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Losartan

Klassificering: A

Preparat: Cozaar, Cozaar Comp, Cozaar®, Cozaar® Comp, Cozaar® Comp Forte, Fortzaar Comp Forte, Forzaar Comp Forte, Klomentan, Klomentan Comp, Losamyl Comp, Losarstad, Losarstad Comp, Losartan Actavis, Losartan Aurobindo, Losartan Bluefish, Losartan Jubilant, Losartan Krka, Losartan Medical Valley, Losartan Mylan, Losartan Orifarm, Losartan Potassium, Losartan Ranbaxy, Losartan Sandoz, Losartan Teva, Losartan/Hydrochlorothiazide Aurobindo, Losartan/Hydrochlorothiazide Bluefish, Losartan/Hydrochlorothiazide Krka, Losartan/Hydrochlorothiazide Medical Valley, Losartan/Hydrochlorothiazide Sandoz, Losartan/Hydrochlorothiazide Teva, Losartan/Hydroklortiazid Actavis, Losartan/hydroklortiazid Jubilant, Losartan/Hydroklortiazid Orifarm, Losatrix, Losatrix comp, Losatrix Comp, Losazid Comp, Losazid Comp Forte, Lostankal, Marozid, Tanlozid

ATC kod: C09CA01, C09DA01

Substanser: losartan, losartankalium

Sammanfattning

Kliniska studier har visat att den blodtryckssänkande effekten av losartan är likvärdig hos män och kvinnor. Hos patienter med högt blodtryck och vänstersidig hjärtkammarförtjockning noterades minskad risk av det sammansatta effektmåttet kardiovaskulär mortalitet, stroke och hjärtinfarkt enbart hos kvinnor.

Biverkningsprofilen av losartan är likartad mellan könen.

Additional information

Pharmacokinetics and dosing

In a pharmacokinetic study, single oral and intravenous doses of losartan produced plasma concentrations of losartan that were two-fold higher in hypertensive women than in hypertensive men, due to reduced systemic clearance in women. However, plasma concentrations of the active metabolite of losartan, E 3174 (ten times more effective than the parent compound), were similar in men and women [1-4].

Even though some pharmacokinetic sex differences of losartan have been described, the clinical relevance of these has not been shown and therefore no dosage adjustment based on patient’s sex has been considered necessary [3].

Effects

A review evaluating clinical experience with losartan from worldwide, double-blind, controlled studies, confirm that the antihypertensive effect of losartan is similar in women and men [1, 3-6].

The large randomized, triple-blind LIFE study (4230 men, 4963 women), conducted by the pharmaceutical company, compared losartan with atenolol in patients, aged 55-80 years, with hypertension and left ventricular hypertrophy [7, 8]. Blood pressure lowering effect of losartan (50 mg daily) was similar in men and women. Only women had a significant reduction in the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction), regardless of treatment with losartan or atenolol. When analyzing the endpoints separately, women on losartan had significant reduction in stroke and total mortality [7-9].

A prospective, randomized trial (4230 men, 4963 women) reported that women had less regression of electrocardiographic (ECG) left ventricular hypertrophy than men during losartan therapy. Regression of ECG left ventricular hypertrophy is associated with improved prognosis. These findings suggest that women may derive less prognostic benefit [10]. In the original LIFE-study [7], a change of the definition of LVH on ECG in women during the study was therefore necessary.

The randomized, double-blind, placebo-controlled RENAAL trial (956 men, 557 women) evaluated losartan 50-100 mg once daily in addition to conventional hypertensive treatment in patients with type 2 diabetes and advanced renal disease. The primary endpoint (a composite of doubling of serum creatinine, end-stage renal disease, or death) was similarly reduced in men and women (HR 0.90 vs. 0.80) [9, 11].

Adverse effects

Reviews and meta-analysis consisting of several double-blind trials, have reported that the overall incidence of adverse clinical events in losartan-treated patients were similar in men and women [5, 6]. In the LIFE study, women had more adverse events than men, regardless of treatment with losartan or atenolol. However, serious adverse events (i.e. events causing hospitalization, prolongation of hospitalization, or death) did not differ between men and women (36.3% vs. 38.3%) [8].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter innehållande losartan (ATC-kod C09CA01) på recept i Sverige år 2019, totalt 173 276 kvinnor och 159 550 män. Det motsvarar 34 respektive 31 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75 år och äldre hos båda könen. I åldersgruppen yngre än 70 år var tabletter innehållande losartan i genomsnitt 1,3 gånger vanligare hos män medan i åldersgruppen 70 år och äldre var det i genomsnitt 1,1 gånger vanligare hos kvinnor [12].

Nästan lika många män och kvinnor hämtade ut tabletter innehållande kombination av losartan och diuretika (ATC-kod C09DA01) på recept i Sverige år 2019, totalt 66 062 män och 63 748 kvinnor. Det motsvarar 13 respektive 13 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70–84 år hos båda könen. I åldersgruppen yngre än 75 år var tabletter innehållande kombination av losartan och diuretika i genomsnitt 1,6 gånger vanligare hos män och i åldersgruppen 75 år och äldre i genomsnitt 1,1 gånger vanligare hos kvinnor [12].

Uppdaterat: 2020-09-04

Litteratursökningsdatum: 2019-10-10

Referenser

  1. McIntyre M, Caffe SE, Michalak RA, Reid JL. Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension. Pharmacol Ther. 1997;74:181-94. PubMed
  2. Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44:797-814. PubMed
  3. Cozaar (losartan potassium). DailyMed [www]. US National Library of Medicine. [updated 2018-10-12, cited 2019-10-10]. länk
  4. Cozaar (losartan). Summary of Product Characetristics. Swedish Medical Products Agency [updated 2019-02-01, cited 2019-10-10]. länk
  5. Mallion JM, Goldberg AI. Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension. Blood Press Suppl. 1996;2:82-6. PubMed
  6. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors. J Hypertens Suppl. 1995;13:S77-80. PubMed
  7. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995-1003. PubMed
  8. Os I, Franco V, Kjeldsen SE, Manhem K, Devereux RB, Gerdts E et al. Effects of losartan in women with hypertension and left ventricular hypertrophy: results from the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension. 2008;51:1103-8. PubMed
  9. Cozaar (losartan) Statistical Review. Drugs@FDA [www]. US Food and Drug Administration. [updated 2003-02-04, cited 2019-10-10]. länk
  10. Okin PM, Gerdts E, Kjeldsen SE, Julius S, Edelman JM, Dahlöf B et al. Gender differences in regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy. Hypertension. 2008;52:100-6. PubMed
  11. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med . 2001;345(12):861-9. PubMed
  12. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler, Carl-Olav Stiller, Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson