Solution for s.c. Injection or Concentrate for Solution for i.v. Injection

Transcription

1 PATIENT INFORMATION LEAFLET SANDOSTATIN 50 micrograms/ml Solution for s.c. or i.v. Injection SANDOSTATIN 100 micrograms/ml Solution for s.c. Injection or Concentrate for Solution for i.v. Injection SANDOSTATIN 500 micrograms/ml Solution for s.c. Injection or Concentrate for Solution for i.v. Injection or Infusion Octreotide (as Acetate) WHAT YOU SHOULD KNOW ABOUT SANDOSTATIN Please read this carefully before you start to take your medicine, even if you have already been using SANDOSTATIN for some time. If you have any questions or are not sure about anything ask your doctor or pharmacist (chemist) for advice. Health care professionals should refer to the technical section of the leaflet. WHAT S IN YOUR MEDICINE SANDOSTATIN contains octreotide (as Acetate). It is a clear, colourless solution for injection and is available in ampoules of three strengths: 50 micrograms octreotide as acetate in 1ml 100 micrograms octreotide as acetate in 1ml 500 micrograms octreotide as acetate in 1ml The ampoules also contain the following inactive ingredients: lactic acid, mannitol (E421), sodium hydrogen carbonate and water for injection. This product contains less than 1mmol sodium (23 mg) per injection, it is essentially sodium-free Each strength of SANDOSTATIN ampoule is available in packs containing 5 ampoules. SANDOSTATIN is a synthetic version of the natural hormone somatostatin. Manufacturer: Novartis Pharmaceuticals UK Limited,

2 Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, England. Product authorisation holder: Novartis Pharmaceuticals UK Limited, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, England. Irish Company Address: Novartis Ireland Limited, Beech House, Beech Hill Office Campus, Clonskeagh, Dublin 4. WHY DOES YOUR DOCTOR WANT YOU TO USE SANDOSTATIN? SANDOSTATIN can be used for the relief of symptoms associated with the over production of some of the body s natural substances. Over-production of these substances upsets your natural hormone balance and causes a variety of signs and symptoms such as flushing, diarrhoea, low blood pressure, sweating, rash and weight loss. SANDOSTATIN can also be used to reduce levels of growth hormone if you have acromegaly. SANDOSTATIN can help to improve symptoms caused by over-production of growth hormone such as headaches, sweating, tiredness, numbness and tingling in the hands and feet. SANDOSTATIN can also be used to prevent complications following surgery of the pancreas gland. Treatment with Sandostatin helps to lower the chance of complication (e.g. abscess in the abdomen, inflammation of the pancreas gland) after the surgery. SANDOSTATIN can also be used to stop bleeding and to protect from re-bleeding from ruptured gastro-esophageal varices in patients suffering from cirrhosis (chronic liver disease). Treatment with Sandostatin helps to control bleeding and reduce transfusion requirements. BEFORE USING YOUR MEDICINE Tell your doctor before you start taking SANDOSTATIN if the answer to any of the following questions is yes: - Do you suspect that you have had an allergic reaction to similar products, or any of the ingredients in SANDOSTATIN (listed in What s in your medicine )? - Have you ever suffered from gallstones or other stomach problems? - Do you have aproblem with your blood sugar level, either too high (diabetes) or too low (hypoglycaemia)? - Do you have any thyroid problems, or have you had a disease which may have affected your thyroid? - Do you have any problems with your liver, or have you had a disease which may have affected your liver?

