6/10/2023

Janusmed kön och genus

Janusmed kön och genus – Ramipril/Hydroklortiazid Actavis

Janusmed kön och genus är ett kunskapsstöd som tillhandahåller information om köns- och genusaspekter på läkemedelsbehandling. Kunskapsstödet är avsedd främst för hälso- och sjukvårdspersonal. Texterna är generella och ska inte ses som behandlingsriktlinjer. Det är alltid behandlande läkare som ansvarar för patientens medicinering.

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C C
C C

Ramipril

Ramipril

Klass: C

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Produkter

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Ramipril 2care4, Ramipril Actavis, Ramipril Aristo, Ram......

Ramipril 2care4, Ramipril Actavis, Ramipril Aristo, Ramipril Arrow, Ramipril Aurobindo, Ramipril Ebb, Ramipril HEXAL, Ramipril Hexal, Ramipril Krka, Ramipril Orifarm, Ramipril Ranbaxy, Ramipril STADA, Ramipril Sandoz, Ramipril Teva, Ramipril Winthrop, Ramipril ratiopharm, Ramipril/Hydrochlorothiazide Krka, Ramipril/Hydroklortiazid 2care4, Ramipril/Hydroklortiazid Actavis, Ramipril/Hydroklortiazid Alternova, Ramipril/Hydroklortiazid Ebb, Ramipril/Hydroklortiazid HEXAL, Ramipril/Hydroklortiazid Orifarm, Riprosil, Triatec, Triatec comp, Triatec comp mite
ATC-koder

C09AA05, C09BA05

C09AA05, C09BA05
Substanser

ramipril

ramipril
Sammanfattning

Ramipril minskar risken för död och allvarlig hjärtsvikt. Nyttan av behandling är lika för båda könen.
Män som behandlas med ramipril vid kronisk nefropati verkar löpa en ökad risk för sjukdomsprogression på grund av lägre behandlingseffekt av ramipril, jämfört med kvinnor.
En vanlig icke-dosberoende biverkan av ACE-hämmare är hosta som förekommer oftare hos kvinnor. Angiotensinreceptorblockerare kan då vara ett alternativ.

Ramipril minskar risken för död och allvarlig hjärtsvikt. Nyttan av behandling är lika för båda könen. Män som behandlas med ramipril vid kronisk nefropati verkar löpa en ökad risk för sjukdomsprogression på grund av lägre behandlingseffekt av ramipril, jämfört med kvinnor. En vanlig icke-dosberoende biverkan av ACE-hämmare är hosta som förekommer oftare hos kvinnor. Angiotensinreceptorblockerare kan då vara ett alternativ.
Background

Pharmacokinetics and dosing
In a pharmacokinetic study (18 men, 18 women), patients received a single 5 mg oral dose of ramipril. Cmax and half-lives of the active metabolite ramiprilat were identical in both sexes, but women showed a higher AUC/kg than men. Since both men and women received a fixed dose, the differences were explained by a higher dose/kg in women, as a consequence of their lower body weight [19].

Effects
Heart failure
A European multicentre cohort study of patients with heart failure with reduced ejection fraction (HFrEF) (3609 men, 1114 women) found similar all-cause mortality for patients treated with ACE inhibitors (enalapril, lisinopril, or ramipril) given at equivalent doses. No differences between men and women or between age groups were seen [1].
In a large cohort study comparing angiotensin converting enzyme (ACE) inhibitors with angiotensin receptor blockers (ARBs) in patients with congestive heart failure (9 475 men, 10 223 women), women on ARBs had better survival than women on ACE inhibitors (HR 0.69, 95%CI 0.59-0.80) while men on ARBs had simil......

