英文药名：Sandostatin LAR kit for i.m.injection(Octreotide Acetate)

中文药名：醋酸奥曲肽长效注射剂

生产厂家：诺华制药
药品介绍
类别名称
可持续性生长抑素类似物的微球型持续释放制剂
欧文商標名
Sandostatin LAR kit for i.m.injection
一般名
オクトレオチド酢酸塩（Octreotide Acetate）
化学名
(−)-D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[(1R，2R)-2-hydroxy-1-(hydroxymethyl)propyl]-L-cysteinamide cyclic(2→7)disulfide diacetate
分子式
C49H66N10O10S2・2CH3COOH
分子量
1139.34
構造式

性状
白是一个很好的黄白色粉末。这是非常易溶于水，甲醇，乙酸（100），乙醇（95）或1可溶于丁醇和极微溶于乙腈，并在乙醚中几乎不溶。本品的水溶液（1→100）的PH值是5.0至7.0。它是吸湿的。
适应症
1.肝硬化所致食道-胃静脉曲张出血的紧急治疗，与特殊治疗（如内窥镜硬化剂治疗）合用。
2.缓解与胃肠胰内分泌肿瘤有关的症状和体征。有充足证据显示，奥曲肽对下列肿瘤有效：具类癌综合症的类癌瘤；VIP瘤等，奥曲肽对下列肿瘤的有效率约为50%。
（1）胃泌素瘤/Zollinger-Ellison综合症（通常与选择性H2受体拮抗剂合用，并可酌情加用抗酸剂）。
（2）胰岛瘤（用于胰岛瘤术前预防低血糖血症，维持正常血糖）。
（3）生长激素释放因子瘤。醋酸奥曲肽治疗仅可减轻症状和体征，而不能治愈。
3.预防胰腺术后并发症
4.经手术、放射治疗或多巴胺受体激动剂治疗失败的肢端肥大症患者，可控制症状、降低生长激素及生长素介质C的浓度。本品亦适用于不能或不愿手术的肢端肥大症患者，以及放射治疗无效的间歇期患者。
用法用量
1．食道-胃底静脉曲张出血
首先0.1mg静脉推注（5分钟），随后以0.6mg溶于5%葡萄糖500ml中，通过输液泵以50μg/小时的速度连续静脉滴注，12小时1次。最多治疗5天。
2．胃肠胰内分泌肿瘤
初始量为0.05mg皮下注射，每天一至二次。根据耐受性和疗效（临床反应、肿瘤分泌的激素浓度）可逐渐增加剂量至0.2mg，每天三次。仅在某些情况下，方可采用更大剂量。维持量则应根据个体差异而定。用药后临床症状和实验室检查结果显示未改善时，醋酸奥曲肽用药不能超过一周。
3．预防胰腺术后并发症
0.1mg皮下注射，每天三次，维持治疗7天，首次注射应在手术前至少1小时进行。
4．肢端肥大症
初始量为0.05～0.1mg皮下注射，每8小时一次，根据对循环生长激素浓度、临床反应及耐受性的每月评估而调整剂量（目标：GH〈2.5ng/ml，IGF正常范围〉）。多数患者的最适剂量为0.2～0.3mg/天。最大剂量不应超过1.5mg/天。在监测血浆生长激素水平的指导下治疗数月后可酌情减量。
醋酸奥曲肽治疗一个月后，若生长激素浓度无下降、临床症状无改善，则应考虑停药。
包装规格[瓶]
长效奥曲肽肌注：10毫克盒/套（注射器+1瓶冻干粉+2毫升生理盐水）

长效奥曲肽肌注：20毫克盒/套（注射器+1瓶冻干粉+2毫升生理盐水）

长效奥曲肽肌注：30毫克盒/套（注射器+1瓶冻干粉+2毫升生理盐水）

生产商；诺华制药日本公司

http://www.oneyao.net
http://www.120ty.net
http://www.novartis.co.jp/news/2014/pr20140630.html
http://www.kegg.jp/medicus-bin/japic_med?japic_code=00063002
Sandostatin LAR 10mg, 20mg and 30mg.Octreotide
1. NAME OF THE MEDICINAL PRODUCT
Sandostatin® LAR®10mg, 20mg and 30mg.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains Octreotide free peptide, 10 mg, 20mg or 30mg (present as octreotide acetate, 4.65% of nominal fill weight).
