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home:protocol:olmesartan:safety [07.19.2019] – [Safety of olmesartan (Benicar)] sallieqhome:protocol:olmesartan:safety [09.14.2022] (current) – external edit 127.0.0.1
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 **//Greg Blaney, M.D.//**</blockquote> **//Greg Blaney, M.D.//**</blockquote>
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 +For those with gastric issues, it is recommended that the pill be crushed and mixed with applesauce or similar to reduce impact on gastric lining.
 + 
  
 ===== FDA safety guidelines ===== ===== FDA safety guidelines =====
  
-Although they do so for many other drugs, the [[http://www.fda.gov/|U.S. Food and Drug Administration]] has set no unsafe upper limit for olmesartan. The FDA bases its safety data on "post-marketing experience" - how many dose-related adverse events have been linked to the drug – and for olmesartan, they are negligible. The FDA has consequently set **no unsafe dosage level** for Olmesartan.+Although they do so for many other drugs, the [[https://www.fda.gov/|U.S. Food and Drug Administration]] has set no unsafe upper limit for olmesartan. The FDA bases its safety data on "post-marketing experience" - how many dose-related adverse events have been linked to the drug – and for olmesartan, they are negligible. The FDA has consequently set **no unsafe dosage level** for Olmesartan.
  
-According to the [[http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021286s020lbl.pdf|FDA's full prescribing information for Benicar]]:+According to the [[https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021286s020lbl.pdf|FDA's full prescribing information for Benicar]]:
   * "The overall frequency of adverse reactions was not dose-related."     * "The overall frequency of adverse reactions was not dose-related."  
   * "Dosage must be individualized."   * "Dosage must be individualized."
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 ===== Data supporting the safety of higher than typical dosing frequencies ===== ===== Data supporting the safety of higher than typical dosing frequencies =====
  
-A 2001 study published in the //Journal of of Pharmacology// found olmesartan to be safe and well tolerated at doses of up to 160 mg/day.(({{pubmed>long:11361048}})) +A 2001 study published in the //Journal of of Pharmacology// found olmesartan to be safe and well tolerated at doses of up to 160 mg/day.(({{pmid>long:11361048}})) 
  
 <blockquote>CS-866 [olmesartan] was safe and well tolerated at doses of up to 160 mg/day.... [Olmesartan] has no serious adverse effects. <blockquote>CS-866 [olmesartan] was safe and well tolerated at doses of up to 160 mg/day.... [Olmesartan] has no serious adverse effects.
  
-//**Lee R. Schwocho, PhD** and **Harvey N. Masonson, MD**// (({{pubmed>long:11361048}}))</blockquote>+//**Lee R. Schwocho, PhD** and **Harvey N. Masonson, MD**// (({{pmid>long:11361048}}))</blockquote>
    
  
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 Animal studies in mice, with olmesartan doses up to 480 times the human dose of 40 mg per day (relative to body weight), showed that olmesartan is not carcinogenic. Animal studies in mice, with olmesartan doses up to 480 times the human dose of 40 mg per day (relative to body weight), showed that olmesartan is not carcinogenic.
  
-The [[http://www.benicar.com/pdf/prescribing_information.pdf|label for olmesartan]] states that the drug is well-tolerated. Adverse events were similar to those experienced by the placebo group – a group of patients who were not given the drug at all. Adverse events were generally “mild, transient and not related to dose.” The frequency of adverse events also had no relationship to the dose of olmesartan.+The [[https://www.benicar.com/pdf/prescribing_information.pdf|label for olmesartan]] states that the drug is well-tolerated. Adverse events were similar to those experienced by the placebo group – a group of patients who were not given the drug at all. Adverse events were generally “mild, transient and not related to dose.” The frequency of adverse events also had no relationship to the dose of olmesartan.
  
 From a MPStudySite topic  From a MPStudySite topic 
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 <blockquote>In the dose-finding study, 792 patients were randomized to olmesartan (2.5-80 mg) or placebo once daily.... The results of the clinical studies in >3000 patients receiving olmesartan showed that the frequency and profile of adverse events with olmesartan were generally similar to those with placebo; the frequency of adverse events was not dose related. Olmesartan, with or without hydrochlorothiazide, was well tolerated over two years of treatment. <blockquote>In the dose-finding study, 792 patients were randomized to olmesartan (2.5-80 mg) or placebo once daily.... The results of the clinical studies in >3000 patients receiving olmesartan showed that the frequency and profile of adverse events with olmesartan were generally similar to those with placebo; the frequency of adverse events was not dose related. Olmesartan, with or without hydrochlorothiazide, was well tolerated over two years of treatment.
  
