Search The Medical Knowledge Base

Drug Details

SANDOSTATIN

• Drug Class Description
  Somatostatin analogues.
• Generic Name
  Octreotide - growth hormone/growth disorders
• Presentation
  Solution for injection (s.c) or concentrate for solution for infusion. The solution is clear and colourless
• Description
  The active substance is octreotide acetate. 0.05 mg octreotide (INN) per ml. 0.1 mg octreotide (INN) per ml. 0.5 mg octreotide (INN) per ml. 0.2 mg octreotide (INN) per ml. Sandostatin solution for injection contains less than 1mmol (23mg) sodium per dose, i.e essentially “sodium-free”.
• Indications
  

  GEP tumours: For the relief of symptoms associated with functional gastroenteropancreatic endocrine tumours including:

  - carcinoid tumours with features of carcinoid syndrome

  - VIPomas

  - glucagonomas Sandostatin is not antitumour therapy and is not curative in these patients.

  Acromegaly:

  - For symptomatic control and reduction of growth hormone and somatomedin c plasma levels in patients with acromegaly:

  - in short term treatment, prior to pituitary surgery, or

  - in long term treatment in those who are inadequately controlled by pituitary surgery, radiotherapy, or in the interim period until radiotherapy becomes effective. Sandostatin is indicated for acromegalic patients for whom surgery is inappropriate.

  Evidence from short term studies demonstrate that tumour size is reduced in some patients (prior to surgery); further tumour shrinkage however cannot be expected as a feature of continued long term treatment. Prevention of complications following pancreatic surgery. Route of administration Subcutaneous or intravenous use.

• Adult Dosage
  

  GEP tumours

  Initially 0.05 mg once or twice daily by s.c. injection. Depending on response, dosage can be gradually increased to 0.2 mg three times daily. Under exceptional circumstances, higher doses may be required. Maintenance doses are variable.

  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 may be administered by the intravenous route, diluted and given as a bolus, whilst monitoring the cardiac rhythm.

  In carcinoid tumours, if there is no beneficial effect within a week, continued therapy is not recommended.

  Acromegaly

  0.1 – 0.2 mg three times daily by s.c. injection. Dosage adjustment should be based on monthly assessment of GH and IGF-1 levels (target: GH less than 2.5ng/ml, 5mU/l; IGF-1 within normal range) and clinical symptoms, and on tolerability. For patients on a stable dose of Sandostatin, assessment of GH should be made every 12 months. Six-monthly monitoring may be necessary in those patients whose clinical and biochemical control is adequate.

  If no relevant reduction of growth hormone levels and no improvement of clinical symptoms have been achieved within three months of starting treatment, therapy should be discontinued.

  For the prevention of complications following pancreatic surgery

  0.1 mg three times daily by subcutaneous injection for 7 consecutive days, starting on the day of operation at least one hour before laparotomy.

  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. therefore, no dose adjustment of Sandostatin 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 maybe reduced in patients with liver cirrhosis, but not in patients with fatty liver disease. In patients with liver cirrhosis, an adjustment of the maintenance dose may therefore be necessary.

• Child Dosage
  

  Experience with Sandostatin in children is very limited.

• Elderly Dosage
  

  In elderly patients treated with Sandostatin, there is no evidence for reduced tolerability or altered dosage requirements.

• Contra Indications
  

  Known hypersensitivity to octreotide or to any of the excipients.

• Special Precautions
  

  General

  As growth hormone secreting pituitary tumours may sometimes expand, causing serious complications (e.g. visual field defects), it is essential that all patients be carefully monitored. If evidence of tumour expansion appears, alternative procedures may be advisable.

  Thyroid function should be monitored in patients receiving long-term Sandostatin therapy.

  Cardiovascular related events

  Uncommon cases of bradycardia have been reported. Dose adjustments of drugs such as beta-blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary.

  GEP endocrine tumours

  Sudden escape of gastroenteropancreatic endocrine tumours from symptomatic control by Sandostatin may occur infrequently, with rapid recurrence of severe symptoms.

