Leitlinien & Arzneimittelsicherheit

HOS-093792 · has-adverse-reaction-information · PDF-Seite 9

The pregabalin clinical programme involved over 8,900 patients exposed to pregabalin, of whom over 5,600 were in double-blind placebo controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence. In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (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), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The adverse reactions listed may also be associated with the underlying disease and/or concomitant medicinal products. In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, CNS adverse reactions and especially somnolence was increased (see section 4.4). 9 Additional reactions reported from postmarketing experience are included in italics in the list below. Table 2. Pregabalin Adverse Drug Reactions System Organ Class Adverse drug reactions Infections and infestations Common Nasopharyngitis Blood and lymphatic system disorders Uncommon Neutropaenia Immune system disorders Uncommon Hypersensitivity Rare Angioedema, allergic reaction Metabolism and nutrition disorders Common Appetite increased Uncommon Anorexia, hypoglycaemia Psychiatric disorders Common Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased Uncommon Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido

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HOS-093798 · has-adverse-reaction-information · PDF-Seite 26

The pregabalin clinical programme involved over 8,900 patients exposed to pregabalin, of whom over 5,600 were in double-blind placebo controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence. In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (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), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The adverse reactions listed may also be associated with the underlying disease and/or concomitant medicinal products. In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, CNS adverse reactions and especially somnolence was increased (see section 4.4). Additional reactions reported from postmarketing experience are included in italics in the list below. Table 2. Pregabalin Adverse Drug Reactions System Organ Class Adverse drug reactions Infections and infestations Common Nasopharyngitis Blood and lymphatic system disorders Uncommon Neutropaenia Immune system disorders Uncommon Hypersensitivity Rare Angioedema, allergic reaction Metabolism and nutrition disorders Common Appetite increased Uncommon Anorexia, hypoglycaemia Psychiatric disorders Common Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased Uncommon Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy Rare

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HOS-093804 · has-adverse-reaction-information · PDF-Seite 42

The pregabalin clinical programme involved over 8,900 patients exposed to pregabalin, of whom over 5,600 were in double-blind placebo controlled trials. The most commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence. In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (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), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The adverse reactions listed may also be associated with the underlying disease and/or concomitant medicinal products. In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, CNS adverse reactions and especially somnolence was increased (see section 4.4). Additional reactions reported from postmarketing experience are included in italics in the list below. Table 2. Pregabalin Adverse Drug Reactions System Organ Class Adverse drug reactions Infections and infestations Common Nasopharyngitis Blood and lymphatic system disorders Uncommon Neutropaenia Immune system disorders Uncommon Hypersensitivity Rare Angioedema, allergic reaction Metabolism and nutrition disorders Common Appetite increased Uncommon Anorexia, hypoglycaemia Psychiatric disorders Common Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased Uncommon Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy Rare

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HOS-093788 · has-contraindication-information · PDF-Seite 5

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

HOS-093794 · has-contraindication-information · PDF-Seite 22

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

HOS-093800 · has-contraindication-information · PDF-Seite 38

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

HOS-093793 · has-indication-information · PDF-Seite 20

Neuropathic pain Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults. Epilepsy Lyrica is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation. Generalised Anxiety Disorder Lyrica is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults.

HOS-093787 · has-indication-information · PDF-Seite 3

Neuropathic pain Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults. Epilepsy Lyrica is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation. Generalised anxiety disorder Lyrica is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults. 3

HOS-093799 · has-indication-information · PDF-Seite 36

Neuropathic pain Lyrica is indicated for the treatment of peripheral and central neuropathic pain in adults. Epilepsy Lyrica is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation. Generalised anxiety disorder Lyrica is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults.

HOS-093790 · has-interaction-information · PDF-Seite 8

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions. In vivo studies and population pharmacokinetic analysis Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance. Oral contraceptives, norethisterone and/or ethinyl oestradiol Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either substance. Central nervous system influencing medical products Pregabalin may potentiate the effects of ethanol and lorazepam. In the postmarketing experience, there are reports of respiratory failure, coma and deaths in patients taking pregabalin and opioids and/or other central nervous system (CNS) depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. Interactions and the elderly No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.

HOS-093796 · has-interaction-information · PDF-Seite 24

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions. In vivo studies and population pharmacokinetic analysis Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance. Oral contraceptives, norethisterone and/or ethinyl oestradiol Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either substance. Central nervous system influencing medical products Pregabalin may potentiate the effects of ethanol and lorazepam. 24 In the postmarketing experience, there are reports of respiratory failure, coma and deaths in patients taking pregabalin and opioids and/or other central nervous system (CNS) depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. Interactions and the elderly No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.

