Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Napp Pharmaceuticals Limited, Cambridge Science Park, Milton Road, Cambridge, CB4 0GW, United Kingdom
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Nyxoid should only be made available once the suitability and competence of an individual to administer naloxone in the appropriate circumstances has been established. Patients or any other person who might be in a position to administer Nyxoid must be instructed in its proper use and the importance of seeking medical assistance.
Nyxoid is not a substitute for emergency medical care and may be used instead of intravenous (IV) injection, when IV access is not immediately available.
Nyxoid is intended to be administered as a part of a resuscitation intervention in suspected overdose casualties, where opioid drugs may be involved or suspected, likely in a non-medical setting. Therefore, the prescriber should take appropriate steps to ensure that the patient and/or any other person who might be in a position to administer Nyxoid thoroughly understands the indications and use of Nyxoid.
The prescriber should describe the symptoms which allow presumptive diagnosis of central nervous system (CNS) / respiratory depression, the indication and the instructions for use with the patient and / or person who might be in a position to administer this product to a patient experiencing a known or suspected opioid overdose event. This should be performed in accordance with the educational guidance for Nyxoid.
Patients who respond satisfactorily to Nyxoid must be closely monitored. The effect of some opioids can be longer than the effect of naloxone, which could lead to reoccurrence of respiratory depression and therefore further doses of naloxone may be required.
Receiving Nyxoid can lead to a rapid reversal of the opioid effect which can cause an acute withdrawal syndrome (see section 4.8). Patients who are receiving opioids for the relief of chronic pain may experience pain and opioid withdrawal symptoms when Nyxoid is administered.
Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted.
Intranasal absorption and efficacy of naloxone can be altered in patients with damaged nasal mucosa and septal defects.
Opioid withdrawal may be life-threatening in neonates if not recognised and properly treated and may include the following signs and symptoms: convulsions, excessive crying and hyperactive reflexes.
Naloxone elicits a pharmacological response due to the interaction with opioids and opioid agonists. When administered to opioid dependent subjects, naloxone can cause acute withdrawal symptoms in some individuals. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been described, more typically when naloxone is used post-operatively (see sections 4.4 and 4.8).
Administration of Nyxoid may decrease the analgesic effects of opioids used primarily to provide pain relief, due to its antagonist properties (see section 4.4).
When administering naloxone to patients who have received buprenorphine as an analgesic, complete analgesia may be restored. It is thought that this effect is a result of the arch-shaped dose-response curve of buprenorphine with decreasing analgesia in the event of high doses. However, reversal of respiratory depression caused by buprenorphine is limited.
There are no adequate data from the use of naloxone in pregnant women. Studies in animals have shown reproductive toxicity only at maternally toxic doses (see section 5.3). The potential risk for humans is unknown. Nyxoid should not be used during pregnancy unless the clinical condition of the woman requires treatment with naloxone.
In pregnant women who have been treated with Nyxoid, the fetus should be monitored for signs of distress.
In opioid dependent pregnant women, naloxone administration can cause withdrawal symptoms in newborn infants (see section 4.4).
It is unknown whether naloxone is excreted in human breast milk and it has not been established whether infants who are breast-fed are affected by naloxone. However, as naloxone is practically not orally bioavailable its potential to affect a breast-fed infant is negligible. Caution should be exercised when naloxone is administered to a breast-feeding mother but there is no need to discontinue breast-feeding. Breast-fed babies from mothers who have been treated with Nyxoid should be monitored to check for sedation or irritability.
No clinical data on effects of naloxone on fertility are available, however data from rat studies (see section 5.3) indicate no effects.
Patients who have received naloxone to reverse the effects of opioids should be warned not to drive, to operate machinery or to engage in other activities demanding physical or mental exertion for at least 24 hours, since the effect of the opioids may return.
The most common adverse drug reaction (ADR) seen with naloxone administration is nausea (frequency very common). Typical opioid withdrawal syndrome is expected with naloxone which may be caused by the abrupt withdrawal of opioid in persons physically dependent on them.
The following adverse reactions have been reported with Nyxoid and/or other naloxone-containing medicinal products during clinical studies and post marketing experience. ADRs are listed below by system organ class and frequency.
Frequency categories are assigned to those adverse reactions considered to be at least possibly causally related to naloxone and are defined as very common: (≥1/10); common: (≥1/100, <1/10); uncommon: (≥1/1,000, <1/100); rare: (≥1/10,000, <1/1,000) very rare: (<1/10,000); not known (cannot be estimated from the available data).
Very rare: Hypersensitivity, Anaphylactic shock
Common: Dizziness, Headache
Uncommon: Tremor
Common: Tachycardia
Uncommon: Arrhythmia, Bradycardia
Very rare: Cardiac fibrillation, Cardiac arrest
Common: Hypotension, Hypertension
Uncommon: Hyperventilation
Very rare: Pulmonary oedema
Very common: Nausea
Common: Vomiting
Uncommon: Diarrhoea, Dry mouth
Uncommon: Hyperhidrosis
Very rare: Erythema multiforme
Uncommon: Drug withdrawal syndrome (in patients dependent on opioids)
Signs and symptoms of drug withdrawal syndrome include restlessness, irritability, hyperaesthesia, nausea, vomiting, gastrointestinal pain, muscle spasms, dysphoria, insomnia, anxiety, hyperhidrosis, piloerection, tachycardia, increased blood pressure, yawning, pyrexia. Behavioural changes including violent behaviour, nervousness and excitement may also be observed.
In reports on intravenous/intramuscular naloxone: hypotension, hypertension, cardiac arrhythmia (including ventricular tachycardia and fibrillation) and pulmonary oedema have occurred with the postoperative use of naloxone. Adverse cardiovascular effects have occurred more frequently in postoperative patients with a pre-existing cardiovascular disease or in those receiving other medicines that produce similar adverse cardiovascular effects.
Nyxoid is intended for use in adolescents 14 years and over. Frequency, type and severity of adverse reactions in adolescents are expected to be the same as in adults.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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