繁体中文
设为首页
加入收藏
当前位置:药品说明书与价格首页 >> 肿瘤 >> 新药推荐 >> 阿瑞吡坦硬胶囊/板装|Emend(Aprepitant hard capsules)

阿瑞吡坦硬胶囊/板装|Emend(Aprepitant hard capsules)

2013-04-26 13:04:09  作者:新特药房  来源:互联网  浏览次数:206  文字大小:【】【】【
简介: 阿瑞吡坦胶囊(Emend)第一种可帮助患者避免恶心及呕吐-通常在患者接受极易引起呕吐的化疗法治疗后第一天即发生,并可持续几天-这种症状持续发生的药物【靶点】为P/神经激肽受体拮抗剂。 英文药名: Em ...

部中文阿瑞吡坦处方资料(仅供参考)
药品英文普通名
aprepitant
药品商品名
EMEND
药物剂型
胶囊:80mg;125mg。
药理作用
本品系神经激肽-1(NK-1)受体拮抗药(P物质拮抗剂),对人NK-1受体有高选择性的亲和力,对5-羟色胺3(5-HT3)、多巴胺和皮质激素受体的亲和力很低。P物质是一种位于中枢和外周神经系统神经元中的速激肽(神经激肽),它与多种功能有关,包括呕吐、抑郁、炎性疼痛以及哮喘和其他疾病的炎症/免疫反应。P物质的作用通过NK-1受体介导,NK-1受体是一种G蛋白受体,与磷酸肌醇信号通路耦合。本品与大脑中NK-1受体结合,对该受体进行拮抗,从而治疗由P物质介导的疾患。临床试验证实,本品与5-HT3受体抑制药(如昂丹司琼及皮质激素地塞米松)合用,可进一步减轻顺铂诱发的急性和(或)延迟性呕吐。单用本品有一定的预防作用。
药动学
口服后4h可达血药峰浓度。首日平均血药峰浓度为1.6μg/ml,平均药时曲线下面积(AUC)约为20μg·h/ml;第3日平均血药峰浓度为1.4μg/ml,平均AUC为21μg·h/ml。生物利用度为60%~65%。食物对本品的体内药代动力学影响不大。血浆蛋白结合率不低于95%,可透过血-脑脊液屏障,在脑脊液中分布亦较多。在稳态时本品的分布容积约为70L。本品主要在肝内代谢,通过细胞色素CYP3A4(主要)和CYPlA2(次要)代谢。本品总体清除率约为75ml/min。消除半衰期为9~13h。本品几乎不能被血液透析所清除。
适应证
用于化疗后的急性和延迟性恶心或呕吐发作。还可用于重度抑郁症(伴焦虑)。
禁忌证
有本品过敏史者禁用。儿童不推荐使用。
注意事项
1.严重肝功能不全者慎用。
2.妊娠安全性分级为B级。
3.动物试验证实,本品可分泌入乳汁,但缺乏相关人体数据资料。
4.本品不能阻止已经发生的恶心和呕吐。
5.本品用于化疗诱发的恶心和呕吐时,常与昂丹司琼(仅首日使用)及地塞米松合用。
6.对于控制顺铂诱发的呕吐,单用本品并不能达到最佳疗效,应该与地塞米松(或地塞米松加一种5-HT3-R拮抗药)合用。
7.室温下保存。
不良反应
1.中枢神经系统:常见嗜睡和虚弱(或疲乏)。
2.呼吸系统:可引起呃逆。
3.泌尿生殖系统:用于重度抑郁症患者时可出现性功能障碍。
4.肝脏:用于预防化疗诱发的呕吐时,可使血清氨基转移酶升高。
5.胃肠道:用于预防化疗诱发的呕吐时,可能会发生腹泻。
6.皮肤:偶见史-约综合征、血管性水肿和风疹。
用法用量
口服给药。
1.化疗诱发的恶心和呕吐:初始剂量为首日125mg,化疗前1h服用;第2~3日,每日80mg,化疗前1h服用。
2.用于重度抑郁症(伴焦虑)每次300mg,每日1次。肾功能不全、轻到中度肝功能不全的患者、老年人、晚期肾病(ERSD)进行血液透析的患者无需调整剂量。
药物相应作用
1.与可抑制CYP3A4活性的药物(如酮康唑、伊曲康唑、奈法唑酮、硫氮酮、那非那韦、利托那韦、醋竹桃霉素)合用,可能升高本品的血浆浓度,合用时应谨慎。
2.与经过CYP3A4代谢的药物(如多西他赛、多西他奇、紫杉醇、长春碱、伊立替康、阿夫唑嗪、阿司咪唑、西沙比得、克拉霉素、依立曲坦、依托泊苷、异环磷酰胺、依马替尼、依立替康、匹莫齐特、特非那定、长春花碱、长春新碱、长春瑞宾)合用,可能增加这些药物的血浆浓度,合用时应谨慎。
3.本品可抑制地塞米松的代谢,合用时应将地塞米松的剂量减少约一半。
4.本品可抑制细胞色素P450介导的苯二氮类药物(如咪达唑仑、三唑仑、阿普唑仑)的代谢,使其血药浓度升高,导致其不良反应增强。与诱导CYP3A4活性的强效药物(如利福平、卡马西平、苯妥英)合用,可能会降低本品的血浆浓度,合用时应谨慎。
6.与经过CYP2C9代谢的药物[如甲苯磺丁脲、S(-) 华法林]合用,可能会降低这些药物的血浆浓度。
7.与口服避孕药(如环戊丙酸雌二醇、乙炔基雌二醇、依托孕烯、炔诺孕酮、


EMEND 80mg, 125mg hard Capsules
1. Name of the medicinal product
EMEND® 125 mg hard capsules
EMEND® 80 mg hard capsules
2. Qualitative and quantitative composition
Each 125 mg capsule contains 125 mg of aprepitant. Each 80 mg capsule contains 80 mg of aprepitant.
Excipient with known effect:
Each capsule contains 125 mg of sucrose (in the 125 mg capsule).
Excipient with known effect:
Each capsule contains 80 mg of sucrose (in the 80 mg capsule).
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Hard capsule.
The 125 mg capsule is opaque with a white body and pink cap with “462” and “125 mg” printed radially in black ink on the body. The 80 mg capsules are opaque with a white body and cap with “461” and “80 mg” printed radially in black ink on the body.
4. Clinical particulars
4.1 Therapeutic indications
Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy in adults.
Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
EMEND 125 mg/80 mg is given as part of combination therapy (see section 4.2).
4.2 Posology and method of administration
Posology
EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose is 125 mg orally once daily one hour before start of chemotherapy on Day 1 and 80 mg orally once daily on Days 2 and 3.
The following regimens are recommended for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy:

Day 1

Day 2

Day 3

Day 4

EMEND

125 mg orally

80 mg orally

80 mg orally

None

Dexamethasone

12 mg orally

8 mg orally

8 mg orally

8 mg orally

5-HT3 antagonists

Standard dose of 5-HT3 antagonists. See the product information for the selected 5-HT3 antagonist for appropriate dosing information

none

none

None

Highly Emetogenic Chemotherapy Regimen
Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 to 4. The dose of dexamethasone accounts for active substance interactions.
Moderately Emetogenic Chemotherapy Regimen

Day 1

Day 2

Day 3

EMEND

125 mg orally

80 mg orally

80 mg orally

Dexamethasone

12 mg orally

none

None

5-HT3 antagonists

Standard dose of 5-HT3 antagonists. See the product information for the selected 5-HT3 antagonist for appropriate dosing information

