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 all of 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Epistatus is and what it is used for
2. What you need to know 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 between 3 and 6 months, this medicine should be used only in a hospital setting where monitoring and resuscitation equipment are available (see section Warnings and precautions).
This medicine may be administered only by parents or caregivers when epilepsy has been diagnosed in the child. The child's doctor 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 condition called myasthenia gravis (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 interruptions during sleep);
• if the patient has severe liver function disorders.

Warnings and precautions
Before starting treatment with Epistatus, consult 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, because this medicine affects the central nervous system (CNS);
• regularly drinks large amounts of alcohol or has previously had problems with alcohol abuse (see section "Epistatus contains ethanol (alcohol)");
• regularly takes medicines for non-medical purposes or has previously had problems with drug abuse.

This medicine may affect the patient's memory after administration (temporary memory loss).
Parents or caregivers should closely monitor patients after administration of this medicine. See also
section 4 ("Possible side effects").
Since delayed severe breathing problems (such as slower or weaker breathing than expected) cannot be ruled out in younger children, infants aged from 3 months up to but not including 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 conditions 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 and 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;
• certain 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 calm the patient);
• 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 remedy). 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 therapy medicines, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may even be life-threatening.
Therefore, concomitant use should only be considered when other treatment options are not feasible.
However, if a doctor prescribes Epistatus to be used 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 a doctor if these symptoms occur.
Epistatus contains a small amount of alcohol and therefore must not be taken together with disulfiram.
Consult a doctor or pharmacist for information on which medicines should be avoided during treatment with Epistatus.

Procedures
If the patient is to receive inhalational anaesthesia (products inhaled 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 enhance the sedative effect of Epistatus and cause increased drowsiness.
Do not drink grapefruit juice while taking Epistatus. Grapefruit juice may enhance 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. Frequent administration of Epistatus during the last three months of pregnancy or during delivery may cause problems in the newborn baby, such as: irregular heartbeat, 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 operating machinery
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 learned tasks such as driving vehicles, 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 consult a 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, meaning the medicine is considered "sodium-free".

3. How to administer Epistatus

This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult the
doctor or pharmacist. The patient's doctor should provide parents or
caregivers with instructions on how to administer Epistatus and what to do if the seizure does not stop.
Epistatus is intended for oral transmucosal use only, which means it must be administered only into the oral cavity.
When administering the medicine, take care to avoid the risk of choking the patient.
Depending on the child's age, the following doses from the package labelled with a label of the specified colour should be administered:

The dose is the entire 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 carried out 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. Do not attach a needle to the
syringe.
Preparation of the medicine for administration
If the patient is having a seizure, allow the body to move freely and do not attempt to restrain the
patient's movements. Move the patient only 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 demonstrate how to take or administer this medicine. If
you have any doubts, contact your doctor, pharmacist, or nurse.

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

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

Step 3
Gently pull and hold the patient's cheek with your index finger and thumb. Place the tip of the syringe
into the back of the space between the inner surface of the cheek and the 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 oral cavity, the entire dose may be
administered on one side of the mouth over 4–5 seconds. Safely dispose of the syringe and tip.
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's condition 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 physician
so they know which medicine and what dose was given.
Administration of a higher than recommended dose of Epistatus
Call emergency medical services immediately.
Symptoms that may occur after administration of an excessive dose 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 it to the emergency medical team or
physician.
If you have any further doubts regarding 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 will experience them.

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

• Severe breathing difficulties, e.g. slow or shallow breathing, or blue lips (blue colouring). 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 side effects
Common side effects (may affect up to 1 in 10 people):

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

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

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

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

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

Side effects occurring with unknown frequency (frequency cannot be determined 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 (tightening of the vocal cords causing difficulty and noisy breathing).

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

5. How to store Epistatus

Keep this medicine out of 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. This will help protect the environment.

6. Contents of the package and other information

What Epistatus contains

• The active substance is midazolam (as 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 as a 1 mL clear,
colourless, plastic, single-use (needle-free) oral syringe, pre-filled (no need for a needle), with a
clear amber plastic 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 polycarbonate container.
Epistatus 2.5 mg, oromucosal solution: yellow label on the syringe, yellow container.
Epistatus 5 mg, oromucosal solution: blue label on the syringe, blue container.
Epistatus 7.5 mg, oromucosal solution: purple label on the syringe, purple container.
Epistatus 10 mg, oromucosal 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 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