Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.3 · PDF-Seite 5

HOS-140296 · Präparat HOS-098498

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 Severe respiratory insufficiency Severe hepatic impairment Acute alcoholism or delirium tremens

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Buvidal

Buvidal 64 mg prolonged-release solution for injection Buvidal 96 mg prolonged-release solution for injection Buvidal 128 mg prolonged-release solution for injection Buvidal 160 mg prolonged-release solution for injection · Abschnitt 4.3 · PDF-Seite 20

HOS-140336 · Präparat HOS-098498

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 Severe respiratory insufficiency

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Buvidal

Buvidal 64 mg prolonged-release solution for injection Buvidal 96 mg prolonged-release solution for injection Buvidal 128 mg prolonged-release solution for injection Buvidal 160 mg prolonged-release solution for injection · Abschnitt 4.3 · PDF-Seite 20–21

HOS-140337 · Präparat HOS-098498

20 Severe hepatic impairment Acute alcoholism or delirium tremens

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 8

HOS-140297 · Präparat HOS-098498

No interaction studies have been performed with Buvidal.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 8

HOS-140298 · Präparat HOS-098498

Buprenorphine should be used cautiously when co-administered with: • naltrexone and nalmefene: These are opioid antagonists that can block the pharmacological effects of buprenorphine. For opioid-dependent patients currently receiving buprenorphine treatment, naltrexone may precipitate a sudden onset of prolonged and intense opioid withdrawal symptoms. For patients currently receiving naltrexone treatment, the intended therapeutic effects of buprenorphine administration may be blocked by naltrexone. • alcoholic drinks or medicinal products containing alcohol as alcohol increases the sedative effect of buprenorphine (see section 4.7). • benzodiazepines: This combination may result in death due to respiratory depression of central origin. Therefore, dosages must be closely monitored and this combination must be avoided in cases where there is a risk of misuse. Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines whilst taking this product, and should also be cautioned to use benzodiazepines concurrently with this product only as directed by their physician (see section 4.4). • gabapentinoids: The concomitant use of Buvidal with gabapentinoids (gabapentin and pregabalin) may result in respiratory depression, hypotension, profound sedation, coma or death. Therefore, dosages must be closely monitored and this combination must be avoided in cases where there is a risk of misuse. Patients should be cautioned to use gabapentinoids concurrently with this product only as directed by their physician (see section 4.4). • Serotonergic medicinal products, such as MAO inhibitors, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4). • other central nervous system depressants: Other opioid derivatives (e.g. methadone, analgesics and antitussives); certain antidepressants, sedative H1-receptor antagonists, barbiturates, anxiolytics other than benzodiazepines, antipsychotics, clonidine and related substances. These combinations increase central nervous system depression. The reduced level of alertness can make driving and using machinery hazardous (see section 4.7). • opioid analgesics: Adequate analgesia may be difficult to achieve when administering a full opioid agonist in patients receiving buprenorphine. The potential for overdose also exists with a full agonist, especially when attempting to overcome buprenorphine partial agonist effects, or when buprenorphine plasma levels are declining (see section 4.4) • Buprenorphine is metabolised to norbuprenorphine primarily by CYP3A4. Interaction with co- administered inducers or inhibitors have been established in studies using transmucosal and transdermal buprenorphine. Buprenorphine is also metabolised to buprenorphine-3β- glucuronide by UGT1A1. • CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine. Buvidal avoids first-pass effects and CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or azole antifungals such as ketoconazole or itraconazole, or macrolide antibiotics) are

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): indinavir (HOS-084518) pregabalin (HOS-112893) norepinephrine (HOS-090547) nelfinavir (HOS-084520) methadone (HOS-086198) protease (HOS-085623) ketoconazole (HOS-084513) clonidine (HOS-088594) naltrexone (HOS-115836) nalmefene (HOS-115837) gabapentin (HOS-090745) serotonin (HOS-085477) itraconazole (HOS-084516) ritonavir (HOS-084521)

Wechselwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 8–9

HOS-140312 · Präparat HOS-098498

8  expected to have less effects on buprenorphine metabolism when co-administered with Buvidal as compared to when co-administered with sublingual buprenorphine. When switching from sublingual buprenorphine to Buvidal, patients may need to be monitored to ensure plasma buprenorphine levels are adequate. Patients already on Buvidal who start treatment with CYP3A4 inhibitors should be treated with weekly Buvidal and be monitored for signs and symptoms of overtreatment. Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4 inhibitor stops treatment with the CYP3A4 inhibitor, the patient should be monitored for symptoms of withdrawal (see section 4.4). • CYP3A4 inducers may induce the metabolism of buprenorphine resulting in decreased buprenorphine levels. Buvidal avoids first-pass effects and CYP3A4 inducers (e.g. phenobarbital, carbamazepine, phenytoin or rifampicin) are expected to have less effects on buprenorphine metabolism when co-administered with Buvidal as compared to when co-administered with sublingual buprenorphine. When switching from sublingual buprenorphine to Buvidal, patients may need to be monitored to ensure plasma buprenorphine levels are adequate. Patients already on Buvidal who start treatment with CYP3A4 inducers should be treated with weekly Buvidal and be monitored for signs and symptoms of withdrawal. Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4 inducer stops treatment with the CYP3A4 inducer, the patient should be monitored for symptoms of overtreatment. • UGT1A1 inhibitors may affect the systemic exposure of buprenorphine. • monoamine oxidase inhibitors (MAOI): Possible exacerbation of the opioids effects, based on experience with morphine. • concomitant administration of buprenorphine with anticholinergics or medications with anticholinergic activity (e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, anti-parkinson drugs) may result in increased anticholinergic adverse effects.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) carbamazepine (HOS-085618) morphine (HOS-086053) phenytoin (HOS-084531)

Wechselwirkungen · Buvidal

Buvidal 64 mg prolonged-release solution for injection Buvidal 96 mg prolonged-release solution for injection Buvidal 128 mg prolonged-release solution for injection Buvidal 160 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 24

HOS-140338 · Präparat HOS-098498

No interaction studies have been performed with Buvidal.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Buvidal

Buvidal 64 mg prolonged-release solution for injection Buvidal 96 mg prolonged-release solution for injection Buvidal 128 mg prolonged-release solution for injection Buvidal 160 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 24

HOS-140339 · Präparat HOS-098498

Buprenorphine should be used cautiously when co-administered with: • naltrexone and nalmefene: These are opioid antagonists that can block the pharmacological effects of buprenorphine. For opioid-dependent patients currently receiving buprenorphine treatment, naltrexone may precipitate a sudden onset of prolonged and intense opioid withdrawal symptoms. For patients currently receiving naltrexone treatment, the intended therapeutic effects of buprenorphine administration may be blocked by naltrexone. • alcoholic drinks or medicinal products containing alcohol as alcohol increases the sedative effect of buprenorphine (see section 4.7). • benzodiazepines: This combination may result in death due to respiratory depression of central origin. Therefore, dosages must be closely monitored and this combination must be avoided in cases where there is a risk of misuse. Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines whilst taking this product, and should also be cautioned to use benzodiazepines concurrently with this product only as directed by their physician (see section 4.4). • gabapentinoids: The concomitant use of Buvidal with gabapentinoids (gabapentin and pregabalin) may result in respiratory depression, hypotension, profound sedation, coma or death. Therefore, dosages must be closely monitored and this combination must be avoided in cases where there is a risk of misuse. Patients should be cautioned to use gabapentinoids concurrently with this product only as directed by their physician (see section 4.4). • Serotonergic medicinal products, such as MAO inhibitors, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4). • other central nervous system depressants: Other opioid derivatives (e.g. methadone, analgesics and antitussives); certain antidepressants, sedative H1-receptor antagonists, barbiturates, anxiolytics other than benzodiazepines, antipsychotics, clonidine and related substances. These combinations increase central nervous system depression. The reduced level of alertness can make driving and using machinery hazardous (see section 4.7). • opioid analgesics: Adequate analgesia may be difficult to achieve when administering a full opioid agonist in patients receiving buprenorphine. The potential for overdose also exists with a full agonist, especially when attempting to overcome buprenorphine partial agonist effects, or when buprenorphine plasma levels are declining (see section 4.4) • Buprenorphine is metabolised to norbuprenorphine primarily by CYP3A4. Interaction with co- administered inducers or inhibitors have been established in studies using transmucosal and transdermal buprenorphine. Buprenorphine is also metabolised to buprenorphine-3β- glucuronide by UGT1A1. • CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine. Buvidal avoids first-pass effects and CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or azole antifungals such as ketoconazole or itraconazole, or macrolide antibiotics) are expected to have less effects on buprenorphine metabolism when co-administered with Buvidal as compared to when co-administered with sublingual buprenorphine. When switching from sublingual buprenorphine to Buvidal, patients may need to be monitored to ensure plasma buprenorphine levels are adequate. Patients already on Buvidal who start treatment with CYP3A4 inhibitors should be treated with weekly Buvidal and be monitored for signs and symptoms of overtreatment. Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): indinavir (HOS-084518) pregabalin (HOS-112893) norepinephrine (HOS-090547) nelfinavir (HOS-084520) methadone (HOS-086198) protease (HOS-085623) ketoconazole (HOS-084513) clonidine (HOS-088594) naltrexone (HOS-115836) nalmefene (HOS-115837) gabapentin (HOS-090745) serotonin (HOS-085477) itraconazole (HOS-084516) ritonavir (HOS-084521)

