Octreostat

/ Easy Care

Acromegaly
Initially 0.05 to 0.1 mg by subcutaneous (s.c.) injection every 8 or 12 hours. 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 1.5 mg per day should not be exceeded. For patients on a stable dose of this medical product, assessment of GH should be made every 6 months.
If no relevant reduction in GH levels and no improvement in clinical symptoms have been achieved within 3 months of starting treatment, therapy should be discontinued.
Gastro-entero-pancreatic endocrine tumours
Initially 0.05 mg once or twice daily by s.c. injection. Depending on clinical response, effect on levels of tumour-produced hormones (in cases of carcinoid tumours, on the urinary excretion of 5-hydroxyindole acetic acid), and on tolerability, dosage can be gradually increased to 0.1 to 0.2 mg 3 times daily. Under exceptional circumstances, higher doses may be required. Maintenance doses have to be adjusted individually.
In carcinoid tumours, if there is no beneficial response within 1 week of treatment at the maximum tolerated dose, therapy should not be continued.
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.
Bleeding gastro-oesophageal varices
25 micrograms/hour for 5 days by continuous intravenous (i.v.) infusion. Can be used in dilution with physiological saline.
In cirrhotic patients with bleeding gastro-oesophageal varices, this medical product has been well tolerated at continuous i.v. doses of up to 50 micrograms/hour for 5 days.
See prescribing information to full details

* Prevention of complications following pancreatic surgery
* Symptomatic control and reduction of growth hormone (GH) and IGF-1 plasma levels in patients with acromegaly who are inadequately controlled by surgery or radiotherapy.
* Acromegalic patients unfit or unwilling to undergo surgery, or in the interim period until radiotherapy becomes fully effective.
Relief of symptoms associated with functional gastro-entero-pancreatic (GEP) endocrine tumors: Carcinoid tumors with features of the carcinoid syndrome, VIPomas, Glucagonomas, Gastrinomas/Zollinger-Ellison syndrome, usually in conjunction with proton pump inhibitors, or H2-antagonist therapy, Insulinomas, for pre-operative control of hypoglycemia and for maintenance therapy, GRFomas.
Octreotide is not an anti-tumors therapy and is not curative in these patients.
* Emergency management of bleeding gastro-esophageal varices secondary to cirrhosis in combination with specific therapy such as endoscopic sclerotherapy.

Hypersensitivity to the active substance or to any of the excipients

General
* As GH-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.
* The therapeutic benefits of a reduction in growth hormone (GH) levels and normalisation of insulin-like growth factor 1 (IGF-1) concentration in female acromegalic patients could potentially restore fertility. Female patients of childbearing potential should be advised to use adequate contraception if necessary during treatment with octreotide.
* Thyroid function should be monitored in patients receiving prolonged treatment with octreotide. Hepatic function should be monitored during octreotide therapy.
Cardiovascular related events
Common cases of bradycardia have been reported. Dose adjustments of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary.
Atrioventricular blocks (including complete atrioventricular block) were reported in patients receiving high doses of continuous infusion (100 micrograms/hour) and in patients receiving bolus octreotide intravenously (50 micrograms bolus followed by 50 micrograms/hour continuous infusion). The maximum dose of 50 microgram/hour should therefore not be exceeded. Patients who receive high doses of intravenous octreotide should be kept under appropriate cardiac monitoring.
Gallbladder and related events
Cholelithiasis is a very common event during Octreotide treatment and may be associated with cholecystitis and biliary duct dilatation. Additionally, cases of cholangitis have been reported as a complication of cholelithiasis in patients taking this medical product in the post-marketing setting. Ultrasonic examination of the gallbladder before, and at about 6- to 12-month intervals during therapy is therefore recommended.
GEP endocrine tumours
During the treatment of GEP endocrine tumours, there may be rare instances of sudden escape from symptomatic control by Octreotide, with rapid recurrence of severe symptoms. If the treatment is stopped, symptoms may worsen or recur.
Glucose metabolism
Because of its inhibitory action on growth hormone, glucagon, and insulin, Octreotide may affect glucose regulation. Post-prandial 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 reported.
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. These patients should be closely monitored during initiation of therapy and at each change of dosage. Marked fluctuations in blood glucose concentration may possibly be reduced by smaller, more frequently administered doses.
Insulin requirements of patients with type I diabetes mellitus therapy may be reduced by administration of Octreotide. In non-diabetics and type II diabetics with partially intact insulin reserves, Octreotide administration can result in post-prandial increases in glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.
Oesophageal varices
Since, following bleeding episodes from oesophageal varices, there is an increased risk for the development of insulin-dependent diabetes or for changes in insulin requirement in patients with pre-existing diabetes, an appropriate monitoring of blood glucose levels is mandatory.
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 in patients who have a history of vitamin B12 deprivation.
See prescribing information to full details

