Leitlinien & Arzneimittelsicherheit

HOS-083634 · has-adverse-reaction-information · PDF-Seite 66

Summary of the safety profile The most frequently reported adverse reactions related to Viramune prolonged-release therapy in treatment naïve patients (including lead-in phase with immediate-release) in clinical study 1100.1486 (VERxVE) were rash, nausea, liver function test abnormal, headache, fatigue, hepatitis, abdominal pain, diarrhoea and pyrexia. There are no new adverse drug reactions for Viramune prolonged-release tablets that have not been previously identified for Viramune immediate-release tablets and oral suspension. 66 The nevirapine postmarketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome/toxic epidermal necrolysis, serious hepatitis/hepatic failure, and drug reaction with eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction. The first 18 weeks of treatment is a critical period which requires close monitoring (see section 4.4). Tabulated summary of adverse reactions The following adverse reactions which may be causally related to the administration of Viramune prolonged-release tablets have been reported. The frequencies given below are based on crude incidence rates of adverse reactions observed in the Viramune immediate-release (lead-in phase, table 1) and Viramune prolonged-release (randomised-phase/maintenance phase, table 2) groups of clinical study 1100.1486 with 1 068 patients exposed to Viramune on a backbone of tenofovir/emtricitabine. Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) Table 1: Lead-in phase with Viramune immediate-release Blood and lymphatic system disorders Uncommon granulocytopenia Rare anaemia Immune system disorders Uncommon hypersensitivity (incl. anaphylactic reaction, angioedema, urticaria), drug reaction with eosinophilia and systemic symptoms, anaphylactic reaction Nervous system disorders Common headache Gastrointestinal disorders Common abdominal pain, nausea, diarrhoea Uncommon vomiting Hepatobiliary disorders Uncommon jaundice, hepatitis fulminant (which may be fatal) Rare

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083628 · has-adverse-reaction-information · PDF-Seite 41

Summary of the safety profile The most frequently reported adverse reactions related to Viramune therapy, across all clinical studies, were rash, allergic reactions, hepatitis, abnormal liver function tests, nausea, vomiting, diarrhoea, abdominal pain, fatigue, fever, headache and myalgia. The postmarketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome/ toxic epidermal necrolysis, serious hepatitis/hepatic failure, and drug reaction with eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction. The first 18 weeks of treatment is a critical period which requires close monitoring (see section 4.4). Tabulated summary of adverse reactions The following adverse reactions which may be causally related to the administration of Viramune have been reported. The frequencies estimated are based on pooled clinical study data for adverse reactions considered related to Viramune treatment. Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Blood and lymphatic system disorders Common granulocytopenia Uncommon anaemia Immune system disorders Common hypersensitivity (incl. anaphylactic reaction, angioedema, urticaria) Uncommon anaphylactic reaction Rare drug reaction with eosinophilia and systemic symptoms Nervous system disorders Common headache Gastrointestinal disorders Common nausea, vomiting, abdominal pain, diarrhoea Hepatobiliary disorders Common hepatitis (including severe and life-threatening hepatotoxicity) (1.9%) Uncommon jaundice Rare hepatitis fulminant (which may be fatal) Skin and subcutaneous tissue disorders Very common rash (12.5%) Uncommon Stevens-Johnson syndrome/ toxic epidermal necrolysis (which may be fatal) (0.2%), angioedema, urticaria 41 Musculoskeletal and connective tissue disorders Uncommon arthralgia, myalgia General disorders and administration site conditions Common pyrexia, fatigue Investigations Common liver function test abnormal (alanine ami

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083622 · has-adverse-reaction-information · PDF-Seite 17

Summary of the safety profile The most frequently reported adverse reactions related to Viramune therapy, across all clinical studies, were rash, allergic reactions, hepatitis, abnormal liver function tests, nausea, vomiting, diarrhoea, abdominal pain, fatigue, fever, headache and myalgia. The postmarketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome/ toxic epidermal necrolysis, serious hepatitis/hepatic failure, and drug reaction with eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction. The first 18 weeks of treatment is a critical period which requires close monitoring (see section 4.4). Tabulated summary of adverse reactions The following adverse reactions which may be causally related to the administration of Viramune have been reported. The frequencies estimated are based on pooled clinical study data for adverse reactions considered related to Viramune treatment. Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Blood and lymphatic system disorders Common granulocytopenia Uncommon anaemia Immune system disorders Common hypersensitivity (incl. anaphylactic reaction, angioedema, urticaria) Uncommon anaphylactic reaction Rare drug reaction with eosinophilia and systemic symptoms Nervous system disorders Common headache Gastrointestinal disorders Common nausea, vomiting, abdominal pain, diarrhoea Hepatobiliary disorders Common hepatitis (including severe and life-threatening hepatotoxicity) (1.9%) Uncommon jaundice Rare hepatitis fulminant (which may be fatal) Skin and subcutaneous tissue disorders Very common rash (12.5%) Uncommon Stevens-Johnson syndrome/ toxic epidermal necrolysis (which may be fatal) (0.2%), angioedema, urticaria Musculoskeletal and connective tissue disorders Uncommon arthralgia, myalgia General disorders and administration site conditions Common pyrexia, fatigue 17 Investigations Common liver function test abnormal (alanine a

