Dzuveo

Dzuveo is to be administered by a healthcare professional in a medically monitored setting only. A medically monitored setting must have equipment and personnel trained to detect and manage hypoventilation, and availability of supplemental oxygen and opioid antagonists, such as naloxone.

4). Posology Dzuveo is provided in a disposable single-dose applicator, to be administered by a healthcare provider as needed by the individual patient, but no more than once every hour, resulting in a maximum dose of 720 micrograms /day.

Patients with a higher pain intensity at one hour after sufentanil treatment was initiated required more frequent redosing compared to patients with lower pain intensity scores at one hour. Dzuveo should not be used beyond 48 hours.

Elderly No specific dose adjustment is required in elderly patients. 2). 4). Paediatric population The safety and efficacy of sufentanil in children and adolescents below 18 years have not been established. No data are available. Method of administration 3 For sublingual use only.

6). The applicator is used as a placement aid for the healthcare professional to deliver the tablet under the tongue, on an as needed basis, per patient request, with a minimum of 1 hour between doses. The dispensed sublingual tablet should dissolve under the tongue and should not be chewed or swallowed.

If swallowed, the oral bioavailability of Dzuveo is only 9% which would result in a sub- therapeutic dose. Patients should not eat or drink and should minimise talking for 10 minutes after each dose of sufentanil 30 mcg sublingual tablet.

In the case of an excessive dry mouth, patients may be given ice cubes. Some insoluble excipients of the tablet may remain in the mouth after dissolution is complete; this is normal and does not indicate lack of absorption of sufentanil from the tablet.

6 for instructions regarding handling of the Dzuveo sublingual tablet and applicator.

6% in sufentanil clinical trials. 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 class Very common Common Uncommon Not known Infections and infestations Bronchitis Conjunctivitis infective Pharyngitis Neoplasm benign, malignant and unspecified (including cysts and polyps) Lipoma Blood and lymphatic system disorders Anaemia Leukocytosis Thrombocytopenia Immune system disorders Hypersensitivity Anaphylactic shock Metabolism and nutrition disorders Hypocalcaemia Hypoalbuminaemia Hypokalaemia Hyponatraemia Hypomagnesaemia Hypoproteinaemia Hyperkalaemia Diabetes mellitus Hyperglycaemia Hyperlipidaemia Hypophosphataemia Hypovolaemia 7 MedDRA system organ class Very common Common Uncommon Not known Psychiatric disorders Insomnia Anxiety Confusional state Agitation Apathy Conversion disorder Disorientation Euphoric mood Hallucination Mental status changes Nervousness Nervous system disorders Headache Dizziness Somnolence Sedation Tremor Ataxia Dystonia Hyperreflexia Burning sensation Presyncope Paraesthesia Hypoaesthesia Lethargy Memory impairment Migraine Tension headache Convulsions Coma Eye disorders Eye pain Visual disturbance Miosis Cardiac disorders Tachycardia Sinus tachycardia Bradycardia Angina pectoris Atrial fibrillation Ventricular extrasystoles Vascular disorders Hypotension Hypertension Orthostatic hypertension Flushing Diastolic hypotension Orthostatic hypotension Respiratory, thoracic and mediastinal disorders Hypoxia Pharyngolaryngeal pain Respiratory Depression Bradypnoea Epistaxis Hiccups Apnoea Atelectasis Hypoventilation Pulmonary embolism Pulmonary oedema Respiratory distress Respiratory failure Wheezing Respiratory arrest Gastrointestinal disorders Nausea Vomiting Constipation Dyspepsia Flatulence Dry Mouth Diarrhoea Eructation Retching Abdominal discomfort Abdominal distension Abdominal Pain upper Epigastric discomfort Gastritis Gastroesophageal reflux disease Hypoaesthesia oral 8 MedDRA system organ class Very common Common Uncommon Not known Hepatobilary disorders Hyperbilirubinaemia Skin and subcutaneous tissue disorders Pruritus Hyperhidrosis Hypoaesthesia facial Pruritus generalized Blister Rash Dry Skin Erythema Musculoskeletal and connective tissue disorders Muscle spasms Muscle twitching Back Pain Musculoskeletal pain Musculoskeletal chest pain Pain in extremity Renal and urinary disorders Urinary retention Urinary hesitation Oliguria Renal failure Urinary tract pain General disorders and administration site conditions Pyrexia Feeling hot Fatigue Asthenia Chills Local swelling Non-cardiac chest pain Chest discomfort Drug withdrawal syndrome Investigations Oxygen saturation decreased Body temperature increased Blood pressure increased Respiratory rate decreased Blood glucose increased Blood bilirubin increased Urine output decreased Aspartate aminotransferase increased Blood urea increased Electrocardiogram T wave abnormal Electrocardiogram abnormal Hepatic enzyme increased Liver function test abnormal Injury, poisoning and procedural complications Anaemia postoperative Procedural nausea Postoperative ileus Procedural vomiting Gastrointestinal stoma complication Procedural pain Reporting of suspected adverse reactions 9 Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Respiratory depression Sufentanil may cause respiratory depression, for which the degree/severity is dose related. 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. 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 4 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. 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.

1. Significant respiratory depression or pulmonary compromise.