Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep PecFent in a safe and secure place, not accessible by others.
Patients and their carers must be instructed that PecFent contains an active substance in an amount that can be fatal to a child.

In order to minimise the risks of opioid-related adverse reactions and to identify the effective dose, it is imperative that patients be monitored closely by health professionals during the titration process.

It is important that the long acting opioid treatment used to treat the patient’s persistent pain has been stabilised before PecFent therapy begins.

Hyperalgesia
As with other opioids, in case of insufficient pain control in response to an increased dose of fentanyl, the possibility of opioid-induced hyperalgesia should be considered. A fentanyl dose reduction or discontinuation of fentanyl treatment or treatment review may be indicated.

Respiratory depression
There is a risk of clinically significant respiratory depression associated with the use of fentanyl.
Patients with pain who receive chronic 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 disease
In patients with chronic obstructive pulmonary diseases, fentanyl may cause more serious adverse reactions. In these patients, opioids may decrease respiratory drive and increase airway resistance.

Increased intracranial pressure
PecFent should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of patients with a head injury and should be used only if clinically warranted.

Cardiac disease
Fentanyl may produce bradycardia. PecFent should, therefore, be used with caution in patients with previous or pre-existing bradyarrhythmias.

Impaired hepatic or renal function
In addition, PecFent should be administered with caution to patients with hepatic or renal impairment.
The influence of hepatic and renal impairment on the pharmacokinetics of the medicinal product has not been evaluated; however, when administered intravenously the clearance of fentanyl has been shown to be altered in hepatic and renal impairment due to alterations in metabolic clearance and plasma proteins. Therefore, special care should be taken during the titration process in patients with moderate or severe hepatic or renal impairment.

Careful consideration should be given to patients with hypovolaemia and hypotension.

Tolerance and Opioid Use Disorder (abuse and dependence)
Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as fentanyl.

Repeated use of PecFent may lead to Opioid Use Disorder (OUD). A higher dose and longer duration of opioid treatment, can increase the risk of developing OUD. Abuse or intentional misuse of PecFent may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).

Before initiating treatment with PecFent and during the treatment, treatment goals and a discontinuation plan should be agreed with the patient (see section 4.2). Before and during treatment the patient should also be informed about the risks and signs of OUD. Patients should be advised to contact their physician if these signs occur.

Patients will require monitoring for signs of drug-seeking behavior (e.g. too early requests for refills).
This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Athletes should be informed that treatment with fentanyl could lead to positive doping tests.

Serotonin Syndrome
Caution is advised when PecFent is coadministered with medicinal products that affect the serotoninergic neurotransmitter systems.

The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic medicinal products such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with medicinal products which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose (see section 4.5).

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 PecFent should be discontinued.

Route of administration
PecFent is only intended for nasal use, and must not be administered by any other route. Due to physico-chemical properties of excipients included in the formulation, intravenous or intra-arterial injection must be avoided in particular.

Nasal conditions
If the patient experiences recurrent episodes of epistaxis or nasal discomfort while taking PecFent, an alternative method of administration for treatment of breakthrough pain should be considered.

Sleep-related breathing disorders
Opioids can cause sleep-related breathing disorders including central sleep apnoea (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.

Concomitant use with sedatives
Concomitant use of PecFent and sedative medicines such as benzodiazepines or related drugs 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. If a decision is made to prescribe PecFent concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation.

In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

PecFent excipients
PecFent contains propyl parahydroxybenzoate (E216). Propyl parahydroxybenzoate may cause allergic reactions (possibly delayed) and, exceptionally, bronchospasm (if the medicinal product is not correctly administered).

Effects on Driving

4.7   Effects on ability to drive and use machines
Opioid analgesics may impair the mental and/or physical ability required for driving or operating machinery.

Patients should be advised not to drive or operate machinery if they experience somnolence, dizziness, or visual disturbance or other adverse reactions which can impair their ability to drive or operate machinery.