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Rhinorrhea, cough and fatigue in patients taking sitagliptin.

Baraniuk JN, Jamieson MJ - Allergy Asthma Clin Immunol (2010)

Bottom Line: Similar changes were found in 4 out of 5 persons who had confirmatory readministration.Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome.Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Family Medicine, Quillen College of Medicine, East Tennessee State University, McMinnville, TN, USA. drmjamieson@gmail.com.

ABSTRACT
Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin. We report fifteen sitagliptin intolerant patients who developed anterior and posterior rhinorrhea, cough, dyspnea, and fatigue. Symptoms typically developed within 1 to 8 weeks of starting, and resolved within 1 week of stopping the drug. Peak expiratory flow rates increased 34% in 8 patients who stopped sitagliptin. Similar changes were found in 4 out of 5 persons who had confirmatory readministration. Chart review identified 17 patients who tolerated sitagliptin and had no symptomatic changes. The sitagliptin intolerant group had higher rates of clinically diagnosed allergic rhinitis (15/15 vs. 6/18; p = 0.00005), Fisher's Exact test) and angiotensin converting enzyme inhibitor - induced cough (6/13 vs. 1/18; p = 0.012). Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome. Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.

No MeSH data available.


Related in: MedlinePlus

Sitagliptin adverse events. The presence of allergic rhinitis (AR) and its treatment (AR Rx), ACE inhibitor intolerance (ACE intol.), duration of sitagliptin treatment before symptoms began, the nature of the symptoms, and effects of discontinuation and subsequent challenge are shown. PEFR values are shown as % change after stopping sitagliptin, or normalized % of predicted (% pred) for tolerant subjects. Five subjects had restrictive patterns on spirometry that may have been related to obesity. Their PEFRs were not reported. Effective use of intranasal and inhaled corticosteroids (INS+ICS) prevented the return of symptoms for Case 5. Cases 16 and 18 used chronic methotrexate for rheumatoid arthritis (*). Case 23 developed a rash with sitagliptin which recurred on rechallenge. Case 9 now requires hemodialysis for hypertensive renal failure. Case 25 developed non Hodgkins lymphoma. Case 7 died from a pulmonary embolism. Case 24 had a sudden unexpected death. (nil, no complaints; n.d., not determined).
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Figure 2: Sitagliptin adverse events. The presence of allergic rhinitis (AR) and its treatment (AR Rx), ACE inhibitor intolerance (ACE intol.), duration of sitagliptin treatment before symptoms began, the nature of the symptoms, and effects of discontinuation and subsequent challenge are shown. PEFR values are shown as % change after stopping sitagliptin, or normalized % of predicted (% pred) for tolerant subjects. Five subjects had restrictive patterns on spirometry that may have been related to obesity. Their PEFRs were not reported. Effective use of intranasal and inhaled corticosteroids (INS+ICS) prevented the return of symptoms for Case 5. Cases 16 and 18 used chronic methotrexate for rheumatoid arthritis (*). Case 23 developed a rash with sitagliptin which recurred on rechallenge. Case 9 now requires hemodialysis for hypertensive renal failure. Case 25 developed non Hodgkins lymphoma. Case 7 died from a pulmonary embolism. Case 24 had a sudden unexpected death. (nil, no complaints; n.d., not determined).

Mentions: All sitagliptin intolerant subjects had seasonal or perennial allergic rhinitis treated with intermittent antihistamines and nasal steroid sprays (Figure 2). Those with mild intermittent asthma generally had been prescribed montelukast, an inhaled glucocorticoid or inhaled albuterol which were used on an ad hoc basis. The median time for onset of sitagliptin - related symptoms was 3 weeks (range 1 to 8 weeks) except for Cases 10 and 15. Case 10 began taking sitagliptin during ragweed season while taking montelukast and had no adverse symptoms. However, during the next ragweed season she developed intolerable rhinitis symptoms despite the montelukast. Symptoms resolved within a week of stopping sitagliptin even though the ragweed season continued unabated. Case 15 began having symptoms during the local grass season. Symptoms persisted for months into the winter and resolved within a week of stopping sitagliptin.