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# Pharmacokinetics and dosing In a pharmacokinetic study (18 men, 18 women), patients received a single 5 mg oral dose of ramipril. Cmax and half-lives of the active metabolite ramiprilat were identical in both sexes, but women showed a higher AUC/kg than men. Since both men and women received a fixed dose, the differences were explained by a higher dose/kg in women, as a consequence of their lower body weight [19]. # Effects **Heart failure** A European multicentre cohort study of patients with heart failure with reduced ejection fraction (HFrEF) (3609 men, 1114 women) found similar all-cause mortality for patients treated with ACE inhibitors (enalapril, lisinopril, or ramipril) given at equivalent doses. No differences between men and women or between age groups were seen [1]. In a large cohort study comparing angiotensin converting enzyme (ACE) inhibitors with angiotensin receptor blockers (ARBs) in patients with congestive heart failure (9 475 men, 10 223 women), women on ARBs had better survival than women on ACE inhibitors (HR 0.69, 95%CI 0.59-0.80) while men on ARBs had similar survival as men on ACE inhibitors (HR 1.10, 95%CI 0.95-1.30). However, other anti-hypertensive agents were more common in those on ARBs, especially women, leading to a larger blood pressure reduction and thus larger reduction in risk of death. Also, more of those on ARBs were hypertensive than those on ACE inhibitors, and more of those on ACE inhibitors had a history of myocardial infarction than those of ARBs [2]. Additional confounding by indication cannot be excluded.   **Hypertension** In general, the activity level of the endogenous renin-angiotensin system (RAS), which regulates blood pressure, is higher in men than in premenopausal women. Postmenopausal women have higher activity than premenopausal women. This suggests that the efficacy of an RAS inhibitor would be lower in premenopausal women. However, studies on sex differences in the effect of RAS inhibition are contradictory [3, 4]. It has been suggested that black hypertensive patients have a smaller antihypertensive efficacy of ACE inhibitors than non-blacks, possibly due to a higher prevalence of low renin state in black hypertensive patients [5-7].   **Acute myocardial infarction** In the large randomized double-blind AIRE trial (1461 men, 525 women), 2.5 mg ramipril daily was compared with placebo, 2-9 days after acute myocardial infarction. Ramipril reduced the risks of death from any cause by 27%. The benefits of ramipril therapy were similar in both men and women [20, 21]. **Non-diabetic nephropathy** Another randomized clinical trial (269 men, 83 women) investigated the impact of sex on the outcome of non-diabetic chronic proteinuric nephropathy and effect of ramipril treatment. Ramipril decreased proteinuria less effectively in men than in women (-7.8 ± 4.2% vs. -21.9 ± 5.7%). Compared to conventional treatment (placebo plus antihypertensive therapy), ramipril decreased the difference in GFR (-52% vs. -19%) and progression to end-stage renal disease (-74% vs. -40%) more effectively in women than in men. Among patients with chronic proteinuric nephropathies, men are at increased risk of progression due to their lower response to ACE inhibitor treatment. ACE inhibition is similarly renoprotective in women regardless of the ACE polymorphism, and in men with a certain genotype (double deletion of the ACE gene) [22]. # Adverse effects Several studies have reported a female predominance in the prevalence of ACE inhibitor induced cough [8-16]. The pathogenesis of the cough reaction is unknown. Different thresholds for coughing in men and women have been proposed [17], as well as ethnic differences in cough tendency [18]. One study suggests that sex hormones do not have any influence on cough, since most of the women in the study were postmenopausal [6]. A pharmacoepidemiological study (5259 men, 5111 women) of ramipril found an incidence of ramipril-induced cough of 7.1%. Female sex was significantly and independently associated with the onset of ramipril-related cough (odds ratio 1.35) [23]. It is suggested that ACE inhibitors cause angioedema to a greater extent in black patients than in non-black patients [7]. # Reproductive health issues ACE inhibitors should not be used in pregnant women. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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Fler män än kvinnor hämtade ut tabletter innehållande ramipril (ATC-kod C09AA05) på recept i Sverige år 20181, totalt 75 894 män och 39 330 kvinnor. Det motsvarar 15 respektive 8 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. I genomsnitt var tabletter innehållande ramipril 2,6 gånger vanligare hos män [24]. Fler män än kvinnor hämtade ut tabletter innehållande kombination av ramipril och hydroklortiazid (ATC-kod C09BA05) på recept i Sverige år 2018, totalt 1 943 män och 1 379 kvinnor. Det motsvarar 0,4 respektive 0,3 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-84 år hos båda könen. I genomsnitt var tabletter innehållande kombination av ramipril och hydroklortiazid 1,8 gånger vanligare hos män [24].
Referenser

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  1. Fröhlich H, Henning F, Täger T, Schellberg D, Grundtvig M, Goode K et al. Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study. Eur Heart J Cardiovasc Pharmacother. 2018;4(2):82-92.

  2. Hudson M, Rahme E, Behlouli H, Sheppard R, Pilote L. Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure--a population study. Eur J Heart Fail. 2007;9(6):602-9.

