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Emtricitabin

Klassificering: A

Preparat: Atripla, Descovy, Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, Efavirenz/Emtricitabine/Tenofovir disoproxil Mylan, Efavirenz/Emtricitabine/Tenofovir disoproxil Teva, Emtenef, Emtricitabine/Tenofovir disoproxil Accord, Emtricitabine/tenofovir disoproxil Krka, Emtricitabine/Tenofovir disoproxil Mylan, Emtricitabine/Tenofovir disoproxil Sandoz, Emtricitabine/Tenofovir disoproxil STADA, Emtricitabine/Tenofovir disoproxil Teva, Emtriva, Eviplera, Genvoya, Odefsey, Padviram, Stribild, Symtuza, Truvada

ATC kod: J05AF09, J05AR03, J05AR06, J05AR08, J05AR09, J05AR17, J05AR18, J05AR19, J05AR22

Substanser: emtricitabin

Sammanfattning

Virologiskt svar på behandling med emtricitabin har i vissa studier visats vara likartad hos kvinnor och män medan andra studier funnit sämre svar hos kvinnor. I dessa studier har kvinnor avbrutit behandlingen i högre utsträckning än män vilket skulle kunna förklara dessa något motstridiga fynd. Vad gäller biverkningar är illamående vanligare hos kvinnor och mardrömmar/konstiga drömmar vanligare hos män.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Antiretrovirals for treatment of HIV are always given as a combination of at least three medicines. Cobicistat is used to boost the effect of other antiretroviral drugs. As studies on HIV patients always include patients receiving combination therapy it is difficult to know which of the studied medicines that cause changes in effect and/or adverse events.

Pharmacokinetics and dosing

In the product information of emtricitabine it is noted that concentrations (Cmax and Cmin) and mean AUC were higher in women compared to men but the differences were less than 20% and not considered clinically significant [1].

Effects

In a randomized study on HIV-1-infected adults (1040 men, 328 women) treated with rilpivirine or efavirenz and an NRTI backbone consisting of either tenofovir/emtricitabine or tenofovir/emtricitabine + zidovudine/lamivudine or abacavir/lamivudine no difference in response rate between men and women was found [2]. However, differences were found in the CASTLE study, where treatment-naive adult HIV-patients (606 men, 277 women) were randomized to receive either atazanavir/ritonavir or lopinavir/ritonavir with fixed-dose tenofovir/emtricitabine. At week 96, virological response was lower in women than men in both treatment arms (67% of women and 77% of men on atazanavir/ritonavir and 63% of women and 71% of men on lopinavir/ritonavir). Discontinuation rates were higher in women than men in both treatment arms (22% of women and 15% of men on atazanavir/ritonavir and 29% of women and 18% of men on lopinavir/ritonavir) [3].

Adverse effects

The general differences in adverse events which have been described for antiretroviral regimens are that women have been reported to have more nausea and gastrointestinal reactions, more lipodystrophy, a higher risk of developing kidney failure and lactic acidosis but a lower risk of LDL-level increase compared to men.

In a randomized study on HIV-1-infected adults (1040 men, 328 women) treated with rilpivirine or efavirenz a backbone consisting of either tenofovir/emtricitabine or tenofovir/emtricitabine + zidovudine/lamivudine or abacavir/lamivudine nausea was more common in women than in men in both treatment groups while abnormal dreams/nightmares were more frequent in men [2].

Safety and tolerability were evaluated in a European HIV cohort (958 men, 336 women). Women had a higher risk of treatment discontinuation than men (hazard ratio [HR] 1.54; 95%CI 1.28-1.85) but no increased risk of virological failure (HR 1.06; 95%CI 0.85-1.33). Compared to men, women had less diarrhoea and severe dyslipidaemia but more lipodystrophy [4] .

In a study in HIV-patients treated with blinded lamivudine or emtricitabine + stavudine, and nevirapine or efavirenz (156 men, 229 women), early hepatotoxicity occurred in 17% of patients in the nevirapine group and none in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Multivariate analysis found women to be at higher risk, as were patients with body-mass index <18.5, serum albumin level <35 g/L, mean corpuscular volume 185 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L [5].

