Dexamethasone

Class: corticosteroid – glucocorticoid

Indications (NB some may be unlicensed): cerebral oedema (raised intracranial pressure), allergy/anaphylaxis, replacement, shock, collagen diseases, asthma, respiratory insufficiency, leukaemia, lymphoma, rheumatic disease, psoriasis, colitis, enteritis, hypercalcaemia of malignancy, nausea/vomiting, sweating, itch, hiccup, pain, liver capsule pain, tenesmus, to improve appetite & wellbeing in palliative care

Contraindications/cautions: infections, GI bleeding; caution in diabetes & psychotic illness; renal or hepatic impairment

Adverse reactions: common: insomnia (decrease by giving as single dose in the morning); less common: sodium/fluid retention, GI ulceration, delayed wound healing, thinning of skin (on prolonged use), muscle weakness (proximal myopathy), Cushing’s syndrome, weight gain, mania, depression, delirium, hyperglycaemia, osteoporosis Metabolism/clearance: metabolised by CYP3A (major) mainly in the liver – caution with drugs that inhibit or induce CYP3A

Interactions:

• increased clinical effect/toxicity of dexamethasone (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) as the metabolism of dexamethasone decreases & thus plasm concentration increases e.g. aprepitant, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, telapravir, voriconazole
• decreased clinical effect/toxicity of dexamethasone (due to decreased blood concentrations) may occur with some CYP metabolising enzyme inducers (see above) e.g. carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s wort
• decreased clinical effect/toxicity of other drugs metabolised by CYP enzymes (due to induction of their metabolism by dexamethasone) may occur e.g. aprepitant, carbamazepine, clonazepam, diazepam, domperidone, fentanyl, itraconazole, ketoconazole, methadone, midazolam, prednisone, quetiapine, triazolam
• increased risk of GI bleed/ulceration when given with NSAIDs (e.g. diclofenac)
• In patients taking warfarin, INR may increase when on dexamethasone – dose reduction required in 50% of cases. Check INR weekly for 2 to 3 weeks

Syringe driver: see syringe drivers BUT best given as a morning bolus by subcut injection/short infusion

Mechanism of action: decreases inflammatory response via induction of lipocortin

Onset: 8 to 24 hours

Notes:

• anti-inflammatory effect: 3 mg dexamethasone = 20 mg prednisone = 80 mg hydrocortisone
• on discontinuation decrease dose slowly (taper) unless the patient has been taking it for less than 5 days in which case dose tapering is not necessary
• alteration in mood is not usually seen below 6 mg dexamethasone (40 mg prednisone) per day
• monitor blood glucose before commencing and every 1 to 2 weeks during treatment
• corticosteroid-induced insomnia responds to benzodiazepines (e.g. temazepam)
• corticosteroid induced mood disorder is usually depression and rarely mania
• the use of steroids in palliative care is common and sometimes, particularly at high dose, consideration should be given to the appropriateness of their use
• the use of 0.5 to 1 mg dexamethasone in a syringe driver may reduce the risk of local irritation at the subcutaneous site but adverse effects can occur even at low dose