For excipients ,see 6.1.
3. PHARMACEUTICAL FORM
Powder and solvent for suspension for injection.
Powder: White to off white powder
Solvent: clear,colourless solution
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Acromegaly
For symptomatic control and reduction of GH and somatomedin C plasma levels in patients with acromegaly:-
(a) who are adequately controlled on s.c. treatment with SANDOSTATIN
(b) in whom surgery or radiotherapy is inappropriate or ineffective, or in the interim period until radiotherapy becomes fully effective. (See 4.2 Posology and method of administration).
GEP tumours:
For the relief of symptoms associated with gastroenteropancreatic tumours including:
• Carcinoid tumours with features of carcinoid syndrome
• VIPomas
• Glucagonomas
• Gastrinomas/ Zollinger-Ellison syndrome
• Insulinomas, for pre-operative control of hypoglycaemia and for maintenance therapy
• GRFomas
in patients whose symptoms are adequately controlled on s.c. treatment with Sandostatin.
4.2 Posology and method of administration
Sandostatin LAR may only be administered by deep intragluteal injection. The site of repeat intragluteal injections should be alternated between the left and right gluteal muscle (see 6.6 Instructions for use/handling).
Acromegaly
In patients who are adequately controlled with the usual therapeutic range of s.c. SANDOSTATIN, it is recommended to start treatment with the administration of 20 mg SANDOSTATIN LAR at 4 week intervals for 3 months, without a washout period of s.c. SANDOSTATIN. Subsequent dosage adjustment should be based on serum growth hormone (GH) and insulin-like growth factor 1 (IGF 1)/ somatomedin C concentrations and clinical symptoms.
In patients in whom, within this 3 month period, clinical symptoms and biochemical parameters (GH; IGF 1) are not fully controlled (GH concentrations still above 2.5μg/L), the dose may be increased to 30mg every 4 weeks.
For patients whose GH concentrations are consistently below 1μg/L, whose IGF 1 serum concentrations have normalized, and in whom most reversible signs/symptoms of acromegaly have disappeared after 3 months of treatment with 20 mg, the dose may be reduced to 10 mg of SANDOSTATIN LAR every 4 weeks. However, in this group of patients, it is recommended to closely monitor adequate control of serum GH and IGF 1 concentrations, as well as clinical signs/symptoms at this low dose of SANDOSTATIN LAR.
For patients on a stable dose of Sandostatin LAR, assessment of Gh and IGF 1 should be made every 6 months.
For patients in whom surgery, or radiotherapy is inappropriate or ineffective, or in the inerim period until radiotherapy becomes fully effective, a short treatment period of s.c. administration with SANDOSTATIN is recommended to assess the response and systemic tolerability of octreotide prior to initiating treatment with SANDOSTATIN LAR as described above.
Gastroenteropancreatic tumours
After adequate control has been established with Sandostatin s.c., treatment should be started with 20mg Sandostatin LAR intramuscularly at 4-week intervals. Treatment with Sandostatin s.c. should be continued at the previously effective dosage for 2 weeks after the first injection of Sandostatin LAR.
For patients who were not previously treated with s.c. Sandostatin, it is recommended to start with the administration of s.c. Sandostatin at a dosage of 0.1mg three times daily for a short period to assess the response and systemic tolerability of octreotide before initiating the treatment with Sandostatin LAR as described above.
For patients in whom symptoms are only partially controlled after 3 months of treatment, the dose may be increased to 30mg Sandostatin LAR every 4 weeks.
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment, the dose may be reduced to 10mg Sandostatin LAR every 4 weeks.
For days when symptoms associated with gastro-enteropancreatic tumours may increase during treatment with Sandostatin LAR, additional administration of s.c. Sandostatin is recommended at the dose used prior to the Sandostatin LAR treatment. This may occur in the first 2 months of treatment until therapeutic concentrations of octreotide are reached.
Use in patients with impaired renal function
Impaired renal function did not affect the total exposure (AUC; area under the curve) to octreotide when administered s.c. as Sandostatin. Therefore, no dose adjustment of Sandostatin LAR is necessary.