none

None

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone accounts for active substance interactions.
Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited. For additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the Summary of Product Characteristics of co-administered 5-HT3 antagonist medicinal products.
Special populations
Older people (≥65 years)
No dose adjustment is necessary for the elderly (see section 5.2).
Gender
No dose adjustment is necessary based on gender (see section 5.2).
Renal impairment
No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal disease undergoing haemodialysis (see section 5.2).
Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).
Paediatric population
The safety and efficacy of EMEND in children and adolescents below 18 years of age has not yet been established. No data are available.
Method of administration
The hard capsule should be swallowed whole.
EMEND may be taken with or without food.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).
4.4 Special warnings and precautions for use
Patients with moderate to severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. EMEND should be used with caution in these patients (see section 5.2).
CYP3A4 interactions
EMEND should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, and quinidine (see section 4.5). Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination might result in increased toxicity.
Co-administration of EMEND with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these active substances. Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant (see section 4.5). Concomitant administration of EMEND with herbal preparations containing St. John's Wort (Hypericum perforatum) is not recommended.
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g. , ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, and protease inhibitors) should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant (see section 4.5).
Co-administration with warfarin (a CYP2C9 substrate)
Co-administration of EMEND with warfarin results in decreased prothrombin time, reported as International Normalised Ratio (INR). In patients on chronic warfarin therapy, the INR should be monitored closely during treatment with EMEND and for 14 days following each 3-day course of EMEND (see section 4.5).
Co-administration with hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of EMEND. Alternative non-hormonal back-up methods of contraception should be used during treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).
Excipients
EMEND contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Aprepitant (125 mg/80 mg) is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. During treatment with EMEND, CYP3A4 is inhibited. After the end of treatment, EMEND causes a transient mild induction of CYP2C9, CYP3A4 and glucuronidation. Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested by the lack of interaction of aprepitant with digoxin.
Effect aprepitant on the pharmacokinetics of other active substances
CYP3A4 inhibition
As a moderate inhibitor of CYP3A4, aprepitant (125 mg/80 mg) can increase plasma concentrations of co-administered active substances that are metabolised through CYP3A4. The total exposure of orally administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment with EMEND; the effect of aprepitant on the plasma concentrations of intravenously administered CYP3A4 substrates is expected to be smaller. EMEND must not be used concurrently with pimozide, terfenadine, astemizole, or cisapride (see section 4.3). Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these active substances, potentially causing serious or life-threatening reactions. Caution is advised during concomitant administration of EMEND and orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, and quinidine (see section 4.4).
Corticosteroids
Dexamethasone: The usual oral dexamethasone dose should be reduced by approximately 50 % when co-administered with EMEND 125 mg/80 mg regimen. The dose of dexamethasone in chemotherapy induced nausea and vomiting clinical trials was chosen to account for active substance interactions (see section 4.2). EMEND, when given as a regimen of 125 mg with dexamethasone co-administered orally as 20 mg on Day 1, and EMEND when given as 80 mg/day with dexamethasone co-administered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate, 2.2-fold on Days 1 and 5.
Methylprednisolone: The usual intravenously administered methylprednisolone dose should be reduced approximately 25 %, and the usual oral methylprednisolone dose should be reduced approximately 50 % when co-administered with EMEND 125 mg/80 mg regimen. EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3.
During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease at later time points within 2 weeks following initiation of the EMEND dose, due to the inducing effect of aprepitant on CYP3A4. This effect may be expected to be more pronounced for orally administered methylprednisolone.
Chemotherapeutic medicinal products
In pharmacokinetic studies, EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on Day 1 or vinorelbine administered intravenously on Day 1 or Day 8. Because the effect of EMEND on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND on the pharmacokinetics of intravenously administered CYP3A4 substrates, an interaction with orally administered chemotherapeutic medicinal products metabolised primarily or partly by CYP3A4 (e.g. etoposide, vinorelbine) cannot be excluded. Caution is advised and additional monitoring may be appropriate in patients receiving medicinal products metabolised primarily or partly by CYP3A4 (see section 4.4). Post-marketing events of neurotoxicity, a potential adverse reaction of ifosfamide, have been reported after aprepitant and ifosfamide coadministration.
Immunosuppressants
During the 3-day CINV regimen, a transient moderate increase followed by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 (e.g. cyclosporine, tacrolimus, everolimus and sirolimus) is expected. Given the short duration of the 3-day regimen and the time-dependent limited changes in exposure, dose reduction of the immunosuppressant is not recommended during the 3 days of co-administration with EMEND.
Midazolam
The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co-administering these medicinal products with EMEND (125 mg/80 mg).
EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of 2 mg midazolam was co-administered on Days 1 and 5 of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2 to 5.
