Isentress · 4.1 Therapeutic indications · 2

HOS-094918 · has-adverse-reaction-information · PDF-Seite 34

Summary of the safety profile In randomised clinical trials raltegravir 400 mg twice daily was administered in combination with fixed or optimised background treatment regimens to treatment-naïve (N=547) and treatment- experienced (N=462) adults for up to 96 weeks. A further 531 treatment-naïve adults have received raltegravir 1,200 mg once daily with emtricitabine and tenofovir disoproxil fumarate for up to 96 weeks. See section 5.1. 34 The most frequently reported adverse reactions during treatment were headache, nausea and abdominal pain. The most frequently reported serious adverse reactions were immune reconstitution syndrome and rash. The rates of discontinuation of raltegravir due to adverse reactions were 5% or less in clinical trials. Rhabdomyolysis was an uncommonly reported serious adverse reaction in post-marketing use of raltegravir 400 mg twice daily. Tabulated summary of adverse reactions Adverse reactions considered by investigators to be causally related to raltegravir (alone or in combination with other ART), as well as adverse reactions established in post-marketing experience, are listed below by System Organ Class. Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and not known (cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Infections and infestations Uncommon genital herpes, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection Neoplasms benign, Uncommon skin papilloma malignant and unspecified (including cysts and polyps) Blood and lymphatic system Uncommon anaemia, iron deficiency anaemia, lymph node disorders pain, lymphadenopathy, neutropenia, thrombocyto

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094924 · has-adverse-reaction-information · PDF-Seite 59

Summary of the safety profile In randomised clinical trials raltegravir 400 mg twice daily was administered in combination with fixed or optimised background treatment regimens to treatment-naïve (N=547) and treatment- experienced (N=462) adults for up to 96 weeks. A further 531 treatment-naïve adults have received raltegravir 1,200 mg once daily with emtricitabine and tenofovir disoproxil fumarate for up to 96 weeks. See section 5.1. The most frequently reported adverse reactions during treatment were headache, nausea and abdominal pain. The most frequently reported serious adverse reaction was immune reconstitution syndrome and rash. The rates of discontinuation of raltegravir due to adverse reactions were 5 % or less in clinical trials. Rhabdomyolysis was an uncommonly reported serious adverse reaction in post-marketing use of raltegravir 400 mg twice daily. Tabulated summary of adverse reactions Adverse reactions considered by investigators to be causally related to raltegravir (alone or in combination with other ART), as well as adverse reactions established in post-marketing experience, are listed below by System Organ Class. Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and not known (cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Infections and infestations Uncommon genital herpes, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection Neoplasms benign, Uncommon skin papilloma malignant and unspecified (including cysts and polyps) 59  System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Blood a

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094912 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile In randomised clinical trials raltegravir 400 mg twice daily was administered in combination with fixed or optimised background treatment regimens to treatment-naïve (N=547) and treatment- experienced (N=462) adults for up to 96 weeks. A further 531 treatment-naïve adults have received raltegravir 1,200 mg once daily with emtricitabine and tenofovir disoproxil fumarate for up to 96 weeks. See section 5.1. The most frequently reported adverse reactions during treatment were headache, nausea and abdominal pain. The most frequently reported serious adverse reaction was immune reconstitution syndrome and rash. The rates of discontinuation of raltegravir due to adverse reactions were 5% or less in clinical trials. Rhabdomyolysis was an uncommonly reported serious adverse reaction in post-marketing use of raltegravir 400 mg twice daily. Tabulated summary of adverse reactions Adverse reactions considered by investigators to be causally related to raltegravir (alone or in combination with other ART), as well as adverse reactions established in post-marketing experience, are listed below by System Organ Class. Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and not known (cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Infections and infestations Uncommon genital herpes, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection Neoplasms benign, Uncommon skin papilloma malignant and unspecified (including cysts and polyps) 10  System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Blood an

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094930 · has-adverse-reaction-information · PDF-Seite 83