Use in patients with impaired hepatic function
In a study with Sandostatin administered s.c. and i.v. it was shown that the elimination capacity may be reduced in patients with liver cirrhosis, but not in patients with fatty liver disease. Due to the wide therapeutic window of octreotide, no dose adjustment of Sandostatin LAR is necessary in patients with liver cirrhosis.
Use in elderly patients
In a study with Sandostatin administered s.c., no dose adjustment was necessary in patients 65 years of age. Therefore, no dose adjustment is necessary in this group with Sandostatin LAR.
Use in children
There is very limited experience with use of Sandostatin LAR in children.
4.3 Contraindications
Hypersensitivity to octreotide or any components of the formulation.
4.4 Special warnings and precautions for use
As GH-secreting pituitary tumours may sometimes expand, causing serious complications (eg. visual field defects), it is essential that all patients be carefully monitored. If evidence of tumour expansion appears, alternative procedures are advisable.
Development of gallstones has been reported in 15 to 30% of long-term recipients of s.c. Sandostatin. The preva lence in the general population (aged 40 to 60 years) is about 5-20%. Long term exposure to Sandostatin LAR of patients with acromegaly or gastroenteropancreatic tumours suggests that treatment with Sandostatin LAR does not increase the incidence of gallstone formation, compared with s.c. treatment. Ultrasonic examination of the gallbladder before and at about 6 monthly intervals during Sandostatin LAR therapy is however recommended. If gallstones do occur, they are usually asymptomatic; symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery.
In patients with concomitant Type I diabetes mellitus, Sandostatin LAR is likely to affect glucose regulation, and insulin requirements may be reduced. In non-diabetics and type II diabetics with partially intact insulin reserves, Sandostatin s.c. administration may result in increases in post-prandial glycemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.
In patients with insulinomas, octreotide, because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin, and because of the shorter duration of the inhibitory action on insulin, may increase the depth and prolong the duration of hypoglycaemia. These patients should be closely monitored.
Thyroid function should be monitored in patients receiving long-term Sandostatin LAR therapy.
Octreotide should only be used under hospital specialist supervision, with the appropriate facilities available for diagnosis and eva luation of response.
Hepatic function should be monitored during octreotide therapy.
4.5 Interaction with other medicinal products and other forms of interaction
Octreotide has been found to reduce the intestinal absorption of cyclosporin and to delay that of cimetidine.
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine.
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolised by cytochrome P450 enzymes, which may be due to suppression of growth hormone. Since it cannot be excluded that Octreotide may have this effect, other drugs mainly metabolised by CYP3A4 and which have a low therapeutic index (e.g.quinidine, terfenadine) should therefore be used with caution.
4.6 Pregnancy and lactation
Experience with Sandostatin LAR in pregnant or nursing women is not available. Studies with Octreotide in animals showed transient growth retardation of offspring, possible consequent upon specific endocrine profiles of the species tested, but there was no evidence of fetotoxic, teratogenic or other reproduction effects. Nevertheless, Sandostatin LAR should not be given during pregnancy except in compelling circumstances. Women receiving treatment with Sandostatin LAR should not breast feed their infants.
4.7 Effects on ability to drive and use machines
No data exist on the effects of Sandostatin LAR on the ability to drive and use machines.
4.8 Undesirable effects
The main side effect encountered with Sandostatin LAR administration are local and gastrointestional.
Gallbladder
Prolonged use of Sandostatin LAR may result in gallstone formation (see 4.4 Special warnings and special precautions for use).
Local Reactions
Local injection site reactions to Sandostatin LAR may occur, and are usually mild and of short duration. They include local pain and, rarely, swelling and rash.
Gastrintestional System
Gastrointestinal side effects include anorexia, nausea, vomiting, crampy abdominal pain, abdominal bloating, flatulence, loose stools, diarrhoea and steatorrhoea. Although measured faecal fat excretion may increase, there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption. In rare instances, gastrointestinal side-effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding.
Body as a whole
Rarely, transient hair loss has been reported in patients receiving Sandostatin LAR treatment. Very rarely, cases of hypersensitivity have been reported.
Pancreas
Because of its inhibitory action on growth hormone, glucagon and insulin release, Sandostatin LAR may affect glucose regulation.
Post-prandial glucose tolerance may be impaired. As reported for patients treated with s.c. Sandostatin, in some instances a state of persistent hyperglycaemia may be induced as a result of chronic administration. Hypoglycaemia has also been observed.
In rare instances, acute pancreatitis has been reported within the first hours or days of s.c. Sandostatin treatment. In addition,cholelithiasis-induced pancreatitis has been reported for patients on long-term s.c. Sandostatin treatment.
Liver
There have been isolated reports of hepatic dysfunction associated with s.c. Sandostatin administration.
These concern:
• acute hepatitis without cholestasis, where there has been normalisation of transaminase values on withdrawal of s.c. Sandostatin
• the slow development of hyperbilirubinaemia in association with elevation of alkaline phosphatase, -glutamyl transferase and, to a lesser extent, transaminases.
4.9 Overdose
To date no data are available on overdosage with Sandostatin LAR. However, no unexpected adverse events have been reported with doses up to 90mg Sandostatin LAR administered to cancer patients every 2 weeks. The signs and symptoms observed after a single dose of 1.0mg octreotide given as an i.v. bolus injection to an adult patient were a brief drop in heart rate, facial flushing, abdominal cramps, diarrhoea, an empty feeling in the stomach and nausea, all of which resolved within 24 hours of drug administration.
The management of overdosage is symptomatic.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Octreotide is a synthetic octapeptide derivative of naturally occurring somatostatin with similar pharmacological effects, but with a considerably prolonged duration of action. It inhibits pathologically increased secretion of GH and of peptides and serotonin produced within the gastroenteropancreatic (GEP) endocrine system.
In animals, octreotide is a more potent inhibitor of GH, glucagon and insulin release than somatostatin, with greater selectivity for GH and glucagon suppression.
In healthy subjects octreotide, like somatostatin, has been shown to inhibit – release of GH stimulated by arginine, exercise and insulin-induced hypoglycaemia post-prandial release of insulin, glucagon, gastrin, other peptides of the GEP system, and arginine-stimulated release of insulin and glucagon thyrotropin-releasing hormone (TRH)-stimulated release of thyroid- stimulating hormone (TSH).
Unlike somatostatin, octreotide inhibits GH preferentially over insulin and its administration is not followed by rebound hypersecretion of hormones (ie. GH in patients with acromegaly).
In patients with acromegaly, Sandostatin LAR, a galenical formulation of octreotide suitable for repeated administration at intervals of 4 weeks, delivers consistent and therapeutic octreotide serum concentrations thus consistently lowering GH and normalising IGF 1 serum concentrations in the majority of patients. In most patients, Sandostatin LAR markedly reduces the clinical symptoms of the disease, such as headache, perspiration, paresthesia, fatigue, osteoarthralgia and carpal tunnel syndrome. In individual patients with GH-secreting pituitary adenoma, Sandostatin LAR was reported to lead to shrinkage of the tumour mass.
For patients with functional tumours of the gastroenteropancreatic endocrine system, treatment with Sandostatin LAR provides continuous control of symptoms related to the underlying disease. The effect of octreotide in different types of gastroenteropancreatic tumours are as follows:
Carcinoid tumours: Administration of octreotide may result in improvement of symptoms, particularly of flushing and diarrhoea. In many cases, this is accompanied by a falling plasma serotonin and reduced urinary excretion of 5-hydroxyindole acetic acid.
VIPomas: The biochemical characteristics of these tumours is overproduction of vasoactive intestinal peptide (VIP). In most cases, administration of octreotide results in alleviation of the severe secretory diarrhoea typical of the condition, with consequent improvement in quality of life. This is accompanied by an improvement in associated electrolyte abnormalities, e.g. hypokalaemia, enabling enteral and parenteral fluid and electrolyte supplementation to be withdrawn. In some patients, computer tomography scanning suggests a slowing or arrest of progression of the tumour, or even tumour shrinkage, particularly of hepatic metastases. Clinical improvement is usually accompanied by a reduction in plasma VIP levels, which may fall into the normal reference range.
Glucagonomas: Administration of octreotide results in most cases in substantial improvement of the necrolytic migratory rash which is characteristic of the condition. The effect of octreotide on the state of mild diabetes mellitus which frequently occurs is not marked and, in general, does not result in a reduction of requirements for insulin or oral hypoglycaemic agents. Octreotide produces improvement of diarrhoea, and hence weight gain, in those patients affected. Although administration of octreotide often leads to an immediate reduction in plasma glucagon levels, this decrease is generally not maintained over a prolonged period of administration, despite continued symptomatic improvement.