  3. Coulter DM, Edwards IR. Cough associated with captopril and enalapril. Br Med J (Clin Res Ed). 1987;294:1521-3.

  4. Strocchi E, Valtancoli G, Ambrosioni E. The incidence of cough during treatment with angiotensin converting enzyme inhibitors. J Hypertens Suppl. 1989;7:S308-9.

  5. Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB, Kohn RM et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD) SOLVD Investigators. Am Heart J. 1996;131:350-5.

  6. Sharma S, Gupta U, Bapna JS, Sahai A. Tolerability of enalapril in mild to moderate hypertension. J Assoc Physicians India. 1995;43:475-6.

  7. Yeşil S, Yeşil M, Bayata S, Postaci N. ACE inhibitors and cough. Angiology. 1994;45:805-8.

  8. Yeo WW, Ramsay LE. Persistent dry cough with enalapril: incidence depends on method used. J Hum Hypertens. 1990;4:517-20.

  9. Just PM. The positive association of cough with angiotensin-converting enzyme inhibitors. Pharmacotherapy. 1989;9:82-7.

  10. Gibson GR. Enalapril-induced cough. Arch Intern Med. 1989;149:2701-3.

  11. Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992;339:372.

  12. Dykewicz MS. Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management. Curr Opin Allergy Clin Immunol. 2004;4:267-70.

  13. Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pract. 2004;10:499-509.

  14. Zapater P, Novalbos J, Gallego-Sandín S, Hernández FT, Abad-Santos F. Gender differences in angiotensin-converting enzyme (ACE) activity and inhibition by enalaprilat in healthy volunteers. J Cardiovasc Pharmacol. 2004;43(5):737-44.

  15. Komukai K, Mochizuki S, Yoshimura M. Gender and the renin-angiotensin-aldosterone system. Fundam Clin Pharmacol. 2010;24(6):687-98.

  16. Renitec (enalapril). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-05-14, cited 2019-05-16].

  17. Zestril (lisinopril). Summary of Product Characteristics. Medical Products Agency Sweden; 2016.

  18. Triatec (ramipril). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-05-14, cited 2019-05-16].

  19. Vree TB, Dammers E, Ulc I, Horkovics-Kovats S, Ryska M, Merkx et al. Lack of male-female differences in disposition and esterase hydrolysis of ramipril to ramiprilat in healthy volunteers after a single oral dose. ScientificWorldJournal. 2003;3:1332-43.

  20. Altace (ramipril) DailyMed 2018. DailyMed [www]. US National Library of Medicine. [updated 2018-02-15, cited 2019-05-16].

  21. [No authors listed]. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821-8.

  22. Ruggenenti P, Perna A, Zoccali C, Gherardi G, Benini R, Testa A et al. Chronic proteinuric nephropathies II Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen). J Am Soc Nephrol. 2000;11:88-96.

  23. Wyskida K, Jura-Szołtys E, Smertka M, Owczarek A, Chudek J. Factors that favor the occurrence of cough in patients treated with ramipril--a pharmacoepidemiological study. Med Sci Monit. 2012;18:PI21-8.

  24. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.]