-//**Hans R. Brunner, MD**// (({{pubmed>long:15291377}}))</blockquote>+//**Hans R. Brunner, MD**// (({{pmid>long:15291377}}))</blockquote>
  
 ==== Results of FDA meeting ==== ==== Results of FDA meeting ====
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 Additional papers on the general safety of olmesartan state: Additional papers on the general safety of olmesartan state:
  
-<blockquote>Frequency of adverse events is not dose related.(({{pubmed>long:15291377}}))+<blockquote>Frequency of adverse events is not dose related.(({{pmid>long:15291377}}))
 </blockquote> </blockquote>
  
-<blockquote>Peak plasma concentrations of olmesartan occur 1-3 hours after administration, after which concentrations decrease with an elimination half-life of 10-15 hours… Frequencies of adverse events during treatment with olmesartan medoxomil and placebo are similar, with no evidence of a dose response. There are no clinically significant effects on laboratory parameters, and the drug-interaction potential of olmesartan medoxomil is low.(({{pubmed>long:11967728}}))</blockquote>+<blockquote>Peak plasma concentrations of olmesartan occur 1-3 hours after administration, after which concentrations decrease with an elimination half-life of 10-15 hours… Frequencies of adverse events during treatment with olmesartan medoxomil and placebo are similar, with no evidence of a dose response. There are no clinically significant effects on laboratory parameters, and the drug-interaction potential of olmesartan medoxomil is low.(({{pmid>long:11967728}}))</blockquote>
  
-<blockquote>High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus an important therapeutic modality with which to achieve further reductions in urinary protein excretion.(({{pubmed>long:16601581}}))</blockquote>+<blockquote>High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus an important therapeutic modality with which to achieve further reductions in urinary protein excretion.(({{pmid>long:16601581}}))</blockquote>
  
-<blockquote>The results of this pilot study suggest that supramaximal doses of ARBs are safe and well tolerated in patients with chronic kidney disease, while reducing both blood pressure and proteinuria.(({{pubmed>long:15192304}}))</blockquote>+<blockquote>The results of this pilot study suggest that supramaximal doses of ARBs are safe and well tolerated in patients with chronic kidney disease, while reducing both blood pressure and proteinuria.(({{pmid>long:15192304}}))</blockquote>
  
  
-<blockquote>Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models.(({{pubmed>long:15592575}}))</blockquote>+<blockquote>Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models.(({{pmid>long:15592575}}))</blockquote>
  
  
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 Other protective effects include: Other protective effects include:
   * [[home:protocol:olmesartan:kidney_disease|reduction and amelioration of kidney disease]]   * [[home:protocol:olmesartan:kidney_disease|reduction and amelioration of kidney disease]]
-  * prevent migraines(({{pubmed>long:12503978}})) +  * prevent migraines(({{pmid>long:12503978}})) 
-  * inhibit liver fibrosis and aid liver healing(({{pubmed>long:12871826}})) +  * inhibit liver fibrosis and aid liver healing(({{pmid>long:12871826}})) 
-  * protect the kidneys in diabetic nephropathy  (({{pubmed>long:20421884}})) +  * protect the kidneys in diabetic nephropathy  (({{pmid>long:20421884}})) 
-  * reduce insulin resistance(({{pubmed>long:15127887}}))+  * reduce insulin resistance(({{pmid>long:15127887}}))
   * //[[home:protocol::olmesartan|complete review of protective effects]]...//   * //[[home:protocol::olmesartan|complete review of protective effects]]...//
  
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 ===== Recent research ===== ===== Recent research =====
  
-olmesartan reduced angiotensin II and aldosterone levels more effectively than azilsartan, resulting in a stable antihypertensive effect. Olmesartan also had an inhibitory effect on cardiac hypertrophy. Accordingly, it may be effective for patients with increased RAAS activity after cardiac surgery or patients with severe cardiac hypertrophy. (({{pubmed>long:4909997}}))+olmesartan reduced angiotensin II and aldosterone levels more effectively than azilsartan, resulting in a stable antihypertensive effect. Olmesartan also had an inhibitory effect on cardiac hypertrophy. Accordingly, it may be effective for patients with increased RAAS activity after cardiac surgery or patients with severe cardiac hypertrophy. (({{pmid>long:4909997}}))
  
-[[http://doi.org/10.5761/atcs.oa.11.01691|angiotensin II and aldosterone are decreased in a change-over from candesartan to olmesartan]]+[[https://doi.org/10.5761/atcs.oa.11.01691|angiotensin II and aldosterone are decreased in a change-over from candesartan to olmesartan]]
  
-With the halt of reimbursement of olmesartan, there was a decrease in the prescription of ARB in France. When olmersartan was replaced by another ARB, a worse blood pressure control was observed in treated hypertensive patients.  (({{pubmed>long:29807620 }}))+With the halt of reimbursement of olmesartan, there was a decrease in the prescription of ARB in France. When olmersartan was replaced by another ARB, a worse blood pressure control was observed in treated hypertensive patients.  (({{pmid>long:29807620 }}))
  
