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Delayed onset of rosiglitazone-induced pulmonary oedema
European Journal of Internal Medicine 17 (2006) 590 www.elsevier.com/locate/ejim
Letter to the Editor
Delayed onset of rosiglitazone-induced pulmonary oedema Devaka J.S. Fernando ⁎, Uditha Bulugahapitiya, Katherine Prior Sherwood Forest Hospitals NHS Trust and University of Sheffield, United Kingdom Received 19 March 2006; accepted 11 May 2006
Keywords: Rosiglitazone; Metformin; Pulmonary oedema; Left ventricular failure; Type 2 diabetes
A 41-year-old woman with type 2 diabetes for 5 years presented with sudden dyspnoea and orthopnoea. She had no past history of ischaemic heart disease, heart failure or micro- or macrovascular complications. She was on gliclazide 80 mg bd, acarbose 50 mg tds, and a tablet combining rosiglitazone 4 mg and metformin 500 mg. This was started in 2001 as 1 tablet bd and was increased to 1 tablet tds (rosiglitazone 12 mg and metformin 3 g) by her family doctor. She presented 1 week after the dose had been increased. Clinical examination and radiography confirmed pulmonary oedema. Her ECG did not show ischaemic heart disease and cardiac enzymes were normal. Echocardiography showed no systolic or diastolic dysfunction. The patient was given a high dose of diuretics after discontinuing the combined formulation. She improved within 24–48 h. Thiazolidinediones are associated with plasma volume expansion, causing both peripheral and pulmonary oedema. A number of vascular mechanisms can cause pulmonary oedema within 48 h of commencing treatment [1]. The effect of rosiglitazone is dose-dependent. High concentrations of rosiglitazone cause a reversible, fourfold increase in pulmonary endothelial permeability, especially at higher doses
and at times of peak plasma drug concentration [2]. This effect on pulmonary endothelial permeability is thought to subside within 48 h [2]. This may cause pulmonary oedema and clinical heart failure in patients with ischaemic heart disease or asymptomatic left ventricular dysfunction, especially when used concomitantly with insulin. Our patient had no evidence of heart failure or ischaemic heart disease prior to admission and she was not on insulin. Her pulmonary oedema was precipitated 1 week after increasing the rosiglitazone dosage. This case highlights the fact that glitazone pulmonary oedema may have a delayed presentation beyond the expected 48 h. It also emphasises the need to use recommended doses and not to exceed maximum doses. References [1] Diamant M, Heine RJ. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs 2003;63:1373–405. [2] Idris I, Gray S, Donnelly R. Rosiglitazone and pulmonary oedema: an acute dose-dependent effect on human endothelial cell permeability. Diabetologia 2003;46(2):288–90.
⁎ Corresponding author. E-mail addresses: [email protected], [email protected] (D.J.S. Fernando). 0953-6205/$ - see front matter © 2006 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2006.05.004
Letter to the Editor
Delayed onset of rosiglitazone-induced pulmonary oedema Devaka J.S. Fernando ⁎, Uditha Bulugahapitiya, Katherine Prior Sherwood Forest Hospitals NHS Trust and University of Sheffield, United Kingdom Received 19 March 2006; accepted 11 May 2006
Keywords: Rosiglitazone; Metformin; Pulmonary oedema; Left ventricular failure; Type 2 diabetes
A 41-year-old woman with type 2 diabetes for 5 years presented with sudden dyspnoea and orthopnoea. She had no past history of ischaemic heart disease, heart failure or micro- or macrovascular complications. She was on gliclazide 80 mg bd, acarbose 50 mg tds, and a tablet combining rosiglitazone 4 mg and metformin 500 mg. This was started in 2001 as 1 tablet bd and was increased to 1 tablet tds (rosiglitazone 12 mg and metformin 3 g) by her family doctor. She presented 1 week after the dose had been increased. Clinical examination and radiography confirmed pulmonary oedema. Her ECG did not show ischaemic heart disease and cardiac enzymes were normal. Echocardiography showed no systolic or diastolic dysfunction. The patient was given a high dose of diuretics after discontinuing the combined formulation. She improved within 24–48 h. Thiazolidinediones are associated with plasma volume expansion, causing both peripheral and pulmonary oedema. A number of vascular mechanisms can cause pulmonary oedema within 48 h of commencing treatment [1]. The effect of rosiglitazone is dose-dependent. High concentrations of rosiglitazone cause a reversible, fourfold increase in pulmonary endothelial permeability, especially at higher doses
and at times of peak plasma drug concentration [2]. This effect on pulmonary endothelial permeability is thought to subside within 48 h [2]. This may cause pulmonary oedema and clinical heart failure in patients with ischaemic heart disease or asymptomatic left ventricular dysfunction, especially when used concomitantly with insulin. Our patient had no evidence of heart failure or ischaemic heart disease prior to admission and she was not on insulin. Her pulmonary oedema was precipitated 1 week after increasing the rosiglitazone dosage. This case highlights the fact that glitazone pulmonary oedema may have a delayed presentation beyond the expected 48 h. It also emphasises the need to use recommended doses and not to exceed maximum doses. References [1] Diamant M, Heine RJ. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs 2003;63:1373–405. [2] Idris I, Gray S, Donnelly R. Rosiglitazone and pulmonary oedema: an acute dose-dependent effect on human endothelial cell permeability. Diabetologia 2003;46(2):288–90.
⁎ Corresponding author. E-mail addresses: [email protected], [email protected] (D.J.S. Fernando). 0953-6205/$ - see front matter © 2006 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2006.05.004