3 - Are you pregnant, or planning to become pregnant? If you do become pregnant whilst taking SANDOSTATIN tell your doctor. - Are you breastfeeding? - Are you taking any other medicines (either bought or prescribed)? - Are you using Sandostatin to treat bleeding from gastro-esophageal varices? If yes, monitoring of blood sugar level is mandatory. - Do you have an history of Vitamin B12 deprivation? If yes, your doctor may wish to check your B12 level periodically. Sandostatin can interact with other medicines, so make sure to check with your doctor or pharmacist before taking any other medicines. In particular, tell your doctor if you are taking cyclosporine, cimetidine and bromocriptine, insulin, quinidine or terfenadine. USING YOUR MEDICINE Follow the instructions given to you by your doctor. He/she will tell you the correct dose and how often to inject your medicine. Follow your doctor s instructions exactly and never change the dose yourself. Ask your doctor or pharmacist if you are unsure about how much medicine to use or when to use it. Your medicine must be injected sub-cutaneously into the tissue under the skin. Your doctor or nurse will show you how to do this and if you are unsure return to them for advice. Use a clean, sterile syringe and needle every time and avoid multiple injections at short intervals at the same site. In rare cases SANDOSTATIN may have to be injected intravenously (into a vein). It this is necessary the doctor or nurse will perform the injection. You must NOT inject SANDOSTATIN into your veins yourself. 1. CLINICAL PARTICULARS 1.1 Therapeutic indications (i) For the relief of symptoms associated with gastroenteropancreatic endocrine tumours, including carcinoid tumours with features of the carcinoid syndrome, VIPomas, glucagonomas, gastrinomas/zollinger-ellison syndrome (usually in conjunction with selective H 2 -antagonist therapy with or without antacids), insulinomas (for pre operative control of hypoglycaemia and for maintenance therapy) and GRFomas. SANDOSTATIN is not an anti-tumour therapy and is not curative in these patients. (ii) For symptomatic control and reduction of GH and somatomedin C plasma levels in patients with acromegaly:- (a) in short term treatment prior to pituitary surgery, or (b) in long-term treatment in those who are inadequately controlled by pituitary surgery, dopamine against treatment, radiotherapy, or in the interim period until radiotherapy becomes fully effective. SANDOSTATIN treatment is also indicated for acromegalic patients unfit or unwilling to undergo surgery. Further SANDOSTATIN has also been shown to reduce tumour size in some patients. Prevention of complications following pancreatic surgery.

4 Emergency management to stop bleeding and to protect from re-bleeding owing to gastro-esophageal varices in patients with cirrhosis. SANDOSTATIN is to be used in association with specific treatment such as endoscopic sclerotherapy. 1.2 Posology and method of administration The recommended route of administration is subcutaneous. However, in instances where a rapid response is required e.g. carcinoid crises, the initial recommended dose of SANDOSTATIN (50 micrograms) may be administered by the intravenous route as a bolus, whilst monitoring the cardiac rhythm. Dilution of the SANDOSTATIN 100 micrograms/ml Solution and SANDOSTATIN 500 micrograms/ml Solution as described below will be necessary in this case. SANDOSTATIN 100 micrograms/ml Solution For intravenous bolus injection SANDOSTATIN 100 microgram/ml should be dilution with sodium chloride 0.9% w/v solution to a ratio of 1:1 to attain the recommended 50 microgram dose. Dilution of SANDOSTATIN with glucose solution is not recommended. ECG monitoring is also advised. SANDOSTATIN 500 micrograms/ml Solution For intravenous bolus injection SANDOSTATIN 500 microgram/ml should be diluted with sodium chloride 0.9% w/v solution to a ratio of 1:9 to attain the recommended 50 microgram dose. Dilution of SANDOSTATIN with glucose solution is not recommended. ECG monitoring is also advised. Adults (i) Carcinoid tumours, VIPomas, glucagonomas, gastrinomas/zollinger-ellison syndrome, insulinomas, GRFomas The initial dose is 50 micrograms once or twice daily by subcutaneous injection. Patients who are to self-administer the drug by s.c. injection must receive precise directions from the physician or the nurse. To reduce local discomfort, it is recommended that the solution should be at room temperature before injection. Multiple injections at short intervals at the same site should be avoided. Ampoules should be open just prior to administration, and any unused portion discarded. Depending on response, dosage can be gradually increased to 200 micrograms three times daily. Under exceptional circumstances higher doses may be required. Maintenance doses are variable. In carcinoid tumours, if there is no beneficial effect within a week continued therapy is not recommended. Adults (ii) Acromegaly 100 to 200 micrograms three times a day by subcutaneous injection. (See 1.2 (i))