  Glucose metabolism

  Because of its inhibitory action on growth hormone, glucagon, and insulin release, octreotide may affect glucose regulation. Postprandial glucose tolerance may be impaired and, in some instances, the state of persistent hyperglycaemia may be induced as a result of chronic administration. Hypoglycaemia has also been observed.

  Octreotide may increase the depth and duration of hypoglycaemia in patients with insulinoma. This is because it is relatively more potent in inhibiting growth hormone and glucagon secretion than in inhibiting insulin and because its duration of insulin inhibition is shorter. If Sandostatin is given to a patient with insulinoma, close monitoring is necessary on introduction of therapy and at each change of dosage. Marked fluctuations of blood glucose may be reduced by more frequent administration of Sandostatin.

  Sandostatin may reduce insulin or oral hypoglycaemic requirements in patients with type I diabetes mellitus. In non-diabetics and type II diabetics with particularly intact insulin reserves, Sandostatin administration can result in prandial increases in glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.

  Gallbladder and related events

  Sandostatin exerts an inhibiting effect on gallbladder motility, bile acid secretion and bile flow and there is an acknowledged association with the development of gallstones. The incidence of gallstone formation with Sandostatin treatment is estimated to be between 15 – 30 %.

  Ultrasonic examination of the gallbladder, before and at about 6 to 12 month intervals during Sandostatin therapy is therefore recommended. If gallstones do occur, they are usually asymptomatic; symptomatic stones should be treated in the normal manner with due attention to abrupt withdrawal of the drug.

  In patients with cirrhosis, dosage adjustment may be necessary.

  Nutrition

  Octreotide may alter absorption of dietary fats in some patients.

  Depressed vitamin B₁₂ levels and abnormal Schilling's tests have been observed in some patients receiving octreotide therapy. Monitoring of vitamin B₁₂ levels is recommended during therapy with Sandostatin in patients who have a history of vitamin B₁₂ deprivation.

• Interactions
  

  Octreotide has been reported to reduce the intestinal absorption of cyclosporin and to delay that of cimetidine.

  Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine.

  Limited published data indicate that somatostatin analogs 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 metabolised by CYP3A4 and which have a low therapeutic index should therefore be used with caution (e.g. carbamazepine, digoxin, warfarin and terfenadine).

• Adverse Drug Reactions
  

  The main side-effects are local injection site reactions and gastrointestinal reactions.

  The most commonly reported adverse reactions in clinical trials with Sandostatin administration were diarrhoea, abdominal pain, flatulence and local injection site pain or irritation.

  In rare instances, gastrointestinal side-effects may resemble acute intestinal obstruction with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding.

  Pain or a sensation of stinging, tingling or burning at the site of s.c. injection, with redness and swelling, rarely lasting more than 15 minutes. Local discomfort may be reduced by allowing the solution to reach room temperature before injection.

  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 to <1/10); uncommon (1/1,000 to 1/100); rare (1/10,000 to 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: Very rare:	Hypersensitivity, rash Anaphylaxis
  Endocrine disorders
  Very rare:	Hypoglycaemia, hyperglycaemia
  Cardiac disorders
  Uncommon:	Bradycardia, tachycardia.
  Respiratory disorders Very rare:	Dyspnoea
  Gastrointestinal disorders
  Common:	Diarrhoea, 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 glutamyl transferase and transaminases.
  Skin and subcutaneous tissue disorder
  Uncommon:	Hair loss
  General disorders and administration site
  Common:	Local injection site pain, swelling and irritation.

  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.

  Occurrence of gastrointestinal side-effects may be reduced by avoiding meals around the time of octreotide administration, that is, by injecting between meals or on retiring to bed.

  In rare instances, acute pancreatitis has been reported; generally, this effect is seen within the first hours or days of Sandostatin treatment and resolves on withdrawal of the drug. In addition, cholelithiasis-induced pancreatitis has been reported for patients on long-term Sandostatin treatment.

  There have been isolated cases of biliary colic following the abrupt withdrawal of the drug in acromegalic patients in whom biliary sludge or gallstones had developed.

   

  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 cases 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 many acromegalic and carcinoid patients have underlying cardiac diseases.