thadone. Patients taking methadone for treatment of opioid addiction were not included in the clinical development programme and use of naloxegol in these patients should be approached with caution.
Gastrointestinal adverse reactions
Reports of severe abdominal pain and diarrhoea have been observed in clinical trials with the 25 mg dose, typically occurring shortly after initiation of treatment. There was a higher incidence of discontinuations in patients taking the 25 mg dose compared to placebo due to diarrhoea (0.7% for placebo versus 3.1% for naloxegol 25 mg) and abdominal pain (0.2% versus 2.9%, respectively). Patients should be advised to promptly report severe, persistent or worsening symptoms to their physician. Consideration may be given to lowering the dose to 12.5mg in patients experiencing severe gastrointestinal adverse events depending upon the response and tolerability of individual patients.
Opioid withdrawal syndrome
Cases of opioid withdrawal syndrome have been reported in the naloxegol clinical programme (DSM-5). Opioid withdrawal syndrome is a cluster of three or more of the following signs or symptoms: dysphoric mood, nausea or vomiting, muscle aches, lacrimation or rhinnorrhea, pupillary dilation or piloerection or sweating, diarrhoea, yawning, fever or insomnia. Opioid withdrawal syndrome typically develops within minutes to several days following administration of an opioid antagonist. If opioid withdrawal syndrome is suspected the patient should discontinue Moventig and contact their physician.
Patients with CV conditions
Naloxegol was not studied in the clinical trial programme in patients who had a recent history of myocardial infarction within 6 months, symptomatic congestive heart failure, overt cardiovascular (CV) disease or patients with a QT interval of ≥ 500 msec. Moventig should be used with caution in these patients. A QTc study performed with naloxegol in healthy volunteers did not indicate any prolongation of the QT interval.
CYP3A4 inducers
Naloxegol is not recommended in patients who are taking strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John's Wort) (see section 4.5).
For information regarding concomitant use with CYP3A4 inhibitors, see sections 4.2, 4.3 and 4.5.
Renal impairment
The starting dose for patients with moderate or severe renal insufficiency is 12.5 mg. If side effects impacting tolerability occur, naloxegol should be discontinued. The dose can be increased to 25 mg if 12.5 mg is well tolerated by the patient (see section 5.2).
Severe hepatic impairment
Naloxegol has not been studied in patients with severe hepatic impairment. The use of naloxegol is not recommended in such patients.
Cancer-related pain
There is limited clinical experience with the use of naloxegol in OIC patients with cancer-related pain. Therefore, caution should be used when prescribing naloxegol to such patients (see section 4.3).
4.5 Interaction with other medicinal products and other forms of interaction
Interaction with CYP3A4 inhibitors and inducers
Interaction with strong CYP3A4 inhibitors
In an open-label, non-randomized, fixed-sequence, 3-period, 3-treatment, crossover study to eva luate the effect of multiple doses of ketoconazole on the single dose PK of naloxegol, co-administration of ketoconazole and naloxegol resulted in a 12.9 fold (90% CI: 11.3-14.6) increase in naloxegol AUC and a 9.6-fold increase in naloxegol Cmax (90% CI: 8 |