Summary of the safety profile In randomised clinical trials raltegravir 400 mg twice daily was administered in combination with fixed or optimised background treatment regimens to treatment-naïve (N=547) and treatment- experienced (N=462) adults for up to 96 weeks. A further 531 treatment-naïve adults have received raltegravir 1,200 mg once daily with emtricitabine and tenofovir disoproxil fumarate for up to 96 weeks. See section 5.1. The most frequently reported adverse reactions during treatment were headache, nausea and abdominal pain. The most frequently reported serious adverse reaction was immune reconstitution syndrome and rash. The rates of discontinuation of raltegravir due to adverse reactions were 5% or less in clinical trials. Rhabdomyolysis was an uncommonly reported serious adverse reaction in post-marketing use of raltegravir 400 mg twice daily. Tabulated summary of adverse reactions Adverse reactions considered by investigators to be causally related to raltegravir (alone or in combination with other ART), as well as adverse reactions established in post-marketing experience, are listed below by System Organ Class. Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and not known (cannot be estimated from the available data). 83  System Organ Class Frequency Adverse reactions Raltegravir (alone or in combination with other ART) Infections and infestations Uncommon genital herpes, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection Neoplasms benign, Uncommon skin papilloma malignant and unspecified (including cysts and polyps) Blood and lymphatic system Uncommon anaemia, iron deficiency anaemia, lymph node disorders pain, lymphadenopathy, neutropenia, thrombocytopenia Immune system disorders Uncommon immu

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094914 · has-contraindication-information · PDF-Seite 26

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

HOS-094908 · has-contraindication-information · PDF-Seite 3

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

HOS-094920 · has-contraindication-information · PDF-Seite 51

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

HOS-094926 · has-contraindication-information · PDF-Seite 76

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

HOS-094925 · has-indication-information · PDF-Seite 74

ISENTRESS is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection (see sections 4.2, 4.4, 5.1 and 5.2).

HOS-094913 · has-indication-information · PDF-Seite 25

ISENTRESS 600 mg film-coated tablets is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adults, and paediatric patients weighing at least 40 kg (see sections 4.2, 4.4, 5.1 and 5.2).

HOS-094907 · has-indication-information · PDF-Seite 2

ISENTRESS is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection (see sections 4.2, 4.4, 5.1 and 5.2).

HOS-094919 · has-indication-information · PDF-Seite 49

ISENTRESS is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection (see sections 4.2, 4.4, 5.1 and 5.2).

HOS-094916 · has-interaction-information · PDF-Seite 28

In vitro, raltegravir is a weak inhibitor of organic anion transporter (OAT) 1 (IC50 of 109 µM) and OAT3 (IC50 of 18.8 µM). Caution is recommended when co-administering raltegravir 1,200 mg once daily with sensitive OAT1 and/or OAT3 substrates. In vitro studies indicate that raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not inhibit UDP glucuronosyltransferases (UGTs) 1A1 and 2B7, does not induce CYP3A4 and is not an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion-transporting polypeptides (OATP) 1B1, OATP1B3, organic cation transporters (OCT)1 and OCT2, or multidrug and toxin extrusion proteins (MATE)1 and MATE2-K. Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or transporters. Based on in vitro and in vivo studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Considerable inter- and intra-individual variability was observed in the pharmacokinetics of raltegravir. 28 Effect of raltegravir on the pharmacokinetics of other medicinal products In drug interaction studies performed using raltegravir 400 mg twice daily, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir disoproxil fumarate, hormonal contraceptives, methadone, midazolam or boceprevir. These findings can be extended to raltegravir 1,200 mg once daily and no dosage adjustment is required for these agents. In some studies, co-administration of raltegravir 400 mg tablets twice daily with darunavir resulted in a modest but clinically insignificant decrease in darunavir plasma concentrations. Based on the magnitude of effect seen with raltegravir 400 mg tablets twice daily, it is expected that the effect of raltegravir 1,200 mg once daily on darunavir plasma concentrations is likely to be not clinically meaningful. Effect of other medicinal products on the pharmacokinetics of raltegravir Inducers of drug metabolizing enzymes The impact of medicinal products that are strong inducers of UGT1A1 such as rifampicin on raltegravir 1,200 mg once daily is unknown, but co-administration is likely to decrease raltegravir trough levels based on the reduction in trough concentrations observed with raltegravir 400

