NASOLAM

Posology Standard dosages are provided in the table 1 below. Additional details are provided in the text following the table. 75 mg * depending on desired level and duration of sedation Conscious sedation and premedication dosage • NASOLAM must only be used by healthcare professionals in conscious sedation or premedication.

Adequate observation of the patient after administration is mandatory. • NASOLAM can be administered in any position, including lying or sitting patients. • The dose indicated in table 1 should be administered intranasally into one nostril, at 5-10 minutes before the procedure is initiated.

• The onset of action is circa 4-8 minutes after the nasal administration of the first dose. The onset of sedation may vary individually depending on the physical status of the patient. • If required, one subsequent dose may be administered intranasally into the opposite nostril of the first dose, at least 10 minutes after the initial dose, according to the individual need.

• The maximum dose for conscious sedation purposes or premedication is 10 mg. • If after administration of the recommended doses of midazolam (see table 1), the level of sedation is not sufficient, no further intranasal midazolam doses should be administered.

Other midazolam options should be considered. • Paediatric patients < 12 kg: The safety and efficacy of NASOLAM in this paediatric patients group have not been established. No data are available. NASOLAM should not be used in this patient group.

• The administration of a second NASOLAM dose may result in prolonged sedation. 4). 5 mg administered intranasally 5-10 minutes before the procedure is initiated. 4). 4). • Premedication with midazolam given shortly before a procedure produces sedation (induction of sleepiness or drowsiness and relief of apprehension) and preoperative impairment of memory.

Close and continuous monitoring of the patients after administration of premedication is mandatory as inter- individual sensitivity varies and symptoms of overdose may occur. Treatment of prolonged, acute, convulsive seizures dosage • NASOLAM must only be used by parents/care givers where the patient has been diagnosed to have epilepsy • NASOLAM prescribers should consider the following prior to starting treatment: 1.

for patients at increased risk of respiratory depression from benzodiazepines, administration of NASOLAM under healthcare professional supervision should be considered prior to starting treatment with NASOLAM. This administration may be performed in the absence of a seizure.

2. g. parents, caregivers) on: - how to identify (convulsive) seizures - how to use NASOLAM appropriately - when to administer a second dose and when not - the risk of concomitant use of opioids/alcohol/CNS depressants/other benzodiazepines; - the risk of respiratory depression, the symptoms and what to do if it occurs • NASOLAM can be administered in any position, including lying or sitting patients • The first dose indicated in table 1 should be administered intranasally in one nostril.

• Carers should only administer a single dose of midazolam. If the seizure has not stopped within 10 minutes after administration of midazolam, emergency medical assistance must be sought, and the empty single-dose container should be given to the healthcare professional to provide information on the dose received by the patient.

• A second or repeat dose when seizures continue or re-occur after an initial response should not be given without prior medical advice. In particular, young children, patients with respiratory impairment and elderly patients should receive a second dose only in the presence of a health care professional.

This second or repeat dose should be administered into the opposite nostril of the first dose Use in Special Populations Renal Impairment In patients with severe renal impairment the pharmacological effects of midazolam can be enhanced and the duration can be prolonged, potentially with clinical relevant suppression of the cardiorespiratory system.

4). Hepatic Impairment Hepatic impairment reduces the clearance of midazolam with a subsequent increase in terminal half-life. 4). NASOLAM is contraindicated in patients with severe hepatic impairment. Elderly In patients from 60 years and in elderly patients NASOLAM should be used with caution and dose reduction is recommended (see Table 1).

Elderly patients should receive a second dose […]

Summary of safety profile The following undesirable effects have been reported (frequency not known, cannot be estimated from the available data) to occur when midazolam is injected: Frequency categories are as follows: 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) Immune System disorders frequency not known Hypersensitivity, angioedema, anaphylactic shock Psychiatric Disorders frequency not known very rare Disorientation, emotional and mood disturbances, changes in libido, excitation*, physical drug dependence and withdrawal syndrome, abuse.

Agitation*, hostility*, aggression*, anger*, confusional state, euphoric mood, hallucinations. Nervous System Disorders common very rare Decreased alertness, depressed levels of consciousness, sedation (prolonged and postoperative), somnolence.

Involuntary movements (including tonic/clonic movements and muscle tremor)*, hyperactivity*, headache, dizziness, ataxia, paradoxical reactions, anterograde amnesia**, the duration of which is directly related to the administered dose.