In a study on glucose tolerance in HIV-infected adults on efavirenz, tenofovir, and emtricitabine (40 men, 30 women) half of the subjects were obese and these were matched with 30 obese HIV-negative controls. HIV-infected women had higher glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between patient’s sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex differences may not be specific to HIV infection [6].

Reproductive health issues

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

Other information

In a retrospective follow-up study in a multisite cohort from the USA (4567 men, 806 women) a combination of efavirenz/emtricitabine/tenofovir was the most commonly prescribed initial antiretroviral treatment. Factors associated with modifying treatment regimen were female sex, intravenous drug use, and CD4 cell count less than 200 cells/μl [7].

A global randomized study on sex differences in antiretroviral treatment with efavirenz+lamivudine/zidovudine, atazanavir+didanosine/emtricitabine or efavirenz+emtricitabine /tenofovir (832 men, 739 women) has been performed [8]. It found women to have higher pre-treatment CD4+ and lower HIV-1 RNA compared to men. For atazanavir+didanosine/emtricitabine, women remained on treatment longer compared to men and were less likely to prematurely discontinue [8].

A review has described drug exposure in the genital tract of men and women which is of interest in viral transferal and in effect of pre-exposure prophylactic treatment. In men, concentrations in seminal fluid were described to be highest for nucleoside analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation of raltegravir and maraviroc was defined as moderate. The rank order of accumulation presented in the review is nucleoside/nucleotide reverse transcriptase inhibitors [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir > indinavir/maraviroc/nevirapine >> efavirenz/protease inhibitors [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] > enfuvirtide. In the female genital tract, the nucleoside analogues were also described as having high accumulation ratios, whereas protease inhibitors have limited penetration; however, substantial variability exists. Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and maraviroc and raltegravir, have been found to demonstrate effective accumulation in cervicovaginal secretions. The rank of accumulation presented in the review is nucleoside/nucleotide reverse transcriptase inhibitor [zidovudine/lamivudine/didanosine > emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine > nevirapine/abacavir > protease inhibitors [amprenavir/atazanavir/ritonavir] > lopinavir/stavudine/efavirenz > saquinavir [9].

Försäljning på recept

Två kvinnor hämtade ut läkemedel innehållande emtricitabin (ATC-kod J05AF09) på recept i Sverige år 2017 [10].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2018-07-23

Referenser

  1. Emtriva (emtricitabin). Summary of Product Characteristics. European Medicines Agency (EMA); 2018.
  2. Hodder S, Arasteh K, De Wet J, Gathe J, Gold J, Kumar P et al. Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE. HIV Med. 2012;13(7):406-15. PubMed
  3. Squires KE, Johnson M, Yang R, Uy J, Sheppard L, Absalon J et al. Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J Antimicrob Chemother. 2011;66(2):363-70. PubMed
  4. Svedhem-Johansson V, Pugliese P, Brockmeyer NH, Thalme A, Michalik C, Esser S et al. Long-term gender-based outcomes for atazanavir/ritonavir (ATV/r)- containing regimens in treatment-experienced patients with HIV. Curr HIV Res. 2013;11(4):333-41. PubMed
  5. Sanne I, Mommeja-Marin H, Hinkle J, Bartlett JA, Lederman MM, Maartens G et al. Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects. J Infect Dis. 2005;191(6):825-9. PubMed
  6. Koethe JR, Jenkins CA, Petucci C, Culver J, Shepherd BE, Sterling TR. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy. Medicine (Baltimore). 2016;95(19):e3634. PubMed
  7. Eaton EF, Tamhane A, Davy-Mendez T, Mathews WC, Moore RD, Saag MS et al. Trends in antiretroviral therapy prescription, durability and modification: new drugs, more changes, but less failure. AIDS. 2018;32(3):347-355. PubMed
  8. Firnhaber C, Smeaton LM, Grinsztejn B, Lalloo U, Faesen S, Samaneka W et al. Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial. HIV Clin Trials. 2015;16(3):89-99. PubMed
  9. Else LJ, Taylor S, Back DJ, Khoo SH. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract. Antivir Ther. 2011;16(8):1149-67. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-07-24.] länk

Författare: Mia von Euler

Faktagranskat av: Karin Schenck-Gustafsson

Godkänt av: Karin Schenck-Gustafsson