The Therapeutic Goods Administration (TGA) is aware that, in Europe, atrioventricular blocks (including complete atrioventricular block) have been reported in patients receiving high doses of continuous intravenous infusion (100 micrograms/hour) of octreotide and in patients receiving bolus octreotide intravenously (50 micrograms bolus followed by 50 micrograms/hour continuous infusion). In Australia, the approved indications for octreotide do not involve intravenous administration.
Octreotide is an octapeptide that mimics natural somatostatin pharmacologically. It is a more potent inhibitor of growth hormone, glucagon and insulin than somatostatin.
It is marketed in Australia under the trade name Sandostatin and Sandostatin LAR (2.0 mL diluent), as well as various generic brands.
Octreotide is approved in Australia for the following indications:
For symptomatic control and reduction of growth hormone and IGF-1 plasma levels in patients with acromegaly, including those who are inadequately controlled by surgery, radiotherapy or dopamine agonist treatment. Octreotide treatment is also indicated in acromegalic patients unfit or unwilling to undergo surgery, or in the interim period until radiotherapy becomes fully effective.
For the relief of symptoms associated with the following functional tumours of the gastro-entero-pancreatic endocrine system:
carcinoid tumours with features of the carcinoid syndrome
For reduction of the incidence of complications following pancreatic surgery.
Additionally, Sandostatin LAR is also indicated for treatment of patients with progression of well-differentiated, advanced neuroendocrine tumours of the midgut or suspected midgut origin.
The TGA has evaluated the risk of atrioventricular blocks associated with octreotide treatment in the Australian context. In Australia, the route of administration approved for octreotide products is only subcutaneous injection for the registered indications, while Sandostatin LAR may only be administered by deep intragluteal injection.
In Europe, octreotide (but not Sandostatin LAR) is approved for use in bleeding gastro-oesophageal varices with a continuous intravenous infusion as the route of administration. The European Union Summary of Product Characteristics (SmPC) for octreotide has been updated to advise that the maximum dose of 50 micrograms/hour should not be exceeded and that patients receiving high doses of intravenous octreotide should be kept under appropriate cardiac monitoring.
In Australia, some clinical guidelines, discuss the off-label use of octreotide in bleeding oesophageal varices with a dose of 50 micrograms by intravenous injection, followed by 50 micrograms/hour by continuous intravenous infusion for up to 5 days.
With this in mind, the TGA is advising health professionals of the identified risk of atrioventricular blocks in patients receiving off-label high doses of continuous infusion (100 micrograms/hour) of octreotide and in patients receiving bolus octreotide intravenously (50 micrograms bolus followed by 50 micrograms/hour continuous infusion).
The severity of atrioventricular block varies, with complete heart block resulting in cardiac arrest. Treatment may include pacemaker insertion.
The TGA has not seen an increase of adverse events of atrioventricular block associated with octreotide.
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
all suspected medicines interactions
suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
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