Document: leaflet MAH GENERIC_PL 20075-0337 change

• leaflet MAH GENERIC_PL 12064-0077
• leaflet MAH GENERIC_PL 20075-0337

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Package leaflet: Information for the user

Midazolam 2 mg/ml Solution for Injection or Infusion

Midazolam 5 mg/ml Solution for Injection or Infusion

Midazolam (as Midazolam hydrochloride)

Read all of this leaflet carefully before you

start 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, ask your doctor or nurse.

-    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.

What is in this leaflet

1.    What Midazolam Injection is and what it is used for

2.    What you need to know before you use Midazolam Injection

3.    How to use Midazolam Injection

4.    Possible side effects

5.    How to store Midazolam Injection

6.    Contents of the pack and other information

1. What Midazolam Injection is and what it is used for

Midazolam Injection belongs to a group of medicines known as benzodiazepines. It is a short- acting medicine that is used to induce sedation (a very relaxed state of calm, drowsiness or sleep) and relieves anxiety and muscle tension.

This medicine is used for:

•    Conscious sedation (an awake but very relaxed state of calm or drowsiness during a medical test or procedure) in adults and children.

•    Sedation of adults and children, in intensive care units.

•    Anaesthesia in adults, used alone or with other medicines.

•    Premedication (medicine used to cause relaxation, calm and drowsiness before an anaesthetic) in adults and children.

2. What you need to know before you use Midazolam Injection

You must not be given Midazolam Injection:

•    if you are allergic to any of the ingredients of the medicine (listed in section 6).

•    if you are allergic to other benzodiazepine medicines, such as diazepam or nitrazepam.

•    if you have severe breathing problems and you are going to have Midazolam Injection for conscious sedation. You must not be given Midazolam Injection if any of the above apply to you. If you are not sure, talk to your doctor or nurse before you are given this medicine.

Warnings and precautions

Talk to your doctor or nurse before using Midazolam Injection

Children and babies

If your child is going to be given this medicine:

•    It is particularly important to tell your doctor or nurse if your child has cardiovascular disease (heart problems). Your child will be carefully monitored and the dose will be adjusted specially.

•    Children must be carefully monitored. For infants and babies under 6 months this will include monitoring of breathing and oxygen levels.

Adults

Before Midazolam Injection is given, let your doctor or nurse knows if:

•    You are over 60 years of age.

•    You have a long term illness (such as breathing problems or kidney, liver or heart problems).

•    You are debilitated (have an illness that makes you feel very weak, run down and short of energy).

•    You have myasthenia gravis (a neuromuscular disease causing muscle weakness).

•    You regularly drink large amounts of alcohol or you have had problems with alcohol use in the past.

•    You regularly take recreational drugs or you have had problems with drug use in the past.

•    You are pregnant or think you may be pregnant (see 'Pregnancy and breast-feeding').

If any of the above apply to you, or if you are not sure, talk to your doctor or nurse before you are given Midazolam Injection.

Other medicines and Midazolam Injection

Tell your doctor or nurse if you are taking, or have recently taken or might take any other medicines.

This is extremely important, as using more than

one medicine at the same time can strengthen or

weaken the effect of the medicines involved.

In particular, tell your doctor or nurse if you are

taking any of the following medicines:

•    tranquilisers (for anxiety or to help you sleep)

•    hypnotics (medicines to make you sleep)

•    sedatives (to make you feel calm or sleepy)

•    antidepressants (medicines for depression)

•    narcotic analgesics (very strong pain killers)

•    antihistamines (used to treat allergies)

•    medicines to treat fungal infections (ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole)

•    macrolide antibiotics (such as erythromycin or clarithromycin)

•    diltiazem (used to treat high blood pressure)

•    medicines for HIV called protease inhibitors (such as saquinavir)

•    atorvastatin (used to treat high cholesterol)

•    rifampicin (used to treat mycobacterial infections such as tuberculosis)

•    herbal medicine St John's Wort.

If any of the above apply to you, or if you are not sure, talk to your doctor or nurse before you are given Midazolam Injection.

Operations

If you are going to have an inhaled anaesthetic (one that you breathe in) for an operation or for dental treatment, it is important to tell your doctor or dentist that you have been given Midazolam Injection.

Midazolam Injection with alcohol

Do not drink alcohol if you have been given Midazolam Injection. This is because alcohol can increase the sedative effect of Midazolam Injection and may cause problems with your breathing.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine.

Do not breast-feed for 24 hours after being given Midazolam Injection. This is because Midazolam Injection may pass into your breast milk.

Driving and using machines

The medicine can affect your ability to drive as it may make you sleepy or dizzy.

•    Do not drive while taking this medicine until you know how it affects you. Your doctor should advise you when you can start these again.

•    Midazolam Injection may make you sleepy, forgetful or affect your concentration and co-ordination. This may affect your performance at skilled tasks such as driving or using machines.