Drug withdrawal convulsions. Cardiac Disorders very rare Cardiac arrest, bradycardia Vascular disorders very rare Hypotension, vasodilatation Respiratory System disorders common very rare Sneezing, cough, itching nose, nasal congestion, nasal dryness, rhinorrhea, yawning, respiratory depression Apnoea, respiratory arrest, dyspnea, laryngospasm, hiccups Gastrointestinal Disorders common very rare Nausea, vomiting Constipation, dry mouth.

Skin and subcutaneous tissue disorder uncommon Rash, urticarial, pruritis General Disorders and Administration Site Conditions very rare Fatigue Injury, Poisoning and Procedural complications frequency unknown Falls, fractures*** Social circumstances very rare Assaults* Eye disorders frequency not known Diplopia, blurred vision, excessive blinking * Such paradoxical drug reactions have been reported, particularly among children and the elderly after intravenous midazolam, which may be of relevance to intranasal administration.

** Anterograde amnesia may still be present at the end of the procedure and in few cases prolonged amnesia has been reported after the use of midazolam. *** The risk of falls and fractures is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.

Severe cardiorespiratory adverse events have occurred after the administration of midazolam. 4) 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.

Paediatric patients For children < 12 kg:

NASOLAM should not be used. The safety and efficacy of midazolam in these children, has not been established. No data are available. 4.

For children > 12 kg:

NASOLAM should be used according to table 1. In particular, young children should receive a second dose only in the presence of a health care professional. 4. Method of administration NASOLAM is for intranasal use only. Each NASOLAM single-dose container contains just one dose and is intended for single use only in a single nostril.

In young children, the nozzle may not fit in the nostril. In this case, make sure the nozzle seals the nostril before administration. Do not test or prime the product before administration as NASOLAM only delivers one single dose. If you need a second dose, use a new single-dose container and administer the second dose in the other nostril than the one that was used for administering the first NASOLAM dose.

6. 1. - severe respiratory failure or acute respiratory depression, - severe hepatic impairment, - myasthenia gravis or sleep apnoea syndrome, - acute angle glaucoma; benzodiazepines can be used with open-glaucoma only if they are administered according to the appropriate dose, - cyanogen congenital heart disease, - severe sepsis.

4 Special warnings and precautions for use Respiratory insufficiency Special caution is required for patients with impaired respiratory function, because midazolam may further depress respiration. 2). g. parents, caregivers) for the correct usage of NASOLAM in case support is needed in the emergency situation.

g. 2) and should be continuously monitored for early signs of alterations of vital functions. g. patients with chronic respiratory insufficiency, patients with chronic renal failure, or with impaired hepatic- or cardiac function that require conscious sedation or premedication.

These high-risk patients should only use NASOLAM in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function and by persons specifically trained in the recognition and management of expected adverse events including respiratory and cardiac resuscitation.

Elderly patients Patients > 60 years should be aware that the use of NASOLAM may result in prolonged sedation. Amnesia Anterograde amnesia could occur at therapeutical dose, with an increased risk at higher doses (frequently this effect is very desirable in situations such as before and during surgical and diagnostic procedures).

The duration of which is directly related to the administered dose. Prolonged amnesia can present problems in outpatients, who are scheduled for discharge following intervention. Discharge criteria following conscious sedation After receiving midazolam, patients should be discharged from hospital or consulting room only when recommended by the treating physician.

It is recommended that the patient is accompanied when returning home after discharge Altered elimination of midazolam Midazolam should be used with caution in patients with chronic renal failure, impaired hepatic- or cardiac function.

5). 2). Midazolam may accumulate in patients with impaired hepatic function whilst in patients with impaired cardiac function it may cause decreased clearance of midazolam. Risk from concomitant use of opioids Concomitant use of NASOLAM and opioids may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as NASOLAM with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe NASOLAM concomitantly with opioids, the lowest effective dose and the shortest possible duration of opioids should be used.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Concomitant use of alcohol / CNS depressants The concomitant use of midazolam with alcohol or/and CNS depressants should be avoided.

Such concomitant use has the potential to increase the clinical effects of midazolam possibly including severe sedation that could result in […]

1. - severe respiratory failure or acute respiratory depression, - severe hepatic impairment, - myasthenia gravis or sleep apnoea syndrome, - acute angle glaucoma; benzodiazepines can be used with open-glaucoma only if they are administered according to the appropriate dose, - cyanogen congenital heart disease, - severe sepsis.