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094922 · has-interaction-information · PDF-Seite 54

In vitro studies indicate that raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not inhibit UDP glucuronosyltransferases (UGTs) 1A1 and 2B7, does not induce CYP3A4 and does not inhibit P-glycoprotein-mediated transport. Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein. Based on in vitro and in vivo studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Considerable inter- and intra-individual variability was observed in the pharmacokinetics of raltegravir. Effect of raltegravir on the pharmacokinetics of other medicinal products In interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir disoproxil fumarate, hormonal contraceptives, methadone, midazolam or boceprevir. In some studies, co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations; the mechanism for this effect is unknown. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful. 54 Effect of other medicinal products on the pharmacokinetics of raltegravir Given that raltegravir is metabolised primarily via UGT1A1, caution should be used when co-administering raltegravir with strong inducers of UGT1A1 (e.g., rifampicin). Rifampicin reduces plasma levels of raltegravir; the impact on the efficacy of raltegravir is unknown. However, if co-administration with rifampicin is unavoidable, a doubling of the dose of raltegravir can be considered in adults. There are no data to guide co-administration of raltegravir with rifampicin in patients below 18 years of age (see section 4.4). The impact of other strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown. Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir. Co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir. Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094910 · has-interaction-information · PDF-Seite 5

In vitro studies indicate that raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not inhibit UDP glucuronosyltransferases (UGTs) 1A1 and 2B7, does not induce CYP3A4 and does not inhibit P-glycoprotein-mediated transport. Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein. Based on in vitro and in vivo studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Considerable inter- and intra-individual variability was observed in the pharmacokinetics of raltegravir. Effect of raltegravir on the pharmacokinetics of other medicinal products In interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir disoproxil fumarate, hormonal contraceptives, methadone, midazolam or boceprevir. In some studies, co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations; the mechanism for this effect is unknown. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful. 5 Effect of other medicinal products on the pharmacokinetics of raltegravir Given that raltegravir is metabolised primarily via UGT1A1, caution should be used when co-administering raltegravir with strong inducers of UGT1A1 (e.g., rifampicin). Rifampicin reduces plasma levels of raltegravir; the impact on the efficacy of raltegravir is unknown. However, if co-administration with rifampicin is unavoidable, a doubling of the dose of raltegravir can be considered in adults. There are no data to guide co-administration of raltegravir with rifampicin in patients below 18 years of age (see section 4.4). The impact of other strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown. Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir. Co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir. Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094928 · has-interaction-information · PDF-Seite 78

In vitro studies indicate that raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not inhibit UDP glucuronosyltransferases (UGTs) 1A1 and 2B7, does not induce CYP3A4 and does not inhibit P-glycoprotein-mediated transport. Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein. Based on in vitro and in vivo studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Considerable inter- and intra-individual variability was observed in the pharmacokinetics of raltegravir. 78 Effect of raltegravir on the pharmacokinetics of other medicinal products In interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir disoproxil fumarate, hormonal contraceptives, methadone, midazolam or boceprevir. In some studies, co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations; the mechanism for this effect is unknown. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful. Effect of other medicinal products on the pharmacokinetics of raltegravir Given that raltegravir is metabolised primarily via UGT1A1, caution should be used when co-administering raltegravir with strong inducers of UGT1A1 (e.g., rifampicin). Rifampicin reduces plasma levels of raltegravir; the impact on the efficacy of raltegravir is unknown. However, if co-administration with rifampicin is unavoidable, a doubling of the dose of raltegravir can be considered in adults. There are no data to guide co-administration of raltegravir with rifampicin in patients below 18 years of age (see section 4.4). The impact of other strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown. Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir. Co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir. Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094911 · has-pregnancy-information · PDF-Seite 9