  
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 The incidence of this adverse drug reaction is not entirely clear, although it is thought to be rare.  The incidence of this adverse drug reaction is not entirely clear, although it is thought to be rare. 
-(({{pubmed>long:26997446}}))+(({{pmid>long:26997446}}))
  
  
-Seven cases (2.8%) reported recurrence of symptoms after restarting olmesartan (({{pubmed>long:31217979}}))+Seven cases (2.8%) reported recurrence of symptoms after restarting olmesartan (({{pmid>long:31217979}}))
  
 Although enteropathy is rare, clinicians should remain vigilant of this potential adverse event even years after medication initiation.  Although enteropathy is rare, clinicians should remain vigilant of this potential adverse event even years after medication initiation. 
-(({{pubmed>long:31217979}}))+(({{pmid>long:31217979}}))
  
-results suggest that SMEEDS formulation improves dissolution and oral bioavailability of OM while reducing adverse effects (celiac-like enteropathy or diarrhea ). (({{pubmed>long:30986085}}))+results suggest that SMEEDS formulation improves dissolution and oral bioavailability of OM while reducing adverse effects (celiac-like enteropathy or diarrhea ). (({{pmid>long:30986085}}))
  
 ==== Collagenous enteritis, a genetic problem? ==== ==== Collagenous enteritis, a genetic problem? ====
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 Collagenous enteritis is an uncommon small intestinal injury pattern with unclear pathogenesis.  Collagenous enteritis is an uncommon small intestinal injury pattern with unclear pathogenesis. 
  
-All subjects with biopsy-proven collagenous enteritis diagnosed between 2002 and 2015 were identified from 2 tertiary care medical centers. Human leukocyte antigen (HLA)-DQ genotyping was performed by polymerase chain reaction on archived tissue. Celiac disease serology, past medical history, medications, smoking history, demographics, histology, clinical management, and follow-up were recorded. A total of 32 subjects were included. In contrast to celiac disease, subjects with collagenous enteritis were mostly elderly (median age at diagnosis, 69 y; range, 33 to 84 y). Seventy percent of collagenous enteritis subjects harbored celiac disease susceptibility alleles HLA-DQ2/DQ8; however, only 1 subject had elevated serum levels of celiac disease-associated autoantibodies while on a gluten-containing diet. Furthermore, 56% of subjects were taking nonsteroidal anti-inflammatory drugs, 36% proton-pump inhibitors, 28% statins, and 32% olmesartan at the time of diagnosis. Discontinuation of olmesartan and treatments with steroids and/or gluten-free diet resulted in symptomatic and histologic improvement. (({{pubmed>long:29324472 }}))+All subjects with biopsy-proven collagenous enteritis diagnosed between 2002 and 2015 were identified from 2 tertiary care medical centers. Human leukocyte antigen (HLA)-DQ genotyping was performed by polymerase chain reaction on archived tissue. Celiac disease serology, past medical history, medications, smoking history, demographics, histology, clinical management, and follow-up were recorded. A total of 32 subjects were included. In contrast to celiac disease, subjects with collagenous enteritis were mostly elderly (median age at diagnosis, 69 y; range, 33 to 84 y). Seventy percent of collagenous enteritis subjects harbored celiac disease susceptibility alleles HLA-DQ2/DQ8; however, only 1 subject had elevated serum levels of celiac disease-associated autoantibodies while on a gluten-containing diet. Furthermore, 56% of subjects were taking nonsteroidal anti-inflammatory drugs, 36% proton-pump inhibitors, 28% statins, and 32% olmesartan at the time of diagnosis. Discontinuation of olmesartan and treatments with steroids and/or gluten-free diet resulted in symptomatic and histologic improvement. (({{pmid>long:29324472 }}))
  
-Olmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population.  (({{pubmed>long:29172402}}))+Olmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population.  (({{pmid>long:29172402}}))
  
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
  
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 **FDA Finds Olmesartan Does Not Cause Cardiovascular Events** **FDA Finds Olmesartan Does Not Cause Cardiovascular Events**
  
-http://www.fda.gov/drugs/drugsafety/ucm402323.htm +https://www.fda.gov/drugs/drugsafety/ucm402323.htm 
-http://www.lgmpharma.com/blog/fda-finds-olmesartan-does-not-cause-cardiovascular-events/+https://www.lgmpharma.com/blog/fda-finds-olmesartan-does-not-cause-cardiovascular-events/
  
  
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-[[http://www.theheart.org/article/1157737.do|New meta-analysis reassuring on ARBs and cancer, but questions remain]]+[[https://www.theheart.org/article/1157737.do|New meta-analysis reassuring on ARBs and cancer, but questions remain]]
  
  
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-http://www.fda.gov/Drugs/DrugSafety/ucm251268.htm+https://www.fda.gov/Drugs/DrugSafety/ucm251268.htm
  
  
 ..Trevor.. ..Trevor..
 </blockquote> </blockquote>
-===== References =====+===== References =====</nodisp> 
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