VENTIZOLVE Nasal spray, solution Ref.[50427] Active ingredients: Naloxone

Instructing patients/users on the proper use of Ventizolve

Ventizolveis 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 Ventizolvethoroughly understands the indications and use of Ventizolve.

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 Ventizolve.

Ventizolve contains one single dose of naloxone. Patients and care takers should therefore receive proper instructions on how to use the device, and that it should not be primed or tested prior to administration and that it cannot be reused after administration of the dose (see section 4.2).

Monitoring of the patient for a response

Administer additional doses as necessary, if the patient is not adequately responding or responds and then relapses back into respiratory depression. See section 4.2.

The importance of seeking medical assistance

Patients should be kept under observation until qualified healthcare personnel are on site. The duration of action of most opioids may exceed that of Ventizolve resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek emergency medical assistance immediately and to keep the patient under continued surveillance.

Effectiveness of naloxone

Naloxone is not effective against CNS- or respiratory depression caused by non-opioid drugs. Reversal of respiratory depression caused by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete and may require higher doses of naloxone hydrochloride or repeated administrations. Intranasal absorption and efficacy of naloxone can be altered in patients with damaged nasal mucosaand septal defects.If an incomplete response occurs, respiration should be mechanically assisted.

Opioid withdrawal syndrome

Abrupt reversal of opioid effects in persons who are physically dependent on opioids can precipitate an acute withdrawal syndrome. The severity and duration of the withdrawal relate to the dose of naloxone and the degree and type of opioid dependency. See section 4.8. Patients who are receiving opioids for the relief of chronicpain may experience pain and opioid withdrawal symptoms when Ventizolveis administered.

Ventizolve contains the preservative benzalkonium chloride. Benzalkonium chloride may cause irritation or swelling inside the nose, especially if used for a long time.

Naloxone elicits a pharmacological response due to the interaction with opioids and opioid agonists.There is no interaction with barbiturates or tranquillizers when using standard doses of naloxone hydrochloride. When administered to opioid dependent subjects, naloxone can cause acute withdrawal symptoms insome individuals. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have beendescribed, more typically when naloxone is used post-operatively (see sections 4.4 and 4.8).

Administration of naloxone may decrease the analgesic effects of opioids used primarily to provide pain relief, due to its antagonist properties (see section 4.4).

In patients receiving buprenorphine for analgesic purposes, full analgesic effect of buprenorphine may be restored by administration of naloxone. It is thought that this effect is a result of the arch-shaped dose-responsecurve of buprenorphine with decreasing analgesia in the event of high doses. Reversal of respiratory depression caused by buprenorphine is however limited.

Data regarding interaction with alcohol are not clear. Depending on the cause of intoxication, the effect following administration of naloxone may be delayed in patients with multi-intoxications effected by opioids and sedatives or alcohol.

Serious hypertension has been reported with use of naloxone in cases of coma caused by clonidine overdose.

Pregnancy

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. The potential risk to humans is not known. Ventizolve should not be used during pregnancy unless the clinical condition of thewoman requires treatment with naloxone.

In pregnant women who have been treated with Ventizolve, the fetus should be monitored for signs ofdistress.

Breastfeeding

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 breastfeeding mother, but there is no need to discontinue breastfeeding. Breast-fed babies from mothers who have been treated with Ventizolve should bemonitored to check for sedation or irritability.

Fertility

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 take part in road traffic, 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.

Summary of the safety profile

The most common adverse drug reaction (ADR) seen with naloxone administration is nausea (frequency very common). Abrupt reversal of opioid effects in persons who are physically dependent on opioids can precipitate an acute withdrawal syndrome.

Tabulated list of adverse reactions

The following adverse reactions have been reported with Ventizolve and/or other naloxone-containingmedicinal products during clinical studies and post marketing experience. ADRs are listed below bysystem 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 to <1/10); uncommon: (≥1/1,000 to <1/100); rare: (≥1/10,000 to <1/1,000) very rare: (<1/10,000); not known (cannot be estimated from the available data).

Description of selected adverse reactions

Drug withdrawal syndrome

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 includingviolent behaviour, nervousness and excitement may also be observed.

Vascular disorders

In reports on intravenous/intramuscular naloxone: hypotension, hypertension, cardiac arrhythmia (including ventricular tachycardia and fibrillation) and pulmonary oedema have occurred with thepostoperative use of naloxone. Adverse cardiovascular effects have occurred more frequently inpostoperative patients with a pre-existing cardiovascular disease or in those receiving other medicinesthat produce similar adverse cardiovascular effects.

Reporting of suspected adverse reactions

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 676497; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Not applicable.