Dexamethasone

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• Dexamethasone tablets are formulated as dexamethasone base; the oral solution, soluble tablets and injectable formulations are formulated as dexamethasone sodium phosphate. The British National Formulary (BNF), Summaries of Product Characteristics (SPCs) and product labels now all use dexamethasone base for labelling and dosing advice.
• Follow local guidance when converting doses between oral and subcutaneous (SC) or intravenous (IV) dexamethasone (see below: Dose conversions).

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Drug interactions

• Hepatic metabolism may be increased by potent CYP3A4 inducers such as carbamazepine, phenobarbital, phenytoin, primidone, rifampicin and rifabutin thus reducing the effect of dexamethasone.
• Hepatic metabolism may be reduced by potent CYP3A4 inhibitors such as itraconazole thus increasing the effect of dexamethasone.
• Dexamethasone is itself an inducer of CYP3A4.
• Concurrent administration of dexamethasone with NSAIDs/aspirin will increase the bleeding risk.
• Concurrent administration of dexamethasone with warfarin may cause a significant increase in the INR in about 50% of patients. The INR should be checked weekly for 2 to 3 weeks when a corticosteroid is started or dose altered.
• Corticosteroids antagonise the effect of:
• oral hypoglycaemics and insulin (glucocoticoid effect)
• antihypertensives and diuretics (mineralocorticoid effect). 

Side effects

• Gastrointestinal bleeding especially when used with NSAIDs and aspirin.
• Hyperglycaemia or worsening of existing type 1 or type 2 diabetes mellitus.
• Masked symptoms of septicaemia.
• Increased susceptibility to infection, particularly oral thrush.
• Mental disturbance – insomnia, agitation, euphoria, paranoia, delirium.
• Proximal muscle wasting and weakness.
• Cushingoid appearance.
• Thinning of the skin.
• Acne.
• Bruising.
• Hirsutism.
• Hunger.
• Increased abdominal fat and reduced subcutaneous fat in limbs.
• Avascular bone necrosis.
• Osteoporosis.

The initial dose of dexamethasone varies according to use. Please refer to the relevant section(s) of the Scottish Palliative Care Guidelines for detailed dosing advice.

The following table is for guidance and the doses prescribed may vary dependent on individual patient assessment.

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Given the many and significant undesirable effects of corticosteroids and the potentially deleterious effect of rapid withdrawal, corticosteroids should be prescribed cautiously and the expected benefits and risks should be discussed with the patient:

• for defined symptoms potentially responsive to corticosteroid therapy
• always bearing in mind potential risk vs. benefit
• at a low to moderate dose, titrated to clinical effect
• for a time-limited trial
• discontinue if no clinical/symptomatic benefit seen or weaned to the lowest effective dose.

Subcutaneous injection

Dexamethasone has a long duration of action, it can be given as a once or twice daily SC injection.

To reduce CSCI site reactions, dexamethasone at a dose of 1mg or less is sometimes added to other drugs, only when compatibility data permits. Seek specialist advice.

Equivalent anti-inflammatory doses of corticosteroids

Approximate equivalent anti-inflammatory doses and duration of action of corticosteroids (note: takes no account of mineralocorticoid effects).

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Converting between oral and SC dexamethasone

Dexamethasone injection 4mg/ml injection is no longer available in the UK and has been replaced by products containing dexamethasone base 3.3mg/ml.

Studies have suggested that dexamethasone has an oral bioavailability in the region of 80%. For pragmatic purposes, 4mg of oral dexamethasone can be considered approximately equivalent to 3.3mg of SC dexamethasone. This conversion results in injection volumes which can be measured accurately using the 3.3mg/ml formulation

Some centres, however, continue to use a 1:1 conversion between dexamethasone oral and subcutaneous doses.

Converting between oral and SC dexamethasone (3.3mg/ml) assuming 4mg of oral dexamethasone is approximately equivalent to 3.3mg of SC dexamethasone

Converting between oral and SC dexamethasone (3.3mg/ml) using a 1:1 conversion between oral and SC doses

*will need to be given via 2 sites as the maximum recommended volume for a single SC bolus injection is 2ml.

≈ approximate

For consistency and to avoid confusion between colleagues and departments, clinicians should observe local guidelines for converting between oral and SC doses and use the locally available injection formulation.

