIO 在给药后 48 小时内显示出对斑花蜱、肩胛硬蜱、血红扇头蜱、多变革蜱和长角血蜱的现有感染的有效性，并且在再次感染后 48 小时内至少持续 28 天仍能维持 $\ge 90.4\mathrm{\%}$$\ge 90.4\mathrm{\%}$>= 90.4%\geq 90.4 \% 的有效性。对于美洲花蜱，SIMPARICA TRIO 在治疗现有感染 72 小时后显示出 $\ge 99.4\mathrm{\%}$$\ge 99.4\mathrm{\%}$>= 99.4%\geq 99.4 \% 的有效性，并且在再次感染后 72 小时内至少持续 28 天仍能维持 $\ge 98.4\mathrm{\%}$$\ge 98.4\mathrm{\%}$>= 98.4%\geq 98.4 \% 的有效性。在两项独立的、严格控制的实验室研究中，SIMPARICA TRIO 在治疗 28 天后，在犬只感染肩胛硬蜱媒介蜱后，可有效预防伯氏疏螺旋体感染。

Elimination of roundworms (immature adult and adult Toxocara canis and adult Toxascaris leonina) and hookworm (L4, immature adult, and adult Ancylostoma caninum and adult Uncinaria stenocephala) was demonstrated in well-controlled laboratory studies.
严格控制的实验室研究表明，蛔虫（未成熟成虫和成年犬弓首蛔虫和成年狮弓首蛔虫）和钩虫（L4、未成熟成虫、成年犬钩虫和成年狭头钩虫）均已被消除。
In a 10-day multi-center field study, SIMPARICA TRIO was effective against Toxocara canis and reduced fecal egg counts 99.2%.
在一项为期 10 天的多中心实地研究中，SIMPARICA TRIO 对犬弓首蛔虫有效，并使粪便虫卵数量减少 99.2%。

Margin of Safety: SIMPARICA TRIO was administered orally to 8 -week-old Beagle puppies at doses of 1,3 , and 5 X the maximum labeled dose ( $2.4\mathrm{mg}/\mathrm{kg}$$2.4\mathrm{mg}/\mathrm{kg}$2.4mg//kg2.4 \mathrm{mg} / \mathrm{kg} sarolaner, $48\mu \mathrm{g}/\mathrm{kg}$$48\mu \mathrm{g}/\mathrm{kg}$48 mug//kg48 \mu \mathrm{~g} / \mathrm{kg} moxidectin, and $10\mathrm{mg}/\mathrm{kg}$$10\mathrm{mg}/\mathrm{kg}$10mg//kg10 \mathrm{mg} / \mathrm{kg} pyrantel) at 28 day intervals for 7 treatments. Dogs in the control group received placebo. There were no clinically-relevant, treatment related effects on clinical observations, body weights, food consumption, clinical pathology (hematology, coagulation, serum chemistry, and urinalysis), gross pathology, histopathology, or organ weights. During the end-of-study ophthalmic examination, the following change was found: one 1X dog had retinal dysplasia (OS folds).
安全范围：给 8 周龄比格犬幼犬口服 SIMPARICA TRIO，剂量分别为标示最大剂量（ $2.4\mathrm{mg}/\mathrm{kg}$$2.4\mathrm{mg}/\mathrm{kg}$2.4mg//kg2.4 \mathrm{mg} / \mathrm{kg} 沙罗拉纳、 $48\mu \mathrm{g}/\mathrm{kg}$$48\mu \mathrm{g}/\mathrm{kg}$48 mug//kg48 \mu \mathrm{~g} / \mathrm{kg} 莫昔克丁和 $10\mathrm{mg}/\mathrm{kg}$$10\mathrm{mg}/\mathrm{kg}$10mg//kg10 \mathrm{mg} / \mathrm{kg} 噻嘧啶）的 1、3 和 5 倍，每 28 天给药一次，共 7 次。对照组犬只接受安慰剂。治疗对临床观察、体重、摄食量、临床病理学（血液学、凝血、血清化学和尿液分析）、大体病理学、组织病理学或器官重量均未产生临床相关的治疗相关影响。在研究结束时的眼科检查中，发现以下变化：一只 1X 犬出现视网膜发育不良（OS 皱褶）。

