Hikma Midazolam contains the active substance midazolam, which 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.

You must not be given Midazolam if:

• You are allergic (hypersensitive) to midazolam or any of the other ingredients of the medicine (listed in section 6).
• You are allergic to other benzodiazepine medicines, such as diazepam or nitrazepam.
• You have severe breathing problems and you are going to have Hikma Midazolam for conscious sedation.

You must not be given Hikma Midazolam 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

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

Talk to your doctor or nurse before you are given Hikma Midazolam 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 a condition called ‘sleep apnoea syndrome’ (where your breathing stops when you are asleep), so you may be closely monitored.
• 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. Alcohol can increase the effects of midazolam, possibly leading to severe sedation that could result in coma or death.
• 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 Hikma Midazolam.

Other medicines and Hikma Midazolam

Tell your doctor or nurse if you are taking, have recently taken or might start taking any other medicines. This includes medicines obtained without a prescription and herbal 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 (protease inhibitors such as saquinavir)
• Medicines for hepatitis C (protease inhibitors such as boceprevir and telaprevir)
• Atorvastatin (used to treat high cholesterol)
• Rifampicin (used to treat mycobacterial infections such as tuberculosis)
• Ticagrelor (used to prevent heart attack)
• The 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 Hikma Midazolam.

Operations

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

Hikma Midazolam with alcohol

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

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, think you may be pregnant or are planning to have a baby. Your doctor will decide if this medicine is suitable for you.

Hikma Midazolam may harm your unborn baby when used in early pregnancy. When high doses are administered during late pregnancy, labour or caesarean section, you might have an inhalation risk and your baby might have an irregular heartbeat, state of low muscle tone (hypotonia), feeding difficulties, a low body temperature and difficulty in breathing. With prolonged administration during late pregnancy, your baby may develop a physical dependence and risk of withdrawal symptoms after birth.

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

Driving and using machines

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

Do not drive or use machinery until you are completely recovered. Your doctor should advise you when you can start these again.

Do not drive while taking this medicine until you know how it affects you.

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

• Lack of sleep or alcohol consumption may further impair your alertness.
• You should always be taken home by a responsible adult after your treatment.

Hikma Midazolam contains sodium

Hikma Midazolam contains sodium. Each ml of Hikma Midazolam 15 mg/3ml Solution for Injection contains 2.16 mg (0.094 mmol) sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

Hikma Midazolam 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.

How much Hikma Midazolam is given

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 Hikma Midazolam 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 Hikma Midazolam. Your doctor will decide on a suitable dose for you.

How Hikma Midazolam is given

Hikma Midazolam 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.

Children and babies

• In infants and babies under 6 months of age Hikma Midazolam 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 Hikma Midazolam into a vein. When midazolam is used for premedication (to cause relaxation, calm and drowsiness before an anaesthetic) it may be given into the back passage (rectum).

If too much Hikma Midazolam is given

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

If you stop receiving Hikma Midazolam

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

• Become tolerant to Hikma Midazolam. 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.

The following effects have been seen with midazolam use, particularly in children and the elderly; restlessness, agitation, irritability, involuntary movements, hyperactivity, hostility, delusion, anger, aggressiveness, anxiety, nightmares, hallucinations (seeing and possibly hearing things that are not really there), psychoses (losing contact with reality), inappropriate behaviour, excitement and assault (these are also known as paradoxical reactions, which are outcomes that are opposite to the effects normally expected for the drug). If you experience these, your doctor will consider stopping midazolam treatment.

Withdrawal symptoms:

Benzodiazepine medicines, like Hikma Midazolam, 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
• Diarrhoea
• Muscle pain
• Feeling very worried (anxious), tense, restless, confused or bad-tempered (irritable)
• Problems with sleeping
• Mood changes
• Hallucinations (seeing and possibly hearing things that are not there)
• Fits (convulsions).

In severe cases of withdrawal, the following can occur: a feeling of losing contact with reality, numbness and tingling of the extremities (e.g. hands and feet), feeling sensitive to light, noise and touch.

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been reported with this medicine (frequency not known).

Stop having midazolam 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:

• Restlessness, agitation, irritability
• Nervousness, anxiety
• Hostility, anger or aggression
• Excitement
• Hyperactivity
• Changes in libido
• Inappropriate behaviour.

Muscle problems:

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

Mental and nervous system problems:

• Confusion, disorientation
• Emotional and mood disturbances
• Involuntary movements
• Nightmares, abnormal dreams
• Hallucinations (seeing and possibly hearing things that are not really there)
• Psychoses (losing contact with reality)
• 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 you were given. You may experience this after your treatment. In isolated cases this has been prolonged (lasted for a long time)
• Drug dependence, abuse.

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 are at risk of falling and breaking bones. This risk is increased in the elderly and those taking other sedatives (including alcohol).

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.

Patients with severe kidney disease:

• Patients with severe kidney disease are more likely to experience side effects.

If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

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

Store below 30°C.

Protect from light.

Store in the original package.

After dilution:

It is recommended that the solutions should be prepared right before use and administered right after its preparation. If any particular circumstances force the storage of the diluted solutions before use, it is recommended to be up to 24 hours at room temperature.

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

Do not use this medicine if you notice visible signs of deterioration.

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.