Emtriva · 4.8 Undesirable effects · 2

HOS-093734 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile In clinical trials of HIV infected adults, the most frequently occurring adverse reactions to emtricitabine were diarrhoea (14.0%), headache (10.2%), elevated creatine kinase (10.2%) and nausea (10.0%). In addition to the adverse reactions reported in adults, anaemia (9.5%) and skin discolouration (31.8%) occurred more frequently in clinical trials involving HIV infected paediatric patients. Discontinuation of Emtriva therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis (see section 4.4). Tabulated summary of adverse reactions Assessment of adverse reactions from clinical study data is based on experience in three studies in adults (n = 1,479) and three paediatric studies (n = 169). In the adult studies, 1,039 treatment-naïve and 440 treatment-experienced patients received emtricitabine (n = 814) or comparator medicinal product (n = 665) for 48 weeks in combination with other antiretroviral medicinal products. The adverse reactions with suspected (at least possible) relationship to treatment in adults from clinical trial and post-marketing experience are listed in Table 2 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) or uncommon (≥ 1/1,000 to < 1/100). Table 2: Tabulated summary of adverse reactions associated with emtricitabine based on clinical study and post-marketing experience Frequency Emtricitabine Blood and lymphatic system disorders: Common: neutropenia Uncommon: anaemia2 Immune system disorders: Common: allergic reaction Metabolism and nutrition disorders: Common: hypertriglyceridaemia, hyperglycaemia Psychiatric disorders: Common: insomnia, abnormal dreams Nervous system disorders: Very common: headache Common: dizziness Gastrointestinal disorders: Very common: diarrhoea, nausea Common: elevated amylase including elevated pancreatic amylase, elevated serum lipase, vomiting, abdominal pain, dyspepsia Hepatobiliary disorders: Common: elevated serum aspartate aminotransferase (AST) and/or elevated serum ALT, hyperbilirubinaemia Skin and subcutaneous tissue disorders: Common

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093740 · has-adverse-reaction-information · PDF-Seite 19

Summary of the safety profile In clinical trials of HIV infected adults, the most frequently occurring adverse reactions to emtricitabine were diarrhoea (14.0%), headache (10.2%), elevated creatine kinase (10.2%) and nausea (10.0%). In addition to the adverse reactions reported in adults, anaemia (9.5%) and skin discolouration (31.8%) occurred more frequently in clinical trials involving HIV infected paediatric patients. Discontinuation of Emtriva therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis (see section 4.4). Tabulated summary of adverse reactions Assessment of adverse reactions from clinical study data is based on experience in three studies in adults (n = 1,479) and three paediatric studies (n = 169). In the adult studies, 1,039 treatment-naïve and 440 treatment-experienced patients received emtricitabine (n = 814) or comparator medicinal product (n = 665) for 48 weeks in combination with other antiretroviral medicinal products. The adverse reactions with suspected (at least possible) relationship to treatment in adults from clinical trial and post-marketing experience are listed in Table 2 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) or uncommon (≥ 1/1,000 to < 1/100). Table 2: Tabulated summary of adverse reactions associated with emtricitabine based on clinical study and post-marketing experience Frequency Emtricitabine Blood and lymphatic system disorders: Common: neutropenia Uncommon: anaemia2 Immune system disorders: Common: allergic reaction Metabolism and nutrition disorders: Common: hypertriglyceridaemia, hyperglycaemia Psychiatric disorders: Common: insomnia, abnormal dreams Nervous system disorders: Very common: headache Common: dizziness 19 Gastrointestinal disorders: Very common: diarrhoea, nausea Common: elevated amylase including elevated pancreatic amylase, elevated serum lipase, vomiting, abdominal pain, dyspepsia Hepatobiliary disorders: Common: elevated serum aspartate aminotransferase (AST) and/or elevated serum ALT, hyperbilirubinae

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093730 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093736 · has-contraindication-information · PDF-Seite 16

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093729 · has-indication-information · PDF-Seite 2

Emtriva is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus-1 (HIV-1) infected adults and children aged 4 months and over. This indication is based on studies in treatment-naïve patients and treatment-experienced patients with stable virological control. There is no experience of the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens (see section 5.1). When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.

HOS-093735 · has-indication-information · PDF-Seite 14

Emtriva is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus-1 (HIV-1) infected adults and children aged 4 months and over. This indication is based on studies in treatment-naïve patients and treatment-experienced patients with stable virological control. There is no experience of the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens (see section 5.1). When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.

HOS-093732 · has-interaction-information · PDF-Seite 6

Interaction studies have only been performed in adults. In vitro, emtricitabine did not inhibit metabolism mediated by any of the following human CYP450 isoforms: 1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4. Emtricitabine did not inhibit the enzyme responsible for glucuronidation. Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low. There are no clinically significant interactions when emtricitabine is co-administered with indinavir, zidovudine, stavudine, famciclovir or tenofovir disoproxil fumarate. Emtricitabine is primarily excreted via glomerular filtration and active tubular secretion. With the exception of famciclovir and tenofovir disoproxil fumarate, the effect of co-administration of emtricitabine with medicinal products that are excreted by the renal route, or other medicinal products known to affect renal function, has not been evaluated. Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may lead to an increase in serum concentrations of either emtricitabine or a co-administered medicinal product due to competition for this elimination pathway. There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.

