Oroxelam

Patient Leaflet: Information for the User

Oroxelam 2.5 mg oral mucosal solution, 5 mg oral mucosal solution, 7.5 mg oral mucosal solution, 10 mg oral mucosal solution

Midazolam
Please read this leaflet carefully before administering 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.
• This medicine has been prescribed for your child only. Do not give it to others, even if their symptoms are the same as your child's, as it could be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Oroxelam is and what it is used for
2. What you need to know before administering Oroxelam
3. How to administer Oroxelam
4. Possible side effects
5. How to store Oroxelam
6. Package contents and other information

1. What Oroxelam is and what it is used for

Oroxelam is an oral mucosal solution containing midazolam. Midazolam belongs to a group of medicines known as benzodiazepines. Oroxelam is used to stop acute, prolonged seizures in children and adolescents (from 3 months up to less than 18 years of age).
In children aged between 3 and 6 months, it should only be used in a hospital setting where monitoring is possible and resuscitation equipment is available.
The patient's doctor must provide instructions to the parents or caregivers on how to administer Oroxelam and what to do if the seizure does not stop.

2. What you should know before administering Oroxelam

Do not administer Oroxelam if the patient has:

• An allergy to midazolam, to benzodiazepines (such as diazepam), or to any of the other components of this medicine (listed in section 6)
• A nerve and muscle disease causing muscle weakness (myasthenia gravis)
• Severe breathing difficulties at rest (Oroxelam may worsen breathing difficulties)
• A condition causing frequent interruptions in breathing during sleep (sleep apnoea syndrome)
• Severe liver problems.

Warnings and precautions
Talk to the doctor or pharmacist before administering Oroxelam if the patient:

• has kidney, liver, or heart disease
• has a lung disorder that regularly causes breathing difficulties
• regularly drinks large amounts of alcohol or has previously had problems with alcohol abuse
• regularly uses recreational drugs or has previously had problems with drug use

This medicine may cause patients to forget what happened after it was administered. Patients must be closely observed after administration of the medicine.
Potentially fatal incidents are more likely in patients with breathing difficulties or heart problems, especially when high doses of Oroxelam are administered.
If you have any doubts whether the patient falls into any of the above categories, consult the doctor or pharmacist before administering this medicine.

Children under 3 months of age:
Oroxelam must not be administered to children under 3 months of age, as there is insufficient information available for this age group.

Other medicines and Oroxelam
Inform the doctor or pharmacist if the patient is taking, has recently taken, or might take any other medicines. If you have any doubts about whether a medicine being taken by the patient could affect the use of Oroxelam, consult the doctor or pharmacist.
This is extremely important, because using more than one medicine at the same time may strengthen or weaken the effects of the medicines.

The effects of Oroxelam may be increased by medicines such as:

• antiepileptics (for the treatment of epilepsy), e.g. phenytoin
• antibiotics, e.g. erythromycin, clarithromycin
• antifungals, e.g. ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole
• anti-ulcer medicines, e.g. cimetidine, ranitidine, omeprazole
• medicines used to treat blood pressure, e.g. diltiazem, verapamil
• some medicines used to treat HIV and AIDS, e.g. saquinavir, lopinavir/ritonavir combination
• narcotic analgesics (very strong painkillers), e.g. fentanyl
• medicines used to lower blood lipids, e.g. atorvastatin
• medicines used to treat nausea, e.g. nabilone
• hypnotics (medicines that induce sleep)
• sedative antidepressants (medicines used to treat depression that cause drowsiness)
• sedatives (medicines that relax)
• anaesthetics (to relieve pain)
• antihistamines (for the treatment of allergies)

The effects of Oroxelam may be reduced by medicines such as:

• rifampicin (used to treat tuberculosis)
• xanthines (used to treat asthma)
• St John’s wort (a herbal medicine). This must be avoided in patients taking Oroxelam.

Oroxelam may increase the effect of certain muscle relaxants, e.g. baclofen (causing increased drowsiness). This medicine may also prevent certain medicines from working, e.g. levodopa (used to treat Parkinson’s disease).
Concomitant use of Oroxelam and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness and breathing difficulties (respiratory depression).
Consult the doctor or pharmacist about which medicines the patient should avoid during treatment with Oroxelam.

Oroxelam with food and drink
The patient must not consume alcohol during treatment with Oroxelam. Alcohol may increase the sedative effects of this medicine and cause severe drowsiness.
The patient must not drink grapefruit juice during treatment with Oroxelam. Grapefruit juice may increase the sedative effects of this medicine and cause severe drowsiness.

