Ozasel

PACKAGE LEAFLET

Package leaflet: Information for the user

OZASED 2 mg/ml, oral solution in single-dose container

Midazolam
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If your child experiences any side effects, including those not listed in this leaflet, contact your child's doctor or pharmacist. See section 4.

Contents of this leaflet

1. What OZASED is and what it is used for
2. What you need to know before giving OZASED to your child
3. How to use OZASED
4. Possible side effects
5. How to store OZASED
6. Contents of the pack and other information

1. What OZASED is and what it is used for

OZASED contains midazolam. It belongs to a class of medicines known as benzodiazepines.
OZASED is used in neonates, children, and adolescents from 6 months to 17 years of age for moderate sedation:

• before a therapeutic or diagnostic procedure to relieve anxiety, distress, and agitation related to the procedure
• as premedication before anaesthesia.

2. What you should know before giving OZASED to your child

Do not use OZASED:

• if your child is allergic to midazolam, benzodiazepines, or any of the other ingredients of this medicine (listed in section 6)
• if your child suffers from neuromuscular diseases causing severe muscle weakness (severe myasthenia gravis)
• if your child has severe breathing difficulties
• if your child suffers from conditions causing frequent interruption of breathing during sleep (sleep apnoea syndrome)
• if your child has severe liver problems.

Warnings and precautions
Talk to your doctor or pharmacist before giving OZASED to your child

• if your child suffers from a chronic illness (such as breathing problems or kidney, liver, or heart problems)
• if your child is in poor general health
• if your child has a history of alcoholism or drug dependence
• if your child is under 6 months of age

Other medicines and OZASED
Inform your doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines, especially if your child is taking any of the following:

• medicines used to treat bacterial infections (antibiotics), for example erythromycin, clarithromycin, telithromycin, roxithromycin
• medicines used to treat fungal infections (antifungals), for example ketoconazole, voriconazole, fluconazole, itraconazolo, and posaconazole
• medicines used to treat stomach ulcers (antiulcer agents), for example cimetidine and ranitidine
• medicines used to treat epilepsy (antiepileptics), for example phenytoin and carbamazepine
• medicines used to treat high blood pressure (antihypertensives), for example diltiazem and verapamil
• medicines used to treat HIV and AIDS, for example saquinavir, including combinations containing ritonavir and efavirenz
• medicines used to prevent nausea and vomiting, for example aprepitant
• medicines used to lower blood lipids, for example atorvastatin
• medicines used to treat depression that cause drowsiness (sedative antidepressants)
• other medicines used to treat depression (antidepressants), for example fluvoxamine
• medicines used to treat cystic fibrosis, for example ivacaftor
• medicines used to treat urinary incontinence, for example propiverine
• medicines used to treat mycobacterial infections such as tuberculosis, for example rifampicin
• medicines used as anaesthetics, for example inhaled anaesthetics, propofol, ketamine, etomidate
• sleeping pills (hypnotics)
• medicines used as strong painkillers (narcotic analgesics), for example fentanyl
• medicines used to relieve cough (antitussives) or used to treat opioid dependence (substitution treatment) containing opioids
• medicines used to treat specific mental disorders such as psychosis (antipsychotics)
• medicines containing benzodiazepines used to treat anxiety or sleep disorders (benzodiazepines used as anxiolytics or hypnotics)
• medicines used to treat allergies (antihistamines)
• herbal medicines, for example St. John's wort, Echinacea purpurea, curcuma rhizome

OZASED with food, drinks and alcohol
General fasting guidelines must be followed before sedation.
Your child must not drink alcohol while taking OZASED, as alcohol may increase the sedative effects of this medicine and thus cause excessive drowsiness.
Your child must not drink grapefruit juice while taking OZASED, as this may increase the sedative effects of this medicine and thus cause excessive drowsiness.

Pregnancy and breastfeeding
Pregnancy
If your daughter is pregnant or you suspect she may be pregnant, consult your doctor before this medicine is administered to her.
Breastfeeding
If your daughter is breastfeeding, she should be advised to stop breastfeeding for 24 hours after administration of midazolam, as it passes into breast milk in small amounts.

Driving and using machines
OZASED may cause drowsiness, distraction, or affect your child's concentration and coordination. Your child must not drive vehicles, bicycles, or operate machinery until fully recovered. Consult your doctor if you need further advice.