HOS-093738 · has-interaction-information · PDF-Seite 18

Interaction studies have only been performed in adults. In vitro, emtricitabine did not inhibit metabolism mediated by any of the following human CYP450 isoforms: 1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4. Emtricitabine did not inhibit the enzyme responsible for glucuronidation. Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low. There are no clinically significant interactions when emtricitabine is co-administered with indinavir, zidovudine, stavudine, famciclovir or tenofovir disoproxil fumarate. Emtricitabine is primarily excreted via glomerular filtration and active tubular secretion. With the exception of famciclovir and tenofovir disoproxil fumarate, the effect of co-administration of emtricitabine with medicinal products that are excreted by the renal route, or other medicinal products known to affect renal function, has not been evaluated. Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may lead to an increase in serum concentrations of either emtricitabine or a co-administered medicinal product due to competition for this elimination pathway. There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.

HOS-093733 · has-pregnancy-information · PDF-Seite 6

Pregnancy A moderate amount of data on pregnant women (between 300 and1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine. Animal studies do not indicate reproductive toxicity. The use of emtricitabine may be considered during pregnancy, if necessary. Breast-feeding Emtricitabine has been shown to be excreted in human milk. There is insufficient information on the effects of emtricitabine in newborns/infants. Therefore Emtriva 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 are available. Animal studies do not indicate harmful effects of emtricitabine on fertility. 6

HOS-093739 · has-pregnancy-information · PDF-Seite 18

Pregnancy A moderate amount of data on pregnant women (between 300 and1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine. Animal studies do not indicate reproductive toxicity. The use of emtricitabine may be considered during pregnancy, if necessary. 18 Breast-feeding Emtricitabine has been shown to be excreted in human milk. There is insufficient information on the effects of emtricitabine in newborns/infants. Therefore Emtriva 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 are available. Animal studies do not indicate harmful effects of emtricitabine on fertility.

HOS-093737 · has-warning-information · PDF-Seite 16

General Emtricitabine is not recommended as monotherapy for the treatment of HIV infection. It must be used in combination with other antiretrovirals. Please also refer to the Summaries of Product Characteristics of the other antiretroviral medicinal products used in the combination regimen. Co-administration of other medicinal products Emtriva should not be taken with any other medicinal products containing emtricitabine or medicinal products containing lamivudine. Opportunistic infections Patients receiving emtricitabine or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases. Renal function Emtricitabine is principally eliminated by the kidney via glomerular filtration and active tubular secretion. Emtricitabine exposure may be markedly increased in patients with severe renal insufficiency (creatinine clearance < 30 mL/min) receiving daily doses of 200 mg emtricitabine as hard capsules or 240 mg as the oral solution. Consequently, either a dose interval adjustment (using Emtriva 200 mg hard capsules) or a reduction in the daily dose of emtricitabine (using Emtriva 10 mg/mL oral solution) is required in all patients with creatinine clearance < 30 mL/min. The safety and efficacy of the reduced doses provided in section 4.2 are based on single dose pharmacokinetic data and modelling and have not been clinically evaluated. Therefore, clinical response to treatment and renal function should be closely monitored in patients treated with a reduced dose of emtricitabine (see sections 4.2 and 5.2). Caution should be exercised when emtricitabine is co-administered with medicinal products that are eliminated by active tubular secretion as such co-administration may lead to an increase in serum concentrations of either emtricitabine or a co-administered medicinal product, due to competition for this elimination pathway (see section 4.5). Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose referen

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093731 · has-warning-information · PDF-Seite 4

General Emtricitabine is not recommended as monotherapy for the treatment of HIV infection. It must be used in combination with other antiretrovirals. Please also refer to the Summaries of Product Characteristics of the other antiretroviral medicinal products used in the combination regimen. Co-administration of other medicinal products Emtriva should not be taken with any other medicinal products containing emtricitabine or medicinal products containing lamivudine. Opportunistic infections Patients receiving emtricitabine or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases. Renal function Emtricitabine is principally eliminated by the kidney via glomerular filtration and active tubular secretion. Emtricitabine exposure may be markedly increased in patients with severe renal insufficiency (creatinine clearance < 30 mL/min) receiving daily doses of 200 mg emtricitabine as hard capsules or 240 mg as the oral solution. Consequently, either a dose interval adjustment (using Emtriva 200 mg hard capsules) or a reduction in the daily dose of emtricitabine (using Emtriva 10 mg/mL oral solution) is required in all patients with creatinine clearance < 30 mL/min. The safety and efficacy of the dose interval adjustment guidelines provided in section 4.2 are based on single dose pharmacokinetic data and modelling and have not been clinically evaluated. Therefore, clinical response to treatment and renal function should be closely monitored in patients treated with emtricitabine at prolonged dosing intervals (see sections 4.2 and 5.2). Caution should be exercised when emtricitabine is co-administered with medicinal products that are eliminated by active tubular secretion as such co-administration may lead to an increase in serum concentrations of either emtricitabine or a co-administered medicinal product, due to competition for this elimination pathway (see section 4.5). Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring o

Auszug; vollständigen Abschnitt im Original lesen.