UK Clinical Pharmacy Association

Deflazacort

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Issues for surgery

For suppression of inflammatory and allergic/autoimmune disorder (including ulcerative colitis, Crohn’s disease, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, polymyalgia rheumatica, giant cell [temporal] arteritis, polyarteritis nodosa, myasthenia gravis etc.) – increased risk of disease relapse if omitted.

For prophylaxis of transplant rejection – increased risk of rejection if omitted.

Increased risk of acute adrenal insufficiency or Addisonian crisis (e.g. severe hypotension, tiredness and weakness, confusion, psychosis, tachycardia) if omitted – see Further Information.

For cerebral oedema associated with malignancy – increased risk of worsening cerebral oedema if omitted.

For neuropathic postural hypotension (fludrocortisone) – increased risk of severe hypotension if omitted.

Increased risk of infection (sometimes with atypical presentation) if continued, especially in patients on prolonged courses.

Advice in the perioperative period

Elective and emergency surgery 

Continue.

Patients should receive their usual pre-operative dose of steroids on the day of surgery. Also see under Addison’s Disease / Primary adrenal insufficiency below.

Abrupt withdrawal should be avoided in patients who have received systemic corticosteroids at the equivalent dose of prednisolone ≥ 10mg for longer than 3 weeks (see Further information). Refer to the British National Formulary (BNF) ‘Equivalent anti-inflammatory doses of corticosteroids’.

Inform anaesthetist on the day of surgery of use of systemic corticosteroids at the equivalent dose of prednisolone ≥ 10mg daily (including use within the last 3 months).

Steroid-dependent patients should be given ‘first-on-the-list’ status to minimise the risk of dehydration.

Addison’s disease/Primary adrenal insufficiency

Consult with the patient’s endocrinologist prior to surgery where possible.

Consider the need to increase the dose of corticosteroid or take an additional dose prior to procedure – consult the guidance available from www.addisons.org.uk/surgery.

Perioperative considerations 

See also Further information.

Consideration should be given to administration of intravenous (IV) hydrocortisone perioperatively for corticosteroid replacement. This will be based on the patient’s risk of adrenal suppression (i.e. dose and duration of corticosteroid therapy) and surgical complexity and stress.

Rheumatology patients

For patients receiving steroid therapy for rheumatology indications – steroid exposure should be minimised prior to surgical procedures, and increases in steroid dose to prevent adrenal insufficiency are not routinely required.

Post-operative advice

Recommence the patient’s usual corticosteroid dose post-operatively, unless an increased dose is clinically indicated (e.g. in Addison’s disease / primary adrenal insufficiency patients – consult the guidance available from www.addisons.org.uk/surgery). Return to normal dose should occur once the patient is stable (e.g. no signs of post-operative infection).

Monitor fluid status, electrolytes, blood pressure and blood glucose post-operatively.

If patients are unable to resume their usual oral medication post-operatively, supplementation with IV hydrocortisone can be considered.

Care is required when considering systemic corticosteroids in patients with recent intestinal anastomoses as administration may lead to anastomotic failure.

Patients undergoing adrenal/pituitary surgery

Patients undergoing adrenal surgery due to Cushing’s disease, cortisol-producing tumours or pituitary tumours, may need to take post-operative corticosteroid medication. The drug, dose, route, frequency and duration should be discussed with the patient’s endocrinologist.

Interactions with common anaesthetic agents

Neuromuscular blocking drugs (NMBDs)

The use of corticosteroids and depolarising or non-depolarising NMBDs can result in prolonged relaxation and acute myopathy, particularly with prolonged use of high-dose corticosteroids. Conversely, an antagonism of the neuromuscular effect has also been seen, although the clinical relevance of the antagonist effect is probably limited. Bear the potential interaction in mind and be alert for the need to increase the dosage of NMBD if necessary.

Interactions with other common medicines used in the perioperative period

Ondansetron

Corticosteroids may cause hypokalaemia, increasing the risk of torsades de pointes, which might be additive with the effects of ondansetron. This is an effective combination for post-operative nausea and vomiting (PONV) prevention and concomitant use is common without adverse effect. Consider the risk with continued post-operative use of this combination. Monitor serum potassium level.

