Epistatus

Package leaflet: Information for the user

Epistatus, 2.5 mg, oral solution
Epistatus, 5 mg, oral solution
Epistatus, 7.5 mg, oral solution
Epistatus, 10 mg, oral solution
Midazolam
Please read this leaflet carefully before using this medicine, because it contains important
information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Epistatus is and what it is used for
2. Important information before using Epistatus
3. How to use Epistatus
4. Possible side effects
5. How to store Epistatus
6. Contents of the pack and other information

1. What Epistatus is and what it is used for

Epistatus contains midazolam as the active substance, which belongs to a group of medicines called benzodiazepines.
Epistatus is used to stop prolonged, acute seizures in infants, young children, children and adolescents aged from 3 months up to less than 18 years.
In infants aged from 3 to 6 months, this medicine should be used only in hospital settings where monitoring and access to resuscitation equipment are available (see section Warnings and precautions for use for more information).
This medicine may be administered only by parents or caregivers when the child has been diagnosed with epilepsy. The treating physician should provide parents or caregivers with instructions on how to administer Epistatus and what to do if the seizure does not stop (see also section "How to use Epistatus").

2. Important information before using Epistatus

When not to give Epistatus

• if the patient is allergic to midazolam, other benzodiazepines (such as diazepam or nitrazepam), or any of the other ingredients of this medicine (listed in section 6);
• if the patient has a disease called myasthenia (which causes muscle weakness);
• if the patient has significant breathing difficulties (Epistatus may worsen breathing problems);
• if the patient has sleep apnoea syndrome (which causes frequent breathing pauses during sleep);
• if the patient has severe liver function disorders.

Warnings and precautions
Before starting treatment with Epistatus, discuss with a doctor or pharmacist if the patient:

• has a lung disease causing breathing problems, as this medicine may worsen breathing;
• has kidney, liver, or heart problems;
• is taking other sedative medicines and feels very weak, exhausted, or lacks energy, as this medicine affects the central nervous system (CNS);
• regularly drinks large amounts of alcohol or has had problems with alcohol abuse in the past (see section “Epistatus contains ethanol (alcohol)”);
• regularly takes medicines for non-medical purposes or has had problems with drug abuse in the past.

This medicine may affect the patient's memory after administration (temporary memory loss).
Parents or caregivers should carefully monitor patients after administration of this medicine. See also
section 4 (“Possible side effects”).
Since delayed severe breathing problems (such as slower or weaker than expected breathing) cannot be ruled out in younger children, infants aged 3 months up to but less than 6 months should be treated only in a hospital setting where vital functions can be monitored and resuscitation equipment is available.
If in doubt whether any of the above situations apply to the patient, consult a doctor or pharmacist before administering this medicine.

Children and adolescents
This medicine must not be given to children under 3 months of age, as there is insufficient information available for this age group.

Epistatus with other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. If in doubt whether any medicine the patient is taking may negatively affect the use of Epistatus, consult a doctor or pharmacist.
This is very important because taking more than one medicine at the same time may increase or reduce the effects of these medicines.

The effect of Epistatus may be increased by medicines such as:

• antiepileptic drugs (used to treat epilepsy), e.g. phenytoin;
• antibiotics, e.g. erythromycin, clarithromycin;
• antifungal medicines, e.g. ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole;
• medicines used to treat stomach and duodenal ulcers, e.g. cimetidine, ranitidine, omeprazole;
• medicines used to treat high blood pressure, e.g. diltiazem, verapamil;
• some medicines used to treat HIV and AIDS, e.g. saquinavir, lopinavir + ritonavir combination;
• opioid painkillers (very strong pain-relieving medicines), e.g. fentanyl;
• medicines used to lower blood fat levels, e.g. atorvastatin;
• medicines used to treat nausea, e.g. nabilone;
• sleeping medicines (medicines that cause sleep);
• sedative antidepressants (medicines used to treat depression that cause drowsiness);
• sedatives (medicines that cause calming);
• anaesthetics (used to relieve pain);
• antihistamines (used to treat allergies).

The effect of Epistatus may be reduced by medicines such as:

• rifampicin (used to treat tuberculosis);
• xanthines (used to treat asthma);
• St. John’s wort (a herbal medicine). Its use should be avoided in patients taking Epistatus.

Epistatus may also increase the effect of certain muscle relaxants, e.g. baclofen (causing increased drowsiness). This medicine may also inhibit the effect of certain other medicines, e.g. levodopa (a medicine used to treat Parkinson’s disease).
Concomitant use of Epistatus and opioids (contained in very strong painkillers, replacement therapies, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may even be life-threatening.
For this reason, concomitant use should only be considered when other treatment options are not possible.
However, if the doctor prescribes Epistatus together with opioids, the dose and duration of concomitant treatment should be limited.
Inform the doctor about all opioid medicines being taken and strictly follow the doctor’s dosing instructions. Consider informing friends or family members about the above-mentioned symptoms. Contact the doctor if these symptoms occur.
Epistatus contains a small amount of alcohol and therefore must not be given simultaneously with disulfiram.
Consult a doctor or pharmacist for information on which medicines should be avoided during treatment with Epistatus.

