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Entecavir

Classification: A

Drug products: Baraclude®, Entecavir Accord, Entecavir Glenmark, Entecavir Mylan, Entecavir Sandoz, Entecavir STADA, Entecavir Teva

ATC code: J05AF10

Substances: entecavir, entecavir monohydrate

Summary

Even though fewer women than men have been included in the trials effect has been shown for both sexes. Some studies have reported a better effect in women but the evidence is sparse. There is an increased risk of lactic acidosis in obese women which needs to be considered.

In our opinion, at present the described differences do not motivate differentiated dosing or treatment in men and women although the risk of lactic acidosis needs to be considered in overweight women.

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

The manufacturer does not recommend different dosing in men and women although kidney function needs to be considered [1]. In the SPC the AUC is reported to be 14% higher in women than in men, a difference that did not remain after adjusting for creatinine clearance and body weight [1].

Effects

Effect of entecavir has been shown in both men and women although the proportion of women in the studies has been rather low (25%) [1]. Some studies have found a better response in women than in men treated with entecavir for chronic hepatitis B. A registry based cohort study in patients treated with entecavir or tenofovir (923 men, 402 women) found the risk of hepatocellular carcinoma to be higher in men (HR 5, 95%CI 1.8-13.9). Other associated risk factors were lower platelet, higher age and presence of cirrhosis [2].A Polish study for of correlation between efficacy of antiviral therapy and prevalence of hepatitis B virus pretreatment drug-resistant variants in patients treated with lamivudine only (55%) or in combination with adefovir (2%), entecavir (30%), or tenofovir (13%) (29 men, 25 women) found good response to antiviral therapy to be more common in women. Other positive predictors of good response were younger age, immunocompetence, a low viral load, and higher ALT activity [3]. In contrast to this, in a study from Taiwan, patients with chronic hepatitis B were treated with lamivudine, telbivudine, or entecavir (65 men, 15 women) (14 on lamivudine, 19 on telbivudine, and 47 on entecavir) no differences between men and women were found in relapse rate, cirrhosis or ALT levels [4]. 

Adverse effects

A prospective study of patients with chronic Hepatitis B (69 men, 38 women) treated with lamivudine (7.5%), tenofovir (35.5%), entecavir (31.8%) or combined treatment (25.2%) found a significant trend for developing lactic acidosis over time in women with cirrhosis [5]. The risk was particularly high in obese women. The products Summary cautions when using entecavir in obese women due to the risk of lactic acidosis [1].

Reproductive health issues

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

Updated: 2019-02-26

Date of litterature search: 2018-07-18

References

  1. Baraclude (entecavir). Summaru of Product Characteristics. European Medicines Agency (EMA); 2018
  2. Papatheodoridis G, Dalekos G, Sypsa V, Yurdaydin C, Buti M, Goulis J et al. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol. 2016;64(4):800-6. PubMed
  3. Stalke P, Rybicka M, Wróblewska A, Dreczewski M, Stracewska E, Smiatacz T et al. An initial assessment of correlations between host- and virus-related factors affecting analogues antiviral therapy in HBV chronically infected patients. Med Sci Monit. 2014;20(1):321-8. PubMed
  4. Lin CC, Bair MJ, Chen CJ, Lee KH, Chen MJ, Liu CY et al. Off-treatment efficacy of 3-year nucleos(t)ide analogues in chronic hepatitis B patients. Kaohsiung J Med Sci. 2016;32(1):10-5. PubMed
  5. Triantos C, Kalafateli M, Aggeletopoulou I, Mandellou M, Assimakopoulos S, Tselekouni P et al. Lactate serum concentrations during treatment with nucleos(t)ide analogues in hepatitis B with or without cirrhosis. Eur J Gastroenterol Hepatol. 2017;29(9):998-1003. PubMed
  6. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-07-24.] länk

Authors: Mia von Euler, Linnéa Karlsson Lind

Reviewed by: Karin Schenck-Gustafsson

Approved by: Karin Schenck-Gustafsson