OZASED contains sodium, ethanol and gammadex
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is essentially sodium-free.
This medicine contains 17.4 mg of alcohol (ethanol) in each 5 ml vial (each dose unit), equivalent to 3.5 mg/ml (ethanol/solution) or 0.32% w/v.
The amount of ethanol in one 5 ml vial of this medicine (17.4 mg) is equivalent to 0.2 ml of wine.
The amount of ethanol in two 5 ml vials of this medicine (34.8 mg) is equivalent to 0.4 ml of wine, at the maximum dosage of 20 mg midazolam.
The small amount of alcohol in this medicine will not produce significant effects.
This medicine contains 400 mg of gammadex per vial, which, at the recommended dose, corresponds to 10 mg/kg/day and is below the permitted daily exposure limit. Therefore, even if OZASED were inadvertently used at a dose of 0.5 mg/kg, the amount of gammadex would not exceed the permitted daily exposure.

3. How to use OZASED

Instructions for use

OZASED must be administered orally.

OZASED will be administered to your child by a healthcare professional. It will be given in a setting equipped with the necessary equipment to monitor the child and to treat any potential side effects.
OZASED is not intended for self-administration.
At discharge, your child must be accompanied by an adult and must leave the room only upon the doctor's authorization.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects may occur during administration of midazolam. Their frequency has not been established and cannot be estimated based on currently available data.

Nervous system disorders

• Prolonged sedation/oversedation
• Agitation, restlessness, hostility, anger or aggressiveness, excitement, confusion, euphoria (excessive feeling of happiness or excitement), or hallucinations (seeing or possibly hearing unreal things)
• Numbness, drowsiness
• Dizziness
• Difficulty in muscle coordination
• Vertigo
• Speech disorders
• Dry mouth
• Salivation
• Urinary incontinence
• Headache
• Temporary memory loss

Immune system disorders

• Hypersensitivity reactions and angioedema may occur in sensitive individuals.
• Chest pain has been observed as a sign of a severe allergic reaction called Kounis syndrome.

Cardiac disorders

• Altered heart rate (slow or fast)

Respiratory disorders

• Laryngospasm (narrowing of the vocal cords causing breathing difficulties and noisy breathing), breathing difficulties (slow breathing), wheezing
• Noisy breathing
• Hiccups

Gastrointestinal disorders

• Vomiting
• Nausea

Eye disorders

• Blurred vision
• Double vision

Skin disorders

• Itching, skin rash with red, raised, itchy blisters (urticarial reaction)
• Skin rash

General disorders and administration site conditions

• Unusual tiredness
• Feeling of weakness

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, please contact your child’s doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OZASED

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label, carton, or container after EXP. The expiry date refers to the last day of that month.
To protect from light, keep this medicine in the original packaging. Do not store above 25 °C. Do not refrigerate or freeze.

6. Package contents and other information

What OZASED contains

• The active substance is midazolam.
• The other components are: citric acid monohydrate, gammadex, sucralose, orange flavour (containing a percentage particularly of 70-80% ethanol), sodium hydroxide (for pH adjustment), water for injection.

Description of the appearance of OZASED and contents of the pack
OZASED consists of a 5 ml amber glass vial, a straw, and an oral applicator,
all packed together inside a single cardboard box.
OZASED is marketed in 3 different pack sizes:

• pack containing one cardboard box
• pack containing five cardboard boxes
• pack containing ten cardboard boxes

It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Istituto Gentili S.r.l.
Via San Giuseppe Cottolengo 15
20143 Milano (MI)
Italy

