MIVACRON 2 mg /Ml Injectable Solution

Зміст інструкції

1. Mivacron 2 mg/ml injectable solution for intravenous use
   1. What is Mivacron and what is it used for
   2. What you need to know before you are given Mivacron
   3. How Mivacron is administered
   4. Possible side effects
   5. How to store Mivacron
   6. Contents of the pack and other information
2. MIVACRON has been administered in this way, with minimal hemodynamic effects, in

Mivacron 2 mg/ml injectable solution for intravenous use

mivacurium

Read this leaflet carefully before you are given this medicine
because it contains
Important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Mivacron and what is it used for

Mivacron contains a substance called mivacurium. This substance belongs to a
group of medicines called muscle relaxants.
Mivacron is used for:

• Relaxing the musculature during surgical procedures in adults and children over 2 months of age, including cardiac surgery.
• To facilitate the insertion of a tube into the trachea (tracheal intubation), if a patient needs help with breathing

Ask your doctor if you want more information about this medicine.

2. What you need to know before you are given Mivacron

Do not use Mivacron:

• if you are allergic to mivacurium, or to other muscle relaxants or any of the excipients of Mivacron (listed in section 6)
• if you, or a family member, have previously had an adverse reaction to the use of an anesthetic. If you think any of these conditions apply to you, do not take Mivacron. If you are not sure, talk to your doctor, nurse or pharmacist first.

Warnings and precautions
Before you are given Mivacron, tell your doctor, nurse or
pharmacist if:

• you have muscle weakness, fatigue or difficulty coordinating movements (myasthenia gravis)
• you have a neuromuscular disease, such as a muscle wasting disease, paralysis, motor neuron disease or cerebral palsy
• If you have a burn that requires medical treatment
• If you have ever had an allergic reaction to any muscle relaxant that has been given to you during surgery.

Ask your doctor before you are given this medicine, if you have or have ever
had any of the following conditions:

• Tetanus
• A serious and long-term infection such as tuberculosis (TB)
• Any long-term illness that has weakened you
• Cancer
• Anemia
• Malnutrition
• Heart disease
• Stomach ulcers
• Burns
• Liver or kidney disease

Tell your doctor if:

• You are pregnant or have recently been pregnant or if you have given birth in the last 6 months
• You have been diagnosed with a genetically abnormal cholinesterase

If you are not sure whether any of the above applies to you, ask your doctor,
nurse or pharmacist before you are given Mivacron.

Other medicines and Mivacron
Tell your doctor, nurse or pharmacist if you are taking, have recently taken or
may take any other medicines, including those available without a prescription,
including herbal medicines. These medicines may affect the way Mivacron works or cause unwanted effects.
In particular, consult your doctor, nurse or pharmacist if you are taking any of these
medicines:

• anesthetics (used to reduce sensitivity and pain during surgery)
• antibiotics (used to treat infections)
• medicines for irregular heartbeats (antiarrhythmics)
• medicines for high blood pressure
• diuretics, such as furosemide
• medicines for joint inflammation, such as chloroquine or d-penicillamine
• steroids
• medicines for convulsions (epilepsy), such as phenytoin or carbamazepine
• medicines for mental illnesses, such as lithium, monoamine oxidase inhibitors (MAOIs) or chlorpromazine (which can also be used for nausea)
• medicines that contain magnesium
• medicines used for the treatment of depression and/or anxiety, SSRIs (selective serotonin reuptake inhibitors), including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before you are
given this medicine.

Driving and using machines
It can be dangerous to drive or use machinery too soon after surgery. Your doctor will tell you how long you need to wait before you can drive a car
or use machinery.

3. How Mivacron is administered

How the injection is given
You should never expect to be able to self-administer this medicine. It will always be
administered to you by a qualified person to do so.
Mivacron can be administered:

• as a single injection into a vein (intravenous bolus injection)
• as a continuous infusion into a vein. In this way, the drug is released slowly over a long period of time.

The doctor will decide on the method of administration and the necessary dose. This will depend on the
following factors:

• body weight
• the amount and duration of muscle relaxation required
• the expected response to the medicine. This medicine should not be given to children under 2 months of age.

If you receive more Mivacron than you should
Mivacron must always be administered under close supervision. However, if you think that
you have been given more than you should, tell your doctor or
nurse immediately.

4. Possible side effects

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

Very rare side effects (may affect up to 1 in 10,000 people)
Allergic reactions
If you have an allergic reaction, tell your doctor or nurse immediately. Signs of allergy
can include:

• sudden shortness of breath, chest pain or feeling of tightness in the chest
• swelling of the eyelids, face, lips, mouth or tongue
• skin rash or “urticaria” on any part of the body
• collapse Very common side effects (may affect up to 1 in 10 people)
• redness of the skin

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

• increased heart rate
• decreased blood pressure
• shortness of breath or cough
• skin rash

Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. You can also report side
effects directly through the national reporting system at
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side
effects you can help provide more information on the safety of this
medicine.