Procedures
If the patient will receive inhalational anaesthesia (products administered during breathing) during a surgical or dental procedure, it is important to inform the doctor or dentist that the patient is taking Epistatus.

Epistatus with food, drink and alcohol
Do not drink alcohol while taking Epistatus. Alcohol may increase the sedative effect of Epistatus and cause increased drowsiness.
Do not drink grapefruit juice while taking Epistatus. Grapefruit juice may increase the sedative effect of Epistatus and cause increased drowsiness.

Pregnancy, breastfeeding and fertility
Pregnancy
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor before using this medicine.
Midazolam may be used during pregnancy if necessary. Repeated administration of Epistatus during the last 3 months of pregnancy or during labour may cause problems in the newborn, such as: heart rhythm disturbances, hypothermia (low body temperature), weak sucking reflex, breathing difficulties, and low muscle tone.

Breastfeeding
Inform the doctor if the patient is breastfeeding. Although small amounts of Epistatus may pass into breast milk, interruption of breastfeeding may not be necessary. The doctor will decide whether the patient should temporarily stop breastfeeding after administration of Epistatus.

Driving and using machines
Epistatus has a major influence on the ability to drive and operate machinery.
Epistatus may cause drowsiness, forgetfulness, or impair concentration and coordination in the patient. These effects may interfere with performing skilled tasks such as driving a vehicle, riding a bicycle, or operating machinery. After administration of this medicine, the patient should not drive, ride a bicycle, or operate machinery until full recovery of abilities.
Consult a doctor if further information is needed.

Epistatus contains maltitol
If the patient has been previously diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking this medicine.

Epistatus contains ethanol (alcohol)
Epistatus 2.5 mg, oral solution
This medicine contains 49 mg of alcohol (ethanol) per dose. The amount of alcohol in one dose of this medicine is equivalent to less than 1 mL of beer or 1 mL of wine.
Epistatus 5 mg, oral solution
This medicine contains 99 mg of alcohol (ethanol) per dose. The amount of alcohol in one dose of this medicine is equivalent to less than 3 mL of beer or 1 mL of wine.
Epistatus 7.5 mg, oral solution
This medicine contains 148 mg of alcohol (ethanol) per dose. The amount of alcohol in one dose of this medicine is equivalent to less than 4 mL of beer or 2 mL of wine.
Epistatus 10 mg, oral solution
This medicine contains 197 mg of alcohol (ethanol) per dose. The amount of alcohol in one dose of this medicine is equivalent to less than 5 mL of beer or 2 mL of wine.
The small amount of alcohol in this medicine will not cause noticeable effects.

Epistatus contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. the medicine is considered “sodium-free”.

3. How to administer Epistatus

This medicine should always be used as directed by the physician. If in doubt, consult a doctor or pharmacist. The physician treating the patient should provide instructions to parents or caregivers on how to administer Epistatus and what to do if the seizure does not stop.

Epistatus is intended for oral mucosal use only, meaning it must be applied only inside the mouth.

Care should be taken during administration to avoid the risk of choking the patient.

Depending on the child's age, the following doses from the package labeled with a label of the specified color should be administered:

The dose is the full contents of one oral syringe. Do not administer more than one dose without
prior medical advice.
For infants aged 3 to 6 months, treatment should be conducted exclusively in a hospital setting,
where monitoring and access to resuscitation equipment are available.
After administration of Epistatus, patients should remain under the supervision of a caregiver who
should stay with the patient.
Epistatus must not be injected intravenously or intramuscularly. A needle must not be attached to
the syringe.
Preparing the medicine for administration
If the patient is having a seizure, allow free movement of their body and do not attempt to restrain
the patient's movements. The patient should only be moved if they are in danger due to surrounding
objects or obstacles—for example, if the patient is near a roadway, open body of water, hot kitchen
appliances, fire, or sharp objects.
Protect the patient's head with something soft, such as a pillow or the caregiver’s knee.
How to administer this medicine
Ask your doctor, pharmacist, or nurse to show you how to take or administer this medicine. If you
have any doubts, contact your doctor, pharmacist, or nurse.

Step 1
Pull the side plastic tamper-evident seal,
open the packaging, and remove the syringe.

Step 2
Holding the syringe by the transparent
handles, unscrew the amber-colored cap
counterclockwise and remove it.

Step 3
Using your index finger and thumb, gently
press and pull the patient’s cheek outward.
Place the tip of the syringe into the back
of the space between the inner cheek and
lower gum (buccal cavity).
Step 4
Slowly administer approximately half of
the solution volume into the buccal cavity
on one side of the mouth, then slowly
administer the remainder on the other side
by pressing the plunger until it stops. If it
is particularly difficult to insert the syringe
into one side of the mouth, administer the
entire dose within 4–5 seconds on one side
of the mouth. Safely dispose of the syringe
and cap.
What to do if the patient's condition does not improve
Call emergency medical services immediately—if seizures do not stop shortly after administration
of Epistatus.
Follow the instructions provided by the treating physician.
Do not administer a second dose of Epistatus without explicit medical instruction.
What to do if the patient improves but the seizure recurs
Call emergency medical services immediately.
Do not administer a second dose of Epistatus without explicit medical instruction.
Provide the empty syringe of the administered medicine to the emergency medical team or doctor
so they know which medicine and what dose was given.
Overdose of Epistatus
Call emergency medical services immediately.
Symptoms that may occur after an overdose of Epistatus:

• drowsiness, fatigue, feeling of exhaustion,
• confusion or disorientation,
• loss of motor coordination,
• muscle weakness,
• low blood pressure—this may cause dizziness and feeling faint,
• breathing difficulties.