5 Dosage adjustment should be based on monthly assessment of GH and IGF-1 levels (target: GH< 2.5 ng/ml; IGF-1 within normal range) and clinical symptoms, and on tolerability. In most patients, the optimal daily dose will be -0.3 mg. A maximum dose of 1.5mg per days should not be exceeded. For patients on a stable dose of SANDOSTATIN, assessment of GH should be made every 6 months. If no relevant reduction of GH levels and no improvement of clinical symptoms have been achieved within 3 months of starting treatment with SANDOSTATIN, therapy should be discontinued. (iii) Complications following pancreatic surgery 0.1 mg 3 times daily by s.c. injection for 7 consecutive days, starting on the day of operation at least 1 hour before laparotomy. See 1.2 (i) for further information on s.c. injection. (iv) Bleeding gastro-oesophagealvarices SANDOSTATIN 500 micrograms/ml Solution only 25 micrograms/hour for 5 days by continuous i.v. infusion. SANDOSTATIN can be used in dilution with physiological saline. In cases where SANDOSTATIN is to be administered by i.v. infusion, the contents of one 0.5 mg ampoule should normally be dissolved in 60 ml physiological saline, and the resulting solution should be infused by means of an infusion pump. This should be repeated as often as necessary until the prescribed duration of treatment is reached. SANDOSTATIN has also been infused in lower concentrations. In cirrhotic patients with bleeding gastro-oesophagealvarices, SANDOSTATIN has been well tolerated at continuous i.v. doses of up to 50 micrograms/hour for 5 days. (v) Children Experience with SANDOSTATIN in children is very limited. (vi) Use in the elderly In elderly patients repeated with SANDOSTATIN there is no evidence of reduced tolerability or altered dosage requirements. (vii) Use in patients with impaired liver function In patients with liver cirrhosis, the half-life of the drug may be increased, necessitating adjustment of the maintenance dosage. 1.3 Contra-indications Hypersensitivity to octreotide or to any of the excipients. 1.4 Special warnings and precautions for use General

6 As GH-secreting pituitary tumours may sometimes expand, causing serious complications (e.g. visual field defects), it is essential that all patients be monitored. If evidence of tumour expansion appears, alternative procedures may be advisable. SANDOSTATIN should only be used under specialist hospital supervision with the appropriate facilities available for diagnosis and evaluation of response. Thyroid function should be monitored in patients receiving long-term SANDOSTATIN therapy. Hepatic function should be monitored during SANDOSTATIN therapy. Cardiovascular related events Uncommon cases of bradycardia have been reported. Dose adjustments of drugs such as betablockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary. GEP endocrine Tum(m)ours Sudden escape of gastroenteropancreatic endocrine tumours from symptomatic control by SANDOSTATIN may occur infrequently, with rapid recurrence of severe symptoms. Glucose metabolism 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 its inhibitory action on insulin, may increase the depth and prolong the duration of hypoglycaemia. Such patients should be closely observed on introduction of SANDOSTATIN therapy and at each change of dosage. Marked fluctuations of blood glucose concentration may be reduced by more frequent administration of SANDOSTATIN. Insulin requirements of patients with type 1 diabetes mellitus therapy may be reduced by administration of SANDOSTATIN. In non-diabetics and type II diabetics with partially intact insulin reserves, SANDOSTATIN administration can result in prandial increases in glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment. SANDOSTATIN may reduce insulin or oral hypo-glycaemia requirements in patients with diabetes mellitus. Gallbladder and related events Ultrasonic examination of the gallbladder is recommended before, and at 6 to 12 month intervals during SANDOSTATIN therapy as gallstones have been reported in patients on long-term SANDOSTATIN treatment. If gallstones do occur, they are usually asymptomatic; symptomatic stones should be treated in the normal manner. Oesophagealvarices Since, following bleeding episodes from oesophagealvarices, there is an increased risk for the development of insulin-dependent diabetes or for changes in insulin requirement in patients with preexisting diabetes, an appropriate monitoring of blood glucose levels is mandatory.