Rhinorrhea, cough and fatigue in patients taking sitagliptin.

Baraniuk JN, Jamieson MJ - Allergy Asthma Clin Immunol (2010)

Sitagliptin adverse events. The presence of allergic rhinitis (AR) and its treatment (AR Rx), ACE inhibitor intolerance (ACE intol.), duration of sitagliptin treatment before symptoms began, the nature of the symptoms, and effects of discontinuation and subsequent challenge are shown. PEFR values are shown as % change after stopping sitagliptin, or normalized % of predicted (% pred) for tolerant subjects. Five subjects had restrictive patterns on spirometry that may have been related to obesity. Their PEFRs were not reported. Effective use of intranasal and inhaled corticosteroids (INS+ICS) prevented the return of symptoms for Case 5. Cases 16 and 18 used chronic methotrexate for rheumatoid arthritis (*). Case 23 developed a rash with sitagliptin which recurred on rechallenge. Case 9 now requires hemodialysis for hypertensive renal failure. Case 25 developed non Hodgkins lymphoma. Case 7 died from a pulmonary embolism. Case 24 had a sudden unexpected death. (nil, no complaints; n.d., not determined).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2877018&req=5

Figure 2: Sitagliptin adverse events. The presence of allergic rhinitis (AR) and its treatment (AR Rx), ACE inhibitor intolerance (ACE intol.), duration of sitagliptin treatment before symptoms began, the nature of the symptoms, and effects of discontinuation and subsequent challenge are shown. PEFR values are shown as % change after stopping sitagliptin, or normalized % of predicted (% pred) for tolerant subjects. Five subjects had restrictive patterns on spirometry that may have been related to obesity. Their PEFRs were not reported. Effective use of intranasal and inhaled corticosteroids (INS+ICS) prevented the return of symptoms for Case 5. Cases 16 and 18 used chronic methotrexate for rheumatoid arthritis (*). Case 23 developed a rash with sitagliptin which recurred on rechallenge. Case 9 now requires hemodialysis for hypertensive renal failure. Case 25 developed non Hodgkins lymphoma. Case 7 died from a pulmonary embolism. Case 24 had a sudden unexpected death. (nil, no complaints; n.d., not determined).
Mentions: All sitagliptin intolerant subjects had seasonal or perennial allergic rhinitis treated with intermittent antihistamines and nasal steroid sprays (Figure 2). Those with mild intermittent asthma generally had been prescribed montelukast, an inhaled glucocorticoid or inhaled albuterol which were used on an ad hoc basis. The median time for onset of sitagliptin - related symptoms was 3 weeks (range 1 to 8 weeks) except for Cases 10 and 15. Case 10 began taking sitagliptin during ragweed season while taking montelukast and had no adverse symptoms. However, during the next ragweed season she developed intolerable rhinitis symptoms despite the montelukast. Symptoms resolved within a week of stopping sitagliptin even though the ragweed season continued unabated. Case 15 began having symptoms during the local grass season. Symptoms persisted for months into the winter and resolved within a week of stopping sitagliptin.

Bottom Line: Similar changes were found in 4 out of 5 persons who had confirmatory readministration.Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome.Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Family Medicine, Quillen College of Medicine, East Tennessee State University, McMinnville, TN, USA. drmjamieson@gmail.com.

ABSTRACT
Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin. We report fifteen sitagliptin intolerant patients who developed anterior and posterior rhinorrhea, cough, dyspnea, and fatigue. Symptoms typically developed within 1 to 8 weeks of starting, and resolved within 1 week of stopping the drug. Peak expiratory flow rates increased 34% in 8 patients who stopped sitagliptin. Similar changes were found in 4 out of 5 persons who had confirmatory readministration. Chart review identified 17 patients who tolerated sitagliptin and had no symptomatic changes. The sitagliptin intolerant group had higher rates of clinically diagnosed allergic rhinitis (15/15 vs. 6/18; p = 0.00005), Fisher's Exact test) and angiotensin converting enzyme inhibitor - induced cough (6/13 vs. 1/18; p = 0.012). Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome. Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.

No MeSH data available.


Related in: MedlinePlus