Midazolam Sandoz 5 mg/ml, oplossing voor injectie

Midazolam Sandoz contains the active substance midazolam and belongs to a group of medicines known as benzodiazepines. It is a short-acting medicine that induces sedation – a state of calm, drowsiness or sleep - and relieves anxiety and muscle tension. It has anticonvulsant effects and causes loss of memory for recent events.

Midazolam Sandoz is used for:

• conscious sedation during a medical test or procedure, in adults and children
• sedation in intensive care units, in adults and children
• anaesthesia in adults, used alone or with other anaesthetic medicines
• sedation before induction of anaesthesia, in adults and children

You must not be given Midazolam Sandoz

if you are/have:

• allergic to:
  • midazolam or any of the other ingredients of this medicine (listed in section 6)or
  • other medicines also belonging to the group of so called benzodiazepines. These have active substance names ending with “azepam”, such as diazepam, nitrazepam
• acute or severe breathing problems and you are going to have Midazolam Sandoz for

conscious sedation

If you are not sure, talk to your doctor or nurse before you are given this medicine.

Warnings and precautions

Midazolam Sandoz should be used only when age- and size-appropriate resuscitation facilities are available due to the possibility of life-threatening side effects, see also section 4. Administration of Midazolam Sandoz may depress myocardial contractility and cause apnoea (suspension of breathing). Severe cardiorespiratory adverse events have occurred. These have included respiratory depression, apnea, respiratory and/or cardiac arrest. To avoid such incidents, the injection should be given slowly and the dose should be as low as possible.

When Midazolam Sandoz is given as a premedication, you will be checked closely to how you respond and to ensure you have received the right dose as the sensitivity varies depending on the patient.

Paradoxical reactions and anterograde amnesia (loss of memory for recent events) have been reported to occur with Midazolam Sandoz (see section 4.).

Long term treatment:

If you receive long-term Midazolam Sandoz, you may become tolerant meaning that Midazolam Sandoz becomes less effective or you may become dependent upon this medicine.

After treatment for a long time (such as in an intensive care unit) withdrawal symptoms may occur. Your doctor will reduce your dose gradually to avoid this happening to you. See section 3 under the headline “Stopping Midazolam Sandoz” for further information.

Talk to your doctor or nurse before Midazolam Sandoz is given if you are/have:

• over 60 years of age Patients of this age require lower doses and careful monitoring for changes in vital functions.
• a long term illness or are debilitated, such as
  • breathing problems Please note that Midazolam Sandoz must not be used in breathing problems described above under “You must not be given Midazolam Sandoz”.
  • kidney failure
  • reduced liver or heart function

Debilitated patients or those with long term illness require lower doses and careful monitoring for changes in vital functions.

• a certain muscle weakness called myasthenia gravis
• a history of alcohol or drug abuse

[Invented name] should be avoided in patients with such history

• taking any other medicines including those not prescribed by your doctor, see “Other

medicines and [invented name]” for more information

• pregnant or think to be pregnant.

Children

Special care needs to be taken if Midazolam Sandoz is used in babies or children. Tell your doctor or nurse if your child is to be given this medicine and:

• has heart and blood circulation problems Your child will be carefully monitored and the dose w ill be adjusted specially.

• is under 6 months of age or a preterm infant
  • Midazolam Sandoz is only recommended in children under 6 months for sedation in intensive care units.
  • Very gradual dosing and special monitoring of breathing and oxygen levels is required, because these patients are more likely to develop breathing problems.

Other medicines and Midazolam Sandoz

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

Inform your doctor or nurse if you are using any of the following medicines, as they may intensify the effects of Midazolam Sandoz:

• medicines which calm, induce sleep, relax muscles or treat anxiety and mental disorders
• medicines to aid sleep or those used during anaesthesia, such as etomidate, ketamine, propofol
• medicines to treat mental or anxiety disorders, with sedative effects
• medicines to treat depression
• medicines to treat strong pain or coughing, or used in substitutive treatment
• medicines to treat allergies and sleep disturbances called antihistamines
• medicines to treat fungal infections, with active substance names ending in “azole”, such as ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole
• medicines to treat bacterial infections with active substance names ending in “mycin”, such as erythromycin, clarithromycin
• diltiazem: a medicine to treat high blood pressure and heart disorders
• medicines to treat high blood pressure which act in the brain
• medicines to treat HIV infections with active substance names ending in “navir”, such as saquinavir
• atorvastatin: a medicine to lower cholesterol levels
• rifampicin: a medicine to treat tuberculosis
• St. John’s wort: a herbal medicine to treat depression
• inhaled anaesthetics

Midazolam Sandoz with food and drink and alcohol

Do not drink any alcohol if you have been given Midazolam Sandoz. Alcohol can markedly increase the sedative effect of Midazolam Sandoz and may cause problems with your breathing.