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083630 · has-contraindication-information · PDF-Seite 53

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Readministration to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN Readministration to patients who previously had ASAT or ALAT > 5 ULN during nevirapine therapy and had recurrence of liver function abnormalities upon readministration of nevirapine (see section 4.4) Coadministration with herbal preparations containing St. John’s wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine (see section 4.5).

HOS-083618 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Readministration to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine. Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN. Readministration to patients who previously had ASAT or ALAT > 5 ULN during nevirapine therapy and had recurrence of liver function abnormalities upon readministration of nevirapine (see section 4.4). Coadministration with herbal preparations containing St. John’s wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine (see section 4.5). 3

HOS-083624 · has-contraindication-information · PDF-Seite 28

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Readministration to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine. Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN. Readministration to patients who previously had ASAT or ALAT > 5 ULN during nevirapine therapy and had recurrence of liver function abnormalities upon readministration of nevirapine (see section 4.4). Coadministration with herbal preparations containing St. John’s wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine (see section 4.5).

HOS-083623 · has-indication-information · PDF-Seite 26

Viramune is indicated in combination with other anti-retroviral medicinal products for the treatment of HIV-1 infected adults, adolescents, and children of any age (see section 4.2). Most of the experience with Viramune is in combination with nucleoside reverse transcriptase inhibitors (NRTIs). The choice of a subsequent therapy after Viramune should be based on clinical experience and resistance testing (see section 5.1).

HOS-083629 · has-indication-information · PDF-Seite 51

Viramune is indicated in combination with other anti-retroviral medicinal products for the treatment of HIV-1 infected adults, adolescents, and children three years and above and able to swallow tablets (see section 4.2). Prolonged-release tablets are not suitable for the 14-day lead-in phase for patients starting nevirapine. Other nevirapine formulations, such as immediate-release tablets or oral suspension should be used (see section 4.2). Most of the experience with Viramune is in combination with nucleoside reverse transcriptase inhibitors (NRTIs). The choice of a subsequent therapy after Viramune should be based on clinical experience and resistance testing (see section 5.1).

HOS-083617 · has-indication-information · PDF-Seite 2

Viramune is indicated in combination with other anti-retroviral medicinal products for the treatment of HIV-1 infected adults, adolescents, and children of any age (see section 4.2). Most of the experience with Viramune is in combination with nucleoside reverse transcriptase inhibitors (NRTIs). The choice of a subsequent therapy after Viramune should be based on clinical experience and resistance testing (see section 5.1).

HOS-083626 · has-interaction-information · PDF-Seite 33

Nevirapine is an inducer of CYP3A and potentially CYP2B6, with maximal induction occurring within 2-4 weeks of initiating multiple-dose therapy. Compounds using this metabolic pathway may have decreased plasma concentrations when co- administered with nevirapine. Careful monitoring of the therapeutic effectiveness of P450 metabolised medicinal products is recommended when taken in combination with nevirapine. The absorption of nevirapine is not affected by food, antacids or medicinal products which are formulated with an alkaline buffering agent. The interaction data is presented as geometric mean value with 90% confidence interval (90% CI) whenever these data were available. ND = Not Determined, ↑ = Increased, ↓ = Decreased,  = No Effect Medicinal products Interaction Recommendations concerning by therapeutic areas co-administration ANTI-INFECTIVES ANTIRETROVIRALS NRTIs Didanosine Didanosine AUC  1.08 Didanosine and Viramune can be 100-150 mg BID (0.92-1.27) co-administered without dose Didanosine Cmin ND adjustments. Didanosine Cmax  0.98 (0.79-1.21) Emtricitabine Emtricitabine is not an inhibitor of Viramune and emtricitabine may human CYP 450 enzymes. be coadministered without dose adjustments. Abacavir In human liver microsomes, Viramune and abacavir may be abacavir did not inhibit cytochrome coadministered without dose P450 isoforms. adjustments. Lamivudine No changes to lamivudine apparent Lamivudine and Viramune can be 150 mg BID clearance and volume of co-administered without dose distribution, suggesting no adjustments. induction effect of nevirapine on lamivudine clearance. Stavudine: Stavudine AUC  0.96 Stavudine and Viramune can be 30/40 mg BID (0.89-1.03) co-administered without dose Stavudine Cmin ND