•    You should always be taken home by a responsible adult after your treatment.

•    It is an offence to drive if this medicine affects your ability to drive.

•    However, you would not be committing an offence if:

-    The medicine has been prescribed to treat a medical or dental problem and

-    You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and

-    It was not affecting your ability to drive safely

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.”

Midazolam Injection contains Sodium

Midazolam Injection is essentially 'sodium free' as it contains less than 1 mmol sodium (23 mg) per ampoule (small glass bottle).

3. How to use Midazolam Injection

Midazolam Injection should be given only by experienced healthcare professionals (doctor or nurse). It should be given in a place (hospital, clinic or surgery) equipped to monitor and support the patient's breathing, heart and circulation (cardiovascular function) and recognise the signs of and manage the expected side effects of anaesthesia.

Normal adult dose

Your doctor will decide on a suitable dose for you. The dose you are given will depend on why you are being treated and the type of sedation needed. Your weight, age, your state of health, how you respond to Midazolam Injection and whether other medicines are needed at the same time will also influence the dose that you are given.

If you need strong painkillers, you will be given these first and then be given Midazolam Injection. The dose will be adjusted specially for you.

Midazolam Injection may be given to you in one of four different ways:

•    by slow injection into a vein (intravenous injection)

•    through a tube into one of your veins (intravenous infusion)

•    by injection into a muscle (intramuscular injection)

•    into your back passage (rectum).

You should always be taken home by a responsible adult after your treatment.

The following information is intended for medical or healthcare professionals only

Midazolam 2 mg/ml Solution for Injection or Infusion

Midazolam 5 mg/ml Solution for Injection or Infusion

Midazolam (as Midazolam hydrochloride)

Please refer to the Summary of Product Characteristics for full prescribing information.

Presentation

Midazolam 2 mg/ml Solution for Injection or Infusion contains 2 mg of the active ingredient midazolam (as hydrochloride) in each millilitre (ml). Midazolam 5 mg/ml Solution for Injection or Infusion contains 5 mg of midazolam (as hydrochloride) in each ml. Both strengths of solution also contain the inactive ingredients sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

The other ingredients in both strengths are sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

Midazolam Solution for Injection or Infusion is a clear, colourless or slightly yellow solution for injection or infusion.

Midazolam 5 mg/ml Solution for Injection or Infusion is available in 1 ml, 2 ml and 5 ml Type I glass ampoules. Midazolam 2 mg /ml Solution for Injection or Infusion is available in 5 ml Type I glass ampoules. The Type I glass ampoules come in pack sizes of 10 or 20's. Not all pack sizes may be marketed.

L

Children and babies

•    In infants and babies under 6 months of age Midazolam Injection is only recommended for sedation in intensive care units. The dose will be given gradually into a vein.

•    Children 12 years and under will usually be given Midazolam Injection into a vein. When Midazolam Injection is used for premedication (to cause relaxation, calm and drowsiness before an anaesthetic) it may be given into the back passage (rectum).

If you receive more Midazolam Injection than you should

Your medicine will be given to you by a doctor or nurse. If you are accidentally given too much Midazolam Injection you may:

•    Feel drowsy.

•    Lose your co-ordination (ataxia) and reflexes.

•    Have problems with your speech (dysarthria).

•    Have involuntary eye movements (nystagmus).

•    Develop low blood pressure (hypotension).

•    Stop breathing (apnoea) and suffer cardiorespiratory depression (slowed or stopped breathing and heart beat) and coma.

Stopping Midazolam Injection

If you receive long term treatment with Midazolam Injection (are given the medicine for a long time) you may:

•    Become tolerant to Midazolam Injection. The medicine becomes less effective and does not work as well for you.

•    Become dependent upon this medicine and get withdrawal symptoms (see below). Your doctor will reduce your dose gradually to avoid these effects happening to you.

Withdrawal symptoms:

Benzodiazepine medicines, like Midazolam Injection, may make you dependent if used for a long time (for instance in intensive care). This means that if you stop treatment suddenly, or lower the dose too quickly, you may get withdrawal symptoms.

The symptoms can include:

•    headache

•    muscle pain

•    feeling very worried (anxious), tense, restless, confused or bad-tempered (irritable)

•    problems with sleeping (insomnia)

•    mood changes

•    hallucinations (seeing and possibly hearing things that are not there)

•    fits (convulsions).

4. Possible side effects

You may experience this after your treatment. In isolated cases this has been prolonged (lasted for a long time).

Heart and circulation problems:

•    low blood pressure

•    slow heart rate

•    redness of the face and neck (flushing), fainting or headache.

Breathing problems:

•    shortness of breath

•    hiccup.

Stomach, gut and mouth problems:

•    feeling sick or being sick

•    constipation

•    dry mouth.

Skin problems:

•    rash

•    hives (lumpy rash)

•    itchiness.

Injection site problems:

•    redness

•    swelling of the skin

•    blood clots or pain at the injection site.

Injury:

•    Patients taking benzodiazepine medicines have a higher risk of falling and breaking bones.

General:

•    tiredness (fatigue).

Elderly patients:

•    Life-threatening side effects are more likely to occur in adults over 60 years of age and those who already have breathing difficulties or heart problems, particularly when the injection is given too quickly or at a high dose.

If you get any side effects, talk to your doctor or

nurse. This includes any side effects not listed in

this leaflet.

5. How to store Midazolam Injection

Your doctor or pharmacist is responsible for storing Midazolam Injection. They are also responsible for disposing of any unused Midazolam Injection correctly.

Keep this medicine out of the sight and reach of children.

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

The following undesirable effects have been reported (frequency not known).

Stop having Midazolam Injection and see a doctor straight away if you notice any of the following side effects. They can be life-threatening and you may need urgent medical treatment:

•    Anaphylactic shock (a life-threatening allergic reaction). Signs may include a sudden rash, itching or lumpy rash (hives) and swelling of the face, lips, tongue or other parts of the body. You may also have shortness of breath, wheezing or trouble breathing.

•    Heart attack (cardiac arrest). Signs may include chest pain which may spread to your neck and shoulders and down your left arm.

•    Breathing problems or complications (sometimes causing the breathing to stop).

•    Choking and sudden blockage of the airway (laryngospasm).

Life-threatening side effects are more likely to occur in adults over 60 years of age and those who already have breathing difficulties or heart problems, particularly if the injection is given too fast or at a high dose

Other possible side effects Immune system problems:

•    general allergic reactions (skin reactions, heart and blood system reactions, wheezing)

Effects on behaviour:

•    agitation

•    restlessness

•    hostility, rage or aggression

•    excitement.

Muscle problems:

•    muscle spasms and muscle tremors (shaking of your muscles that you cannot control).

Mental and Nervous system problems:

•    confusion

•    euphoria (an excessive feeling of happiness or excitement)

•    hallucinations (seeing and possibly hearing things that are not really there)

•    drowsiness and prolonged sedation

•    reduced alertness

•    headache

•    dizziness

•    difficulty co-ordinating muscles

•    fits (convulsions) in premature infants and new-born babies

•    temporary memory loss. How long this lasts depends on how much Midazolam Injection you were given.

Do not use this medicine after the expiry date (EXP) which is stated on the pack. The expiry date refers to the last day of that month.

This medicinal product does not require any special temperature storage conditions. Keep the ampoules (small glass bottle) in the outer carton in order to protect from light.

Do not use this medicine if you notice that the solution is discoloured

6. Contents of the pack and other information

What Midazolam Injection contains

The active substance in Midazolam Injection is midazolam (as midazolam hydrochloride). Midazolam Injection comes in two different strengths

Midazolam 2 mg/ml solution for injection or infusion contains 2 mg of the active ingredient midazolam (as hydrochloride) in each millilitre (ml). Midazolam 5 mg/ml solution for injection or infusion contains 5 mg of midazolam (as hydrochloride) in each ml. Both strengths of solution also contain the inactive ingredients sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

The other ingredients in both strengths are sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

What Midazolam Injection looks like and contents of the pack

Midazolam 2 mg/ml solution for injection or infusion is a clear, colourless or slightly yellow solution for injection or infusion.

Midazolam 5 mg/ml solution for injection or infusion is available in 1 ml, 2 ml and 5 ml Type I glass ampoules. Midazolam 2 mg /ml solution for injection or infusion is available in 5 ml Type I glass ampoules. The Type I glass ampoules come in pack sizes of 10 or 20's. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Accord Healthcare Limited Sage House,

319 Pinner Road,

North Harrow Middlesex, HA1 4HF United Kingdom

This leaflet was last revised in April 2014.

Shelf life and storage

For single use only.

Midazolam Solution for Injection or Infusion is stable, both physically and chemically, for up to 24 hours at 2°C-8°C when mixed aseptically with 500 ml infusion fluids containing Dextrose 4% with Sodium Chloride 0.18%, Dextrose 5% or Sodium Chloride 0.9%. Diluted product should be discarded if not used within 24 hours.

Do not use the product if the solution is discoloured.

to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Incompatibilities

Admixture with Hartmann's solution is not recommended as the potency of midazolam decreases.

Special precautions for storage

This medicinal product does not require any special temperature storage conditions Keep the container in the outer carton in order to protect from light.

From a microbiological point of view, the product    This healthcare professional leaflet was last

should be used immediately. If not used    revised in April 2014.

immediately, in-use storage times and conditions

prior to use are the responsibility of the user and

would normally not be longer than 24 hours at 2