Pregnancy A large amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the first trimester (more than 1,000 prospective pregnancy outcomes) indicates no malformative toxicity. Animal studies have shown reproductive toxicity (see section 5.3). A moderate amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the second and/or third trimester (between 300-1,000 prospective pregnancy outcomes) indicates no increased risk of feto/neonatal toxicity. Raltegravir 400 mg twice daily can be used during pregnancy if clinically needed. Anti-retroviral Pregnancy Registry To monitor maternal-foetal outcomes in patients inadvertently administered raltegravir while pregnant, an Anti-retroviral Pregnancy Registry has been established. Physicians are encouraged to register patients in this registry. As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account in order to characterise the safety for the foetus. 9 Breast-feeding Raltegravir/metabolites are excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Available pharmacodynamics/toxicological data in animals have shown excretion of raltegravir/metabolites in milk (for details see section 5.3). A risk to the newborns/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility No effect on fertility was seen in male and female rats at doses up to 600 mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose.

HOS-094929 · has-pregnancy-information · PDF-Seite 82

Pregnancy There are no data for the use of raltegravir granules for oral suspension in pregnant women. A large amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the first trimester (more than 1,000 prospective pregnancy outcomes) indicates no malformative toxicity. Animal studies have shown reproductive toxicity (see section 5.3). A moderate amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the second and/or third trimester (between 300-1,000 prospective pregnancy outcomes) indicates no increased risk of feto/neonatal toxicity. Raltegravir granules for oral suspension should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. See section 4.2 for dosing recommendations. Anti-retroviral Pregnancy Registry To monitor maternal-foetal outcomes in patients inadvertently administered raltegravir while pregnant, an Anti-retroviral Pregnancy Registry has been established. Physicians are encouraged to register patients in this registry. 82 As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account in order to characterise the safety for the foetus. Breast-feeding Raltegravir/metabolites are excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Available pharmacodynamics/toxicological data in animals have shown excretion of raltegravir/metabolites in milk (for details see section 5.3). A risk to the newborns/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility No effect on fertility was seen in male and female rats at doses up to 600 mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose.

HOS-094923 · has-pregnancy-information · PDF-Seite 58

Pregnancy There are no data for the use of raltegravir chewable tablets in pregnant women. A large amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the first trimester (more than 1,000 prospective pregnancy outcomes) indicates no malformative toxicity. Animal studies have shown reproductive toxicity (see section 5.3). A moderate amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the second and/or third trimester (between 300-1,000 prospective pregnancy outcomes) indicates no increased risk of feto/neonatal toxicity. Raltegravir chewable tablets should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. See section 4.2 for dosing recommendations. Anti-retroviral Pregnancy Registry To monitor maternal-foetal outcomes in patients inadvertently administered raltegravir while pregnant, an Anti-retroviral Pregnancy Registry has been established. Physicians are encouraged to register patients in this registry. As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account in order to characterise the safety for the foetus. 58 Breast-feeding Raltegravir/metabolites are excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Available pharmacodynamics/toxicological data in animals have shown excretion of raltegravir/metabolites in milk (for details see section 5.3). A risk to the newborns/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility No effect on fertility was seen in male and female rats at doses up to 600 mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose.

HOS-094917 · has-pregnancy-information · PDF-Seite 34

Pregnancy There are no data for the use of raltegravir 1,200 mg once daily in pregnant women. A large amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the first trimester (more than 1,000 prospective pregnancy outcomes) indicates no malformative toxicity. Animal studies have shown reproductive toxicity (see section 5.3). A moderate amount of data on pregnant women with exposure to raltegravir 400 mg twice daily during the second and/or third trimester (between 300-1,000 prospective pregnancy outcomes) indicates no increased risk of feto/neonatal toxicity. Raltegravir 1,200 mg is not recommended during pregnancy. Anti-retroviral Pregnancy Registry To monitor maternal-foetal outcomes in patients inadvertently administered raltegravir while pregnant, an Anti-retroviral Pregnancy Registry has been established. Physicians are encouraged to register patients in this registry. As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account in order to characterise the safety for the foetus. Breast-feeding Raltegravir/metabolites are excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Available pharmacodynamics/toxicological data in animals have shown excretion of raltegravir/metabolites in milk (for details see section 5.3). A risk to the newborns/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility No effect on fertility was seen in male and female rats at doses up to 600 mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose.