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083632 · has-interaction-information · PDF-Seite 57

The following data were generated using the Viramune immediate-release tablets but are expected to apply to all dosage forms. Nevirapine is an inducer of CYP3A and potentially CYP2B6, with maximal induction occurring within 2-4 weeks of initiating multiple-dose therapy. Compounds using this metabolic pathway may have decreased plasma concentrations when co- administered with nevirapine. Careful monitoring of the therapeutic effectiveness of P450 metabolised medicinal products is recommended when taken in combination with nevirapine. 57 The absorption of nevirapine is not affected by food, antacids or medicinal products which are formulated with an alkaline buffering agent. The interaction data is presented as geometric mean value with 90% confidence interval (90% CI) whenever these data were available. ND = Not Determined, ↑ = Increased, ↓ = Decreased,  = No Effect Medicinal products Interaction Recommendations concerning by therapeutic areas co-administration ANTI-INFECTIVES ANTIRETROVIRALS NRTIs Didanosine Didanosine AUC  1.08 Didanosine and Viramune can be 100-150 mg BID (0.92-1.27) co-administered without dose Didanosine Cmin ND adjustments. Didanosine Cmax  0.98 (0.79-1.21) Emtricitabine Emtricitabine is not an inhibitor of Viramune and emtricitabine may human CYP 450 enzymes. be coadministered without dose adjustments. Abacavir In human liver microsomes, Viramune and abacavir may be abacavir did not inhibit cytochrome coadministered without dose P450 isoforms. adjustments. Lamivudine No changes to lamivudine apparent Lamivudine and Viramune can be 150 mg BID clearance and volume of co-administered without dose distribution, suggesting no adjustments. induction effect of nevirapine on lamivudine clearance. Stavudine: Stavudine AUC  0.96 Sta

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083620 · has-interaction-information · PDF-Seite 8

Nevirapine is an inducer of CYP3A and potentially CYP2B6, with maximal induction occurring within 2-4 weeks of initiating multiple-dose therapy. Compounds using this metabolic pathway may have decreased plasma concentrations when co- administered with nevirapine. Careful monitoring of the therapeutic effectiveness of P450 metabolised medicinal products is recommended when taken in combination with nevirapine. The absorption of nevirapine is not affected by food, antacids or medicinal products which are formulated with an alkaline buffering agent. The interaction data is presented as geometric mean value with 90% confidence interval (90% CI) whenever these data were available. ND = Not Determined, ↑ = Increased, ↓ = Decreased,  = No Effect Medicinal products Interaction Recommendations concerning by therapeutic areas co-administration ANTI-INFECTIVES ANTIRETROVIRALS NRTIs Didanosine Didanosine AUC  1.08 Didanosine and Viramune can be 100-150 mg BID (0.92-1.27) co-administered without dose Didanosine Cmin ND adjustments. Didanosine Cmax  0.98 (0.79-1.21) Emtricitabine Emtricitabine is not an inhibitor of Viramune and emtricitabine may human CYP 450 enzymes. be coadministered without dose adjustments. Abacavir In human liver microsomes, Viramune and abacavir may be abacavir did not inhibit cytochrome coadministered without dose P450 isoforms. adjustments. Lamivudine No changes to lamivudine apparent Lamivudine and Viramune can be 150 mg BID clearance and volume of co-administered without dose distribution, suggesting no adjustments. induction effect of nevirapine on lamivudine clearance. Stavudine: Stavudine AUC  0.96 Stavudine and Viramune can be 30/40 mg BID (0.89-1.03) co-administered without dose Stavudine Cmin

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083621 · has-pregnancy-information · PDF-Seite 16

Women of childbearing potential / Contraception in males and females Women of childbearing potential should not use oral contraceptives as the sole method for birth control, since nevirapine might lower the plasma concentrations of these medicinal products (see sections 4.4 & 4.5). Pregnancy Currently available data on pregnant women indicate no malformative or foeto/ neonatal toxicity. To date no other relevant epidemiological data are available. No observable teratogenicity was detected in reproductive studies performed in pregnant rats and rabbits (see section 5.3). There are no adequate and well-controlled studies in pregnant women. Caution should be exercised when prescribing nevirapine to pregnant women (see section 4.4). As hepatotoxicity is more frequent in women with CD4+ cell counts above 250 cells/mm3 with detectable HIV-1 RNA in plasma (50 or more copies/mL), these conditions should be taken in consideration on therapeutic decision (see section 4.4). There is not enough evidence to substantiate that the absence of an increased risk for toxicity seen in pre-treated women initiating nevirapine with an undetectable viral load (less than 50 copies/mL of HIV-1 in plasma) and CD4+ cell counts above 250 cells/mm3 also applies to pregnant women. All the randomised studies addressing this issue specifically excluded pregnant women, and pregnant women were under-represented in cohort studies as well as in meta-analyses. Breast-feeding It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility In reproductive toxicology studies, evidence of impaired fertility was seen in rats.

HOS-083627 · has-pregnancy-information · PDF-Seite 40

Women of childbearing potential / Contraception in males and females Women of childbearing potential should not use oral contraceptives as the sole method for birth control, since nevirapine might lower the plasma concentrations of these medicinal products (see sections 4.4 & 4.5). Pregnancy Currently available data on pregnant women indicate no malformative or foeto/ neonatal toxicity. To date no other relevant epidemiological data are available. No observable teratogenicity was detected in reproductive studies performed in pregnant rats and rabbits (see section 5.3). There are no adequate and well-controlled studies in pregnant women. Caution should be exercised when prescribing nevirapine to pregnant women (see section 4.4). As hepatotoxicity is more frequent in women with CD4+ cell counts above 250 cells/mm3 with detectable HIV-1 RNA in plasma (50 or more copies/mL), these conditions should be taken in consideration on therapeutic decision (see section 4.4). There is not enough evidence to substantiate that the absence of an increased risk for toxicity seen in pre-treated women initiating nevirapine with an undetectable viral load (less than 50 copies/mL of HIV-1 in plasma) and CD4+ cell counts above 250 cells/mm3 also applies to pregnant women. All the randomised studies addressing this issue specifically excluded pregnant women, and pregnant women were under-represented in cohort studies as well as in meta-analyses. Breast-feeding It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. 40 Fertility In reproductive toxicology studies, evidence of impaired fertility was seen in rats.

HOS-083633 · has-pregnancy-information · PDF-Seite 66

Women of childbearing potential / Contraception in males and females Women of childbearing potential should not use oral contraceptives as the sole method for birth control, since nevirapine might lower the plasma concentrations of these medicinal products (see sections 4.4 & 4.5). Pregnancy Currently available data on pregnant women indicate no malformative or foeto/ neonatal toxicity. To date no other relevant epidemiological data are available. No observable teratogenicity was detected in reproductive studies performed in pregnant rats and rabbits (see section 5.3). There are no adequate and well-controlled studies in pregnant women. Caution should be exercised when prescribing nevirapine to pregnant women (see section 4.4). As hepatotoxicity is more frequent in women with CD4+ cell counts above 250 cells/mm3 with detectable HIV-1 RNA in plasma (50 or more copies/mL), these conditions should be taken in consideration on therapeutic decision (see section 4.4). There is not enough evidence to substantiate that the absence of an increased risk for toxicity seen in pre-treated women initiating nevirapine with an undetectable viral load (less than 50 copies/mL of HIV-1 in plasma) and CD4+ cell counts above 250 cells/mm3 also applies to pregnant women. All the randomised studies addressing this issue specifically excluded pregnant women, and pregnant women were under-represented in cohort studies as well as in meta-analyses. Breast-feeding It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV. Fertility In reproductive toxicology studies, evidence of impaired fertility was seen in rats.

HOS-083619 · has-warning-information · PDF-Seite 4

Viramune should only be used with at least two other antiretroviral agents (see section 5.1). Viramune should not be used as the sole active antiretroviral, as monotherapy with any antiretroviral has shown to result in viral resistance. The first 18 weeks of therapy with nevirapine are a critical period which requires close monitoring of patients to disclose the potential appearance of severe and life-threatening skin reactions (including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) and serious hepatitis/hepatic failure. The greatest risk of hepatic and skin reactions occurs in the first 6 weeks of therapy. However, the risk of any hepatic event continues past this period and monitoring should continue at frequent intervals. Female gender and higher CD4+ counts (> 250/mm3 in adult females and > 400/mm3 in adult males) at the initiation of nevirapine therapy are associated with a greater risk of hepatic adverse reactions if the patient has detectable plasma HIV-1 RNA - i.e. a concentration ≥ 50 copies/mL - at the initiation of nevirapine. As serious and life threatening hepatotoxicity has been observed in controlled and uncontrolled studies predominantly in patients with a plasma HIV-1 viral load of 50 copies/mL or higher, nevirapine should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm3 or in adult males with CD4+ cell counts greater than 400 cells/mm3, who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk. In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients developing signs or symptoms of hepatitis, severe skin reaction or hypersensitivity reactions must discontinue nevirapine and seek medical evaluation immediately. Nevirapine must not be restarted following severe hepatic, skin or hypersensitivity reactions (see section 4.3). The dose must be strictly adhered to, especially the 14-days lead-in period (see section 4.2). Cutaneous reactions Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity reactions characterised by rash, constitutional findings and visceral involvement. Patients should be intensively monitored during the first 18 weeks of treatment. Patients should be closely monitored if an isolated rash occur

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083625 · has-warning-information · PDF-Seite 28

Viramune should only be used with at least two other antiretroviral agents (see section 5.1). Viramune should not be used as the sole active antiretroviral, as monotherapy with any antiretroviral has shown to result in viral resistance. 28 The first 18 weeks of therapy with nevirapine are a critical period which requires close monitoring of patients to disclose the potential appearance of severe and life-threatening skin reactions (including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) and serious hepatitis/hepatic failure. The greatest risk of hepatic and skin reactions occurs in the first 6 weeks of therapy. However, the risk of any hepatic event continues past this period and monitoring should continue at frequent intervals. Female gender and higher CD4+ counts (> 250/mm3 in adult females and > 400/mm3 in adult males) at the initiation of nevirapine therapy are associated with a greater risk of hepatic adverse reactions if the patient has detectable plasma HIV-1 RNA - i.e. a concentration ≥ 50 copies/mL - at the initiation of nevirapine. As serious and life threatening hepatotoxicity has been observed in controlled and uncontrolled studies predominantly in patients with a plasma HIV-1 viral load of 50 copies/mL or higher, nevirapine should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm3 or in adult males with CD4+ cell counts greater than 400 cells/mm3, who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk. In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients developing signs or symptoms of hepatitis, severe skin reaction or hypersensitivity reactions must discontinue nevirapine and seek medical evaluation immediately. Nevirapine must not be restarted following severe hepatic, skin or hypersensitivity reactions (see section 4.3). The dose must be strictly adhered to, especially the 14-days lead-in period (see section 4.2). Cutaneous reactions Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity reactions characterised by rash, constitutional findings and visceral involvement. Patients should be intensively monitored during the first 18 weeks of treatment. Pa

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083631 · has-warning-information · PDF-Seite 53

Viramune should only be used with at least two other antiretroviral agents (see section 5.1). Viramune should not be used as the sole active antiretroviral, as monotherapy with any antiretroviral has shown to result in viral resistance. The first 18 weeks of therapy with nevirapine are a critical period which requires close monitoring of patients to disclose the potential appearance of severe and life-threatening skin reactions (including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) and serious hepatitis/hepatic failure. The greatest risk of hepatic and skin reactions occurs in the first 6 weeks of therapy. However, the risk of any hepatic event continues past this period and monitoring should continue at frequent intervals. Female gender and higher CD4+ counts (> 250/mm3 in adult females and > 400/mm3 in adult males) at the initiation of nevirapine therapy are associated with a greater risk of hepatic adverse reactions if the patient has detectable plasma HIV-1 RNA - i.e. a concentration ≥ 50 copies/mL - at the initiation of nevirapine. As serious and life threatening hepatotoxicity has been observed in controlled and uncontrolled studies predominantly in patients with a plasma HIV-1 viral load of 50 copies/mL or higher, nevirapine should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm3 or in adult males with CD4+ cell counts greater than 400 cells/mm3, who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk. In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients developing signs or symptoms of hepatitis, severe skin reaction or hypersensitivity reactions must discontinue nevirapine and seek medical evaluation immediately. Nevirapine must not be restarted following severe hepatic, skin or hypersensitivity reactions (see section 4.3). The dose must be strictly adhered to, especially the 14-days lead-in period (see section 4.2). 53 Cutaneous reactions Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity reactions characterised by rash, constitutional findings and visceral involvement. Patients should be intensively monitored during the first 18 weeks of treatment. Pati

Auszug; vollständigen Abschnitt im Original lesen.