Manufacturer
CIT S.r.l.
Via Primo Villa 17, 20875 Burago di Molgora (MB) - Italy

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria OZASED 2 mg/ml Lösung zum Einnehmen im Einzeldosisbehältnis
Belgium Ozalin 2 mg/ml solution buvable en récipient unidose /
drank in verpakking voor éénmalig gebruik /
Lösung zum Einnehmen im Einzeldosisbehältnis
Denmark Ozalin 2 mg/ml oral opløsning i enkeltdosisbeholder
Finland Ozalin 2 mg/ml oraaliliuos kerta-annospakkaus
France Ozalin 2 mg/ml solution buvable en récipient unidose
Germany Ozalin 2 mg/ml Lösung zum Einnehmen im Einzeldosisbehältnis
Greece Ozalin 2 mg/ml πόσιμο διάλυμα σε περιέκτη μίας δόσης
Ireland Ozalin 2 mg/ml oral solution in single-dose container
Italy Ozased 2 mg/ml soluzione orale in contenitore monodose
Netherlands Ozalin 2 mg/ml drank in verpakking voor eenmalig gebruik
Norway Ozalin 2 mg/ml mikstur, oppløsning i endosebeholder
Poland OZASED, 2 mg/ml, roztwór doustny w pojemniku jednodawkowym
Portugal Ozalin 2 mg/ml solução oral em recipiente unidose
Spain Ozalin 2 mg/ml solución oral en envase unidosis

The following information is intended exclusively for healthcare professionals:

The solution should be inspected visually before use. Do not use this medicine if you notice
any visible signs of deterioration in the solution or in the container. OZASED must be
administered only with the dedicated oral dosing device graduated in kg.
How to open the vial

(1) The medicine must be administered to the patient using the vial, the straw, and
the oral dosing device.
(2) Attach the straw to the end of the oral dosing device.
(3) Tap the top of the vial gently to ensure all liquid has settled to the
bottom. Cover the top of the vial with a cloth and place your thumb
on the white spot.
(4) Firmly hold the vial with the white spot facing upward toward you.
Push down on the neck of the vial to open it easily.

Preparation and administration of the solution

(5) Insert the straw into the vial. Before adjusting the dose, and in order to remove any air possibly present in the filter, it is recommended to perform a brief priming step (filling and emptying) of the solution within the vial using the dosing device while it is inside the vial.
(6) Keeping the vial in an upright position, fill the oral dosing device up to the graduation mark corresponding to the patient’s weight in kilograms (kg). Align the reference line with the top of the flange to ensure accurate dosing.
(7) Remove the straw from the end of the oral dosing device.

(8) Empty the contents of the oral dosing device into the patient’s mouth. The solution should be swallowed immediately.

(9) After use, dispose of the vial, the straw, the oral dosing device, and any unused contents in a container designated for this purpose, according to local requirements for controlled pharmaceutical substances and accessories.

Dosage
The dose must be adjusted according to the patient’s body weight.
OZASED must be administered orally as a single dose of 0.25 mg/kg in children aged six months and older.
The maximum dose must not exceed 20 mg of midazolam (equivalent to 2 vials), even in children and adolescents weighing more than 80 kg.
In obese children and adolescents, the dose should be based on actual body weight, up to the maximum limit of 20 mg.
The oral dosing device is graduated in kilograms, from 3 kg to 40 kg body weight, with three types of graduation marks:

• A small graduation mark corresponding to 1 kg, i.e. 0.25 mg of midazolam.
• An intermediate graduation mark corresponding to 5 kg, i.e. 1.25 mg of midazolam.
• A large graduation mark corresponding to 10 kg, i.e. 2.50 mg of midazolam.

For patients weighing more than 40 kg, two vials are required. The minimum amount to be withdrawn from a vial must correspond to a 3 kg dose. For patients weighing 41 and 42 kg who require more than one vial, withdraw a dose less than 40 kg from the first vial and complete the required dose using the second vial; see examples below:

• For a patient weighing 41 kg, it is recommended to withdraw 30 kg from the first vial and 11 kg from the second vial.
• For a patient weighing 42 kg, withdraw a dose corresponding to 30 kg from the first vial and 12 kg from the second vial.

The oral dosing device and the straw are single-use dispensing and administration devices.
OZASED should be administered approximately 30 minutes before the procedure or anesthesia.
OZASED is not recommended in neonates (term and preterm) and children under 6 months of age.
In case of overdose, vomiting should be induced (as soon as possible and in any case within one hour of oral administration of midazolam) if the patient is conscious, or gastric lavage should be performed while protecting the airways if the patient is unconscious. If gastric lavage is ineffective, activated charcoal should be administered to reduce absorption.
Flumazenil, a benzodiazepine antagonist, is indicated in cases of severe intoxication associated with respiratory depression or coma. This treatment must be administered exclusively under close supervision and in accordance with local guidelines.

Straw with filter – specific information