Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Concomitant use of medicinal products containing sodium oxybate and fentanyl is contraindicated (see section 4.3). The treatment of sodium oxybate should be discontinued before start of treatment with PecFent.

Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when PecFent is given concurrently with medicinal products that affect CYP3A4 activity. Coadministration with medicinal products that induce 3A4 activity may reduce the efficacy of PecFent. The concomitant use of PecFent with strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression. Patients receiving PecFent concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. Dose increase should be undertaken with caution.
The concomitant use of other central nervous system depressants, including other opioids, sedatives or hypnotics, general anaesthetics, phenothiazines, tranquillisers, skeletal muscle relaxants, gabapentinoids (gabapentin and pregabalin), sedating antihistamines and alcohol may produce additive depressant effects. Concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The lowest effective dose of sedative medicines should be used and duration of concomitant use should be limited (see section 4.4).

Serotoninergic medicinal products:
Coadministration of fentanyl with a serotoninergic medicinal product, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition.

PecFent is not recommended for use in patients who have received monoamine oxidase (MAO) inhibitors within the previous 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

The concomitant use of partial opioid agonists/antagonists (e.g. buprenorphine, nalbuphine, pentazocine) is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and, therefore, partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients.

Concomitant use of nasally administered oxymetazoline has been shown to decrease the absorption of PecFent (see section 5.2). The concomitant use of nasally administered vasoconstrictive decongestants during titration is, therefore, not recommended as this may lead to patients titrating to a dose that is higher than required. PecFent maintenance treatment may also be less effective in patients with rhinitis when administered concomitantly with a nasal vasoconstrictive decongestant. If this occurs, patients should be advised to discontinue their decongestant.

Concomitant use of PecFent and other medicinal products (other than oxymetazoline) administered via the nose has not been evaluated in the clinical trials. Other nasally administered treatments should be avoided within 15 minutes of dosing with PecFent.