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Amlodipin

Klassificering: B

Preparat: Amlarrow, Amlobesyl, Amlodipin Accord, Amlodipin Actavis, Amlodipin Aurobindo, Amlodipin Bluefish, Amlodipin BMM Pharma, Amlodipin Hexal, Amlodipin Jubilant, Amlodipin Krka, Amlodipin Orifarm, Amlodipin ratiopharm, Amlodipin Sandoz, Amlodipin STADA®, Amlodipin/Valsartan Krka, Amlodipin/Valsartan STADA, Amlodipine, Amlodipine Teva, Amlodipine Vitabalans, Amlodistad, Amloratio, Amlori, Exforge®, Milodimyl, Norvasc, Norvasc®

ATC kod: C08CA01, C09DB01

Substanser: amlodipin, amlodipinbesilat, amlodipinmaleat, amlodipinmesilat, amlodipinmesilatmonohydrat

Sammanfattning

Kliniska studier har visat motsägande resultat om kvinnor eller män får en större blodtryckssänkning av amlodipin.
En vanlig biverkan av amlodipin är ödem, främst benödem, och förekommer oftare hos kvinnor.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling.

Additional information

Pharmacokinetics and dosing

In a single-dose bioequivalence study comparing two forms of amlodipine in healthy volunteers (18 men, 18 women), women had a slightly higher bioavailability of amlodipine compared with men. The difference disappeared after adjusting for weight [2]. The clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [3].

Effects

There are conflicting results whether men or women have more blood pressure (BP) reduction with amlodipine therapy. Clinical trials have reported a greater BP reduction with amlodipine in women compared with men [4-6]. The Amlodipine Community Trial (702 men, 382 women) observed that women had a greater absolute decrease in BP compared with men following amlodipine therapy (5-10 mg/day for 12 weeks). The percentage of patients achieving goal BP was higher in women than in men (91.4% vs. 83.0%). Reasons for these sex differences could be due to several mechanisms [4]. Also in the study by Abad-Santos et al. [3], women demonstrated a more pronounced reduction in systolic BP than men. The clinical significance of the sex difference remains to be determined.Contrary to these findings, the large randomized double-blind ALLHAT study (17 719 men, 15 638 women) reported that the achieved BP reductions from amlodipine therapy (20 mg/day) were comparable in both sexes, although decreases in systolic BP were more pronounced in men [7]. Also, another clinical trial found a slightly less BP reduction in women compared with men [8].

Adverse effects

Clinical trials have report similar incidence of adverse events in men and women [2,6]. In the Amlodipine Cardiovascular Community Trial [4], the most common adverse event was edema which occurred in 24% of treated patients, and was more common in women. A few cases, most men, of gingival overgrowth have been reported [9], but no statistically significant difference between the sexes has been shown [10].There are conflicting results from studies reporting that calcium channel blockers could be associated with cancer. One study reported suspected increase in breast cancer in women taking calcium channel blockers; however the study was criticised due to methodological problems of the study [1].

Reproductive health issues

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

Other information

A randomized clinical trial (76 men, 61 women) found that BP response to amlodipine among African-American men and women with early hypertensive nephrosclerosis appears to be determined by CYP4A4 genotypes and sex specificity may be an important consideration [11].

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande amlodipin (ATC-kod C08CA01) på recept i Sverige år 2015, totalt 225 883 män och 192 800 kvinnor. Det motsvarar 46 respektive 40 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 amlodipin 1,6 gånger vanligare hos män [12].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2014-02-04

Referenser

  1. Coogan PF. Calcium-channel blockers and breast cancer: a hypothesis revived. JAMA Intern Med. 2013;173:1637-8. PubMed
  2. Abad-Santos F, Novalbos J, Gálvez-Múgica MA, Gallego-Sandín S, Almeida S, Vallée F et al. Assessment of sex differences in pharmacokinetics and pharmacodynamics of amlodipine in a bioequivalence study. Pharmacol Res. 2005;51:445-52. PubMed
  3. Norvasc (amlodipin). Summary of Procuct Characteristics. Medical Products Agency Sweden; 2016.
  4. Kloner RA, Sowers JR, DiBona GF, Gaffney M, Wein M. Sex- and age-related antihypertensive effects of amlodipine The Amlodipine Cardiovascular Community Trial Study Group. Am J Cardiol. 1996;77:713-22. PubMed
  5. Feldman RD, Flack J, Howes L, Jenssen T, Reeves R, Shi H et al. Impact of age and gender on blood pressure and low-density lipoprotein cholesterol reduction: results of a pooled analysis. Curr Med Res Opin. 2012;28:1421-33. PubMed
  6. Schmieder RE, Böhm M. Efficacy and safety of olmesartan medoxomil plus amlodipine in age, gender and hypertension severity defined subgroups of hypertensive patients. J Hum Hypertens. 2011;25:354-63. PubMed
  7. Oparil S, Davis BR, Cushman WC, Ford CE, Furberg CD, Habib GB et al. Mortality and morbidity during and after Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: results by sex. Hypertension. 2013;61:977-86. PubMed
  8. Lewis CE, Grandits A, Flack J, McDonald R, Elmer PJ. Efficacy and tolerance of antihypertensive treatment in men and women with stage 1 diastolic hypertension Results of the Treatment of Mild Hypertension Study. Arch Intern Med. 1996;156:377-85. PubMed
  9. Seymour RA, Ellis JS, Thomason JM, Monkman S, Idle JR. Amlodipine-induced gingival overgrowth. J Clin Periodontol. 1994;21:281-3. PubMed
  10. Karnik R, Bhat KM, Bhat GS. Prevalence of gingival overgrowth among elderly patients under amlodipine therapy at a large Indian teaching hospital. Gerodontology. 2012;29:209-13. PubMed
  11. Bhatnagar V, Garcia EP, O'Connor DT, Brophy VH, Alcaraz J, Richard E et al. CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol. 2010;31:95-103. PubMed
  12. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Karin Schenck-Gustafsson, Mia von Euler

Godkänt av: Karin Schenck-Gustafsson