Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Irbesartan

Klassificering: C

Preparat: Aprovel, CoAprovel, Ifirmacombi, Ifirmasta, Irbesartan Accord, Irbesartan Actavis, Irbesartan Aurobindo, Irbesartan Bluefish, Irbesartan Hydrochlorothiazide Zentiva, Irbesartan Jubilant, Irbesartan Mylan, Irbesartan Ranbaxy, Irbesartan Sandoz, Irbesartan STADA, Irbesartan Teva, Irbesartan/Hydrochlorothiazide Sandoz, Irbesartan/Hydrochlorothiazide STADA, Irbesartan/Hydrochlorothiazide Teva, Irbesartan/Hydroklortiazid Actavis, Karvea, Karvezide

ATC kod: C09CA04, C09DA04

Substanser: irbesartan, irbesartanhydroklorid (vattenfri), irbesartanhydrokloridseskvihydrat

Sammanfattning

Inga stora könsrelaterade skillnader i irbesartans farmakokinetik har observerats och dosjustering beroende på kön är inte nödvändigt.

Den blodtryckssänkande effekten av irbesartan bedöms överlag vara samma för kvinnor och män och risken för plötslig död var dubbelt så stor hos män vilket medförde att kvinnor överlag hade bättre prognos. Icke-fatal hjärtinfarkt var vanligare hos kvinnor. Trots att kvinnor i en del hjärtsviktsstudier varit mer sjuka vid inklusion, har kvinnor haft lika många sjukhusinläggningar och en bättre överlevnad än män.

Additional information

Clinical and epidemiologic evidence suggests that women with renal disease have a slower progression to end stage compared with men, but the underlying mechanisms remain unknown. A possible contributing phenomenon is physiologic sex-based difference in the function of the renin-angiotensin system (RAS). In a study (15 men, 15 women) with incremental dosages of irbesartan, blood pressure declined in both men and women. Women, but not men, achieved a significant reduction of angiotensin II sensitivity. Men, but not women, continued to show pressor response with increasing doses of irbesartan. Receptor expression at baseline was similar in men and women but by week eight there was a significant decrease in women and unchanged in men. This suggests that men may require larger doses of angiotensin receptor blocker than women and the blood pressure response cannot be used as a surrogate marker for adequate RAS blockade of the renal microvasculature [1].

Polymorphism in the kininogen 1 gene has shown a sex-specific association with plasma irbesartan concentrations in Chinese patients (488 men, 612 women) with essential hypertension. Male, but not female, GG allele carriers had significantly lower irbesartan concentrations relative to TT genotype [2]. 

Pharmacokinetics and dosing

No sex-related differences in pharmacokinetics are observed in healthy elderly (age 65-80 years) or in healthy young (age 18-40 years) patients treated with irbesartan. In studies of hypertensive patients, there is no sex difference in half-life or accumulation, but somewhat higher plasma concentrations of irbesartan are observed in women (11% to 44%) [3]. 

In a small study (12 young men, 12 young women, 12 elderly men, 12 elderly women) with irbesartan, no statistically sex-effects were observed in peak plasma concentration, AUC and terminal elimination half-life of irbesartan. No adjustment in irbesartan is necessary with respect to the patient’s sex [3, 4], which is also concluded in other pharmacokinetic studies [5].  

Effects

There is some conflicting evidence regarding the effects of irbesartan depending on the patient’s sex. Some sources claim that the efficacy of irbesartan is not affected by the patient’s sex [6].In an observational study (8317 men, 7906 women), the effect of irbesartan in reducing cardiovascular risk in hypertensive type 2 diabetic patients was examined. No important differences were noted between men and women in mean 10-year cardiovascular risk as calculated with SCORE [7, 8]. In a subgroup analysis of antihypertensive effi acy of irbesartan/hydrochlorothiazide (HCTZ) in patients with metabolic syndrome and type 2 diabetes, no significant differences between the sexes were found in blood pressure change from baseline to week 18 [9].

Other sources state differences in the effects depending on the patient’s sex. The effects of irbesartan on cardiovascular and renal events in patients with hypertension, diabetes type 2 and renal disease, seemed lower in women [6]. Nonfatal myocardial infarction was increased in women while it decreased in men when compared to placebo. No proper explanation for these findings has been identified [6].In heart failure with preserved ejection fraction there are significant differences between men and women treated with irbesartan. Despite worse symptoms, more congestion, and lower quality of life, women had similar rates of hospitalization and better survival than men. Their risk of sudden death was half that of men [10] and therefore women had better overall prognosis [11].Blood pressure control rates with irbesartan/HCTZ treatment were slightly better for women compared to men (58% vs 45%) in a study (252 men, 197 women) where valsartan/HCTZ was compared to irbesartan/HCTZ [12].  