In another study with intravenous administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and 2 mg midazolam was given intravenously prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15. EMEND increased the AUC of midazolam 25 % on Day 4 and decreased the AUC of midazolam 19 % on Day 8 and 4 % on Day 15. These effects were not considered clinically important.
In a third study with intravenous and oral administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, together with ondansetron 32 mg Day 1, dexamethasone 12 mg Day 1 and 8 mg Days 2-4. This combination (i.e. EMEND, ondansetron and dexamethasone) decreased the AUC of oral midazolam 16 % on Day 6, 9 % on Day 8, 7 % on Day 15 and 17 % on Day 22. These effects were not considered clinically important.
An additional study was completed with intravenous administration of midazolam and EMEND. Intravenous 2 mg midazolam was given 1 hour after oral administration of a single dose of EMEND 125 mg. The plasma AUC of midazolam was increased by 1.5-fold. This effect was not considered clinically important.
Induction
As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma concentrations of substrates eliminated by these routes within two weeks following initiation and treatment. This effect may become apparent only after the end of a 3-day treatment with EMEND. For CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days after end of the EMEND 3-day treatment. The effect is maintained for a few days, thereafter slowly declines and is clinically insignificant by two weeks after end of EMEND treatment. Mild induction of glucuronidation is also seen with 80 mg oral aprepitant given for 7 days. Data are lacking regarding effects on CYP2C8 and CYP2C19. Caution is advised when warfarin, acenocoumarol, tolbutamide, phenytoin or other active substances that are known to be metabolised by CYP2C9 are administered during this time period.
Warfarin
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely during treatment with EMEND and for 2 weeks following each 3-day course of EMEND for chemotherapy induced nausea and vomiting (see section 4.4). When a single 125 mg dose of EMEND was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilised on chronic warfarin therapy, there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin determined on Day 3; however, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14 % decrease in INR 5 days after completion of treatment with EMEND.
Tolbutamide
EMEND, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8, and 15 % on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15.
Hormonal contraceptives
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of EMEND. Alternative non-hormonal back-up methods of contraception should be used during treatment with EMEND and for 2 months following the last dose of EMEND.
In a clinical study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone were administered on Days 1 through 21 with EMEND, given as a regimen of 125 mg on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg intravenously on Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and 11. During days 9 through 21 in this study, there was as much as a 64 % decrease in ethinyl estradiol trough concentrations and as much as a 60 % decrease in norethindrone trough concentrations.
5-HT3 antagonists
In clinical interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron).
Effect of other medicinal products on the pharmacokinetics of aprepitant
Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, and protease inhibitors) should be approached cautiously, as the combination is expected to result several-fold in increased plasma concentrations of aprepitant (see section 4.4).
Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of EMEND. Concomitant administration of EMEND with herbal preparations containing St. John's Wort (Hypericum perforatum) is not recommended.
Ketoconazole
When a single 125 mg dose of aprepitant was administered on Day 5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.
Rifampicin
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 600 mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91 % and the mean terminal half-life decreased 68 %.
4.6 Fertility, pregnancy and lactation
Contraception in males and females
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of EMEND. Alternative non-hormonal back-up methods of contraception should be used during treatment with EMEND and for 2 months following the last dose of EMEND (see sections 4.4 and 4.5).
Pregnancy
For aprepitant no clinical data on exposed pregnancies are available. The potential for reproductive toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic exposure in humans at the 125 mg/80 mg dose could not be attained in animal studies. These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential effects on reproduction of alterations in neurokinin regulation are unknown. EMEND should not be used during pregnancy unless clearly necessary.
Breast-feeding
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in human milk; therefore, breast-feeding is not recommended during treatment with EMEND.
Fertility
The potential for effects of aprepitant on fertility has not been fully characterised because exposure levels above the therapeutic exposure in humans could not be attained in animal studies. These fertility studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, embryonic/foetal development, or sperm count and motility (see section 5.3).
4.7 Effects on ability to drive and use machines
EMEND may have minor influence on the ability to drive and use machines. Dizziness and fatigue may occur following administration of (see section 4.8).
4.8 Undesirable effects
Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 individuals.
The most common adverse reactions reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving Highly Emetogenic Chemotherapy (HEC) were: hiccups (4.6 % versus 2.9 %), alanine aminotransferase (ALT) increased (2.8 % versus 1.1 %), dyspepsia (2.6 % versus 2.0 %), constipation (2.4 % versus 2.0 %), headache (2.0 % versus 1.8 %), and decreased appetite (2.0 % versus 0.5 %). The most common adverse reaction reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving Moderately Emetogenic Chemotherapy (MEC) was fatigue (1.4 % versus 0.9 %).
Tabulated list of adverse reactions
The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a greater incidence with aprepitant than with standard therapy or in postmarketing use:
Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).