SIMPARICA TRIO was administered orally once at 1,3 and 5 X the maximum labeled dose to Collies that had been pre-screened for avermectin sensitivity. Dogs in the control group received placebo. Clinical signs (ataxia, muscle fasciculations, mydriasis) associated with avermectin sensitivity were observed in the 5 X group. All dogs were completely recovered by the third day of the study.
对已进行阿维菌素敏感性预筛选的牧羊犬，分别以 1 倍、3 倍和 5 倍最大标示剂量口服 SIMPARICA TRIO 一次。对照组犬只接受安慰剂。在 5 倍剂量组观察到与阿维菌素敏感性相关的临床症状（共济失调、肌肉颤抖、瞳孔散大）。所有犬只在研究第三天完全康复。

SIMPARICA TRIO was administered orally at 1 and 3 X the maximum labeled dose at 28 day intervals for 3 treatments to Beagle dogs with patent adult heartworm infections and circulating microfilariae. Dogs in the control group received placebo. Diarrhea occurred more commonly in the treated dogs and also more often in the 3X group compared with the 1X group. Two dogs (1 each in 1X and 3X) developed a fever less than 24 hours after the first dose. The fever may have been a transient reaction to a rapid microfilaria reduction. Both dogs recovered without treatment.
研究人员对感染了明显心丝虫成虫感染和循环微丝蚴的比格犬，以 1 倍和 3 倍最大标示剂量，每 28 天一次，共进行 3 次口服 SIMPARICA TRIO。对照组犬只接受安慰剂。与 1 倍剂量组相比，接受治疗的犬只腹泻发生率更高，3 倍剂量组的腹泻发生率也更高。两只犬只（1 倍剂量组和 3 倍剂量组各 1 只）在首次给药后不到 24 小时内出现发烧。发烧可能是对微丝蚴快速减少的短暂反应。两只犬均未接受治疗就康复了。
Field Safety: In three well-controlled field studies, SIMPARICA TRIO was used concurrently with other medications such as vaccines, antimicrobials, anthelmintics, antiprotozoals, steroidal and non-steroidal anti-inflammatory agents, anesthetic agents and analgesics. No adverse reactions were associated with the concurrent use of SIMPARICA TRIO and other medications.
现场安全性：在三项严格控制的现场研究中，SIMPARICA TRIO 与其他药物（例如疫苗、抗菌药物、驱虫药、抗原虫药、甾体类和非甾体类抗炎药、麻醉药和镇痛药）同时使用。SIMPARICA TRIO 与其他药物同时使用未发生任何不良反应。

Store at or below ${30}^{\circ }\mathrm{C}\left({86}^{\circ }\mathrm{F}\right)$${30}^{\circ }\mathrm{C}\left({86}^{\circ }\mathrm{F}\right)$30^(@)C(86^(@)F)30^{\circ} \mathrm{C}\left(86^{\circ} \mathrm{F}\right).
储存在 ${30}^{\circ }\mathrm{C}\left({86}^{\circ }\mathrm{F}\right)$${30}^{\circ }\mathrm{C}\left({86}^{\circ }\mathrm{F}\right)$30^(@)C(86^(@)F)30^{\circ} \mathrm{C}\left(86^{\circ} \mathrm{F}\right) 或以下。

SIMPARICA TRIO (sarolaner, moxidectin, and pyrantel chewable tablets) is available in six flavored tablet sizes (see DOSAGE AND ADMINISTRATION). Each tablet size is available in packages of one, three, or six tablets.
SIMPARICA TRIO（沙罗拉纳、莫昔克丁和噻嘧啶咀嚼片）有六种口味的片剂规格（参见“剂量和用法”）。每种片剂规格有一片、三片或六片装可供选择。

Approved by FDA under NADA # 141-521
经 FDA 批准，符合 NADA 编号 141-521

Distributed by:  发行人：
Zoetis Inc.  硕腾公司
Kalamazoo, Ml 49007  卡拉马祖，密西西比州 49007
Revised: October 2024  修订日期：2024 年 10 月
40050385A&P