7 Nutrition Octreotide may alter absorption of dietary fats in some patients. Depressed vitamin B 12 levels and abnormal Schilling s tests have been observed in some patients receiving octreotide therapy. Monitoring of vitamin B 12 levels is recommended during therapy with SANDOSTATIN in patients who have a history of vitamin B 12 deprivation. 1.5 Interaction with other medicaments and other forms of interaction SANDOSTATIN has been reported to reduce the intestinal absorption of cyclosporinand to delay that of cimetidine. Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine. Limited published data indicate that somatostatin analogues might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index should therefore be used with caution (e.g. quinidine, terfenadine). 1.6 Pregnancy and lactation Experience with SANDOSTATIN in pregnant or breast-feeding women is not available. Studies in animals showed transient growth retardation of offspring, possibly consequent upon the specific endocrine profiles of the species tested, but there was no evidence of foetotoxic, teratogenic or other reproduction effects. Nevertheless, SANDOSTATIN should not be given during pregnancy except in compelling circumstances. Women receiving treatment with SANDOSTATIN should not breast-feed their infants. 1.7 Effects on ability to drive and to use machines No data exists on the effects of SANDOSTATIN on the ability to drive and use machines. 1.8 Undesirable effects The main side effects are local injection site reactions and gastrointestinal reactions. Local reactions after s.c. administration include pain, a sensation of stinging, tingling or burning at the site of injection, with redness or swelling. They rarely last more than fifteen minutes. Local discomfort may be reduced by allowing the solution to reach room temperature before injection. The most commonly reported adverse reactions in clinical trials with SANDOSTATIN administration were diarrhoea, abdominal pain, flatulence and local injection site pain or irritation. Intermittent gastrointestinal side effects resembling acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding can occur in about 10% of patients but usually decline with continued treatment. Gastrointestinal side effects include anorexia, nausea, vomiting, abdominal pain, abdominal bloating, flatulence, loose stools, diarrhoea and steatorrhoea. Although measured faecal fat excretion may

8 increase, there is no evidence to date that long-term treatment with SANDOSTATIN has led to nutritional deficiency due to malabsorption. Occurrence of gastrointestinal side effects may be reduced by avoiding meals around the time of SANDOSTATIN administration, that is, by injecting between meals or on retiring to bed. The following adverse drug reactions, listed in Table 1, have been accumulated from clinical studies with octreotide and spontaneously reported adverse reactions: Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common ( 1/10); common ( 1/100, <1/10); uncommon ( 1/1,000, < 1/100); rare ( 1/10,000, < 1/1,000);very rare (< 1/10,000), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. Table 1 Immune system disorders Rare: Hypersensitivity, rash Very rare: Anaphylaxis Endocrine disorders Very rare: Hypoglycaemia, hyperglycaemia Cardiac disorders Uncommon: Bradycardia, tachycardia Respiratory disorders Very rare: Dyspnoea Gastrointestinal disorders Common: Diarrhoea, crampy abdominal pain, constipation, flatulence. Rare: Steatorroea, nausea, vomiting, abdominal bloating Very rare: Acute pancreatitis, anorexia, loose stools Hepatobiliary disorders Uncommon:Cholecystitis Rare: Gallstones Very rare: Acute hepatitis without cholestasis, hyperbilirubinaemia, elevated alkaline phosphatase, gamma glutamyltransferase and transaminases. Skin and subcutaneous tissue disorders Uncommon: Transient hair loss General disorders and administration site Common: Local injection site pain, swelling and irritation. In very rare instances, acute pancreatitis has been reported; generally, this effect is seen within the first hours or days of SANDOSTATIN treatment and resolved on withdrawal of the drug. In addition, cholelithiasis-induced pancreatitis has been reported for patients on long-term SANDOSTATIN treatment. Post-marketing The following adverse drug reactions have been observed during post-marketing experience. On rare occasions thyroid dysfunction has been reported both under and over activity. In some instances dyspepsic signs have been reported in patients receiving octreotide acetate. Symptoms and episodes of arrhythmia have been reported in patients receiving octreotide acetate. Other ECG changes such as QT prolongation, axis shifts, early repolarisation, low voltage, R/S transition, early R wave progression, and non-specific ST-T wave changes, have been reported during octreotide acetate therapy. The relationship of these events to octreotide acetate is however not established because