System organ class

Adverse reaction

Frequency

Infection and infestations

candidiasis, staphylococcal infection

rare

Blood and lymphatic system disorders

febrile neutropenia, anaemia

uncommon

Immune system disorders

hypersensitivity reactions including anaphylactic reactions

not known

Metabolism and nutrition disorders

decreased appetite

common

Polydipsia

rare

Psychiatric disorders

Anxiety

uncommon

disorientation, euphoric mood

rare

Nervous system disorders

Headache

common

dizziness, somnolence

uncommon

cognitive disorder, lethargy, dysgeusia

rare

Eye disorders

Conjunctivitis

rare

Ear and labyrinth disorders

Tinnitus

rare

Cardiac disorders

Palpitations

uncommon

bradycardia, cardiovascular disorder

rare

Vascular disorders

hot flush

uncommon

Respiratory, thoracic and mediastinal disorders

Hiccups

common

oropharyngeal pain, sneezing, cough, postnasal drip, throat irritation

rare

Gastrointestinal disorders

constipation, dyspepsia

common

eructation, nausea*, vomiting*, gastroesophageal reflux disease, abdominal pain, dry mouth, flatulence

uncommon

duodenal ulcer perforation, stomatitis, abdominal distension, faeces hard, neutropenic colitis

rare

Skin and subcutaneous tissue disorders

rash, acne

uncommon

photosensitivity reaction, hyperhidrosis, seborrhoea, skin lesion, rash pruritic, Stevens-Johnson syndrome/toxic epidermal necrolysis

rare

pruritus, urticarial

not known

Musculoskeletal and connective tissue disorders

muscular weakness, muscle spasms

rare

Renal and urinary disorders

Dysuria

uncommon

Pollakiuria

rare

General disorders and administration site conditions

Fatigue

common

asthaenia, malaise

uncommon

oedema, chest discomfort, gait disturbance

rare

Investigations

ALT increased

common

AST increased, blood alkaline phosphatase increased

uncommon

red blood cells urine positive, blood sodium decreased, weight decreased, neutrophil count decreased, glucose urine present, urine output increased