Pregnancy and breast-feeding and fertility

• Pregnancy Talk to your doctor if you are pregnant, or think you are pregnant. Your doctor will decide if this medicine is suitable for you. If your doctor decides that you should be given this medicine during late pregnancy, labour or caesarean section, you might have inhalation risk and your baby might have an irregular heartbeat, hypotonia (resistance to movement in a muscle), feeding difficulties, a low body temperature and respiratory depression. If you have passed through prolonged treatment during last phase of pregnancy with this medicine, your baby may develop physical dependence and risk of withdrawal symptoms after birth.
• Breast-feeding Do not breast-feed for 24 hours after being given Midazolam Sandoz as it may pass into your breast milk.
• Fertility Midazolam Sandoz does not affect fertility according to present data.

Driving and using machines

• Do not drive or use machines until you are completely recovered. Your doctor should advise as to when you may resume these activities.
• You should always be taken home by a responsible adult following treatment.

Midazolam Sandoz can cause sleepiness, forgetfulness or affect concentration and co-ordination. This may affect your performance at skilled tasks such as driving or operating machinery.

Important information about some of the ingredients of Midazolam Sandoz

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially

“sodium-free”.

This medicine should be given only by an experienced doctor or nurse. It should be given in a hospital, clinic or surgery, equipped to:

• monitor and support the patient’s breathing, heart and circulation
• recognise and manage expected side effects of anaesthesia

The recommended dose is:

The doctor will decide the dose individually dependent on:

• reason for your treatment
• type of sedation required
• patient’s age, weight and general state of health
• concomitant medication
• how you react to Midazolam Sandoz

• whether other medicines are needed at the same time

If you are to receive strong pain killers, you will receive these first and then have your Midazolam Sandoz dose individually adjusted.

Route and method of administration

• intravenous: by slow injection into a vein
• infusion: through a tube into one of your veins
• intramuscular: by injection into a muscle
• rectal: into your rectum

Midazolam Sandoz will usually be given into the vein in children 12 years and younger. It may be given into the rectum in this age group if being used for sedation before anaesthesia. Please note the information in section 2, under the heading “Children”.

Instructions for proper use

Midazolam Sandoz is compatible with the following solutions for infusion:

• sodium chloride 0.9 % (9 mg/ml) solution
• glucose 5 % (50 mg/ml) solution
• glucose 10 % (100 mg/ml) solution
• Ringer solution
• Hartmann’s solution

Midazolam Sandoz is not compatible with the following solutions for infusion:

• dextran 6% w/v (with 0.9% sodium chloride) in dextrose
• alkaline solutions for injection. Midazolam precipitates in sodium bicarbonate.

To avoid potential incompatibility with other solutions, Midazolam Sandoz must not be mixed with other solutions except those mentioned above.

Midazolam Sandoz ampoules are for single use only. Discard any unused solution.

The ampoule and the solution should be visually inspected prior to use. Only intact ampoules and clear solutions without particles and discoloration should be used.

If you receive more Midazolam Sandoz than you should

Inform your doctor, who will treat you appropriately, if you experience signs of overdose:

• feeling drowsy
• difficulty in controlling movements or speaking
• loss of reflexes
• involuntary eye movements
• low blood pressure
• stopped breathing
• slowed or stopped breathing or heartbeat
• coma

Overdose may require intense monitoring of vital signs, symptomatic treatment of cardiorespiratory effects and use of a benzodiazepine antagonist.

Stopping Midazolam Sandoz

If Midazolam Sandoz is given for a long time:

 the medicine may become less effective and not work as well

• you may become dependent upon this medicine and get withdrawal symptoms If treatment is stopped suddenly, or the dose lowered too quickly, you may get the following withdrawal symptoms:
  • headache
  • muscle pain
  • anxiety
  • tension
  • restlessness
  • confusion
  • irritability
  • difficulty sleeping
  • mood swings
  • hallucinations: seeing and possibly hearing things that do not exist
  • fits

Your doctor will reduce your dose gradually to avoid these effects occurring.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

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

STOP having Midazolam Sandoz and see/tell your doctor straight away if you notice any side effect, highlighted in bold print. They can be life -threatening and you may need urgent medical treatment.

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

• severe allergic shock reaction Signs are sudden rash, itching or nettle-rash; swelling of the face, lipps, tongue or other parts of the body. You may also have shortness of breath, wheezing or trouble breathing.
• heart attack Signs are chest pain which may spread to your neck and shoulders and down your left arm.
• breathing problems or complications
• larynx spasm

These life-threatening side effects are more likely in patients over 60 years of age, or patients with breathing or heart problems. This occurs particularly if the injection is given too fast or at a high dose.

You may experience any of the other following side effects listed below.

