Leitlinien & Arzneimittelsicherheit

HOS-097549 · has-adverse-reaction-information · PDF-Seite 28

Summary of the safety profile HIV-1 infection: The most frequently reported adverse reactions considered possibly or probably related to emtricitabine and/or tenofovir disoproxil were nausea (12%) and diarrhoea (7%) in an open-label randomised clinical study in adults (GS-01-934, see section 5.1). The safety profile of emtricitabine and tenofovir disoproxil in this study was consistent with the previous experience with these agents when each was administered with other antiretroviral agents. Pre-exposure prophylaxis: No new adverse reactions to emtricitabine/tenofovir disoproxil were identified from two randomised placebo-controlled studies (iPrEx, Partners PrEP) in which 2,830 HIV-1 uninfected adults received emtricitabine/tenofovir disoproxil once daily for pre-exposure prophylaxis. Patients were followed for a median of 71 weeks and 87 weeks, respectively. The most frequent adverse reaction reported in the emtricitabine/tenofovir disoproxil group in the iPrEx study was headache (1%). Tabulated summary of adverse reactions The adverse reactions considered at least possibly related to treatment with the components of emtricitabine/tenofovir disoproxil from clinical study and post-marketing experience in HIV- 1 infected patients are listed in Table 3, below, by body system organ class and frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) or rare (≥ 1/10,000 to < 1/1,000). 28 Table 3: Tabulated summary of adverse reactions associated with the individual components of emtricitabine/tenofovir disoproxil based on clinical study and post-marketing experience Frequency Emtricitabine Tenofovir disoproxil Blood and lymphatic system disorders: Common: neutropenia Uncommon: anaemia 2 Immune system disorders: Common: allergic reaction Metabolism and nutrition disorders: Very common: hypophosphataemia 1 Common: hyperglycaemia, hypertriglyceridaemia Uncommon: hypokalaemia 1 Rare: lactic acidosis Psychiatric disorders: Common:

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HOS-097545 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Use for pre-exposure prophylaxis in individuals with unknown or positive HIV-1 status.

HOS-097544 · has-indication-information · PDF-Seite 2

Treatment of HIV-1 infection: Emtricitabine/Tenofovir disoproxil Mylan is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults (see section 5.1). Emtricitabine/Tenofovir disoproxil Mylan is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, (see sections 4.2, 4.4 and 5.1). Pre-exposure prophylaxis (PrEP): Emtricitabine/Tenofovir disoproxil Mylan is indicated in combination with safer sex practices for pre- exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents at high risk (see sections 4.2, 4.4 and 5.1).

HOS-097547 · has-interaction-information · PDF-Seite 10

Interaction studies have only been performed in adults. As emtricitabine/tenofovir disoproxil fixed-dose combination tablets contains emtricitabine and tenofovir disoproxil, any interactions that have been identified with these agents individually may occur with the fixed-dose combination. Interaction studies have only been performed in adults. The steady-state pharmacokinetics of emtricitabine and tenofovir were unaffected when emtricitabine and tenofovir disoproxil were administered together versus each medicinal product dosed alone. In vitro and clinical pharmacokinetic interaction studies have shown the potential for CYP450 mediated interactions involving emtricitabine and tenofovir disoproxil with other medicinal products is low. Concomitant use not recommended Emtricitabine/tenofovir disoproxil should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil, tenofovir alafenamide or other cytidine analogues, such as lamivudine (see section 4.4). Emtricitabine/tenofovir disoproxil should not be administered concomitantly with adefovir dipivoxil. Didanosine: The co-administration of emtricitabine/tenofovir disoproxil and didanosine is not recommended (see section 4.4 and Table 2). Renally eliminated medicinal products: Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of emtricitabine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion (e.g. cidofovir) may increase serum concentrations of emtricitabine, tenofovir and/or the co-administered medicinal products. Use of emtricitabine/tenofovir disoproxil should be avoided with concurrent or recent use of a nephrotoxic medicinal product. Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (see section 4.4). Other interactions 10 Interactions between emtricitabine/tenofovir disoproxil or its individual component(s) and other medicinal products are listed in Table 2 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, twice daily as “b.i.d.” and once daily as “q.d.”). If available, 90% confidence intervals are shown in parentheses. Table 2: Interactions between emtricitabine/tenofovir disoproxil or its individual component(s) and other medicinal products Medicinal

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HOS-097548 · has-pregnancy-information · PDF-Seite 27

27 Pregnancy A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil. Animal studies on emtricitabine and tenofovir disoproxil do not indicate reproductive toxicity (see section 5.3). Therefore, the use of emtricitabine/tenofovir disoproxil may be considered during pregnancy, if necessary. Breast-feeding Emtricitabine and tenofovir have been shown to be excreted in human milk. There is insufficient information on the effects of emtricitabine and tenofovir in newborns/infants. Therefore, emtricitabine/tenofovir disoproxil should not be used during breast-feeding. In order to avoid transmission of HIV to the infant it is recommended that women living with HIV do not breast-feed their infants. Fertility No human data on the effect of emtricitabine/tenofovir disoproxil are available. Animal studies do not indicate harmful effects of emtricitabine or tenofovir disoproxil on fertility.

HOS-097546 · has-warning-information · PDF-Seite 4

Patients with HIV-1 harbouring mutations Emtricitabine/tenofovir disoproxil should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R mutation (see section 5.1). Overall HIV-1 infection prevention strategy Emtricitabine/tenofovir disoproxil is not always effective in preventing the acquisition of HIV-1. The time to onset of protection after commencing emtricitabine/tenofovir disoproxil is unknown. Emtricitabine/tenofovir disoproxil should only be used for pre-exposure prophylaxis as part of an overall HIV-1 infection prevention strategy including the use of other HIV-1 prevention measures (e.g. consistent and correct condom use, knowledge of HIV-1 status, regular testing for other sexually transmitted infections). Risk of resistance with undetected HIV-1 infection Emtricitabine/tenofovir disoproxil should only be used to reduce the risk of acquiring HIV-1 in individuals confirmed to be HIV negative (see section 4.3). Individuals should be re-confirmed to be HIV-negative at frequent intervals (e.g. at least every 3 months) using a combined antigen/antibody test while taking emtricitabine/tenofovir disoproxil for pre-exposure prophylaxis. Emtricitabine/tenofovir disoproxil alone does not constitute a complete regimen for the treatment of HIV-1 and HIV-1 resistance mutations have emerged in individuals with undetected HIV-1 infection who are only taking emtricitabine/tenofovir disoproxil. If clinical symptoms consistent with acute viral infection are present and recent (< 1 month) exposures to HIV-1 are suspected, use of emtricitabine/tenofovir disoproxil should be delayed for at least one month and HIV-1 status reconfirmed before starting emtricitabine/tenofovir disoproxil for pre- exposure prophylaxis. Importance of adherence The effectiveness of Emtricitabine/tenofovir disoproxil in reducing the risk of acquiring HIV-1 is strongly correlated with adherence as demonstrated by measurable drug levels in blood (see 4 section 5.1). HIV-1 uninfected individuals should be counselled at frequent intervals to strictly adhere to the recommended Emtricitabine/tenofovir disoproxil daily dosing schedule. Patients with hepatitis B or C virus infection HIV-1 infected patients with chronic hepatitis B or C treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Physicians should refer to current HIV treatment guidel

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