Pregnancy and breastfeeding
Pregnancy
If the patient to whom this medicine is to be administered is pregnant, suspects she might be pregnant, is planning a pregnancy, or is breastfeeding, ask the doctor for advice before taking this medicine.
Administration of high doses of Oroxelam during the last three months of pregnancy may cause irregular heartbeat in the newborn. Babies born after administration of this medicine during delivery may also experience poor sucking, breathing difficulties, hypothermia, and low muscle tone at birth.

Breastfeeding
Inform the doctor if the patient is breastfeeding. Although small amounts of Oroxelam may pass into breast milk, it may not be necessary to stop breastfeeding. The doctor will advise the patient whether to breastfeed after administration of a single dose of this medicine.

Driving and using machines
Oroxelam may cause drowsiness, forgetfulness, or affect concentration and coordination. This may impair the ability to perform tasks requiring skill, such as driving a vehicle, riding a bicycle, or operating machinery.
After administration of this medicine, the patient must not drive, ride a bicycle, or operate machinery until fully recovered. Consult the doctor if further advice is needed.

Oroxelam contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose unit, i.e. essentially “sodium-free”.

3. How to administer Oroxelam

Administer this medicine exactly as instructed by the doctor. If in doubt, consult the
doctor or pharmacist. The patient's doctor will provide parents/caregivers with instructions on
how to administer Oroxelam, and what to do if the seizure does not stop.
Dosage
The doctor will prescribe the correct dose of Oroxelam needed for your child, usually based on
the child's age. Different doses are each associated with a different color, shown on the carton,
tube, and syringe containing the medicine.
Depending on age, the child will have been prescribed one of the following doses, contained in
packages distinguished by different colors:

The dose is the full content of one oral administration syringe. Do not administer more than one dose.
If the seizure does not stop within 10 minutes after midazolam administration, seek emergency medical assistance and call an ambulance. A second dose of Oroxelam must not be administered without first consulting the doctor.

How to prepare to administer this medicine
If the child is having a seizure, allow the body to move freely and do not try to restrain it. Move the child only if they are in danger, for example near deep water, fire, or sharp objects. Support the child's head with something soft, such as a pillow or your lap. Check that the medicine is the correct dose for the child, according to the doctor's prescription.

How to administer this medicine
Ask your doctor, pharmacist, or nurse to show you how to take or administer this medicine. Always consult them if you have any doubts. Instructions on how to administer this medicine are also provided on the tube label.

Oroxelam must not be injected. Do not attach a needle to the syringe.

Step 1
Hold the plastic tube, break the

seal at one end and remove the cap. Remove the syringe from the tube.

Step 2
Remove the transparent cap from the tip of the

syringe and dispose of it safely.

Step 3
Using your index finger and thumb, gently pinch the child’s cheek and pull it slightly backward.

Insert the tip of the syringe into the space at the back between the inside of the cheek and the lower gum (buccal cavity).

Step 4
Slowly push the plunger of the syringe until it stops.

The entire amount of solution should be slowly delivered into the space between the gum and the cheek.
If prescribed by the doctor (for larger volumes and/or smaller patients), you may slowly administer approximately half the dose into one side of the child’s mouth, then the other half into the opposite side.

When to call an ambulance
ALWAYS follow the treatment advice provided by the patient’s doctor or explained by a healthcare professional. Seek immediate medical assistance if:

• the seizure does not stop within 10 minutes
• you are unable to empty the syringe or some of the contents leak out
• the child’s breathing slows down or stops, e.g., slow or shallow breathing or blue lips
• you observe symptoms of a heart attack, which may include chest pain or pain spreading to the neck, shoulders, and down the left arm
• the child is unwell (vomiting) and the seizure does not stop within 10 minutes
• you administer an excessive amount of Oroxelam

Keep the syringe to show it to the ambulance staff or doctor.
Do not administer more medicine than prescribed by the doctor for the patient. A second dose of Oroxelam must not be administered without first consulting the doctor.

If the child vomits

• Do not give the patient another dose of Oroxelam.
• If the seizure does not stop within 10 minutes, call an ambulance.

If you administer more Oroxelam than you should
Seek urgent medical assistance – call immediately for an ambulance.
Signs that the patient has been given too much Oroxelam may include:

• drowsiness, tiredness, fatigue
• confusion or feeling disoriented
• loss of coordination
• development of muscle weakness
• low blood pressure – this may cause dizziness or feeling faint
• breathing difficulties

Keep the oral administration syringe to show it to the ambulance staff or doctor.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects
Contact a doctor immediately or call an ambulance if the patient experiences:

• Severe breathing difficulties, e.g. slow or shallow breathing or blue lips. In very rare cases, breathing may stop.
• Heart attack. Symptoms may include chest pain, which may spread to the child's neck and shoulders and radiate down the left arm.
• Swelling of the face, lips, tongue or throat making swallowing or breathing difficult.

