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EDITOR
The case, fully documented by Faul et al (1) about loss of diabetic
control in a patient who began a treatment with inhaled fluticasone shows
an example of the infrequently suspected systemic effects of inhaled
corticosteroids. But was the case a genuine adverse reaction or simply
overdose?
The safe dose of inhaled corticosteroids in adults is now considered to be
below 1.000 µg/day (2); greater doses have only slightly more
antiasthmatic activity with an inverted risk-benefit ratio. Fluticasone
propionate has been shown to have systemic effects 3.5 to 5-fold stronger
than budesonide (3) and greater accumulation in the body and more
frequently produces adrenal suppression (4,5), especially when used above
500 µg/day.
In the case by Faul et al, the patient started treatment with inhaled
fluticasone 2000 µg/day, that would be equivalent to about 7000 µg/day of
budesonide, with consequent loss of diabetic control. Glycosuria and
glycated haemoglobin returned to the previous level when the dose of
fluticasone was lowered towards 500 µg/day (equivalent to about 1.750
µg/day of budesonide). When dose was increased to 1.000 µg/day (about
3.500 µg/day of budesonide) diabetes control worsened again.
Nevertheless the patient information leaflets of different brands of
inhaled fluticasone recommend, at least in Spain and in Great Britain, a
dose between 200 and 1000 µg/day, with a maximal dose of 2000 µg/day.
Taking account of the greater potency of inhaled fluticasone these values
should be modified to indicate that the safe dose should not be greater
than 500 µg/day and that with larger amounts of fluticasone systemic
effects may appear. In addition, this recommendation would perhaps
contribute to reduce the false feeling of safety usually associated with
inhaled drugs.
E Sempere Verdú, Family practitioner
Health Centre of Paterna, 46980 Paterna, Valencia, Spain
J M Soler Torró, Family practitioner
Health Centre of Tavernes de la Valldigna, 46760 Tavernes de la Valldigna,
Valencia, Spain
1 Faul JL, Tormey W, Tormey V, Burke C. High dose inhaled
corticosteroids and dose dependent loss of diabetic control. BMJ 1998;
317: 1491.
2 Lipworth BJ. Airway and Systemic Effects of Inhaled Corticosteoids
in Asthma: Dose-Response Relationship. Pulmonary Pharmacology 1996; 9: 19-
27.
3 Boorsma M, Anderson N, Larsson P, Ullman A. Assesment of the
relative systemic potency of inhaled fluticasone and budesonide. Eur
Respir J 1996;9: 1427-32.
4 Clark DJ, Lipworth BJ. Adrenal supression with chronic dosing of
fluticasone propionate compared with budesonide in adults asthmatic
patients. Thorax 1997; 52: 55-8.
5 Lonnebo A, Grahnen A, Jansson B, Brundin RM, Ling-Andersson A,
Eckernas SA. An assessment of the systemic effects of single and repeated
doses of inhaled fluticasone propionate and inhaled budesonide in healthy
volunteers. Eur J Clin Pharmacol 1996; 49(6): 459-63.
Genuine adverse drug reaction to fluticasone or merely overdose?
EDITOR
The case, fully documented by Faul et al (1) about loss of diabetic
control in a patient who began a treatment with inhaled fluticasone shows
an example of the infrequently suspected systemic effects of inhaled
corticosteroids. But was the case a genuine adverse reaction or simply
overdose?
The safe dose of inhaled corticosteroids in adults is now considered to be
below 1.000 µg/day (2); greater doses have only slightly more
antiasthmatic activity with an inverted risk-benefit ratio. Fluticasone
propionate has been shown to have systemic effects 3.5 to 5-fold stronger
than budesonide (3) and greater accumulation in the body and more
frequently produces adrenal suppression (4,5), especially when used above
500 µg/day.
In the case by Faul et al, the patient started treatment with inhaled
fluticasone 2000 µg/day, that would be equivalent to about 7000 µg/day of
budesonide, with consequent loss of diabetic control. Glycosuria and
glycated haemoglobin returned to the previous level when the dose of
fluticasone was lowered towards 500 µg/day (equivalent to about 1.750
µg/day of budesonide). When dose was increased to 1.000 µg/day (about
3.500 µg/day of budesonide) diabetes control worsened again.
Nevertheless the patient information leaflets of different brands of
inhaled fluticasone recommend, at least in Spain and in Great Britain, a
dose between 200 and 1000 µg/day, with a maximal dose of 2000 µg/day.
Taking account of the greater potency of inhaled fluticasone these values
should be modified to indicate that the safe dose should not be greater
than 500 µg/day and that with larger amounts of fluticasone systemic
effects may appear. In addition, this recommendation would perhaps
contribute to reduce the false feeling of safety usually associated with
inhaled drugs.
E Sempere Verdú, Family practitioner
Health Centre of Paterna, 46980 Paterna, Valencia, Spain
J M Soler Torró, Family practitioner
Health Centre of Tavernes de la Valldigna, 46760 Tavernes de la Valldigna,
Valencia, Spain
1 Faul JL, Tormey W, Tormey V, Burke C. High dose inhaled
corticosteroids and dose dependent loss of diabetic control. BMJ 1998;
317: 1491.
2 Lipworth BJ. Airway and Systemic Effects of Inhaled Corticosteoids
in Asthma: Dose-Response Relationship. Pulmonary Pharmacology 1996; 9: 19-
27.
3 Boorsma M, Anderson N, Larsson P, Ullman A. Assesment of the
relative systemic potency of inhaled fluticasone and budesonide. Eur
Respir J 1996;9: 1427-32.
4 Clark DJ, Lipworth BJ. Adrenal supression with chronic dosing of
fluticasone propionate compared with budesonide in adults asthmatic
patients. Thorax 1997; 52: 55-8.
5 Lonnebo A, Grahnen A, Jansson B, Brundin RM, Ling-Andersson A,
Eckernas SA. An assessment of the systemic effects of single and repeated
doses of inhaled fluticasone propionate and inhaled budesonide in healthy
volunteers. Eur J Clin Pharmacol 1996; 49(6): 459-63.
Competing interests: No competing interests