• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• an allergy to midazolam, any other benzodiazepine (such as diazepam or nitrazepam), or any of the other ingredients of this medicine (listed in section 6).
• an illness called ‘myasthenia gravis’ (which causes muscle weakness).
• a severe breathing problems (Epistatus can make breathing difficulties worse).
• a sleep apnoea syndrome (which causes breathing to be frequently interrupted during sleep).
• a severe liver problems.

Talk to the doctor or pharmacist before using Epistatus if the patient:

• has a lung condition causing breathing problems as this medicine could make your breathing worse.
• has kidney, liver or heart problems, or is elderly.
• is taking any other medication with sedative effects and feels very weak, run down and is short of energy because this medicinal product affects the central nervous system (CNS).

This medicine may affect the patient’s memory of the period after they have been given it (temporary memory loss). Patients should be carefully observed by the parents or caregivers after being given this medicine. See also section 4 (possible side effects).

This medicine should be avoided in patients with a medical history of alcohol or drug abuse.

Since delayed severe breathing problems (such as breathing more slowly or weakly than expected) cannot be excluded in younger children, infants aged from 3 months to less than 6 months should only be treated in a hospital setting where monitoring is possible and resuscitation equipment is available.

If you are not sure whether any of the above applies to the patient, please speak to a doctor or pharmacist before giving this medicine.

This medicine should not be given to children younger than 3 months since there is not enough information in this age group.

Tell the doctor or pharmacist if the patient is taking, has recently taken, or might take any other medicines. If you have any doubt about whether any medicine the patient is taking may affect the use of Epistatus, please speak to your doctor or pharmacist.

This is extremely important, as using more than one medicine at the same time can strengthen or weaken the effect of the medicines involved.

The effects of Epistatus may be intensified by medicines such as:

• antiepileptics, (for treating epilepsy) e.g. phenytoin
• antibiotics, e.g. erythromycin, clarithromycin
• antifungals, e.g. ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole
• anti-ulcer medicines, e.g. cimetidine, ranitidine and 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 pain killers), e.g. fentanyl
• medicines used to reduce fat in the blood, e.g. atorvastatin
• medicines used to treat nausea, e.g. nabilone
• hypnotics (sleep inducing medicines)
• sedative antidepressants (medicines used to treat depression that make you sleepy)
• sedatives (medicines that relax you)
• anaesthetics (for pain relief)
• antihistamines (to treat allergies).

The effects 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). This should be avoided in patients taking Epistatus.

Epistatus may increase the effect of some muscle relaxants e.g. baclofen (causing increased drowsiness). This medicine may also stop some other medicines from working as well, e.g. levodopa (used to treat Parkinson’s disease).

Concomitant use of Epistatus and opioids (strong pain killers, medicines for substitution therapy and some cough medicines) increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible.

However if your doctor does prescribe Epistatus together with opioids the dose and duration of concomitant opioid treatment should be limited by your doctor.

Please tell your doctor about all opioid medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.

Epistatus contains a small amount of alcohol and therefore should not be co-administered with disulfiram.

Talk to your doctor or pharmacist about medicines the patient should avoid whilst taking Epistatus.

If the patient is going to have an inhaled anaesthetic (one that the patient breathes in) for an operation or for dental treatment, it is important to tell the doctor or dentist that they have been given Epistatus.

The patient must not drink alcohol if they have been given Epistatus. Alcohol may increase the sedative effects of Epistatus and make them very sleepy.

The patient must not drink grapefruit juice while taking Epistatus. Grapefruit juice may increase the sedative effect of Epistatus and make them more sleepy.

Pregnancy

If the patient is pregnant, thinks she might be pregnant or is planning to have a baby, ask a doctor for advice before giving this medicine.

Midazolam may be used during pregnancy if clearly necessary. Frequent doses of this medicine during the last 3 months of pregnancy or during childbirth can cause problems for the baby; these can include abnormal heart rhythms, hypothermia (low body temperature), poor suckling, breathing difficulties and poor muscle tone at birth.

Breast-feeding

Tell a doctor if the patient is breast-feeding. Even though small amounts of this medicine may pass into breast milk, it may not be necessary to stop breast-feeding. The doctor will advise if the patient should temporarily stop breast-feeding after being given Epistatus.

Epistatus has a major influence on the ability to drive and use machines.

This medicine may make the patient sleepy, forgetful or affect their concentration or coordination. This may affect their ability to perform skilled tasks such as driving, riding a bicycle or operating machinery. After receiving this medicine, the patient should not drive, ride a bicycle or operate machinery until they are completely recovered.

Please discuss with the doctor if you need further advice.

If the patient has been told by their doctor that they have an intolerance to some sugars, tell the doctor before you give this medicine.

Epistatus 2.5 mg oromucosal solution

This medicine contains 49 mg of alcohol (ethanol) in each dose. The amount per dose of this medicine is equivalent to less than 1 ml beer, or 1 ml wine.

Epistatus 5 mg oromucosal solution

This medicine contains 99 mg of alcohol (ethanol) in each dose. The amount per dose of this medicine is equivalent to less than 3 ml beer, or 1 ml wine.