Wechselwirkungen · Buvidal

Buvidal 64 mg prolonged-release solution for injection Buvidal 96 mg prolonged-release solution for injection Buvidal 128 mg prolonged-release solution for injection Buvidal 160 mg prolonged-release solution for injection · Abschnitt 4.5 · PDF-Seite 24–25

HOS-140340 · Präparat HOS-098498

24  inhibitor stops treatment with the CYP3A4 inhibitor, the patient should be monitored for symptoms of withdrawal (see section 4.4). • CYP3A4 inducers may induce the metabolism of buprenorphine resulting in decreased buprenorphine levels. Buvidal avoids first-pass effects and CYP3A4 inducers (e.g. phenobarbital, carbamazepine, phenytoin or rifampicin) are expected to have less effects on buprenorphine metabolism when co-administered with Buvidal as compared to when co-administered with sublingual buprenorphine. When switching from sublingual buprenorphine to Buvidal, patients may need to be monitored to ensure plasma buprenorphine levels are adequate. Patients already on Buvidal who start treatment with CYP3A4 inducers should be treated with weekly Buvidal and be monitored for signs and symptoms of withdrawal. Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4 inducer stops treatment with the CYP3A4 inducer, the patient should be monitored for symptoms of overtreatment. • UGT1A1 inhibitors may affect the systemic exposure of buprenorphine. • monoamine oxidase inhibitors (MAOI): Possible exacerbation of the opioids effects, based on experience with morphine. • concomitant administration of buprenorphine with anticholinergics or medications with anticholinergic activity (e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, anti-parkinson drugs) may result in increased anticholinergic adverse effects.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) carbamazepine (HOS-085618) morphine (HOS-086053) phenytoin (HOS-084531)

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140317 · Präparat HOS-098498

Summary of the safety profile

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140318 · Präparat HOS-098498

The adverse reactions most frequently reported for buprenorphine are headache, nausea, hyperhidrosis, insomnia, drug withdrawal syndrome and pain.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140319 · Präparat HOS-098498

Tabulated list of adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140320 · Präparat HOS-098498

Table 2 presents adverse reactions reported for buprenorphine, including Buvidal. The following terms and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100) and frequency not known (cannot be estimated from available data).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140321 · Präparat HOS-098498

Table 2. Adverse reactions listed by body system System Organ Class Very common Common Uncommon Not known

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140322 · Präparat HOS-098498

Infections and Infection Injection site infestations Influenza cellulitis Pharyngitis Rhinitis Blood and lymphatic Lymphadenopathy system disorders

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-140323 · Präparat HOS-098498

Immune system Hypersensitivity disorders Metabolism and Decreased appetite nutrition disorders Psychiatric disorders Insomnia Anxiety Hallucinations Agitation Euphoric mood Depression Hostility Nervousness Thinking abnormal Paranoia Medical dependence Nervous system Headache Somnolence disorders Dizziness Migraine Paraesthesia Syncope Tremor Hypertonia Speech disorders Eye disorders Lacrimal disorder Mydriasis Miosis

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 10–11

HOS-140324 · Präparat HOS-098498

10 Table 2. Adverse reactions listed by body system System Organ Class Very common Common Uncommon Not known

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 11

HOS-140325 · Präparat HOS-098498

Ear and labyrinth Vertigo disorders Cardiac disorders Palpitations Vascular disorders Vasodilation Hypotension Respiratory, thoracic Cough and mediastinal Dyspnoea disorders Yawning Asthma Bronchitis Gastrointestinal Nausea Constipation disorders Vomiting Abdominal pain Flatulence Dyspepsia Dry mouth Diarrhoea Gastrointestinal disorder Hepatobiliary Alanine disorders aminotransferase increased Aspartate aminotransferase increased Hepatic enzymes increased Skin and Rash Rash macular Erythema subcutaneous tissue Pruritus disorders Urticaria Musculoskeletal and Arthralgia connective tissue Back pain disorders Myalgia Muscle spasms Neck pain Bone pain Renal and urinary Urinary retention disorders Reproductive system Dysmenorrhoea and breast disorders

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 11

HOS-140326 · Präparat HOS-098498

General disorders Hyperhidrosis Injection site pain Injection site Injection site and administration Drug withdrawal Injection site pruritus inflammation abscess site conditions syndrome Injection site erythema Injection site Injection site Pain Injection site swelling bruising ulceration Injection site reaction Injection site Injection site Injection site urticaria necrosis induration Injection site mass Oedema peripheral Asthenia Malaise Pyrexia Chills Neonatal withdrawal syndrome Chest pain

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Buvidal

Buvidal 8 mg prolonged-release solution for injection Buvidal 16 mg prolonged-release solution for injection Buvidal 24 mg prolonged-release solution for injection Buvidal 32 mg prolonged-release solution for injection · Abschnitt 4.8 · PDF-Seite 11–12

HOS-140327 · Präparat HOS-098498

11  Table 2. Adverse reactions listed by body system System Organ Class Very common Common Uncommon Not known

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.