Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-130337 · Präparat HOS-096899

Although clinical data do not identify a pharmacokinetic interaction between bupropion and alcohol, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in 9 patients drinking alcohol during bupropion treatment. There are no known pharmacokinetic interactions between naltrexone and alcohol. The consumption of alcohol during naltrexone/bupropion treatment should be minimised or avoided.

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

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130338 · Präparat HOS-096899

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure including: • as treatment with naltrexone/bupropion may result in lowered glucose in patients with diabetes, the dose of insulin and/or oral diabetic medicinal products should be assessed to minimise the risk of hypoglycaemia, which could predispose patients to seizure • concomitant administration of medicinal products that may lower the seizure threshold, including antipsychotics, antidepressants, antimalarials, tramadol, theophylline, systemic steroids, quinolones and sedating antihistamines

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): glucose (HOS-088412) theophylline (HOS-085910) tramadol (HOS-112871)

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130340 · Präparat HOS-096899

Naltrexone/bupropion is contraindicated in patients receiving concomitant treatment with monoamine oxidase inhibitors, bupropion or naltrexone, patients undergoing acute alcohol, opioid or benzodiazepine withdrawal, patients currently dependent on opioids (see section 4.3).

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

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130341 · Präparat HOS-096899

Administration of naltrexone/bupropion to patients receiving either levodopa or amantadine concurrently should be undertaken with caution. Limited clinical data suggest a higher incidence of adverse reactions (e.g., nausea, vomiting, and neuropsychiatric adverse reactions – see section 4.8) in patients receiving bupropion concurrently with either levodopa or amantadine.

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): amantadine (HOS-086615) levodopa (HOS-086559)

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130342 · Präparat HOS-096899

Administration of naltrexone/bupropion with inhibitors or inducers of UGT 1A2 and 2B7 should be undertaken with caution as these may alter the exposure of naltrexone.

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

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130343 · Präparat HOS-096899

Coadministration of naltrexone/bupropion with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with naltrexone/bupropion and digoxin. Clinicians should be aware that digoxin levels may rise on discontinuation of naltrexone/bupropion and the patient should be monitored for possible digoxin toxicity.

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): digoxin (HOS-086172)

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130344 · Präparat HOS-096899

Naltrexone/bupropion has not been studied in conjunction with alpha-adrenergic blockers or clonidine.

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): clonidine (HOS-088594)

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130345 · Präparat HOS-096899

Since bupropion is extensively metabolised, caution is advised when naltrexone/bupropion is co-administered with medicinal products known to inhibit metabolism (e.g. valproate), as these may affect its clinical efficacy and safety.

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): valproate (HOS-085955)

Wechselwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130347 · Präparat HOS-096899

Naltrexone/bupropion should preferably be taken with food, as it is known that both naltrexone and bupropion plasma concentrations are increased with food and the safety and efficacy data from clinical trials is based on dosing with food.

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130348 · Präparat HOS-096899

Summary of the safety profile

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130349 · Präparat HOS-096899

In clinical studies, 23.8% of subjects receiving naltrexone/bupropion and 11.9% of subjects receiving placebo discontinued treatment due to an adverse reaction. The most frequent adverse reactions for naltrexone/bupropion are nausea (very common), constipation (very common), vomiting (very common), dizziness (common), and dry mouth (common). The most frequent adverse reactions leading to discontinuation with naltrexone/bupropion were nausea (very common), headache (very common), dizziness (common) and vomiting (very common).

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130350 · Präparat HOS-096899

Tabulated list of adverse reactions

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130351 · Präparat HOS-096899

The safety profile of naltrexone/bupropion (NB) summarised in Table 1 below is based on clinical studies performed with the fixed-dose combination (adverse reactions at an incidence of at least 0.1% and twice that of placebo) and/or post marketing data sources.The list of terms in Table 2 provides information on the adverse reactions of the individual components naltrexone (N) and bupropion (B) identified in their respective approved SmPCs for different indications.

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-130352 · Präparat HOS-096899

11 The frequencies of adverse reactions are ranked according to the following: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130353 · Präparat HOS-096899

Table 1. Adverse reactions reported in subjects who received naltrexone/bupropion as a fixed- dose combination System Organ Class Frequency Adverse reaction Blood and lymphatic system disorders Rare Decreased haematocrit Lymphocyte count decreased Not known Lymphadenopathy Immune system disorders Uncommon Hypersensitivity Urticaria Rare Angioedema Metabolism and nutrition disorders Rare Dehydration Psychiatric disorders Common Anxiety Insomnia Uncommon Abnormal dreams Agitation Mood swings Nervousness Tension Dissociation (feeling spacey) Rare Hallucination Not known Panic attack Not known Affective disorders Aggression Confusional state Delusions Depression Disorientation Disturbance in attention Hostility Loss of libido Nightmares Paranoia Psychotic disorder Suicidal ideation* Suicide attempt Suicidal behaviour Nervous system disorders Very common Headache Common Dizziness Tremor Dysgeusia Lethargy Somnolence Uncommon Intention tremor Balance disorder Amnesia Rare Loss of consciousness Paraesthesia Presyncope Seizure** Syncope