  1. Fröhlich H, Henning F, Täger T, Schellberg D, Grundtvig M, Goode K et al. Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study. Eur Heart J Cardiovasc Pharmacother. 2018;4(2):82-92.
  2. Hudson M, Rahme E, Behlouli H, Sheppard R, Pilote L. Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure--a population study. Eur J Heart Fail. 2007;9(6):602-9.
  3. Coulter DM, Edwards IR. Cough associated with captopril and enalapril. Br Med J (Clin Res Ed). 1987;294:1521-3.
  4. Strocchi E, Valtancoli G, Ambrosioni E. The incidence of cough during treatment with angiotensin converting enzyme inhibitors. J Hypertens Suppl. 1989;7:S308-9.
  5. Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB, Kohn RM et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD) SOLVD Investigators. Am Heart J. 1996;131:350-5.
  6. Sharma S, Gupta U, Bapna JS, Sahai A. Tolerability of enalapril in mild to moderate hypertension. J Assoc Physicians India. 1995;43:475-6.
  7. Yeşil S, Yeşil M, Bayata S, Postaci N. ACE inhibitors and cough. Angiology. 1994;45:805-8.
  8. Yeo WW, Ramsay LE. Persistent dry cough with enalapril: incidence depends on method used. J Hum Hypertens. 1990;4:517-20.
  9. Just PM. The positive association of cough with angiotensin-converting enzyme inhibitors. Pharmacotherapy. 1989;9:82-7.
  10. Gibson GR. Enalapril-induced cough. Arch Intern Med. 1989;149:2701-3.
  11. Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992;339:372.
  12. Dykewicz MS. Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management. Curr Opin Allergy Clin Immunol. 2004;4:267-70.
  13. Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pract. 2004;10:499-509.
  14. Zapater P, Novalbos J, Gallego-Sandín S, Hernández FT, Abad-Santos F. Gender differences in angiotensin-converting enzyme (ACE) activity and inhibition by enalaprilat in healthy volunteers. J Cardiovasc Pharmacol. 2004;43(5):737-44.
  15. Komukai K, Mochizuki S, Yoshimura M. Gender and the renin-angiotensin-aldosterone system. Fundam Clin Pharmacol. 2010;24(6):687-98.
  16. Renitec (enalapril). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-05-14, cited 2019-05-16].
  17. Zestril (lisinopril). Summary of Product Characteristics. Medical Products Agency Sweden; 2016.
  18. Triatec (ramipril). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-05-14, cited 2019-05-16].
  19. Vree TB, Dammers E, Ulc I, Horkovics-Kovats S, Ryska M, Merkx et al. Lack of male-female differences in disposition and esterase hydrolysis of ramipril to ramiprilat in healthy volunteers after a single oral dose. ScientificWorldJournal. 2003;3:1332-43.
  20. Altace (ramipril) DailyMed 2018. DailyMed [www]. US National Library of Medicine. [updated 2018-02-15, cited 2019-05-16].
  21. [No authors listed]. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821-8.
  22. Ruggenenti P, Perna A, Zoccali C, Gherardi G, Benini R, Testa A et al. Chronic proteinuric nephropathies II Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen). J Am Soc Nephrol. 2000;11:88-96.
  23. Wyskida K, Jura-Szołtys E, Smertka M, Owczarek A, Chudek J. Factors that favor the occurrence of cough in patients treated with ramipril--a pharmacoepidemiological study. Med Sci Monit. 2012;18:PI21-8.
  24. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.]
Uppdaterat

Litteratursökningsdatum 5/16/2019

Litteratursökningsdatum 5/16/2019
Se även

Enalapril

Lisinopril

A A
A A

Hydroklortiazid

Hydroklortiazid

Klass: A

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Produkter

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Amiloferm, Amiloferm mite, Atacand Plus, Blopresid Comp......

Amiloferm, Amiloferm mite, Atacand Plus, Blopresid Comp, Blopress Comp, Candemox Comp, Candesarstad Comp, Candesartan/Hydrochlorothiazide 2care4, Candesartan/Hydrochlorothiazide Actavis, Candesartan/Hydrochlorothiazide Bijon, Candesartan/Hydrochlorothiazide Krka, Candesartan/Hydrochlorothiazide Navamedic, Candesartan/Hydrochlorothiazide Orion, Candesartan/Hydrochlorothiazide STADA, Candesartan/Hydrochlorothiazide Teva, Candexetil comp, Corixil Comp, Cozaar Comp, Cozaar Comp Forte, Diovan Comp, Enalapril Comp STADA, Enalapril Comp Sandoz, Enalapril comp ratiopharm, Enalapril/Hydrochlorothiazide 2care4, Enalapril/Hydrochlorothiazide Medical Valley, Enalapril/Hydrochlorothiazide Mylan, Enalapril/Hydrochlorothiazide Orion, Enalapril/Hydrochlorothiazide Teva, Esidrex, Etilbo, Fortzaar Comp Forte, Forzaar Comp Forte, Hydrochlorothiazide Bluefish, Hydrochlorothiazide Orifarm, Hydrochlorothiazide Orion, Hydroklortiazid Ebb, Hydroklortiazid Evolan, Klomentan Comp, Linatil comp, Linatil comp mite, Lisinopril/Hydrochlorthiazid Sandoz, Lisinopril/Hydroklortiazid Actavis, Lisinopril/Hydroklortiazid Copyfarm, Lisinopril/Hydroklortiazid Ebb, Lisinopril/Hydroklortiazid STADA, Losamyl Comp, Losarstad Comp, Losartan/Hydrochlorothiazide Aurobindo, Losartan/Hydrochlorothiazide Bluefish, Losartan/Hydrochlorothiazide Krka, Losartan/Hydrochlorothiazide Medical Valley, Losartan/Hydrochlorothiazide Sandoz, Losartan/Hydrochlorothiazide Teva, Losartan/Hydroklortiazid Actavis, Losartan/Hydroklortiazid Orifarm, Losartan/hydroklortiazid Jubilant, Losatrix Comp, Losatrix comp, Losazid Comp, Losazid Comp Forte, Marozid, Moduretic, Moduretic mite, Normorix, Normorix mite, Ramipril/Hydrochlorothiazide Krka, Ramipril/Hydroklortiazid 2care4, Ramipril/Hydroklortiazid Actavis, Ramipril/Hydroklortiazid Alternova, Ramipril/Hydroklortiazid Ebb, Ramipril/Hydroklortiazid HEXAL, Ramipril/Hydroklortiazid Orifarm, Ratacand Plus, Renitec comp., Rocaval, Sparkal, Sparkal mite, Synerpril, Tanlozid, Tareg Comp, Triatec comp, Triatec comp mite, Valsartan/Hydrochlorothiazide 2care4, Valsartan/Hydrochlorothiazide Krka, Valsartan/Hydrochlorothiazide Rivopharm, Valsartan/Hydrochlorothiazide Sandoz, Valsartan/Hydrochlorothiazide Teva, Valsartan/Hydroklortiazid Abacus Medicine, Valsartan/Hydroklortiazid Ebb, Valsartan/Hydroklortiazid Jubilant, Valsartore Comp, Valtsu comp, Zestoretic
ATC-koder

