Zalviso

Zalviso is to be administered in a hospital setting only. 4). Posology Zalviso sublingual tablets are to be self-administered by the patient in response to pain using the Zalviso administration device. The Zalviso administration device is designed to deliver a single sufentanil 15 micrograms sublingual tablet, on a patient-controlled as needed basis, with a minimum of 20 minutes (lockout interval) between doses, over a period of up to 72 hours, which is the maximum recommended treatment duration.

See section “Method of administration”. Elderly No special population studies were performed using sufentanil sublingual tablets in elderly patients. In clinical trials approximately 30 % of enrolled patients were 65 to 75 years of age.

2). Hepatic or renal impairmentMedicinal Product no longer authorised 3 No special population studies were performed using sufentanil sublingual tablets in hepatic and renal impaired patients. Only limited data are available for the use of sufentanil in such patients.

4). Paediatric population The safety and efficacy of Zalviso in children aged below 18 years have not been established. No data are available. Method of administration For sublingual use only. 6). The dispensed sublingual tablet should dissolve under the tongue and should not be crushed, chewed, or swallowed.

Patients should not eat or drink and minimize talking for 10 minutes after each dose of Zalviso. The maximum amount of sublingual sufentanil that can be delivered via the Zalviso administration device over an hour is 45 micrograms (3 doses).

In the event of repeated maximal usage by the patient, one cartridge will last for a period of 13 hours 20 minutes. Additional Zalviso cartridges may be utilized if needed. 6.

4). Based on the combined safety data from these clinical studies, nausea and vomiting were the most frequently reported adverse reactions (≥1/10 frequency). 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 and <1/10 Uncommon ≥1/1,000 and <1/100 Rare ≥1/10,000 and <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 Immune system disorders Hypersensitivity* Anaphylactic shock Psychiatric disorders Confusional state Apathy* Nervousness* Nervous system disorders Dizziness Headache Sedation Somnolence Paraesthesia Ataxia* Dystonia* Hyperreflexia* Convulsions Coma Eye disorders Vision disturbances MiosisMedicinal Product no longer authorised 7 Cardiac disorders Heart rate increased Heart rate decreased* Vascular disorders Blood pressure increased Blood pressure decreased Respiratory, thoracic and mediastinal disorders Respiratory depression Apnoea Respiratory arrest Gastrointestinal disorders Nausea Vomiting Constipation Dyspepsia Dry mouth Skin and subcutaneous tissue disorders Pruritus Hyperhidrosis Rash Dry skin* Erythema Musculoskeletal and connective tissue disorders Involuntary muscle spasms Muscle twitching* Renal and urinary disorders Urinary retention General disorders and administration site conditions Pyrexia Chills Asthenia Drug Withdrawal Syndrome * see “Description of selected adverse reactions” Description of selected adverse reactions After prolonged use of other substances with μ-opioid receptor activity, symptoms of withdrawal were observed after abrupt interruption of the treatment.

Some adverse reactions were not observed in the clinical trials with Zalviso. Their frequencies were established based on data from intravenous administration of sufentanil: common – muscle twitching; uncommon – hypersensitivity, apathy, nervousness, ataxia, dystonia, hyperreflexia, heart rate decreased and dry skin.

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. 9). Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep- related hypoxemia.

Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. 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 impairedMedicinal Product no longer authorised 4 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 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 Zalviso in such patients. 9). Abuse potential and tolerance Sufentanil has potential for abuse.

This should be considered when prescribing or administering sufentanil where there is concern about an increased risk of misuse, abuse or diversion. Patients on chronic opioid therapy or opioid addicts may require higher analgesic doses than the Zalviso administration device can deliver.

1. - Significant respiratory depression.