Prescrire International - Free Special Edition - 2022

MARKETING AUTHORISATIONS

NEW PRODUCT/ NEW PHARMACEUTICAL FORM

Nasal naloxone 1.8 mg (NYXOID°) in opioid overdose

Nyxoid° was granted marketing authorisation mainly on the basis of a pharmacokinetic study comparing various doses of nasal naloxone versus 0.4 mg of intramuscular or intravenous naloxone , as well as previously published data. No studies have specifically evaluated this product (3,4). Each box of Nyxoid° contains two ready-to-use, single-dose spray devices, each delivering 1.8 mg of naloxone . The patient is positioned on their back with their head tilted back, and the entire contents of one spray device is administered into one nostril, in a single actuation of the device. If after 2 to 3 minutes the effect is deemed insufficient, the procedure is repeated in the other nostril (1,5). Whenever naloxone is used outside a hospital setting, re gardless of the form administered, the emergency services must be contacted (for example by calling the European emer gency number 112), since they may need to administer additional doses of naloxone , which has a shorter duration of action than some opioids (1). It is useful to help the family and friends of opioid users to learn how to use the device. In general, opioid users and their close contacts stand to gain from knowing the signs of an opioid overdose and the factors that increase the risk of overdose (1). Nyxoid°’s European marketing authorisation specifies that it can only be obtained with a prescription. This requirement has the drawback of hindering access to this drug, for example in healthcare facilities that treat opioid-dependent patients but have no prescribing doctors on staff. Since 2017, access to ready to-use naloxone for intramuscular or intranasal administration has remained too limited in France, yet these medicines help prevent overdose-related deaths (5-7). ©Prescrire

OFFERS ANADVANTAGE Nasal naloxone is effective at pre venting death in the event of an opi oid overdose resulting frommedical or illicit opioid use. It has a favourable harm-benefit balance in both medical and non-­ medical settings. NYXOID° - naloxone nasal spray solution • 1.8mg of naloxone in 0.1 ml of solution per single-dose spray device Mundipharma ■ Antidote; opioid receptor antagonist ■ Indication : emergency therapy for known or suspectedopioidover dose, presenting as respiratory and/or central nervous systemdepres sion, in both non-medical and healthcare settings, in adults and ado lescents aged 14 years and over. [EU centralised procedure] ■ Dosage : 1.8 mg (i.e. the contents of one spray device) into a single nostril. If the patient’s state does not improve within 2 to 3 minutes after receiving this dose, a second dose, administered into the other nostril, is recommended. Opioid overdoses occur in persons using opioid medications or illicit opioids. They reduce the respiratory rate and can cause loss of consciousness, sometimes leading to respiratory arrest, then cardiac arrest. Several hundred fatal opioid overdoses are estimated to occur every year in France (1-3). Naloxone is an opioid receptor antagonist. It is an effective antidote for preventing death following an opioid overdose, whether administered by injection or intranasally. In this situ ation, naloxone ’s main adverse effect is an acute opioid with drawal syndrome, consisting primarily of agitation, anxiety, nausea, myalgia and sweating. This is a minor risk, however, in a life-threatening emergency (1-3). Naloxone has been available for several decades as an in jectable solution supplied in ampoules, for use in the commu nity, restricted to healthcare professionals, and in the hospital. Two additional formats were then authorised in France, in 2017 and 2018, for emergency use in medical or non-medical settings, for example by friends or relatives of opioid users: a nasal spray authorised for use in adults and children from the age of one month (no longer marketed since late 2020); and a solution for intramuscular injection supplied in a prefilled syringe, for use in adults only (1-3). A new naloxone -containing nasal spray (Nyxoid°) has been authorised in the European Union for emergency use in medi cal and non-medical settings in adults and adolescents aged 14 years and over (3,4).

▶ Translated from Rev Prescrire November 2021 Volume 41 N° 457 • Pages 805-806

Literature search up to 13 September 2021

In response to our request for information, SanofiAventis provided us with no documentation on its product.

1- Prescrire Editorial Staff “Nasal naloxone in opioid overdose. Opioid antidote nasal spray, useful and convenient in an emergency” Prescrire Int 2018; 27 (199): 285-287. 2- Prescrire Rédaction “Naloxone (Prenoxad°) en kit pour injection IM dans les surdoses d’opioïdes” Rev Prescrire 2018; 38 (417): 488-489. 3- HAS - Commission de la Transparence “Avis-Nyxoid” 5 February 2020: 19 pages. 4- EMA - CHMP “Public assessment report for Nyxoid. EMEA/H/C/004325/0000” 14 September 2017: 59 pages. 5- EMA “SPC + PIL-Nyxoid” 5 February 2021: 29 pages. 6- Jehanne C et al. “Chroniques de la mise à disposition des kits naloxone (Nalscue, Prenoxad et bientôt Nyxoid), échec ou succès en demi-teinte?” Le Flyer 2021; 79 : 6 pages. 7- France Patients Experts Addictions et al. “Overdose day 2021. Journée inter nationale de sensibilisation aux surdoses. Où en sommes-nous?” Press release 31 August 2021: 2 pages. Prescrire Int • February 2022

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