HOS-094909 · has-warning-information · PDF-Seite 3

General Patients should be advised that current anti-retroviral therapy does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood contact. Raltegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, raltegravir should be administered with two other active ARTs to minimise the potential for virological failure and the development of resistance (see section 5.1). In treatment-naïve patients, the clinical study data on use of raltegravir are limited to use in combination with two nucleotide reverse transcriptase inhibitors (NRTIs) (emtricitabine and tenofovir disoproxil fumarate). Depression Depression, including suicidal ideation and behaviours, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness. 3 Hepatic impairment The safety and efficacy of raltegravir have not been established in patients with severe underlying liver disorders. Therefore, raltegravir should be used with caution in patients with severe hepatic impairment (see sections 4.2 and 5.2). Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination anti-retroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Patients with chronic hepatitis B or C and treated with combination anti-retroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to combination anti-retroviral therapy. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. Immune reactivation syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination anti- retroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportun

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094915 · has-warning-information · PDF-Seite 26

General Patients should be advised that current anti-retroviral therapy does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood contact. Raltegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, raltegravir should be administered with two other active ARTs to minimise the potential for virological failure and the development of resistance (see section 5.1). In treatment-naïve patients, the clinical study data on use of raltegravir are limited to use in combination with two nucleotide reverse transcriptase inhibitors (NRTIs) (emtricitabine and tenofovir disoproxil fumarate). Depression Depression, including suicidal ideation and behaviours, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness. 26 Hepatic impairment The safety and efficacy of raltegravir have not been established in patients with severe underlying liver disorders. Therefore, raltegravir should be used with caution in patients with severe hepatic impairment (see sections 4.2 and 5.2). Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination anti-retroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Patients with chronic hepatitis B or C and treated with combination anti-retroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to combination anti-retroviral therapy. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. Immune reactivation syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination anti- retroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportun

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HOS-094921 · has-warning-information · PDF-Seite 51

General Patients should be advised that current anti-retroviral therapy does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood contact. Raltegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, raltegravir should be administered with two other active ARTs to minimise the potential for virological failure and the development of resistance (see section 5.1). In treatment-naïve patients, the clinical study data on use of raltegravir are limited to use in combination with two nucleotide reverse transcriptase inhibitors (NRTIs) (emtricitabine and tenofovir disoproxil fumarate). Depression Depression, including suicidal ideation and behaviours, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness. 51 Hepatic impairment The safety and efficacy of raltegravir have not been established in patients with severe underlying liver disorders. Therefore, raltegravir should be used with caution in patients with severe hepatic impairment (see sections 4.2 and 5.2). Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination anti-retroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Patients with chronic hepatitis B or C and treated with combination anti-retroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to combination anti-retroviral therapy. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. Immune reactivation syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination anti- retroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportun

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HOS-094927 · has-warning-information · PDF-Seite 76

General Patients should be advised that current anti-retroviral therapy does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood contact. Raltegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, raltegravir should be administered with two other active ARTs to minimise the potential for virological failure and the development of resistance (see section 5.1). In treatment-naïve patients, the clinical study data on use of raltegravir are limited to use in combination with two nucleotide reverse transcriptase inhibitors (NRTIs) (emtricitabine and tenofovir disoproxil fumarate). Depression Depression, including suicidal ideation and behaviours, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness. 76 Hepatic impairment The safety and efficacy of raltegravir have not been established in patients with severe underlying liver disorders. Therefore, raltegravir should be used with caution in patients with severe hepatic impairment (see sections 4.2 and 5.2). Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination anti-retroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Patients with chronic hepatitis B or C and treated with combination anti-retroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to combination anti-retroviral therapy. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. Immune reactivation syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination anti- retroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportuni

Auszug; vollständigen Abschnitt im Original lesen.