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C03AA03, C03EA01, C09BA02, C09BA03, C09BA05, C09DA01......

C03AA03, C03EA01, C09BA02, C09BA03, C09BA05, C09DA01, C09DA03, C09DA06
Substanser

hydroklortiazid

hydroklortiazid
Sammanfattning

Studier har visat motsägande resultat huruvida det finns eller inte finns könsskillnader i den blodtryckssänkande effekten av hydroklortiazid.

Vid spontanrapportering har allvarliga biverkningar av hydroklortiazid, såsom akut lungödem och akut allergisk interstitiell lunginflammation, rapporterats förekomma oftare hos kvinnor än hos män. Skivepitelcancer (ej lokaliserad på läppen), har rapporterats vara vanligare hos kvinnor. För övrig hudcancer av icke-melanomtyp sågs inga könsskillnader.

Studier har visat motsägande resultat huruvida det finns eller inte finns könsskillnader i den blodtryckssänkande effekten av hydroklortiazid. Vid spontanrapportering har allvarliga biverkningar av hydroklortiazid, såsom akut lungödem och akut allergisk interstitiell lunginflammation, rapporterats förekomma oftare hos kvinnor än hos män. Skivepitelcancer (ej lokaliserad på läppen), har rapporterats vara vanligare hos kvinnor. För övrig hudcancer av icke-melanomtyp sågs inga könsskillnader.
Background

Pharmacokinetics and dosing
No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of hydrochlorothiazide have been found.

Effects
Studies report conflicting results on sex differences in response to hydrochlorothiazide (HCTZ ). Results from the randomized, double-blind HANE study (113 men, 102 women) showed similar antihypertensive response rates to HCTZ (12.5-50 mg daily over 48 weeks) between men and women [1]. However, a prospective clinical trial (1209 men, 2326 women) found that women had a better diastolic BP response to HCTZ (12.5-25 mg daily for 8 weeks) than men. Women were 57% more likely to reach the control goal of diastolic BP than men [2]. Also a small randomized clinical trial (29 men, 23 women) showed that women had higher systolic/diastolic ambulatory BP response to HCTZ than men after 25 mg daily for 4 weeks [3].

Diuretic response to 50 mg oral HCTZ was measured in healthy volunteers (6 men, 6 women) in a randomized, cross-over study. No clinical relevant sex differences in diuretic response, urine flow rate, potassium exc......