rare

*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were reported as adverse reactions only thereafter.
Description of selected adverse reactions
The adverse reactions profiles in the Multiple-Cycle extension of HEC and MEC studies for up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.
In an additional active-controlled clinical study in 1,169 patients receiving aprepitant and HEC, the adverse reactions profile was generally similar to that seen in the other HEC studies with aprepitant.
Additional adverse reactions were observed in patients treated with aprepitant for postoperative nausea and vomiting (PONV) and a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.
*Reported in patients taking a higher dose of aprepitant.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard.
4.9 Overdose
In the event of overdose, EMEND should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of aprepitant, emesis induced by a medicinal product may not be effective.
Aprepitant cannot be removed by haemodialysis.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12
Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.
3-day regimen of aprepitant
In 2 randomised, double-blind studies encompassing a total of 1,094 patients receiving chemotherapy that included cisplatin ≥70 mg/m2, aprepitant in combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on Day 1 and 8 mg orally twice daily on Days 2 to 4). Although a 32 mg intravenous dose of ondansetron was used in clinical trials, this is no longer the recommended dose. See the product information for the selected 5-HT3 antagonist for appropriate dosing information.
Efficacy was based on evaluation of the following composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated for each individual study and for the 2 studies combined.
A summary of the key study results from the combined analysis is shown in Table 1.
Table 1
Percent of patients receiving Highly Emetogenic Chemotherapy responding by treatment group and phase — Cycle 1

Aprepitant regimen

(N= 521)

Standard therapy

(N= 524)

Differences*

%

%

%

(95 % CI)

Complete response (no emesis and no rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

67.7

86.0

71.5

47.8

73.2

51.2

19.9

12.7

20.3

(14.0, 25.8)

(7.9, 17.6)

(14.5, 26.1)

INDIVIDUAL MEASURES

 

No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

71.9

86.8

76.2

49.7

74.0

53.5

22.2

12.7

22.6

(16.4, 28.0)

(8.0, 17.5)

(17.0, 28.2)

No significant nausea (maximum VAS <25 mm on a scale of 0-100 mm)

Overall (0-120 hours)

25-120 hours

72.1

74.0

64.9

66.9

7.2

7.1

(1.6, 12.8)

(1.5, 12.6)

* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which were included in the primary analysis of odds ratios and logistic models.
† One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses; one patient in the Standard regimen only had data in the delayed phase and was excluded from the overall and acute phase analyses.
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.
Figure 1
Percent of patients receiving Highly Emetogenic Chemotherapy who remain emesis free over time – Cycle 1


Statistically significant differences in efficacy were also observed in each of the 2 individual studies.
In the same 2 clinical studies, 851 patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently maintained during all cycles.
In a randomised, double-blind study in a total of 866 patients (864 females, 2 males) receiving chemotherapy that included cyclophosphamide 750-1,500 mg/m2; or cyclophosphamide 500-1,500 mg/m2 and doxorubicin (<60 mg/m2) or epirubicin (<100 mg/m2), aprepitant in combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).
Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1.
A summary of the key study results is shown in Table 2.
Table 2
Percent of patients responding by treatment group and phase —Cycle 1
Moderately Emetogenic Chemotherapy

COMPOSITE MEASURES

Aprepitant regimen

(N= 433)

Standard therapy

(N= 424) 

Differences*

%

%

%

(95 % CI)

Complete response (no emesis and no rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

50.8

75.7

55.4

42.5

69.0

49.1

8.3

6.7

6.3

(1.6, 15.0)

(0.7, 12.7)

(-0.4, 13.0)

INDIVIDUAL MEASURES

 

No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

75.7

87.5

80.8

58.7

77.3

69.1

17.0

10.2

11.7

(10.8, 23.2)

(5.1, 15.3)

(5.9, 17.5)

No significant nausea (maximum VAS <25 mm on a scale of 0-100 mm)

Overall (0-120 hours)

0-24 hours

25-120 hours

60.9

79.5

65.3

55.7

78.3

61.5

5.3

1.3

3.9

(-1.3, 11.9)

(-4.2, 6.8)

(-2.6, 10.3)

* The confidence intervals were calculated with no adjustment for age category (<55 years, ≥55 years) and investigator group, which were included in the primary analysis of odds ratios and logistic models.
† One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses.
In the same clinical study, 744 patients continued into the Multiple-Cycle extension for up to 3 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently maintained during all cycles.
In a second multicenter, randomised, double-blind, parallel-group, clinical study, the aprepitant regimen was compared with standard therapy in 848 patients (652 females, 196 males) receiving a chemotherapy regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenously (<1,500 mg/m2); or cytarabine intravenously (>1 g/m2). Patients receiving the aprepitant regimen were receiving chemotherapy for a variety of tumour types including 52 % with breast cancer, 21 % with gastrointestinal cancers including colorectal cancer, 13 % with lung cancer and 6 % with gynecological cancers. The aprepitant regimen in combination with an ondansetron/dexamethasone regimen (see section 4.2) was compared with standard therapy (placebo in combination with ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).
Efficacy was based on the evaluation of the following primary and key secondary endpoints: No vomiting in the overall period (0 to 120 hours post-chemotherapy), evaluation of safety and tolerability of the aprepitant regimen for chemotherapy induced nausea and vomiting (CINV), and complete response (defined as no vomiting and no use of rescue therapy) in the overall period (0 to 120 hours post-chemotherapy). Additionally, no significant nausea in the overall period (0 to 120 hours post-chemotherapy) was evaluated as an exploratory endpoint, and in the acute and delayed phases as a post-hoc analysis.
A summary of the key study results is shown in Table 3.
Table 3
Percent of patients responding by treatment group and phase for Study 2 – Cycle 1
Moderately Emetogenic Chemotherapy

Aprepitant regimen

(N= 425)

Standard therapy

(N= 406)

Differences*

%

%

%

(95 % CI)

Complete response (no emesis and no rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

68.7

89.2

70.8

56.3

80.3

60.9

12.4

8.9

9.9

(5.9, 18.9)

(4.0, 13.8)

(3.5, 16.3)

No emesis (no emetic episodes regardless of use of rescue therapy)

Overall (0-120 hours)

0-24 hours

25-120 hours

76.2

92.0

77.9

62.1

83.7

66.8

14.1

8.3

11.1

(7.9, 20.3)

(3.9, 12.7)

(5.1, 17.1)

No significant nausea (maximum VAS <25 mm on a scale of 0-100 mm)

Overall (0-120 hours)

0-24 hours

25-120 hours

73.6

90.9

74.9

66.4

86.3

69.5

7.2

4.6

5.4

(1.0, 13.4)

(0.2, 9.0)

(-0.7, 11.5)

*The confidence intervals were calculated with no adjustment for gender and region, which were included in the primary analysis using logistic models.
The benefit of aprepitant combination therapy in the full study population was mainly driven by the results observed in patients with poor control with the standard regimen such as in women, even though the results were numerically better regardless of age, tumour type or gender. Complete response to the aprepitant regimen and standard therapy, respectively, was reached in 209/324 (65 %) and 161/320 (50 %) in women and 83/101 (82 %) and 68/87 (78 %) of men.
Paediatric population
Studies evaluating the use of aprepitant in paediatric patients are on-going (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease with increasing dose.
Absorption
The mean absolute oral bioavailability of aprepitant is 67 % for the 80 mg capsule and 59 % for the 125 mg capsule. The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 4 hours (tmax). Oral administration of the capsule with an approximately 800 Kcal standard breakfast resulted in an up to 40 % increase in AUC of aprepitant. This increase is not considered clinically relevant.
The pharmacokinetics of aprepitant is non-linear across the clinical dose range. In healthy young adults, the increase in AUC0-∞ was 26 % greater than dose proportional between 80 mg and 125 mg single doses administered in the fed state.
Following oral administration of a single 125 mg dose of EMEND on Day 1 and 80 mg once daily on Days 2 and 3, the AUC0-24hr (mean±SD) was 19.6 ± 2.5 µg•h/ml and 21.2 ± 6.3 µg •h/ml on Days 1 and 3, respectively. Cmax was 1.6 ± 0.36 µg/ml and 1.4 ± 0.22 µg/ml on Days 1 and 3, respectively.
Distribution
Aprepitant is highly protein bound, with a mean of 97 %. The geometric mean apparent volume of distribution at steady state (Vdss) is approximately 66 l in humans.
Biotransformation
Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for approximately 19 % of the radioactivity in plasma over 72 hours following a single intravenous administration 100-mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side chains and the resultant metabolites were only weakly active. In vitro studies using human liver microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor contribution by CYP1A2 and CYP2C19.
Elimination
Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary excretion in faeces. Following a single intravenously administered 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, to healthy subjects, 57 % of the radioactivity was recovered in urine and 45 % in faeces.
The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from approximately 60 to 72 ml/min in the therapeutic dose range. The terminal half-life ranged from approximately 9 to 13 hours.
Pharmacokinetics in special populations
Older people: Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 through 5, the AUC0-24hr of aprepitant was 21 % higher on Day 1 and 36 % higher on Day 5 in elderly (≥65 years) relative to younger adults. The Cmax was 10 % higher on Day 1 and 24 % higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically meaningful. No dose adjustment for EMEND is necessary in elderly patients.
Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 16 % higher in females as compared with males. The half-life of aprepitant is 25 % lower in females as compared with males and its tmax occurs at approximately the same time. These differences are not considered clinically meaningful. No dose adjustment for EMEND is necessary based on gender.
Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh class C).
Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal impairment (CrCl< 30 ml/min) and to patients with end stage renal disease (ESRD) requiring haemodialysis.
In patients with severe renal impairment, the AUC0-∞of total aprepitant (unbound and protein bound) decreased by 21 % and Cmax decreased by 32 %, relative to healthy subjects. In patients with ESRD undergoing haemodialysis, the AUC0-∞ of total aprepitant decreased by 42 % and Cmax decreased by 32 %. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC of pharmacologically active unbound aprepitant was not significantly affected in patients with renal impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had no significant effect on the pharmacokinetics of aprepitant; less than 0.2 % of the dose was recovered in the dialysate.
No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with ESRD undergoing haemodialysis.
Relationship between concentration and effect
Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose- and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 3-day regimen of EMEND are predicted to provide greater than 95 % occupancy of brain NK1 receptors.
5.3 Preclinical safety data
Pre-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction. However, it should be noted that systemic exposure in rodents was similar or even lower than therapeutic exposure in humans at the 125 mg/80 mg dose. In particular, although no adverse effects were noted in reproduction studies at human exposure levels, the animal exposures are not sufficient to make an adequate risk assessment in man.
6. Pharmaceutical particulars
6.1 List of excipients
Capsule content
Sucrose
Microcrystalline cellulose (E 460)
Hydroxypropyl cellulose (E 463)
Sodium laurilsulfate
Capsule shell (125 mg)
Gelatin
Titanium dioxide (E 171)
Red iron oxide (E 172)
Yellow iron oxide (E 172)
Capsule shell (80 mg)
Gelatin
Titanium dioxide (E 171)
Printing ink
Shellac
Potassium hydroxide
Black iron oxide (E 172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years
6.4 Special precautions for storage
Store in the original package in order to protect from moisture.
6.5 Nature and contents of container
Different pack sizes including different strengths are available.
Aluminium blister containing one 125 mg capsule and two 80 mg capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements for disposal.
7. Marketing authorisation holder
Merck Sharp & Dohme Ltd.
Hertford Road, Hoddesdon
Hertfordshire EN 11 9BU
United Kingdom
8. Marketing authorisation number(s)
EU/1/03/262/006
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 11 November 2003
Date of latest renewal: 11 November 2008
10. Date of revision of the text
December 2013
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/.