HOS-093802 · has-interaction-information · PDF-Seite 40

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (< 2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions. In vivo studies and population pharmacokinetic analysis Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance. Oral contraceptives, norethisterone and/or ethinyl oestradiol Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steady-state pharmacokinetics of either substance. 40 Central nervous system influencing medical products Pregabalin may potentiate the effects of ethanol and lorazepam. In the postmarketing experience, there are reports of respiratory failure, coma and deaths in patients taking pregabalin and opioids and/or other central nervous system (CNS) depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone. Interactions and the elderly No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.

HOS-093797 · has-pregnancy-information · PDF-Seite 25

Women of childbearing potential/Contraception Women of childbearing potential have to use effective contraception during treatment (see section 4.4). Pregnancy Studies in animals have shown reproductive toxicity (see section 5.3). Pregabalin has been shown to cross the placenta in rats (see section 5.2). Pregabalin may cross the human placenta. Major congenital malformations Data from a Nordic observational study of more than 2700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations (MCM) among the paediatric population (live or stillborn) exposed to pregabalin compared to the unexposed population (5.9% vs. 4.1%). The risk of MCM among the paediatric population exposed to pregabalin in the first trimester was slightly higher compared to unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared to population exposed to lamotrigine (1.29 (1.01–1.65)) or to duloxetine (1.39 (1.07–1.82)). The analyses on specific malformations showed higher risks for malformations of the nervous system, the eye, orofacial clefts, urinary malformations and genital malformations, but numbers were small and estimates imprecise. Lyrica should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). Breast-feeding Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no clinical data on the effects of pregabalin on female fertility. In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility. A fertility study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown (see section 5.3). 25

HOS-093803 · has-pregnancy-information · PDF-Seite 41

Women of childbearing potential/Contraception Women of childbearing potential have to use effective contraception during treatment (see section 4.4). Pregnancy Studies in animals have shown reproductive toxicity (see section 5.3). Pregabalin has been shown to cross the placenta in rats (see section 5.2). Pregabalin may cross the human placenta. Major congenital malformations Data from a Nordic observational study of more than 2700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations (MCM) among the paediatric population (live or stillborn) exposed to pregabalin compared to the unexposed population (5.9% vs. 4.1%). The risk of MCM among the paediatric population exposed to pregabalin in the first trimester was slightly higher compared to unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared to population exposed to lamotrigine (1.29 (1.01–1.65)) or to duloxetine (1.39 (1.07–1.82)). The analyses on specific malformations showed higher risks for malformations of the nervous system, the eye, orofacial clefts, urinary malformations and genital malformations, but numbers were small and estimates imprecise. Lyrica should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). Breast-feeding Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no clinical data on the effects of pregabalin on female fertility. In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility. 41 A fertility study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown (see section 5.3).

HOS-093791 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception Women of childbearing potential have to use effective contraception during treatment (see section 4.4). Pregnancy Studies in animals have shown reproductive toxicity (see section 5.3). Pregabalin has been shown to cross the placenta in rats (see section 5.2). Pregabalin may cross the human placenta. Major congenital malformations Data from a Nordic observational study of more than 2700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations (MCM) among the paediatric population (live or stillborn) exposed to pregabalin compared to the unexposed population (5.9% vs. 4.1%). The risk of MCM among the paediatric population exposed to pregabalin in the first trimester was slightly higher compared to unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared to population exposed to lamotrigine (1.29 (1.01–1.65)) or to duloxetine (1.39 (1.07–1.82)). 8 The analyses on specific malformations showed higher risks for malformations of the nervous system, the eye, orofacial clefts, urinary malformations and genital malformations, but numbers were small and estimates imprecise. Lyrica should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). Breast-feeding Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no clinical data on the effects of pregabalin on female fertility. In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility. A fertility study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown (see section 5.3).

HOS-093801 · has-warning-information · PDF-Seite 38

Diabetic patients In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products. Hypersensitivity reactions There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Severe cutaneous adverse reactions (SCARs) SCARs including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate). Dizziness, somnolence, loss of consciousness, confusion and mental impairment Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product. Vision-related effects In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients (see section 5.1). In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms. 38 Renal failure Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction. Withdrawal

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HOS-093789 · has-warning-information · PDF-Seite 5

Diabetic patients In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products. Hypersensitivity reactions There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Severe cutaneous adverse reactions (SCARs) SCARs including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate). 5 Dizziness, somnolence, loss of consciousness, confusion and mental impairment Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product. Vision-related effects In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients (see section 5.1). In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms. Renal failure Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction. Withdrawal

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HOS-093795 · has-warning-information · PDF-Seite 22

Diabetic patients In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products. Hypersensitivity reactions There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Severe cutaneous adverse reactions (SCARs) SCARs including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate). Dizziness, somnolence, loss of consciousness, confusion and mental impairment Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product. Vision-related effects In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients (see section 5.1). In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms. Renal failure Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction. Withdrawal of concomitant anti-epileptic medicinal products There ar

Auszug; vollständigen Abschnitt im Original lesen.