One study (67 men, 35 women) found a sex-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during treatment with irbesartan or atenolol. Men, but not women, with the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype [13]. 

Adverse effects

No studies with a clinically relevant sex analysis regarding non-cardiovascular adverse effects of irbesartan have been found.

Reproductive health issues

Angiotensin II-antagonists should not be used during pregnancy, especially not during the second or third trimester. Treatment during this period has been associated with complications during pregnancy and the neonatal period [14]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler män än kvinnor hämtade ut läkemedel innehållande irbesartan (ATC-kod C09CA04) på recept i Sverige år 2020, totalt 6 555 män och 5 933 kvinnor. Det motsvarar 1,3 respektive 1,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75-84 år hos män och i åldersgruppen 80 år och äldre hos kvinnor. I genomsnitt var läkemedel innehållande irbesartan 1,4 gånger vanligare hos män [15].

Uppdaterat: 2021-03-15

Litteratursökningsdatum: 2021-01-22

Referenser

  1. Miller JA, Cherney DZ, Duncan JA, Lai V, Burns KD, Kennedy CR et al. Gender differences in the renal response to renin-angiotensin system blockade. J Am Soc Nephrol. 2006;17(9):2554-60. PubMed
  2. Hu S, Cheng J, Weinstock J, Fan X, Venners SA, Hsu YH et al. A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension. J Hum Hypertens. 2018;32(11):781-788. PubMed
  3. Food and Drug Administration (FDA). Drug label - Avapro (irbesartan). Drugs@FDA [www]. [updated 2020-12-15, cited 2021-01-22]. länk
  4. Vachharajani NN, Shyu WC, Smith RA, Greene DS. The effects of age and gender on the pharmacokinetics of irbesartan. Br J Clin Pharmacol. 1998;46(6):611-3. PubMed
  5. Marino MR, Vachharajani NN. Pharmacokinetics of irbesartan are not altered in special populations. J Cardiovasc Pharmacol 2002 Jul;40(1):112-22 PubMed
  6. Aprovel (irbesartan). Summary of Product Characteristics. European Medicines Agency [updated 2021-01-14, cited 2021-01-22]
  7. Bramlage P, Pittrow D, Kirch W. The effect of irbesartan in reducing cardiovascular risk in hypertensive type 2 diabetic patients: an observational study in 16,600 patients in primary care. Curr Med Res Opin. 2004;20(10):1625-31. PubMed
  8. Wilhelmsen L, Wedel H, Conroy R, Fitzgerald T. [The Swedish SCORE chart for cardiovascular risk Better possibilities for prevention of cardiovascular diseases]. Lakartidningen. 2004;101(20):1798-801. PubMed
  9. Sowers JR, Neutel JM, Saunders E, Bakris GL, Cushman WC, Ferdinand KC, Ofili EO, Weber MA; INCLUSIVE Investigators. Antihypertensive efficacy of Irbesartan/HCTZ in men and women with the metabolic syndrome and type 2 diabetes. J Clin Hypertens (Greenwich). 2006;8(7):470-80. länk
  10. Dewan P, Rørth R, Raparelli V, Campbell RT, Shen L, Jhund PS, Petrie MC, Anand IS, Carson PE, Desai AS, Granger CB, Køber L, Komajda M, McKelvie RS, O'Meara E, Pfeffer MA, Pitt B, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Sex-Related Differences in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2019;12(12). länk
  11. Lam CS, Carson PE, Anand IS, Rector TS, Kuskowski M, Komajda M, McKelvie RS, McMurray JJ, Zile MR, Massie BM, Kitzman DW. Sex differences in clinical characteristics and outcomes in elderly patients with heart failure and preserved ejection fraction: the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail. 2012;5(5):571-8. länk
  12. Asmar R, Oparil S. Comparison of the antihypertensive efficacy of irbesartan/HCTZ and valsartan/HCTZ combination therapy: impact of age and gender. Clin Exp Hypertens. 2010;32(8):499-503. länk
  13. Hallberg P, Karlsson J, Lind L, Michaëlsson K, Kurland L, Kahan T et al. Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004;27(5):287-90. PubMed
  14. Janusmed Drugs and Birth Defects. Stockholm: Region Stockhoilm. 2020 [updated 2020-04-07, cited 2021-01-22.] länk
  15. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Författare: Ishita Huq

Faktagranskat av: Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson