Rebif · 4.5 Interaction with other medicinal products and other forms of interaction · 4

HOS-083354 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30% of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common: Depression, insomnia Rare: Suicide

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083372 · has-adverse-reaction-information · PDF-Seite 41

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70 % of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30 % of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. 41 List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common:

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083384 · has-adverse-reaction-information · PDF-Seite 64

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30% of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. 64 List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common:

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083366 · has-adverse-reaction-information · PDF-Seite 30

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70 % of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30 % of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* 30 Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common: Depres

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083360 · has-adverse-reaction-information · PDF-Seite 18

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30% of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. 18 List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common:

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083378 · has-adverse-reaction-information · PDF-Seite 53

Summary of the safety profile The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Approximately 30% of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells are also common. The majority of adverse reactions observed with interferon beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. List of adverse reactions The adverse reactions presented have been identified from clinical studies as well as from post- marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: 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), frequency not known (cannot be estimated from the available data). Blood and the lymphatic system disorders Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products, see section 4.4), pancytopenia* Endocrine disorders Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism Immune system disorders Rare: Anaphylactic reactions* 53 Hepatobiliary disorders Very common: Asymptomatic transaminase increase Common: Severe elevations in transaminases Uncommon: Hepatitis with or without icterus* Rare: Hepatic failure* (see section 4.4), autoimmune hepatitis* Psychiatric disorders Common: Depressi

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083350 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8).

HOS-083380 · has-contraindication-information · PDF-Seite 60

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8). 60

HOS-083374 · has-contraindication-information · PDF-Seite 49

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8).

HOS-083356 · has-contraindication-information · PDF-Seite 14

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8).

HOS-083368 · has-contraindication-information · PDF-Seite 37

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8). 37

HOS-083362 · has-contraindication-information · PDF-Seite 26

• Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1. • Current severe depression and/or suicidal ideation (see sections 4.4 and 4.8).

HOS-083379 · has-indication-information · PDF-Seite 59

Rebif is indicated for the treatment of • patients with a single demyelinating event with an active inflammatory process, if alternative diagnoses have been excluded, and if they are determined to be at high risk of developing clinically definite multiple sclerosis (see section 5.1) • patients with relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083373 · has-indication-information · PDF-Seite 48

Rebif is indicated for the treatment of relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083349 · has-indication-information · PDF-Seite 2

Rebif is indicated for the treatment of relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083361 · has-indication-information · PDF-Seite 25

Rebif is indicated for the treatment of relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083367 · has-indication-information · PDF-Seite 36

Rebif is indicated for the treatment of • patients with a single demyelinating event with an active inflammatory process, if alternative diagnoses have been excluded, and if they are determined to be at high risk of developing clinically definite multiple sclerosis (see section 5.1) • patients with relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083355 · has-indication-information · PDF-Seite 13

Rebif is indicated for the treatment of • patients with a single demyelinating event with an active inflammatory process, if alternative diagnoses have been excluded, and if they are determined to be at high risk of developing clinically definite multiple sclerosis (see section 5.1) • patients with relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1). Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (see section 5.1).

HOS-083358 · has-interaction-information · PDF-Seite 17

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses. 17

HOS-083352 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.

HOS-083382 · has-interaction-information · PDF-Seite 63

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses. 63

HOS-083364 · has-interaction-information · PDF-Seite 29

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.

HOS-083370 · has-interaction-information · PDF-Seite 40

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses. 40

HOS-083376 · has-interaction-information · PDF-Seite 52

No interaction studies have been performed with interferon beta-1a in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.

HOS-083371 · has-pregnancy-information · PDF-Seite 41

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. Fertility The effects of Rebif on fertility have not been investigated.

HOS-083383 · has-pregnancy-information · PDF-Seite 64

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. Fertility The effects of Rebif on fertility have not been investigated.

HOS-083377 · has-pregnancy-information · PDF-Seite 52

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. 52 Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. Fertility The effects of Rebif on fertility have not been investigated.

HOS-083353 · has-pregnancy-information · PDF-Seite 6

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. 6 Fertility The effects of Rebif on fertility have not been investigated.

HOS-083359 · has-pregnancy-information · PDF-Seite 18

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. Fertility The effects of Rebif on fertility have not been investigated.

HOS-083365 · has-pregnancy-information · PDF-Seite 29

Pregnancy A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited. Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far. If clinically needed, the use of Rebif may be considered during pregnancy. 29 Breast-feeding Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding. Fertility The effects of Rebif on fertility have not been investigated.

HOS-083363 · has-warning-information · PDF-Seite 26

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, 26 further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their ep

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083375 · has-warning-information · PDF-Seite 49

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, 49 further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their ep

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HOS-083381 · has-warning-information · PDF-Seite 61

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with antiepileptics (

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HOS-083351 · has-warning-information · PDF-Seite 3

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. 3 Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epi

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HOS-083357 · has-warning-information · PDF-Seite 14

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 14 General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their e

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HOS-083369 · has-warning-information · PDF-Seite 38

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. General recommendations Patients should be informed of the most frequent adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (see section 4.8). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Thrombotic microangiopathy (TMA) Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Rebif is recommended. Depression and suicidal ideation Rebif should be administered with caution to patients with previous or current depressive disorders in particular to those with antecedents of suicidal ideation (see section 4.3). Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Rebif should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Rebif and treated appropriately. Cessation of therapy with Rebif should be considered (see sections 4.3 and 4.8). Seizure disorders Rebif should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with antiepileptics (

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