Betamethasone

An increase in the incidence of gastrointestinal bleeding may occur if NSAIDS are taken concomitantly with corticosteroids.

Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Particular care is required when considering the use of systemic corticosteroids in patients with liver failure – blood levels of corticosteroid may be increased, as with other drugs which are metabolised in the liver. Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with renal insufficiency. Frequent patient monitoring is necessary.

The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.

Increased toxicity may result if hypokalaemia occurs in patients on cardiac glycosides.

Steroids may reduce the effects of anticholinesterases in myasthenia gravis, cholecystographic X-ray media and non-steroidal anti-inflammatory agents.

Concurrent use of corticosteroids and fluoroquinolones may result in increased risk of tendon rupture.

The effect of corticosteroids may be reduced for 3-4 days after mifepristone.

Concomitant use of betamethasone with quetiapine may result in the increased metabolism of quetiapine and, depending on the clinical response, a higher dose of quetiapine may need to be considered.

Rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, aminoglutethimide and ephedrine enhance the metabolism of corticosteroids; thus the corticosteroid therapeutic effect may be reduced.

Ritonavir and oral contraceptives may result in increased plasma concentrations of corticosteroids.

The growth promoting effect of somatropin may be inhibited by corticosteroids.

The risk of hypokalaemia is increased with theophylline, ulcer healing drugs such as carbenoxolone and antifungals such as amphotericin B.

Corticosteroids may enhance the metabolism of tretinoin resulting in decreased levels of tretinoin.

Corticosteroids may antagonise the effects of neuromuscular blocking drugs such as vecuronium.

Patients/and or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting treatment. Risks may be higher with high doses/systemic exposure, although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.

Particular care is required when considering the use of systemic corticosteroids in patients with history of, or active, peptic ulceration. Frequent patient monitoring is necessary.

Caution is advised with the use of corticosteroids in patients who have suffered a recent myocardial infarction because of the risk of myocardial rupture.

Particular care is required when considering the use of systemic corticosteroids in patients with glaucoma (or a family history of glaucoma). Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with previous corticosteroid-induced myopathy. Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with diverticulitis. Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with thromboembolic tendencies. Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with hypertension or congestive heart failure. Frequent patient monitoring is necessary.

Caution is advised on the use of corticosteroids in patients with hypothyroidism or myasthenia gravis.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders (especially previous steroid psychosis). Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with history of, or active, tuberculosis. Frequent patient monitoring is necessary.

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Particular care is required when considering the use of systemic corticosteroids in patients with osteoporosis (post-menopausal females are particularly at risk). Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with diabetes mellitus (or a family history of diabetes). Frequent patient monitoring is necessary.

Corticosteroids should not be used for management of head injury or stroke because it is unlikely to be of benefit and may even be harmful.

Particular care is required when considering the use of systemic corticosteroids in patients with epilepsy. Frequent patient monitoring is necessary.

Particular care is required when considering the use of systemic corticosteroids in patients with herpes simplex keratitis. Frequent patient monitoring is necessary.

There are limited data from the use of betamethasone valerate in pregnant women.

Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development.

The relevance of this finding to humans has not been established; however, administration of betamethasone valerate during pregnancy should only be considered if the expected benefit to the mother outweighs the risk to the foetus. The minimum quantity should be used for the minimum duration.

IV administration

The ability of corticosteroids to cross the placenta varies between individual drugs, however, betamethasone readily crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. Myocardial hypertrophy and gastroesophageal reflux have been reported in association with in-utero exposure to betamethasone.

As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid state. Patients with pre-eclampsia or fluid retention require close monitoring.

Betamethasone, systemically administered to a woman during pregnancy may result in a transient suppression of the foetal heart rate parameters and biophysical activities that are widely used for the assessment of foetal well – being. These characteristics can include a reduction in foetal breathing movements, body movements and heart rate.

The safe use of topical corticosteroids during lactation has not been established.

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Administration of betamethasone valerate during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.

If used during lactation betamethasone valerate should not be applied to the breasts to avoid accidental ingestion by the infant.

Intravenous corticosteroids may pass into breast milk, although no data are available for betamethasone. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression.

Fertility

There are no data in humans to evaluate the effect of topical corticosteroids on fertility.

There have been no studies to investigate the effect of betamethasone valerate on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated from the adverse reaction profile of topical betamethasone valerate.