Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.3 · PDF-Seite 5

HOS-138576 · Präparat HOS-098216

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Severe respiratory insufficiency. Severe hepatic impairment. Acute alcoholism or delirium tremens. Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of alcohol or opioid dependence.

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): naltrexone (HOS-115836) nalmefene (HOS-115837)

Wechselwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-138579 · Präparat HOS-098216

Zubsolv must not be taken together with:

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

Wechselwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-138580 · Präparat HOS-098216

Zubsolv should not be taken together with: • Alcoholic drinks or medicinal products containing alcohol, as alcohol increases the sedative effect of buprenorphine (see section 4.7).

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

Wechselwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-138581 · Präparat HOS-098216

Zubsolv should be used cautiously when co-administered with: • Sedatives such as benzodiazepines or related medicinal products The concomitant use of opioids with sedative medicinal products such as benzodiazepines or related medicinal products increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use of sedative medicinal products should be limited (see section 4.4). Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines while taking this medicinal product and should also be cautioned to use benzodiazepines concurrently with this medicinal product only as directed by their physician (see section 4.4). • The concomitant use of Zubsolv with gabapentinoids (gabapentin and pregabalin) may result in respiratory depression, hypotension, profound sedation, coma or death (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, neuroleptics, clonidine and related substances: these combinations increase central nervous system depression. The reduced level of alertness can make driving and using machines hazardous. • Furthermore, adequate analgesia may be difficult to achieve when administering a full opioid agonist in patients receiving buprenorphine/naloxone. Therefore the potential to overdose with a full agonist exists, especially when attempting to overcome buprenorphine partial agonist effects, or when buprenorphine plasma levels are declining • 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) • naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of buprenorphine. Co-administration during buprenorphine/naloxone treatment is 9  contraindicated due to the potentially dangerous interaction that may precipitate a sudden onset of prolonged and intense opioid withdrawal symptoms (see section 4.3). • CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of buprenorphine (approximately 50 % and 70 % respectively) and, to a lesser extent, of norbuprenorphine Patients receiving Zubsolv should be closely monitored, and may require dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole, macrolide antibiotics). • CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid dependence with buprenorphine. It is recommended that patients receiving buprenorphine/naloxone should be closely monitored if inducers (e.g. phenobarbital, carbamazepine, phenytoin, rifampicin) are co-administered. The dose of buprenorphine or the CYP3A4 inducer may need to be adjusted accordingly. • The concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of the effects of opioids, based on experience with morphine.

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) phenobarbital (HOS-085617) ketoconazole (HOS-084513) clonidine (HOS-088594) carbamazepine (HOS-085618) naltrexone (HOS-115836) nalmefene (HOS-115837) morphine (HOS-086053) gabapentin (HOS-090745) serotonin (HOS-085477) itraconazole (HOS-084516) ritonavir (HOS-084521) phenytoin (HOS-084531)

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138583 · Präparat HOS-098216

Summary of the safety profile

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138584 · Präparat HOS-098216

The most commonly reported treatment related adverse reactions reported during the pivotal clinical trials were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious.

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138585 · Präparat HOS-098216

Tabulated list of adverse reactions

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138586 · Präparat HOS-098216

Table 1 summarises adverse reactions reported from pivotal clinical trials in which, 342 of 472 patients (72.5%) reported adverse reactions and adverse reactions reported during post-marketing surveillance.

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138587 · Präparat HOS-098216

The frequency of possible adverse reactions listed below is defined using the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1 000 to <1/100), Rare (≥/10 000 to <1/1 000), Very rare (<1/10 000), 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 · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-138588 · Präparat HOS-098216

Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing surveillance of buprenorphine/naloxone

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 11–13

HOS-138589 · Präparat HOS-098216

System Organ Very Common Uncommon Not known Class common Infections and Influenza Urinary tract infestations Infection infection Pharyngitis Vaginal infection Rhinitis Blood and Anaemia lymphatic Leukocytosis system Leukopenia disorders Lymphadenopathy Thrombocytopenia Immune system Hypersensitivity Anaphylactic disorders shock Metabolism and Decreased appetite nutrition Hyperglycaemia disorders Hyperlipidaemia Hypoglycaemia Psychiatric Insomnia Anxiety Abnormal dreams Hallucination disorders Depression Agitation Libido Apathy decreased Depersonalisation Nervousness Drug dependence Thinking Euphoric mood abnormal Hostility Nervous system Headache Migraine Amnesia Hepatic disorders Dizziness Hyperkinesia encephalopathy Hypertonia Seizure Syncope 11 System Organ Very Common Uncommon Not known Class common Paraesthesia Speech disorder Somnolence Tremor Eye disorders Amblyopia Conjunctivitis Miosis Lacrimal disorder Ear and Vertigo labyrinth disorders Cardiac Angina pectoris disorders Bradycardia Myocardial infarction Palpitations Tachycardia Vascular Hypertension Hypotension Orthostatic disorders Vasodilatation hypotension Respiratory, Cough Asthma Dyspnoea Bronchospasm thoracic and Yawning Respiratory mediastinal depression disorders Gastrointestinal Constipation Abdominal Mouth ulceration Dental caries disorders Nausea pain Diarrhoea Tongue Dyspepsia discolouration Flatulence Vomiting Hepatobiliary Hepatitis disorders Hepatitis acute Jaundice Hepatic necrosis Hepatorenal syndrome Skin and Hyperhidrosis Pruritus Rash Acne Alopecia Angioedema subcutaneous Urticaria Dermatitis exfoliative tissue disorders Dry skin Skin mass Musculoskeletal Back pain Arthritis and connective Arthralgia tissue disorders Muscle spasms Myalgia Renal and Urine Albuminuria urinary abnormality Dysuria disorders Haematuria Nephrolithiasis Urinary retention Reproductive Erectile Amenorrhoea system and dysfunction Ejaculation breast disorders disorder Menorrhagia Metrorrhagia General Drug Asthenia Hypothermia Drug disorders and withdrawal Chest pain withdrawal administration syndrome Chills syndrome site conditions Pyrexia neonatal Malaise pain 12  System Organ Very Common Uncommon Not known Class common Oedema peripheral Investigations Liver function Blood creatinine Transaminases test abnormal increased increased Weight decreased Injury, Injury Heat stroke poisoning and procedural complications

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-138590 · Präparat HOS-098216

Description of selected adverse reactions

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-138591 · Präparat HOS-098216

In cases of intravenous drug misuse, some adverse reactions are attributed to the act of misuse rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), and potentially serious acute hepatitis, and other infections such as pneumonia, endocarditis have been reported (see section 4.4).

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-138592 · Präparat HOS-098216

In patients presenting with marked drug dependence, initial administration of buprenorphine can produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 4.4).

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-138593 · Präparat HOS-098216

Reporting of suspected adverse reactions

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

Nebenwirkungen · Zubsolv

Zubsolv 0.7 mg/0.18 mg sublingual tablets Zubsolv 1.4 mg/0.36 mg sublingual tablets Zubsolv 2.9 mg/0.71 mg sublingual tablets Zubsolv 5.7 mg/1.4 mg sublingual tablets Zubsolv 8.6 mg/2.1 mg sublingual tablets Zubsolv 11.4 mg/2.9 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-138594 · Präparat HOS-098216

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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