Dzuveo · 4.3 Contraindications · 1

HOS-098120 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most serious adverse reaction of sufentanil is respiratory depression, which occurred at a rate of 0.6% in sufentanil clinical trials. The most commonly reported adverse reactions seen in clinical trials and from post marketing experience with sufentanil containing products were nausea, vomiting and pyrexia (≥1/10 patients) (see section 4.4). Tabulated list of adverse reactions Adverse reactions identified either from clinical studies or from post marketing experience with other medicinal products containing sufentanil are summarised in the table below. The frequencies are defined as: 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. MedDRA system organ Very Common Uncommon Not known class common Infections and Bronchitis infestations Conjunctivitis infective Pharyngitis Neoplasm benign, Lipoma malignant and unspecified (including cysts and polyps) Blood and lymphatic Anaemia Thrombocytopenia system disorders Leukocytosis Immune system Hypersensitivity Anaphylactic disorders shock Metabolism and Hypocalcaemia Hypomagnesaemia nutrition disorders Hypoalbuminaemia Hypoproteinaemia Hypokalaemia Hyperkalaemia Hyponatraemia Diabetes mellitus Hyperglycaemia Hyperlipidaemia Hypophosphataemia Hypovolaemia 6 MedDRA system organ Very Common

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HOS-098116 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Significant respiratory depression or pulmonary compromise.

HOS-098115 · has-indication-information · PDF-Seite 2

Dzuveo is indicated for the management of acute moderate to severe pain in adult patients.

HOS-098118 · has-interaction-information · PDF-Seite 4

Interaction with cytochrome P450-3A4 enzyme Sufentanil is primarily metabolised by the human cytochrome P450-3A4 enzyme. Ketoconazole, a potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil (maximal plasma levels (Cmax) increase of 19%, overall exposure to the active substance (AUC) increase of 77% and prolong the time to reach maximum concentration by 41%. Similar effects with other potent CYP3A4 inhibitors (e. g. itraconazole, ritonavir) cannot be excluded. Any change in efficacy/tolerability associated with the increased exposure would be compensated in practice by an increase in the amount of time between doses (see section 4.2). Interaction with calcium channel and/or beta blockers 4 The incidence and degree of bradycardia and hypotension with sufentanil may be greater in patients on chronic calcium channel and/or beta blocker therapy. Caution should be exercised in patients on these concomitant medicinal products and they should be closely monitored. Central nervous system (CNS) depressants The concomitant use of CNS depressants including barbiturates, benzodiazepines, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression. The concomitant use of opioids and gabapentinoids (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression and death. When considering the use of sufentanil in a patient taking a CNS depressant, the duration of use of the CNS depressant and the patient’s response should be assessed, including the degree of tolerance that has developed to CNS depression. If the decision to begin sufentanil is made, the patient should be closely monitored and a lower dose of the concomitant CNS depressant should be considered. Co-administration of sufentanil with a serotonergic agent, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), or Monoamine Oxidase Inhibitors (MAOIs), may increase the risk of serotonin syndrome, a potentially life threatening condition. Monoamine Oxidase Inhibitors must not be taken in the 2 weeks before or at the same time as Dzuveo is given. Others Interaction with other sublingually administered products or products intended to dilute/establish an effect in the oral cavity were not evaluated and simultaneous administration should be avoided.

HOS-098119 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited amount of data from the use of sufentanil in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Sufentanil should not be used in pregnancy, because it crosses the placenta and the foetal respiratory center is sensitive to opiates. If sufentanil is administered to the mother during this time, an antidote for the child should be readily available. Following long-term treatment sufentanil may cause withdrawal symptoms in the newborn. Sufentanil is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding Sufentanil is excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sufentanil 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 sufentanil on fertility. Studies in rats have revealed reduced fertility and enhanced embryo mortality (see section 5.3).

HOS-098117 · has-warning-information · PDF-Seite 3

Respiratory depression Sufentanil may cause respiratory depression, for which the degree/severity is dose related. The respiratory effects of sufentanil should be assessed by clinical monitoring, e.g. respiratory rate, sedation level and oxygen saturation. Patients at higher risk are those with respiratory impairment or reduced respiratory reserve. Respiratory depression caused by sufentanil can be reversed by opioid antagonists. Repeat antagonist administration may be required as the duration of respiratory depression may last longer than the duration of the effect of the antagonist (see section 4.9). Risk from concomitant use of sedative medicines such as benzodiazepines or related medicinal products Concomitant use of sufentanil and sedative medicines such as benzodiazepines or related medicinal products may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible, or when sufentanil is used in an emergency setting. Intracranial pressure Sufentanil should be used with caution in patients who may be particularly susceptible to the cerebral effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Sufentanil may obscure the clinical course of patients with head injury. Sufentanil should be used with caution in patients with brain tumours. Cardiovascular effects Sufentanil may produce bradycardia. Therefore, it should be used with caution in patients with previous or pre-existing bradyarrhythmias. Sufentanil may cause hypotension, especially in hypovolemic patients. Appropriate measures should be taken to maintain stable arterial pressure. Impaired hepatic or renal function 3 Sufentanil is primarily metabolised in the liver and excreted in the urine and faeces. The duration of activity may be prolonged in patients with severe hepatic and renal impairment. Only limited data are available for the use of sufentanil in such patients. Patients with moderate to severe hepatic or severe renal impairment should be monitored carefully for symptoms of sufentanil overdose (see section 4.9). Tolerance and Opioid Use Disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids. Ab

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