Gastrinomas/ Zollinger-Ellison syndrome:
Although therapy with proton pump inhibitors, selective H2-receptor blocking agents and antacids controls the recurrent peptic ulceration which results from chronic gastrin-stimulated hypersecretion of gastric acid, such control may be incomplete. Diarrhoea may also be a prominent symptom not alleviated in all patients by this therapy.
Octreotide alone or in conjunction with proton pump inhibitors H2-receptor antagonists may reduce gastric acid hypersecretion and improve symptoms, including diarrhoea. Other symptoms possibly due to peptide production by the tumour, e.g. flushing, may also be relieved. Plasma gastrin levels fall in some patients.
Insulinomas: Administration of octreotide produces a fall in circulating immunoreactive insulin. In patients with operable tumours, octreotide may help to restore and maintain normoglycaemia pre-operatively. In patients with inoperative benign or malignant turmours, glycaemic control may be improved even without concomitant sustained reduction in circulating insulin levels.
GRFomas: These rare tumours are characterised by production of GH releasing factor (GRF) alone or in conjunction with other active peptides. Octreotide produces improvement in the features and symptoms of the resultant acromegaly. This is probably due to inhibition of GRF and GH secretion, and a reduction in pituitary enlargement may follow.
5.2 Pharmacokinetic properties
After single i.m. injections of Sandostatin LAR, the octreotide concentration reaches a transient initial peak within 1 hour after administration, followed by a progressive decrease to a low undetectable octreotide level within 24 hours. After this peak on day 1, octreotide remains at sub-therapeutic levels in the majority of the patients for the following 7 days.
Thereafter, octreotide concentrations increase again, reach plateau concentrations at around day 14 and remain relatively constant during the following 3 to 4 weeks. The peak level during day 1 is lower than levels during the plateau phase, and no more than 0.5% of the total drug release occurs during day 1. After about day 42, the octreotide concentration decreases slowly, concomitant with the terminal degradation phase of the polymer matrix of the dosage form.
In patients with acromegaly, mean plateau octreotide concentrations after single doses of 10mg, 20mg and 30mg of Sandostatin LAR amount to 358ng/L, 926ng/L and 1710ng/L, respectively. Steady-state serum octreotide concentrations, reached after 3 injections at 4-week intervals, are higher by a factor of approximately 1.6 to 1.8 and amount to 1557ng/L, and 2384ng/L after multiple injections of 20mg and 30mg of Sandostatin LAR, respectively.
In patients with carcinoid tumours, the mean (and median) steady-state serum concentrations of octreotide after multiple injections of 10mg, 20mg and 30mg of Sandostatin LAR given at 4-week intervals also increase linearly with dose and were 1231 (894) ng/L, 2620 (2270) ng/L, and 3928 (3010) ng/L respectively.
No accumulation of octreotide beyond that expected from overlapping release profiles occurred over a duration of up to 28 monthly injections of Sandostatin LAR.
The pharmacokinetic profile of octreotide after injection of Sandostatin LAR reflects the release profile from the polymer matrix and its biodegradation. Once released into the systemic circulation, octreotide distributes according to its known pharmacokinetic properties, as described for s.c. administration. The volume of distribution of octreotide at steady state is 0.27 L/kg and the total body clearance is 160 ml/min. Plasma protein binding amounts to 65% and essentially no drug is bound to blood cells.
5.3 Preclinical safety data
Acute toxicity
Acute toxicity studies of octreotide in mice revealed LD50 values of 72mg/kg by the i.v. route and of 470mg/kg by the s.c. route. The acute i.v. LD50 value of octreotide in rats was determined at 18mg/kg. Octreotide acetate was well tolerated by dogs receiving up to 1mg/kg body weight by i.v. bolus injection.
Repeated dose toxicity
In a repeat dose study performed in rats by i.m. injection of 2.5mg Sandostatin LAR in 50mg microspheres every 4 weeks for 21 weeks, with necropsy at 26 weeks, no drug-related necropsy findings were observed. The only histopathological findings considered to be of significance were at the injection site in treated and control animals, where the microspheres had provoked a reversible granulomatous myositis. After a single i.m. injection of Sandostatin LAR in rats and rabbits, biodegradation of microspheres was complete by day 75 after injection in both species.
Mutagenicity
Octreotide and/or its metabolites were devoid of mutagenic potential when investigated in vitro in validated bacterial and mammalian cell test systems.
Increased frequencies of chromosomal changes were observed in V79 Chinese hamster cells in vitro, albeit at high and cytotoxic concentrations only. Chromosomal aberrations were however not increased in human lymphocytes incubated with octreotide acetate in vitro.
In vivo, no clastogenic activity was observed in the bone marrow of mice treated with octreotide i.v. (micronucleus test) and no evidence of genotoxicity was obtained in male mice using a DNA repair assay of sperm heads. The microspheres were devoid of mutagenic potential when tested in a validated in vitro bacterial assay.
Carcinogenicity/chronic toxicity
In studies in rats in which s.c. Sandostatin at daily doses up to 1.25mg/kg body weight were administered, fibrosarcomas were observed, predominantly in a number of male animals, at the s.c. injection site after 52, 104 and 113/116 weeks. Local tumours occurred also in the control rats, however development of these tumours was attributed to disordered fibroplasia produced by sustained irritant effects at the injection sites, enhanced by the acidic lactic acid/mannitol vehicle. This non-specific tissue reaction appeared to be particular to rats.
Neoplastic lesions were observed neither in mice receiving daily s.c. injections of Sandostatin at doses up to 2mg/kg for 98 weeks, nor in dogs which were treated with daily s.c. doses of the drug for 52 weeks.
The 116-week carcinogenicity study in rats with s.c. Sandostatin also revealed uterine endometrial adenocarcinomas, their incidence reaching statistical significance at the highest s.c. dose level of 1.25mg/kg per day.
The finding was associated with an increased incidence of endometritis, a decreased number of ovarian corpora lutea, a reduction in mammary adenomas and the presence of uterine glandular and luminal dilation, suggesting a state of hormonal imbalance. The available information clearly indicates that the findings of endocrine-mediated tumours in rats are species-specific and are not relevant for the use of the drug in humans.
Reproduction toxicity
Fertility as well as pre-, peri- and post-natal studies in female rats revealed no adverse effects on reproductive performance and development of the offspring, when s.c. doses up to 1mg/kg body weight per day were administered.
Some retardation of the physiological growth noted in pups was transient and attributable to GH inhibition brought about by excessive pharmacodynamic activity.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
(Microspheres) Vial
Poly (DL-lactide-co-glycolide); mannitol.
(Solvent) Prefilled syringe
Carmellose, sodium; mannitol; water for injection.
6.2 Incompatibilities
Sandostatin LAR is presented as a single dose container, for reconstitution with the solvent provided. Dilution with other products is not recommended, therefore, no compatibility data with other products has been generated.
6.3 Shelf life
Unopened: 3 years
The product should be used immediately after opening.
6.4 Special precautions for storage
Store at 2 to 8oC (in a refrigerator). Keep vial in the outer carton in order to protect from light. Sandostatin LAR can remain below 25 oC on the day of injection. However, the suspension must only be prepared immediately prior to the i.m. injection.
6.5 Nature and contents of container
Powder Vial
The microspheres are packaged in 5ml glass vials with a Teflon faced rubber stopper and sealed with an aluminium flip-off seal.
Solvent
3ml syringe made of colourless Ph.Eur. type I glass and closed with2 rubber stoppers (a front and a plunger stopper) containing 2.5ml solution.
Injection set [40mm (1.1mm), 19 gauge].
Needles and syringe packed individually.
Pack of one vial and one syringe with an injection set.
6.6 Special precautions for disposal and other handling
For single use only. Discradany unused contents.
Instructions for i.m. injection of Sandostatin LAR for deep intragluteal injection only
Follow the instructions below carefully to ensure complete saturation of the powder and its uniform suspension before intramuscular injection.
Sandostatin LAR suspension must only be prepared immediately before administration.
Sandostatin LAR should only be administered by a trained health professional.
Allow the Sandostatin LAR vial and the solvent syringe to reach room temperature.
Remove the cap from vial containing Sandostatin LAR. Assure that the powder is settled at the bottom of the vial by lightly tapping the vial. Remove the cap from the solvent syringe. Attach one of the supplied needles to the solvent syringe.
Disinfect the rubber stopper of the vial with an alcohol swab. Insert needle through centre of rubber stopper of the Sandostatin LAR vial.
Without disturbing the Sandostatin LAR powder, gently inject the solvent into the vial by running the vehicle down the inside wall of the vial. Do not inject the solvent directly into the powder. Withdraw the needle from the vial.
Do not disturb the vial until the solvent has totally wetted the Sandostatin LAR powder (approximately 2-5 minutes). Without inverting the vial check the powder on the walls and bottom of the vial. If dry spots exist, allow undisturbed wetting to continue.
Once complete wetting has occurred, the vial should be moderately swirled for about 30 to 60 seconds until a uniform milky suspension is achieved. Do not vigorously shake the vial as this may cause the suspension to flocculate, making it unusable.
Immediately re-insert the needle through the rubber stopper and then, with the bevel down and the vial tipped at approximately 45 degree angle, slowly draw the contents of the vial into the syringe. Do not invert the vial when filling the syringe as this may affect the amount withdrawn.
It is normal for a small amount of suspension to remain on the walls and bottom of the vial. This is a calculated overfill.
Immediately change the needle (supplied).
Administration must occur immediately after the suspension has been prepared. Gently invert the syringe as needed to maintain a uniform suspension. Eliminate air from syringe and disinfect the injection site with an alcohol swab. Insert needle into right or left gluteus and draw back to ensure that no blood vessel has been penetrated. Inject slowly i.m. by deep intragluteal injection with steady pressure.
If the needle blocks, attach a new needle of the same diameter [1.1 mm, 19 gauge].
Sandostatin LAR must be given only by deep intragluteal injection, never i.v. If a blood vessel has been penetrated, attach a new needle and select another injection site.
CE 0123. The device conforms with Directive 93/42/EEC.
7. MARKETING AUTHORISATION HOLDER
Novartis Pharmaceuticals UK Limited
Frimley Business Park
Frimley
Camberley
Surrey GU16 7SR
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PA 13/43/5
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13 July 1998/13 July 2003
10. DATE OF REVISION OF THE TEXT
January 2005
Sandostatin LAR 在日本通过审批用于治疗肢端肥大症及胃肠激素分泌肿瘤症状
2013年5月15日，Sandostatin(r)LAR(r)（醋酸奥曲肽(Octreotideacetate)混悬注射液）已通过日本卫生当局审批。该药用于治疗手术及其他药物疗法无效或不适宜的肢端肥大症(acromegaly)和垂体性巨人症(pituitarygigantism)以及与胃肠激素分泌肿瘤(gastrointestinalhormonesecretingtumor)（又称为胃肠胰脏(GEP)神经内分泌肿瘤(NET)），包括类癌瘤、促胃液素瘤和VIP肿瘤(一种分泌肠血管活性肽的肿瘤)）相关的症状。
日本厚生省在日本和西方国家（包括已经批准SandostatinLAR的美国及欧盟成员国）的研究临床数据的基础上做出了批准决定。SandostatinLAR已在70多个国家获得认可。
NovartisOncology总裁DavidEpstein表示：“SandostatinLAR是这些疾病治疗的世界标准。我们十分高兴日本卫生当局核准了该药品，因而使日本患者现在可以受益于它。”
临床数据： 日本两项试验（一个针对肢端肥大症和垂体性巨人症，另一个针对类癌综合症）数据，与之前作为美国和欧洲批准该药品的基础的西方国家第三阶段研究结果一致。
西方国家针对肢端肥大症的第三阶段研究数据表明，通过SandostatinLAR治疗，128名患者中有89人（69.5%）的生长激素(GH)水平有效降至2.5ng/mL以下。
此外，128名患者中有85人（66.4%）的IGF-1（胰岛素样生长因子-1）水平恢复正常。该药品显著减轻了头痛、疲乏、出汗、关节痛、以及腕管综合症(CarpalTunnelSyndrome)等肢端肥大症的临床症状。 在西方国家关于恶性类癌瘤综合症的第三阶段临床试验中，接受SandostatinInjection（善宁注射剂）皮下注射治疗并有效控制住临床症状的93名患者的数据表明，SandostatinLAR在控制临床症状方面具有与SandostatinInjection同等的疗效。