附:
EMEND 125 mg Hard Capsules(https://www.medicines.org.uk/emc/medicine/27648
EMEND 80 mg Hard Capsules(https://www.medicines.org.uk/emc/medicine/27649


FDA批准默沙东止吐药Emend用于儿童患者预防化疗引起的恶心呕吐
2015年9月6日,FDA已批准止吐药Emend(aprepitant,阿瑞吡坦)胶囊的补充新药申请(sNDA)。此次扩大适应症,将使Emend胶囊联合其他止吐药,用于12岁及以上患者以及12岁以下体重至少30千克(约66磅)的患者,预防中度致吐性癌症化疗(MEC)和高度致吐性癌症化疗(HEC,包括大剂量顺铂治疗方案)初次或多次治疗时所致的急性和迟发性恶心及呕吐。
Emend(aprepitant)是一种止吐药,用于预防化疗引起的恶心及呕吐(CINV),该药是一种选择性高亲和性P物质/神经激肽-1(NK1)受体抑制剂,对5-羟色胺(5HT3)、多巴胺和皮质激素受体的亲和力很低。此次批准,使Emend成为首个也是唯一一个可用于接受MEC或HEC的12-17岁患者及12岁以下体重至少30千克患者群体预防急性和迟发性化疗诱导的恶心和呕吐(CINV)的NK1受体拮抗剂。
此次批准,是基于一项关键III期研究的积极顶线数据。该研究在接受MEC或HEC治疗的12-17岁患者及12岁以下且体重至少30千克的患者中开展,调查了Emend联合昂丹司琼(Emend方案组,n=63)与昂丹司琼单药(ondansetron,对照方案组,n=69)预防化疗所致恶心呕吐(CINV)的疗效和安全性。研究中,静脉注射地塞米松在医生的自由裁量权内被允许。主要终点是延迟期(开始化疗后25-120小时)的完全缓解(无呕吐、干呕,未使用急救药物),其他预先定义的终点包括急性期(开始化疗后0-24小时)的完全缓解率,整个时期(开始化疗后一直到120小时)的完全缓解率,安全性和耐受性。
数据显示,将Emend添加至标准方案,可减少CINV事件;在迟发期,Emend方案组完全缓解率(CRR)为49.2%(n=31/63),对照组为18.8%(n=13/69);在急性期,Emend方案组完全缓解率为55.6%(n=35/63),对照组为37.7%(n=26/69);在整个时期(急性期+迟发期),Emend方案组完全缓解率为34.9%(n=22/63),对照组为13.0%(n=9/69)。
Emend:为癌症患者战胜病魔保驾护航
目前,癌症已成为仅次于心血管疾病的第二大致死病因,由癌症导致的死亡率正呈逐年上升趋势。化疗是许多癌症患者的一种重要治疗手段,然而,伴随而来的是脱发、恶心、呕吐等不良反应,这些不良反应会严重影响患者的生活质量,使治疗依从性明显下降,甚至有些患者可能因此丧失生活的信心,选择放弃治疗。
Emend填补了这一空白,该药是全球第一个高度选择性的NK-1受体拮抗剂,可以穿过血脑屏障,高选择性、高亲和性地占领大脑中的NK-1受体,从而在中枢层面抑制CINV的根源。该药可以用于预防中度和高度致吐性抗肿瘤化疗的初次和重复治疗过程中出现的急性和迟发性恶心和呕吐。
Emend于2003年在美国上市,目前已在90多个国家销售,全球使用已超过1000万个化疗疗程,该药可帮助广大的化疗患者有效预防恶心呕吐,为患者战胜病魔保驾护航。
----------------------------------------------------
注:以下产品不同规格和不同价格,购买以咨询为准!
----------------------------------------------------
产地国家: 意大利
原产地英文商品名:
Emend Trifold Pack 3Cap/DS PK(1*125mg+2*80mg)
原产地英文药品名:
Aprepitant
中文参考商品译名:
Emend 3胶囊/板装(1*125毫克+2*80毫克)
中文参考药品译名:
阿瑞吡坦
生产厂家中文参考译名:
美国默克
生产厂家英文名:
Merck
---------------------------------------------------------------
产地国家: 德国
原产地英文商品名:
Emend 80mg/cap 3Caps/box
原产地英文药品名:
Aprepitant
中文参考商品译名:
Emend 80毫克/胶囊 3胶囊/盒
中文参考药品译名:
阿瑞吡坦
生产厂家中文参考译名:
默沙东
生产厂家英文名:
MSD Sharp & Dohme GmbH
---------------------------------------------------------------
产地国家: 德国
原产地英文商品名:
Emend 80mg/cap 2Caps/box
原产地英文药品名:
Aprepitant
中文参考商品译名:
Emend 80毫克/胶囊 2胶囊/盒
中文参考药品译名:
阿瑞吡坦
生产厂家中文参考译名:
默沙东
生产厂家英文名:
MSD Sharp & Dohme GmbH
---------------------------------------------------------------
产地国家: 德国
原产地英文商品名:
Emend Trifold Pack 3Cap/DS PK(1*125mg+2*80mg)
原产地英文药品名:
Aprepitant
中文参考商品译名:
Emend 3胶囊/板装(1*125毫克+2*80毫克)
中文参考药品译名:
阿瑞吡坦
生产厂家中文参考译名:
美国默克
生产厂家英文名:
Merck
该药品相关信息网址1:
http://www.emend.com/

责任编辑:admin


相关文章
阿瑞吡坦(aprepitant)对癌症患者能减轻化疗副作用
阿瑞吡坦胶囊,止敏吐|Emend(Aprepitant Capsules)
胶囊 Emend(Aprepitant)-阿瑞吡坦
美国研发出能减轻患者手术后呕吐反应的新药
阿瑞吡坦胶囊Emend(Aprepitant)
 

最新文章

更多

· Nasea OD Tablets(Ramo...
· DOXIL(doxorubicin hydr...
· KYTRIL Injection(盐酸...
· NEULASTA(非格司亭注射...
· KEYTRUDA(派姆单抗 pemb...
· ZOLINZA(VORINOSTAT)C...
· Zoladex(GOSERELIN ACE...
· Zofran Injection(盐酸...
· Keytruda(pembrolizumab...
· ODOMZO(sonidegib capsules)

推荐文章

更多

· Nasea OD Tablets(Ramo...
· DOXIL(doxorubicin hydr...
· KYTRIL Injection(盐酸...
· NEULASTA(非格司亭注射...
· KEYTRUDA(派姆单抗 pemb...
· ZOLINZA(VORINOSTAT)C...
· Zoladex(GOSERELIN ACE...
· Zofran Injection(盐酸...
· Keytruda(pembrolizumab...
· ODOMZO(sonidegib capsules)

热点文章

更多

· KEYTRUDA(派姆单抗 pemb...
· DOXIL(doxorubicin hydr...
· NEULASTA(非格司亭注射...
· KYTRIL Injection(盐酸...
· Nasea OD Tablets(Ramo...