Epistatus 7.5 mg oromucosal solution

This medicine contains 148 mg of alcohol (ethanol) in each dose. The amount per dose of this medicine is equivalent to less than 4 ml beer, or 2 ml wine.

Epistatus 10 mg oromucosal solution

This medicine contains 197 mg of alcohol (ethanol) in each dose. The amount per dose of this medicine is equivalent to less than 5 ml beer, or 2 ml wine.

The small amount of alcohol in this medicine will not have any noticeable effects.

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

If the patient is having a seizure (‘fit’), allow their body to move freely and do not try to restrain them. Only move the patient if they are in danger from the surroundings, for example, a road, open water, hot cooking appliances, fire or sharp objects.

Support the patient’s head with something soft, such as a cushion or your lap.

Ask a doctor, pharmacist or nurse to show you how to take or administer this medicine. Always check with them if you are not sure.

Step 1

Pull the tamper evident tab on the side of the plastic outer case, open it and take the syringe out.

Step 2

Holding the clear finger grips, unscrew the amber sheath cap in an anti-clockwise direction and remove the amber sheath cap.

Step 3

Using your finger and thumb, gently pinch and pull back the patient’s cheek. Place the tip of the syringe into the back of the space between the inside cheek and the lower gum (buccal cavity).

Step 4

Slowly administer approximately half of the solution to the buccal cavity on one side of the mouth, and then administer the remainder slowly to the other side, by pressing the syringe plunger until it stops. If it is particularly difficult to get the syringe into one buccal cavity, then administer the whole dose over a duration of 4 – 5 seconds into the other buccal cavity. Dispose of the syringe and cap safely.

Seek emergency medical assistance – telephone for an ambulance immediately – if the patient’s seizure does not stop shortly after administering Epistatus.

Follow the instruction you have received from the patient’s doctor on how to act in this situation.

A second dose of Epistatus should not be given without medical advice.

Seek emergency medical assistance – telephone for an ambulance immediately.

A second dose of Epistatus should not be given without medical advice.

The empty syringe must be given to the ambulance staff or doctor to provide information on the dose and product received by the patient.

You should seek emergency medical assistance – telephone for an ambulance immediately.

Signs that a patient has been given too much Epistatus may be:

• drowsiness, tiredness, fatigue
• confusion or feeling disorientated
• losing their co-ordination
• developing muscle weakness
• low blood pressure – this can make them feel dizzy and faint
• breathing difficulties

Keep the syringe to show to the ambulance staff or doctor.

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

• Severe breathing difficulties e.g. slow or shallow breathing or blue lips. In very rare cases breathing might stop.
• Cardiac arrest (heart stopped) reported in very rare cases. Signs include loss of consciousness associated with no pulse.
• Swelling of the face, lips, tongue or throat which makes it difficult to swallow or breathe, or a pale skin, a weak and rapid pulse, or feeling of loss of consciousness. You may be having a serious allergic reaction.

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

• Sleepiness or losing consciousness, muscle spasms and muscle tremors (shaking of your muscles that you cannot control), reduced alertness, headache, dizziness
• Feeling and being sick
• Tiredness

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

• Agitation, hallucinations (seeing and possibly hearing things that are not really there)
• Temporary memory loss
• Rash, hives (lumpy rash), itchiness

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

• Aggression, difficulty co-ordinating muscles, physical assault
• Fits (convulsions), restlessness
• Low blood pressure, slow heart rate, or redness of the face and neck (flushing)
• Breathlessness
• Constipation
• Dry mouth
• Hiccups

Frequency not known (cannot be estimated from the available data):

• Rage, confusion, hostility, euphoria (an excessive feeling of happiness or excitement)
• Thrombosis (local coagulation or clotting of the blood in a part of the circulatory system), laryngospasm (tightening of the vocal cords causing difficult and noisy breathing)

If the patient gets side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is midazolam (as midazolam maleate).
  Each pre-filled oral syringe (0.25 ml) contains 2.5 mg midazolam.
  Each pre-filled oral syringe (0.5 ml) contains 5 mg midazolam.
  Each pre-filled oral syringe (0.75.ml) contains 7.5 mg midazolam.
  Each pre-filled oral syringe (1 ml) contains 10 mg midazolam.
• The other ingredients are ethanol, saccharin sodium, glycerol, purified water, sodium hydroxide (for pH adjustment) and maltitol, liquid.

Epistatus oromucosal solution is a clear, colourless to pale yellow solution. It is supplied in a 1 ml pre-filled, single-use (needle free) clear colourless plastic oral syringe with a clear amber plastic oversheath cap with different fill volumes. Each pre-filled oral syringe contains a single dose of 0.25 ml, 0.5 ml, 0.75 ml or 1 ml of product.

Each oral syringe is individually packed in a tamper evident polypropylene container.

Epistatus 2.5 mg oromucosal solution: Yellow syringe label, yellow container

Epistatus 5 mg oromucosal solution: Blue syringe label, blue container

Epistatus 7.5 mg oromucosal solution: Purple syringe label, purple container

Epistatus 10 mg oromucosal solution: Orange syringe label, orange container