Keep the used syringe of the administered medicine to show to the emergency medical team or
doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.

Serious adverse reactions
Seek immediate medical advice or call an ambulance immediately
if any of the following adverse reactions occur:

• Severe breathing difficulties, e.g. slow or shallow breathing, or blue lips (blue colour); in very rare cases, breathing may stop completely.
• Cardiac arrest (heart stops beating) occurs very rarely. Symptoms include loss of consciousness associated with absence of pulse.
• Swelling of the face, lips, tongue or throat, which makes swallowing or breathing difficult, or pale skin, weak and rapid pulse, or feeling faint. This may indicate a serious allergic reaction.

Other adverse reactions
Common adverse reactions (may affect up to 1 in 10 people):

• Drowsiness or loss of consciousness, muscle twitching and tremor (involuntary muscle shaking), reduced alertness, headache, dizziness;
• Nausea and vomiting;
• Fatigue.

Uncommon adverse reactions (may affect up to 1 in 100 people):

• Agitation, hallucinations (seeing and sometimes also hearing things that are not really there);
• Transient memory loss;
• Rash, urticaria (lumpy rash), itching.

Very rare adverse reactions (may affect up to 1 in 10,000 people):

• Aggression, muscle incoordination, physical assault;
• Seizure (convulsions), restlessness;
• Low blood pressure, slow heartbeat or redness of the face and neck (flushing);
• Shortness of breath;
• Constipation;
• Dry mouth;
• Hiccups.

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):

• Irritability, confusion, hostility, euphoria (excessive feeling of happiness or excitement);
• Thrombosis (blood clotting or formation of clots in certain parts of the circulatory system), laryngospasm (constriction of the vocal cords causing difficulty in breathing and noisy respiration).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 492 13 01, fax: +48 22 492 13 09, website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Epistatus

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the container after:
EXP. The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Do not store in the refrigerator or freeze.
Keep in the original packaging to protect from light.
Do not use this medicine if the syringe is damaged or if the solution is not clear (e.g. if cloudiness or white particles are visible).
Medicines must not be disposed of in household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the package and other information

What Epistatus contains

• The active substance is midazolam (in the form of midazolam maleate). Each filled oral syringe (0.25 mL) contains 2.5 mg of midazolam. Each filled oral syringe (0.5 mL) contains 5 mg of midazolam. Each filled oral syringe (0.75 mL) contains 7.5 mg of midazolam. Each filled oral syringe (1 mL) contains 10 mg of midazolam.
• The other ingredients are: anhydrous ethanol, sodium saccharin, glycerol, purified water, sodium hydroxide (for pH adjustment) and liquid maltitol.

What Epistatus looks like and contents of the pack
Epistatus is a clear, colourless to pale yellow solution. Epistatus is available in a 1 mL clear,
colourless, plastic, single-use (needle-free) oral syringe, pre-filled (no need for a needle), with a
clear amber plastic protective cap, in various fill volumes. Each syringe contains a single dose of
0.25 mL, 0.5 mL, 0.75 mL or 1 mL of the medicinal product.
Each oral syringe is supplied in an individual sealed package within a polypropylene container.
Epistatus 2.5 mg, oral solution: yellow label on the syringe, yellow container.
Epistatus 5 mg, oral solution: blue label on the syringe, blue container.
Epistatus 7.5 mg, oral solution: purple label on the syringe, purple container.
Epistatus 10 mg, oral solution: orange label on the syringe, orange container.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
SERB SA
Avenue Louise 480
1050 Brussels
Belgium
Tel. +48 22 307 03 61

Manufacturer/Importer
MoNo chem-pharm Produkte GmbH, Leystraße 129, 1-1200 Vienna, Austria

This medicinal product is authorised for sale in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Denmark Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Mundhulevæske, opløsning
Finland Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Liuos suuonteloon
Sweden Epistatus
Slovenia Epistatus 2.5 mg, 5 mg, 7.5 mg, 10 mg
oralna raztopina
Norway Epistatus
Germany Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Lösung zur Anwendung in der Mundhöhle
Greece Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Στοματικό διάλυμα
Ireland Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Oromucosal Solution
Italy Epistatus
Poland Epistatus
Hungary Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
szájnyálkahártyán alkalmazott oldat
Portugal Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
solução bucal
Austria Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
Lösung zur Anwendung in der Mundhöhle
United Kingdom (Northern Ireland) Epistatus 2.5 mg/5 mg/7.5 mg/10 mg
oromucosal solution