• Clear documentation should highlight all elements of the treatment plan when prescribing corticosteroids. This should include the indication, expected outcomes, predicted timescale for response, prior corticosteroid use and a planned date for review of both response to treatment and adverse effects.
• Documented plans should be readily available to the multidisciplinary team and shared appropriately when patients transfer between care environments.
• Dexamethasone has a long duration of action and can be prescribed as a single morning dose. At higher doses, the tablet burden may be reduced by giving two divided doses. Do not give later than 2pm to minimise sleep disturbance. In an emergency situation, the dose can be given at any time.
• Higher doses given by SC injection may need to be divided with the recommended maximum volume of 2ml for a single SC bolus injection.
• Dexamethasone may be stopped abruptly in those whose symptoms are unlikely to relapse if it has been taken for less than 3 weeks at a maximum dose of 6mg (unless the patient has had repeated courses or are within 1 year of stopping long term treatment).
• Following high dose or prolonged treatment, the dose should be reduced gradually, under supervision, and be guided by whether the disease is likely to relapse as steroids are reduced. The dose can be reduced fairly rapidly, for example by 50% every 3 to 5 days to 2mg daily, then more slowly as the physiological dose is reached, for example reduce by 0.5mg every 5 to 7 days.
• A more gradual dose reduction may be required in some patients. Monitor for symptom recurrence and consider maintaining at the lowest dose which controls symptoms.
• When a patient is no longer able to take oral medications, the balance of benefit and burden of SC injections versus the potential for withdrawal reaction should be taken into consideration. 
• In dying patients it is usually appropriate to discontinue corticosteroids. However, all cases should be assessed individually and it may be beneficial to continue to achieve symptom control. 
• Consider prophylactic gastro protection in patients taking aspirin or NSAIDs or if previous gastrointestinal bleed.
• Consider osteoporosis prophylaxis for patients expected to take dexamethasone for more than 3 months.
• Consider oral hygiene. Patients taking corticosteroids are more susceptible to oral thrush.
• For patients on corticosteroids (or recently discontinued), consider additional doses for physiological stresses, for example infection.

Corticosteroid induced hyperglycaemia

• An individualised plan on the frequency of monitoring for hyperglycaemia should be agreed and shared.
• Once daily dexamethasone can cause a characteristic pattern of a late afternoon/early evening rise in glucose levels. Monitoring for hyperglycaemia should therefore be carried out at this time.
• If capillary blood glucose > 8mmol/L - refer to the following guidance: Diabetes UK (2021) End of Life Guidance for Diabetes Care 4th Edition.
• Where treatment for hyperglycaemia is introduced or adjusted aim for blood glucose 6 to 15mmol/L or < 1+ glycosuria before the evening meal.
• If steroids are taken twice daily, an alternative approach to monitoring and subsequent treatment will be required. Seek specialist advice.

Patient and carer advice points

• Patients expected to be taking corticosteroids for more than 3 weeks should be given a Steroid Treatment Card and the leaflet contained in the manufacturer’s packaging.

• Doses should not be taken after 2pm to prevent sleep disturbance.
• Dexamethasone should be taken with or after food.

British National Formulary (BNF). 76th ed. England: Pharmaceutical Press; 2018.

UK Medicines Information (UKMi). In use product safety assessment report for Dexamethasone injection 2014 [cited 2018 Oct 02]; Available from: https://www.ukmi.nhs.uk/filestore/ukmiaps/Dexamethasonereportversion2Oct2014final.pdf

Diabetes UK. End of Life Guidance for Diabetes Care 4th Edition. 2021 [cited 2021 Dec 23]; available from:  https://diabetes-resources-production.s3.eu-west-1.amazonaws.com/resources-s3/public/2021-11/EoL_TREND_FINAL2_0.pdf 

Duggan DE, Yeh KC, Matalia N, Ditzler CA, McMahon FG. Bioavailability of oral dexamethasone. Clin Pharmacol Ther. 1975;18(2):205-9.

Summaries of Product Characteristics (SPCs) www.medicines.org.uk.

Twycross R, Wilcock A, Howard P. Palliative Care Formulary PCF6. 6th ed. England: Pharmaceutical Press; 2017.