Non-steroidal anti-inflammatory drugs (NSAIDs)

There may be an increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs. Consider gastroprotection with either a proton-pump inhibitor or histamine-H2 antagonist if concomitant use of NSAID and corticosteroid is required.

Further information

Adrenal suppression, perioperative stress and corticosteroid replacement

During prolonged therapy with systemic corticosteroids, adrenal atrophy develops. Abrupt withdrawal can lead to acute adrenal insufficiency, hypotension, or death. To compensate for a diminished adrenocortical response, patients undergoing a surgical procedure may require temporary increase in corticosteroid dose, or if already stopped, a temporary reintroduction of corticosteroid treatment. Adrenal suppression can last for a year or more after stopping treatment. The suppressive action of corticosteroid on cortisol secretion is least when it is given as a single dose in the morning.

Current evidence on the necessity of administering perioperative stress-dose steroids for patients with suspected secondary adrenal insufficiency is inadequate to either support or refute this practice. If adrenal insufficiency is a clinical concern, corticosteroid replacement appears to carry minimal risk compared with the risk of adrenal crisis.

Hydrocortisone is the drug of choice for stress and rescue dose steroid coverage. In secondary adrenal insufficiency, the problem is a glucocorticoid deficiency (as opposed to a mineralocorticoid insufficiency). Furthermore, the mineralocorticoid activity of a corticosteroid may result in result in a dose-dependent oedema/fluid retention and hypokalaemia. Where doses greater than 100mg IV hydrocortisone are required, consideration may be given to switching to methylprednisolone due to it having a higher glucocorticoid to mineralocorticoid activity ratio.

References

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 29th August 2019]

Interactions of Corticosteroids. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th August 2019]

Freudzon L. Perioperative steroid therapy: where’s the evidence? Curr Opin Anaesthesiol. 2018; 31(1):39 – 42

Liu MM, Reidy AB, Saatee S et al. Perioperative Steroid Management: Approaches Based on Current Evidence. Anesthesiology. 2017; 127:166-172

Summary of Product Characteristics – Betamethasone 500 microgram Soluble Tablets. RPH Pharmaceuticals AB. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text April 2018]

Summary of Product Characteristics – Calcort® (deflazacort) 6mg Tablets. SANOFI. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text August 2019]

Withdrawal of Corticosteroids. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th August 2019]

Summary of Product Characteristics – Dexamethasone 2mg Tablets. Aspen. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text January 2018]

Summary of Product Characteristics – Fludrocortisone Acetate 0.1mg Tablets. Aspen. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text August 2017]

Summary of Product Characteristics – Hydrocortisone 20mg Tablets. Auden McKenzie (Pharma Division) Ltd (a subsidiary of Actavis PLC). Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text August 2019]

Summary of Product Characteristics – Medrone® (methylprednisolone) 4 mg Tablets. Pfizer Limited. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text April 2019]

Summary of Product Characteristics – Prednisolone 5mg Tablets. Wockhardt UK Ltd. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text October 2017]

Surgical Guidelines for Addison’s Disease and other forms of Adrenal Insufficiency. Available at www.addisions.org.uk/surgery [Accessed on 13th September 2019]

Ledingham J et al. Rheumatology Guidelines. The British Society of Rheumatology and British Health Professionals in Rheumatology. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs (2017). www.rheumatology.oxfordjournals.org.

Dumitru R. Perioperative Management of the Surgical Patient on Chronic Steroid Therapy. Pharmacy Times, 2013. Available at www.pharmacytimes.com [Accessed on 29th August 2019]

Summary of Product Characteristics – Kenalog® (triamcinolone) Intra-articular / Intramuscular Injection. Bristol-Myers Squibb Pharmaceuticals limited. Accessed via www.medicines.org.uk 29/08/2019 [date of revision of the text December 2017]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 29th August 2019