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# Pharmacokinetics and dosing No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of hydrochlorothiazide have been found. # Effects Studies report conflicting results on sex differences in response to hydrochlorothiazide (HCTZ ). Results from the randomized, double-blind HANE study (113 men, 102 women) showed similar antihypertensive response rates to HCTZ (12.5-50 mg daily over 48 weeks) between men and women [1]. However, a prospective clinical trial (1209 men, 2326 women) found that women had a better diastolic BP response to HCTZ (12.5-25 mg daily for 8 weeks) than men. Women were 57% more likely to reach the control goal of diastolic BP than men [2]. Also a small randomized clinical trial (29 men, 23 women) showed that women had higher systolic/diastolic ambulatory BP response to HCTZ than men after 25 mg daily for 4 weeks [3]. Diuretic response to 50 mg oral HCTZ was measured in healthy volunteers (6 men, 6 women) in a randomized, cross-over study. No clinical relevant sex differences in diuretic response, urine flow rate, potassium excretion rate and natriuretic response were found [4]. # Adverse effects Large pharmacoepidemiological studies have shown an increased risk of non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma) after exposure of increased cumulative doses of HCTZ [5-7]. Men and women had similar risk of lip cancer [5] and basal cell carcinoma [6], while the risk of squamous cell carcinoma (not lip) was higher in women (OR 4.46; 95%CI 4.04-4.94) than in men (OR 3.26; 95%CI 2.85-3.72) [5, 6]. HCTZ-induced acute pulmonary edema has been described as a rare adverse event. In a review of reported cases, 16 out of 17 patients were women [8]. Cases of acute allergic interstitial pneumonitis induced by HCTZ have been described in the literature. In a series of case reports, female sex was reported as a risk factor, since 27 (90%) of the 30 described patients were women, mostly postmenopausal [9].  Hyponatremia is reported to be more common in women treated with HCTZ. A medical record review of patients with hyponatremia treated with diuretics (31 men, 149 women) revealed that women had three times higher risk of hyponatremia than men in all age groups (OR 3.10, 95%CI 2.07-4.67). Almost all received HCTZ (75%). Duration of diuretic treatment was only reported in 57 patients; 44% of the patients had developed hyponatremia within 1 month of treatment and 45% after 6 months [10]. In another review of medical records, female sex was a risk factor for hyponatremia among patients treated with HCTZ or indapamide (391 men and 608 women on HCTZ) [11]. # Reproductive health issues Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan). # Other information Studies have found interacting effects between patient’s sex and ACE genotype on blood pressure response to HCTZ in blacks, whites [12] and Han Chinese patients [13] with hypertension. The genotypes associated with the greatest decline in blood pressure were DD homozygotes in men and II homozygotes in women [12, 13]. A Canadian cohort study evaluating age and sex-related use of thiazide diuretics and beta-blockers showed that women were 8% more likely than men to be dispensed a low-dose thiazide diuretic (OR 1.08, 95% CI 1.05-1.11) [14].
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Fler kvinnor än män hämtade ut tabletter innehållande HCTZ (ATC-kod C03AA03) på recept i Sverige år 2018, totalt 41 152 kvinnor och 34 296 män. Det motsvarar 8,2 respektive 6,8 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70 år och äldre hos båda könen. I genomsnitt var tabletter innehållande HCTZ 1,1 gånger vanligare hos kvinnor [15].
Referenser

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  1. Philipp T, Anlauf M, Distler A, Holzgreve H, Michaelis J, Wellek S. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study HANE Trial Research Group. BMJ. 1997;315:154-9.

  2. Fan X, Han Y, Sun K, Wang Y, Xin Y, Bai Y et al. Sex differences in blood pressure response to antihypertensive therapy in Chinese patients with hypertension. Ann Pharmacother. 2008;42:1772-81.

  3. Falconnet C, Bochud M, Bovet P, Maillard M, Burnier M. Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent. J Hypertens. 2004;22:1213-20.

  4. Franson KL, Kuk JM, Lam NP, Lau AH. Gender effect on diuretic response to hydrochlorothiazide and furosemide. Int J Clin Pharmacol Ther. 1996;34:101-5.

  5. Pottegård A, Hallas J, Olesen M, Svendsen MT, Habel LA, Friedman GD et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med. 2017;282(4):322-331.

  6. Pedersen SA, Gaist D, Schmidt SAJ, Hölmich LR, Friis S, Pottegård A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018;78(4):673-681e9.

  7. Läkemedelsverket. Hydroklortiazid - Risk för icke-melanom hudcancer (basalcellscancer, skivepitelcancer). Läkemedelsverket [www]. [updated 2019-10-15, cited 2019-03-12].

  8. Kavaru MS, Ahmad M, Amirthalingam KN. Hydrochlorothiazide-induced acute pulmonary edema. Cleve Clin J Med. 1990;57:181-4.