9 many acromegalic and carcinoid patients have underlying cardiac diseases (see Section 1.4 Special warnings and precautions for use). 1.9 Overdosage No life-threatening reactions have been reported after acute overdosage. The maximum single dose so far given to an adult has been 1 mg by intravenous bolus injection. The observed signs and symptoms were a brief drop in heart rate, facial flushing, abdominal cramps, diarrhoea, an empty feeling in the stomach and nausea, which resolved within twenty-four hours of drug administration. One patient has been reported to have received an accidental overdosage of SANDOSTATIN by continuous infusion (250 micrograms per hour for forty-eight hours instead of 25 micrograms per hour). He experienced no side effects. Doses of up to 2000 micrograms octreotide given as subcutaneous injection t.i.d for several months have been well tolerated. No life-threatening reactions have been reported after acute overdose. The management of overdose is symptomatic. 2 PHARMACEUTICAL PARTICULARS 2.1 List of excipients Lactic acid Mannitol (E421) Sodium hydrogen carbonate Water for injection. 2.2 Incompatibilities Dilution with glucose solution is not recommended. Octreotide acetate is not stable in Total Parenteral Nutrition (TPN) solutions. 2.3 Shelf life Unopened: 3 years This product should be used immediately after opening. After dilution: SANDOSTATIN 100 micrograms/ml Solution SANDOSTATIN 500 micrograms/ml Solution When SANDOSTATIN is diluted with sodium chloride 0.9% w/v solution, the resulting diluted solution is physically and chemically stable for 24 hours when stored below 25 C.

10 From a microbiological point of view, the diluted solution should be used immediately. If the solution is not used immediately, in-use storage times and conditions are the responsibility of the user and dilution must take place in controlled and validated aseptic conditions. The cumulated time between opening of the ampoules, dilution with sodium chloride 0.9% w/v solution and end of administration must not be longer than 24 hours. Before administration the solution has to be brought to room temperature. 2.4 Special precautions for storage For prolonged storage, SANDOSTATIN ampoules should be stored in a refrigerator (at 2-8 C). Do not freeze. For day-to-day use store unopened ampoules below 25 C for up to 2 weeks. Keep the ampoules in the outer carton. See 2.3 for storage of diluted product 2.5 Nature and contents of container Type 1(Ph.Eur.) clear glass 1ml ampoule. This product is presented as a pack of 5 ampoules of 1ml. 2.6 Instructions for use/handling For single use only. Discard any unused contents. Parenteral drug products should be inspected visually for discoloration and particulate matter prior to administration. For instructions on preparation and administration of the product, see section 1.2. Health care professionals should refer to the technical portion of this leaflet. Do not use the injections straight from the fridge. Let it reach room temperature naturally first. Avoid meals around the time of administration of SANDOSTATIN. SANDOSTATIN is best injected between meals or on retiring to bed. This may reduce the gastrointestinal side effects of Sandostatin. Do not open the ampoule until it is time to give your injection. Please note that SANDOSTATIN ampoules have a small etch at the breaking point of the ampoule together with a blue spot at the top of each ampoule. To snap open an ampoule, you should carefully apply thumb pressure from one hand to the blue spot at the top of the ampoule holding the lower half of the ampoule with your other hand. DOSAGE For the relief of symptoms associated with the over-production of some of the body s natural substances, treatment is usually started with 50 micrograms once or twice daily by subcutaneous injection. Your doctor may feel it is necessary to gradually increase your dose, until your ideal dose is established. Follow your doctor s instructions carefully and do not change your dose unless your doctor tells you to. For the treatment of acromegaly the usual dose is micrograms three times a day by subcutaneous injection.

