Download Shortage memo phenotolamine and phenoxybenzamine

Name of Trust / logo
Memo – shortage of supply
To:
From:
Date: 16th July 2014
Re: Phentolamine mesilate injection
Description of products affected
Phentolamine mesilate injection is licensed for the management of hypertensive
episodes that may occur in patients with phaeochromocytoma, for example during
pre-operative preparation and surgical manipulation. It is also licensed for the
diagnosis of phaeochromocytoma by Rogitine blocking test if other more specific tests
are not available.1
Background
A phaeochromocytoma is a catecholamine producing tumour arising mainly from the
chromaffin cells of the adrenal medulla. Although it may be malignant, symptoms
usually result from the excess secretion of catecholamines 2 and include hypertension,
headaches, palpitations, and excessive sweating. If the effects of the release of
catecholamines are not controlled, a life-threatening crisis ultimately occurs and may
range from a shock-like syndrome with multiple organ failure to hypertensive crisis,
depending on the predominance of the catecholamine secreted.3 Long-term
management involves surgery but this must be preceded by pharmacological therapy
to block the pressor and other effects of the excess catecholamines. This is important
for symptom control, but is also necessary in asymptomatic patients undergoing
surgery since massive release of catecholamines and resulting acute increases in
blood pressure may occur during induction of anaesthesia or when the tumour is
handled. Choice of therapy is not entirely clear since there is a lack of evidence from
controlled studies.3
Alpha-blockers are used in the short-term management of hypertensive episodes in
phaeochromocytoma, one of which is phentolamine, a short-acting intravenous agent
used mainly during surgery.4 Its use for the diagnosis of phaeochromocytoma has
been superseded by measurement of catecholamines in blood and urine.4.
Intravenous phenoxybenzamine, a non-selective, long-acting a-blocker, is also used
in the management of phaeochromocytoma but it has many side effects4 and there
have been ongoing supply problems with this preparation.5
Why we are providing this information
Alliance Pharmaceuticals/Novartis discontinued the UK production of phentolamine
injection in August 2012 therefore use of other parenteral agents for the treatment of
hypertensive episodes in phaeochromocytoma are required.6
Implications for patient care
Since massive release of catecholamines and resulting acute increases in blood
pressure may occur during induction of anaesthesia or when the tumour is handled, it
is necessary to have available an alternative parenteral antihypertensive agent
following the discontinuation of phentolamine injection and ongoing supply problems
with phenoxybenzamine injection.
Alternative agents and management options
Although rarely used, the availability of a parenteral alpha blocker is considered
essential for phaeochromocytomas, as well as other acute hypertensive crises, as
alternative agents such as remifentanyl and GTN are not as effective in this situation
and have a much slower onset of action.
However, there are currently no alternative injectable alpha blockers available within
the UK and importers are experiencing difficulties sourcing unlicensed formulations of
either phentolamine or phenoxybenzamine injections.7
It is important to note that there are potential patient safety issues associated with
use of imported products in terms of varying strengths of preparations available and
Trusts are advised to check carefully which version of the product they receive and to
highlight any differences to departments and practitioners so that patients are not
exposed to incorrect doses of the drug.
A possible oral alternative is phenoxybenzamine 10mg capsules (Dibenyline™) which
is licensed for the management of hypertensive episodes associated with
phaeochromocytoma.8 The Society for Endocrinology has published a protocol from
the Royal Hallamshire in Sheffield for its use in the preparation of patients with
phaeochromocytoma and paraganglioma for surgery.5
References
1. Alliance Pharmaceuticals. Rogitine Ampoules 10mg. SPC (date of revision
17/02/2006):
http://www.medicines.org.uk/emc/medicine/128/SPC/Rogitine+Ampoules+10mg/
#INDICATIONS
2. Jones AG, Evans PH, Vaidya B, et al. Phaeochromocytoma. BMJ 2012; 344: e1042
3. Martindale. Phaeochromocytoma (Latest modification: 05-Jan-2011), accessed via
Medicines Complete 30/6/2014
4. BNF 66; September 2013
5. Society for Endocrinology. Protocol using oral phenoxybenzamine to prepare
patients with catecholamine-secreting phaeochromocytoma and paraganglioma for
surgery (October 2010): http://www.endocrinology.org/policy/docs/1010_Protocol_using_oral_phenoxybenzamine.pdf
6. Alliance Pharmaceuticals/Novartis. Personal communication. 30th June 2014
7. Personal communication with importers; 30th June 2014
8. Amdipharm Mercury. Phenoxybenzamine. SPC (date of revision April 2012):
http://www.medicines.org.uk/emc/medicine/25769
Original document prepared by:
Guy’s and St Thomas’ NHS Foundation Trust Medicines Information Centre
Prepared 14 Jul 2014
Document modified by:
Name of individual at other centre using the product with modifications, centre, date
For all correspondence please contact:
Name of person at base hospital where memo is circulated (i.e. NOT the original
author at Guy’s and St Thomas’ NHS Foundation Trust
Disclaimer: The content of some of this memo is based on consensus opinion from clinical
practitioners. Users should bear this in mind in deciding whether to base their policy on this
document. Individual trusts should ensure that procedures for unlicensed medicines are
followed where a foreign import drug is required in the interim.