Other side effects
Common side effects (may affect up to 1 in 10 people):

• Nausea and vomiting
• Drowsiness or loss of consciousness

Uncommon side effects (may affect up to 1 in 100 people):

• Rash, urticaria (skin rash with swelling), itching

Very rare side effects (may affect up to 1 in 10,000 people):

• Agitation, restlessness, hostility, anger or aggression, excitement, confusion, euphoria (an excessive feeling of happiness or excitement) or hallucinations (seeing and in some cases hearing things that are not there)
• Muscle spasms and muscle tremors (involuntary muscle trembling)
• Reduced alertness
• Headache
• Dizziness
• Difficulty with muscle coordination
• Seizures (convulsions)
• Temporary memory loss. The duration of this effect depends on the dose of Oroxelam administered.
• Low blood pressure, slowed heart rate or redness of the face and neck (flushing)
• Laryngospasm (stiffening of the vocal cords causing difficult and noisy breathing)
• Constipation
• Dry mouth
• Fatigue
• Hiccups

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Oroxelam

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, on the tube and on the oral syringe labels after Exp. The expiry date refers to the last day of that month.
Store the oral syringe in its protective plastic tube.
Do not store above 30°C.
Do not use this medicine if you notice that the packaging has been opened or damaged.
Disposal of oral syringes
Do not dispose of any medicines or oral syringes via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Oroxelam contains

• The active substance is midazolam.
• 2.5 mg - Each pre-filled oral syringe contains midazolam hydrochloride equivalent to 2.5 mg of midazolam in 0.5 ml of solution.
• 5 mg - Each pre-filled oral syringe contains midazolam hydrochloride equivalent to 5 mg of midazolam in 1 ml of solution.
• 7.5 mg - Each pre-filled oral syringe contains midazolam hydrochloride equivalent to 7.5 mg of midazolam in 1.5 ml of solution.
• 10 mg - Each pre-filled oral syringe contains midazolam hydrochloride equivalent to 10 mg of midazolam in 2 ml of solution.

The other components are sodium chloride, purified water, hydrochloric acid and sodium hydroxide (for pH adjustment).

Description of the appearance of Oroxelam and package contents

2.5 mg - package with yellow label
5 mg - package with blue label
7.5 mg - package with purple label
10 mg - package with orange label

Oroxelam oromucosal solution is a clear, colourless liquid.
It is supplied in an amber-coloured, needle-free, pre-filled oral syringe with plunger and closure cap. Each oral syringe is individually packaged in a protective plastic tube.
Oroxelam is available in cardboard packs containing 2 or 4 pre-filled oral syringes (of the same strength).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Exeltis Italia S.r.l.
Via Lombardia, 2/a
20068 Peschiera Borromeo (MI)
Italy

Manufacturer
Laboratorios Liconsa S.A.
Avenida Miralcampo, 7
19200 Azuqueca de Henares
Guadalajara
Spain

This medicinal product is authorised in the European Economic Area (EEA) Member States under the following names:

• SE: Midazolam Medical Valley 2.5 mg, 5 mg, 7.5 mg, 10 mg munhålelösning.
• FI: Midazolam Medical Valley 2.5 mg, 5 mg, 7.5 mg, 10 mg liuos suuonteloon.
• DE: Midazolam Desitin 2.5 mg, 5 mg, 7.5 mg, 10 mg Lösung zur Anwendung in der Mundhöhle.
• NO: Midazolam Medical Valley 2.5 mg, 5 mg, 7.5 mg, 10 mg munnvann, oppløsning.
• NL: Midazolam Xiromed 2.5 mg, 5 mg, 7.5 mg, 10 mg oplossing voor oromucosaal gebruik.
• DK: Midazolam Medical Valley 2.5 mg, 5 mg, 7.5 mg, 10 mg mundhulevæske, opløsning.
• IS: Midazolam Medical Valley 2.5 mg, 5 mg, 7.5 mg, 10 mg munnholslausn.
• FR: Midazolam Liconsa 2.5 mg, 5 mg, 7.5 mg, 10 mg solution buccale.
• IE: Midazolam Liconsa 2.5 mg, 5 mg, 7.5 mg, 10 mg oromucosal solution.
• RO: Midazolam Desitin 2.5 mg, 5 mg, 7.5 mg, 10 mg soluție bucofaringiană
• ES: Oroxelam 2.5 mg, 5 mg, 7.5 mg, 10 mg solución oromucosa.
• PL: Soloxelam
• IT: Oroxelam

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu