Respiratory depressionClinical significant respiratory depression may occur with fentanyl, and patients must be observed for these effects. Patients with pain who receivechronic opioid therapy develop tolerance to respiratory depression and hence the risk of respiratory depression in these patients is reduced. The use of concomitant central nervous system depressants may increase the risk of respiratory depression (see section 4.5).
Chronic pulmonary diseaseIn patients with chronic obstructive pulmonary diseases, fentanyl may have more severe adverse reactions. In these patients, opioids may decrease respiratory drive and increase airway resistance.
Impaired renal or hepatic functionFentanyl should be administered with caution to patients with moderate to severe hepatic or renal impairment. The influence of hepatic and renal impairment on the pharmacokinetics of Instanyl have not been evaluated; however, when administered intravenously the clearance of fentanyl has shown to be altered due to hepatic and renal impairment caused by alterations in metabolic clearance and plasma proteins.
Increased intracranial pressureFentanyl should be used with caution in patients with evidence of increased intracranial pressure, impaired consciousness or coma. Instanyl should be used with caution in patients with cerebral tumour or head injury.
Cardiac diseaseFentanyl may produce bradycardia. Fentanyl should therefore be used with caution in patients with previous or pre-existing bradyarrhythmias. Opioids may cause hypotension, especially in patients with hypovolaemia. Instanyl should therefore be used with caution in patients with hypotension and/or hypovolaemia.
Serotonin SyndromeCaution is advised when Instanyl is coadministered with drugs that affect the serotoninergic neurotransmitter systems.The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose.Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).If serotonin syndrome is suspected, treatment with Instanyl should be discontinued.
Nasal conditionsIf the patient experience recurrent episodes of epistaxis or nasal discomfort while taking Instanyl, an alternative administration form for treatment of breakthrough pain should be considered.
Common coldThe overall extent of fentanyl exposure in subjects with common cold without prior treatment with nasal vasoconstrictor is comparable to that in healthy subjects. For concomitant use of nasal vasoconstrictor see section 4.5.
Abuse potential and dependenceTolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as fentanyl. However, iatrogenic addiction following therapeutic use of opioids is rare in the treatment of cancer related pain.
Withdrawal symptomsWithdrawal symptoms may be precipitated through the administration of substances with opioid antagonist activity, e.g. naloxone, or mixed agonist/antagonist analgesic (e.g. pentazocine, butorphanol, buprenorphine, nalbuphine).