Very common: Headache, Cholelithiasis, Hyperglycaemia, Injection site reactions
Common: Dizziness, Hypothyroidism, thyroid disorder (e.g. decreased TSH, decreased total T4, and decreased free T4), Cholecystitis, biliary sludge, hyperbilirubinaemia, Hypoglycaemia, impaired glucose tolerance, anorexia, Asthenia, Elevated transaminase levels, Pruritus, rash, alopecia, Dyspnoea, Bradycardia
See prescribing information to full details

* Dose adjustment of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance may be necessary.
* Dose adjustments of insulin and antidiabetic medicinal products may be required
* 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 analogues might decrease the metabolic clearance of compounds known to be metabolised 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. quinidine, terfenadine).
Concomitant use with radioactive somatostatin analogues
Somatostatin and its analogues such as octreotide competitively bind to somatostatin receptors and may interfere with the efficacy of radioactive somatostatin analogues.
The administration of Octreotide should be avoided for 24 hours prior to the administration of lutetium (177Lu) oxodotreotide, a radiopharmaceutical binding to somatostatin receptors.

Pregnancy: There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women, and in approximately one third of the cases the pregnancy outcomes are unknown. The majority of reports were received after post-marketing use of octreotide and more than 50% of exposed pregnancies were reported in patients with acromegaly. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 micrograms/day of Octreotide s.c. or 10-40 mg/month of Octreotide LAR. Congenital anomalies were reported in about 4% of pregnancy cases for which the outcome is known. No causal relationship to octreotide is suspected for these cases. As a precautionary measure, it is preferable to avoid the use of Octreotide during pregnancy
Lactation: It is unknown whether octreotide is excreted in human breast milk. Patients should not breast-feed during Octreotide treatment.

A limited number of accidental overdoses of Octreostat in adults and children have been reported. In adults, the doses ranged from 2,400-6,000 micrograms/day administered by continuous infusion (100-250 micrograms/hour) or subcutaneously (1,500 micrograms three times a day). The adverse events reported were arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatic steatosis, diarrhoea, weakness, lethargy, weight loss, hepatomegaly, and lactic acidosis. Atrioventricular blocks (including complete atrioventricular block) were reported in patients receiving 100 micrograms/hour of continuous infusion and/or bolus octreotide intravenously (50 micrograms bolus followed by 50 micrograms/hour continuous infusion).
In children, the doses ranged from 50-3,000 micrograms/day administered by continuous infusion (2.1-500 micrograms/hour) or subcutaneously (50-100 micrograms). The only adverse event reported was mild hyperglycaemia.
No unexpected adverse events have been reported in cancer patients receiving Octreostat at doses of 3,000-30,000 micrograms/day in divided doses subcutaneously.
The management of overdosage is symptomatic.

For prolonged storage, the ampoules must be stored at 2 to 8°C.
For day-to-day use, the ampoules may be stored not above 25°C for up to 2 weeks.