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

• general allergic reactions, such as skin reactions, heart and blood system reactions, wheezing
• restlessness
• involuntary movements
• hostility, anger or aggression

• excitement
• sudden, extreme outbursts
• dependence on use of Midazolam Sandoz
• confusion
• excessive feeling of happiness or excitement
• seeing and possibly hearing things that are not exist
• drowsiness and prolonged sedation
• reduced alertness
• headache
• dizziness
• difficulty co-ordinating muscles
• fits in premature infants and new-born babies
• temporary memory loss The duration of memory loss depends upon duration of treatment and dosage. You may experience this after your treatment. In isolated cases, this has lasted for a long time.
• low blood pressure
• slow heart rate
• redness of the face and neck, fainting or headache
• shortness of breath, breathlessness
• hiccups
• nausea, vomiting
• constipation
• dry mouth
• skin rash, nettle-rash
• itchiness
• skin reddening and pain at the injection site
• blood clot in a blood vessel or combined with inflammation of veins
• tiredness
• falling and breaking bones in elderly patients

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

Store in the outer packaging in order to protect from light

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

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

After opening of the ampoule:

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

After dilution:

Chemical and physical in-use stability of the dilutions has been demonstrated for 24 hours at room temperature (15 – 25°C) or for 3 days at +2 °C to +8 °C.

From a microbiological point of view, the product should be used immediately after dilution. If not used 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°C to 8°C unless dilution has taken place in controlled and validated aseptic conditions.

Midazolam ampoules are intended for single use. Discard any unused solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Do not use this medicine if you notice that the ampoule is found leaking, or the solution is not clear and not free from particles or if you notice any discoloration of the solution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Midazolam Sandoz contains

• The active substance is midazolam (as hydrochloride)
• For Midazolam Sandoz 1 mg/ml, oplossing voor injectie of infusie the other ingredients are sodium chloride, hydrochloric acid and water for injections.
• For Midazolam Sandoz 5 mg/ml, oplossing voor injectie of infusie the other ingredients are sodium chloride, hydrochloric acid. sodium hydroxide and water for injections.

What Midazolam Sandoz looks like and contents of the pack

Midazolam Sandoz is a clear, slightly yellow solution contained in a clear glass ampoule.

Midazolam Sandoz 1 mg/ml, oplossing voor injectie of infusie is marketed with pack sizes of 5 ampoules with each 5 ml solution for injection or infusion.

Midazolam Sandoz 5 mg/ml, oplossing voor injectie of infusie is marketed with pack sizes of 5 ampoules with each 1 ml, 3 ml, or 10 ml solution for injection or infusion.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Sandoz B.V., Veluwezoom 22, Almere, Nederland

Correspondentie: Postbus 10332, 1301 AH Almere

Manufacturer

Salutas Pharma GmbH

Otto-von-Guericke Allee 1

39179 Barleben

Duitsland

In het register ingeschreven onder:

Midazolam Sandoz 1 mg/ml, RVG 110832

Midazolam Sandoz 5 mg/ml, RVG 110837

This medicinal product is authorised in the Member States of the EEA under the following names:

The Netherlands	Midazolam Sandoz 1 mg/ml, oplossing voor injectie
	Midazolam Sandoz 5 mg/ml, oplossing voor injectie
Czech Republic	Midazolam Sandoz 1 mg/ml
	Midazolam Sandoz 5 mg/ml
Hungary	Midazolam Sandoz 1 mg/ml oldatos injekció
	Midazolam Sandoz 5 mg/ml oldatos injekció
Poland	Midazolam Sandoz
Slovenia	Midazolam Lek 1 mg/ml raztopina za injiciranje ali infundiranje
	Midazolam Lek 5 mg/ml raztopina za injiciranje ali infundiranje

This leaflet was last revised in November 2012

[To be completed nationally]

The following information is intended for healthcare professionals only

Preparation of solution for infusion

Midazolam Sandoz can be diluted with 0.9% sodium chloride solution, glucose 50 mg/ml (5%) or 100 mg/ml (10%) solution, or Ringer or Hartmann solution at a ratio of 15 mg of midazolam to 100-1,000 ml of infusion solution. These solutions remain stable for 24 hours at room temperature, and 3 days at +2 °C to +8 °C. Midazolam Sandoz must not be mixed with any

solution other than those listed above. In particular, Midazolam Sandoz must not be diluted with 6% w/v dextran (with 0.9% sodium chloride) in dextrose or mixed with alkaline injection injections. Midazolam precipitates in sodium bicarbonate.

The ampoule and the solution should be visually inspected prior to use. Only intact ampoules and clear solutions without particles and discoloration should be used.

Shelf life and storage

Midazolam Sandoz ampoules are intended for single use only.

Ampoule before opening

Store in the original package in order to protect from light

Ampoule after dilution

Chemical and physical in-use stability of the dilutions has been demonstrated for 24 hours at room temperature (15 – 25°C) or for 3 days at +2 °C to +8 °C.

From the microbiological point of view, the dilutions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are at the responsibility of the user and would normally not be longer than 24 hours at +2 to +8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

In case of continuous intravenous infusion, midazolam injection solution may be diluted in the range of 0.015 to 0.15 mg with one of the solution mentioned above.

Disposal of waste

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.