  9. Biron P, Dessureault J, Napke E. Acute allergic interstitial pneumonitis induced by hydrochlorothiazide. CMAJ. 1991;145:28-34.

  10. Sharabi Y, Illan R, Kamari Y, Cohen H, Nadler M, Messerli FH et al. Diuretic induced hyponatraemia in elderly hypertensive women. J Hum Hypertens. 2002;16(9):631-5.

  11. Al Qahtani M, Alshahrani A, Alskaini A, Abukhalid N, Al Johani N, Al Ammari M et al. Prevalence of hyponatremia among patients who used indapamide and hydrochlorothiazide: a single center retrospective study. Saudi J Kidney Dis Transpl. 2013;24(2):281-5.

  12. Schwartz GL, Turner ST, Chapman AB, Boerwinkle E. Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. Kidney Int. 2002;62(5):1718-23.

  13. Li Y, Yang P, Wu S, Yuan J, Shen C, Wu Y et al. Gender-specific association between ACE gene I/D polymorphism and blood pressure response to hydrochlorothiazide in Han Chinese hypertensive patients. Biochem Genet. 2011;49:704-14.

  14. Rochon PA, Anderson GM, Tu JV, Gurwitz JH, Clark JP, Shear NH et al. Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose. J Am Geriatr Soc. 1999;47(8):954-9.

  15. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.]

  1. Philipp T, Anlauf M, Distler A, Holzgreve H, Michaelis J, Wellek S. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study HANE Trial Research Group. BMJ. 1997;315:154-9.
  2. Fan X, Han Y, Sun K, Wang Y, Xin Y, Bai Y et al. Sex differences in blood pressure response to antihypertensive therapy in Chinese patients with hypertension. Ann Pharmacother. 2008;42:1772-81.
  3. Falconnet C, Bochud M, Bovet P, Maillard M, Burnier M. Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent. J Hypertens. 2004;22:1213-20.
  4. Franson KL, Kuk JM, Lam NP, Lau AH. Gender effect on diuretic response to hydrochlorothiazide and furosemide. Int J Clin Pharmacol Ther. 1996;34:101-5.
  5. Pottegård A, Hallas J, Olesen M, Svendsen MT, Habel LA, Friedman GD et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med. 2017;282(4):322-331.
  6. Pedersen SA, Gaist D, Schmidt SAJ, Hölmich LR, Friis S, Pottegård A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018;78(4):673-681e9.
  7. Läkemedelsverket. Hydroklortiazid - Risk för icke-melanom hudcancer (basalcellscancer, skivepitelcancer). Läkemedelsverket [www]. [updated 2019-10-15, cited 2019-03-12].
  8. Kavaru MS, Ahmad M, Amirthalingam KN. Hydrochlorothiazide-induced acute pulmonary edema. Cleve Clin J Med. 1990;57:181-4.
  9. Biron P, Dessureault J, Napke E. Acute allergic interstitial pneumonitis induced by hydrochlorothiazide. CMAJ. 1991;145:28-34.
  10. Sharabi Y, Illan R, Kamari Y, Cohen H, Nadler M, Messerli FH et al. Diuretic induced hyponatraemia in elderly hypertensive women. J Hum Hypertens. 2002;16(9):631-5.
  11. Al Qahtani M, Alshahrani A, Alskaini A, Abukhalid N, Al Johani N, Al Ammari M et al. Prevalence of hyponatremia among patients who used indapamide and hydrochlorothiazide: a single center retrospective study. Saudi J Kidney Dis Transpl. 2013;24(2):281-5.
  12. Schwartz GL, Turner ST, Chapman AB, Boerwinkle E. Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. Kidney Int. 2002;62(5):1718-23.
  13. Li Y, Yang P, Wu S, Yuan J, Shen C, Wu Y et al. Gender-specific association between ACE gene I/D polymorphism and blood pressure response to hydrochlorothiazide in Han Chinese hypertensive patients. Biochem Genet. 2011;49:704-14.
  14. Rochon PA, Anderson GM, Tu JV, Gurwitz JH, Clark JP, Shear NH et al. Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose. J Am Geriatr Soc. 1999;47(8):954-9.
  15. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.]
Uppdaterat

Litteratursökningsdatum 3/8/2019

Litteratursökningsdatum 3/8/2019