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 12–13

HOS-130354 · Präparat HOS-096899

12  Not known Dystonia Memory impairment Parkinsonism Restlessness Serotonin syndrome**** Eye disorders Not known Eye irritation Eye pain or asthenopia Eye swelling Lacrimation increased Photophobia Vision blurred Ear and labyrinth disorders Common Tinnitus Vertigo Uncommon Motion sickness Not known Ear discomfort Ear pain Cardiac disorders Common Palpitations Heart rate increased Uncommon Tachycardia Vascular disorders Common Hot flush Hypertension***** Blood pressure increased Not known Blood pressure fluctuation Respiratory, thoracic and mediastinal Not known Cough disorders Dysphonia Dyspnoea Nasal congestion Nasal discomfort Oropharyngeal pain Rhinorrhea Sinus disorder Sneezing Yawning Gastrointestinal disorders Very common Nausea Constipation Vomiting Common Dry mouth Abdominal pain upper Abdominal pain Uncommon Abdominal discomfort Dyspepsia Eructation Rare Haematochezia Hernia Lip swelling Lower abdominal pain Dental caries*** Toothache*** Not known Diarrhoea Flatulence Haemorrhoids Ulcer

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 13–14

HOS-130355 · Präparat HOS-096899

13 Hepatobiliary disorders Uncommon Cholecystitis ALT increased AST increased Hepatic enzyme increased Rare Drug induced liver injury Not known Hepatitis Skin and subcutaneous tissue disorders Common Hyperhidrosis Pruritus Alopecia Rash Not known Acne Erythema multiforme and Stevens Johnson syndrome Cutaneous lupus erythematosus Systemic lupus erythematosus syndrome aggravated Acute generalised exanthematous pustulosis (AGEP) Musculoskeletal and connective tissue Rare Jaw pain disorders Not known Arthralgia Groin pain Myalgia Rhabdomyolysis Renal and urinary disorders Uncommon Blood creatinine increased Rare Micturition urgency Not known Dysuria, Pollakiuria Urinary frequency and/or retention Reproductive system and breast Uncommon Erectile Dysfunction disorders Rare Irregular menstruation Vaginal haemorrhage Vulvovaginal dryness General disorders and administration Common Fatigue site conditions Feeling jittery Irritability Uncommon Asthenia Feeling abnormal Feeling hot Increased appetite Thirst Rare Chest pain Peripheral coldness Pyrexia Not known Chills Energy increased

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 14–15

HOS-130356 · Präparat HOS-096899

14 * Cases of suicidal ideation and suicidal behaviour have been reported during NB therapy (see section 4.4). ** The incidence of seizures is approximately 0.1% (1/1,000). The most common type of seizures is generalised tonic-clonic seizures, a seizure type which can result in some cases in post-ictal confusion or memory impairment (see section 4.4). *** Toothache and dental caries, while not meeting the criteria for inclusion in this table, are listed based on the subset of patients with dry mouth, in which a higher incidence of toothache and dental caries was observed in subjects treated with NB versus placebo. **** Serotonin syndrome may occur as a consequence of an interaction between bupropion and a serotonergic medicinal product (e.g., Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Re- uptake Inhibitors (SNRIs) and opioids (see sections 4.4 and 4.5). *****Post-marketing cases of hypertensive crisis have been reported during the initial titration phase.

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-130357 · Präparat HOS-096899

As NB is a fixed combination of two active ingredients, in addition to the terms listed in Table 1, additional adverse reactions seen with one of the active substances may potentially occur. The additional undesirable effects occurring with either of the individual components (bupropion or naltrexone) when used for non-obesity indications are summarized in Table 2.

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

Nebenwirkungen · Mysimba

Mysimba 8 mg/90 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-130358 · Präparat HOS-096899

Table 2. Adverse reactions of the individual components naltrexone and bupropion identified in the respective approved SmPCs. System Organ Class Frequency Adverse Reaction Infections and infestations Uncommon Oral herpes (N) Tinea pedis (N) Blood and lymphatic system Uncommon Idiopathic thrombocytopenic purpura (N) disorders Immune system disorders Very rare More severe hypersensitivity reactions including angioedema, dyspnoea/ bronchospasm and anaphylactic shock. Arthralgia, myalgia and fever have also been reported in association with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness. (B) Metabolism and nutrition disorders Common Decreased appetite (N) Uncommon Anorexia (B) Blood glucose disturbances (B) Psychiatric disorders Common Concentration disturbance (B) Uncommon Delusions (B) Depersonalisation (B) Libido disorder (N) Paranoid ideation (B) Nervous system disorders Uncommon Ataxia (B) Incoordination (B) Eye disorders Uncommon Visual disturbance (B) Cardiac disorders Common Electrocardiogram change (N) Vascular disorders Uncommon Postural hypotension (B) Vasodilatation (B) Respiratory, thoracic and Uncommon Sputum increased (N) mediastinal disorders Gastrointestinal disorders Common Taste disorders (B) Hepatobiliary disorders Uncommon Blood bilirubin increased (N) Jaundice (B) Skin and subcutaneous tissue Uncommon Exacerbation of psoriasis (B) disorders Seborrhea (N) Not known Toxic epidermal necrolysis (B) Drug reaction with eosinophilia and systemic symptoms (B)

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