11 For the treatment of complications following pancreatic surgery the suggested starting dose is 100 micrograms three times a day by subcutaneous injection. For the treatment of bleeding gastro-esophageal varices the recommended dose is 25 micrograms/hour for 5 days by continuous intravenous infusion. Health care professionals should note that only the 500mcg/ml strength may be used as a concentrate for i.v. infusion and refer to the technical portion of the leaflet for instructions. MISSED DOSE If you forget to inject a dose then inject another as soon as you remember, unless it is almost time for your next dose then go on as before. Do NOT double your dose or inject two doses at once. OVERDOSE If you accidently use too much of your medicine, tell your doctor immediately or go to your nearest Casualty Department. AFTER USING YOUR MEDICINE Most people who are prescribed SANDOSTATIN will benefit from taking it, but a few can be upset by it. If you are receiving this medicine on a long term basis then you will go to hospital from time to time to have regular check-ups. The following reactions at the site of injection are common: - Pain. - Sensation of stinging, tingling or burning. - Redness and swelling. These rarely last more than 15 minutes and are reduced by letting your medicine reach room temperature before injecting and also by gently rubbing the site of injection for a few seconds afterwards. Sandostatin sometimes causes side effects. Some are common: - Stomach pain - Diarrhoea - Constipation - Flatulence (wind) Some are uncommon: - Temporary hair loss Some are rare: - Nausea - Vomiting

12 - Feeling of fullness in the stomach - Change in activity of thyroid gland causing changes in heart rate, appetite or weight; tiredness, feeling cold or sweating too much, anxiety or swelling at the front of the neck. Some are very rare: - Loss of appetite - Loose stools - Shortness of breath - Change in liver function tests - Stomach discomfort after meal (dyspepsia). Some side effects could be serious and might need immediate medical attention. Some are uncommon: - Slow or fast heart beat - Inflammation of the gallbladder (cholecystitis) Some are rare: - Hypersensitivity (allergic) reactions including skin rash - Gallstones Some are very rare: - A type of allergic reaction (anaphylaxis) which causes difficulty in breathing or dizziness. - Too much or too little sugar in the blood. - And inflammation of the pancreas gland (pancreatitis). - Liver inflammation (hepatitis); symptoms may include yellowing of the skin and eyes (jaundice), nausea, vomiting, loss of appetite, generally feeling unwell, itching, light-coloured urine. Tell your doctor immediately if you have any other symptoms not mentioned in this leaflet. STORING YOUR MEDICATION Do not use this medicine after the expiry date printed on the ampoule label and carton. For prolonged storage, Sandostatin Ampoules should be stored in a refrigerator between 2-8 C. Do not Freeze. For day to day use, store unopened ampoules below 25 C for up to 2 weeks. Keep the ampoules in the outer carton to protect from light. Health care professionals should refer to the technical portion of the leaflet for further information. Store your medicine in a safe place. Keep out of reach and sight of children. Your medicine could harm them. If you doctor decides to stop your treatment, return any left over medicine to the pharmacist. Only keep it if your doctor tells you to. LEAFLET REVISED May 2013

13 FURTHER INFORMATION Remember: This medicine is only for you. Only a doctor can prescribe it for you. Never give it to anyone else. It may harm them, even if their symptoms appear to be the same as yours. If you have any further questions about your medicine or are unsure about any of the advice in this leaflet, ask your doctor or pharmacist. PRODUCT/AUTHORISATION NUMBERS 50 mcg/1 ml ampoules PA 13/43/1 100 mcg/1 ml ampoules PA 13/43/2 500 mcg/1 ml ampoules PA 13/43/3