5. How to store Mivacron

• Keep Mivacron out of the sight and reach of children.
• Do not use Mivacron after the expiry date which is stated on the pack after SCAD. The expiry date refers to the last day of that month.
• Store at a temperature below 25 C. Do not freeze.
• Store in the original container to protect the product from light.
• When Mivacron is reconstituted it must be used immediately. Any unused solution must be discarded. Do not dispose of any medicine in wastewater. Ask your pharmacist or nurse how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Mivacron contains

• The active ingredient is mivacurium chloride
• The other ingredients are hydrochloric acid and water for injections.

Description of the appearance of Mivacron and contents of the pack

• Mivacron injection solution is available in vials containing 5 ml or 10 ml of product.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24,
Ireland
Tel: +39 0687 502 429
Manufacturer:

• GlaxoSmithKline Manufacturing S.p.A. - Strada Provinciale Asolana, n. 90 - S. Polo di Torrile, Parma (Italy)
• Aspen Pharma Ireland Limited - One George’s Quay Plaza, Dublin 2, Ireland
• Aspen Bad Oldesloe GmbH, 32-36 Industriestrasse, 23843 Bad Oldesloe, Germany

The following information is intended exclusively for healthcare professionals:
For detailed information on Mivacron, refer to the Summary of Product Characteristics
Dosage and method of administration

Use in adults

Administration by injection
MIVACRON must be administered by intravenous (i.v.) injection. In those receiving narcotic anesthesia, the average dose required to reduce the single twitch contraction of the thumb adductor muscle by 95% after ulnar nerve stimulation (ED), is 0.07 mg/kg of body weight (range 0.06-0.09 mg/kg).

The following doses are recommended for tracheal intubation:

• a dose of MIVACRON of 0.2 mg/kg, administered over 30 seconds, generally produces good to excellent conditions for endotracheal intubation within 2-2.5 minutes of its administration;
• a dosage of MIVACRON of 0.25 mg/kg administered in two divided doses (0.15 mg/kg followed 30 seconds later by 0.1 mg/kg), produces good to excellent conditions for endotracheal intubation within 1.5-2 minutes of the administration of the first portion of the dose. In adults, the initial bolus dose ranges from 0.07 to 0.25 mg/kg. The duration of neuromuscular block is correlated with the dosage; dosages of 0.07, 0.15, 0.20, 0.25 mg/kg generally produce a clinically effective relaxation in approximately 13, 16, 20, 23 minutes, respectively. Dosages up to 0.15 mg/kg can be administered in 5-15 seconds. Higher dosages must be administered over 30 seconds to minimize the possibility of cardiovascular effects. Complete neuromuscular block can be prolonged, as needed, with supplemental doses of MIVACRON. Maintenance doses of 0.1 mg/kg, administered during narcotic anesthesia, generally prolong each clinically effective neuromuscular block by approximately 15 minutes. Within the recommended doses, the depth and duration of neuromuscular block do not increase with consecutive supplemental doses of MIVACRON. Neuromuscular block produced by MIVACRON is potentiated by anesthesia with isoflurane and enflurane. If stable anesthesia has been achieved with isoflurane or enflurane, the recommended initial dose of MIVACRON should be reduced by up to 25%. Halothane appears to have only a minimal potentiating effect on mivacurium and it may not be necessary to reduce the MIVACRON dosage. Full and spontaneous recovery of neuromuscular function occurs in approximately 15 minutes and is independent of the dose of MIVACRON administered. The neuromuscular block produced by mivacurium can be antagonized with standard doses of cholinesterase inhibitors. However, since spontaneous recovery after mivacurium administration is rapid, the administration of these substances may not always be necessary, as they would reduce the recovery period by only 5-6 minutes. Administration by infusionMIVACRON can be used in continuous infusion to maintain neuromuscular block. After the appearance of the first signs of spontaneous recovery from the initial dose of MIVACRON, an infusion rate of 8 to 10 micrograms/kg/min (0.5 to 0.6 mg/kg/hour) is recommended. The initial infusion rate should be adjusted according to the patient's response to peripheral nerve stimulation and clinical criteria. Changes in the infusion rate should be made by increasing the drug administration by approximately 1 microgram/kg/min (0.06 mg/kg/hour). In general

a given dose should be maintained for at least 3 minutes before being
modified. On average, in adults receiving narcotic anesthesia, an infusion
rate of 6-7 micrograms/kg/min maintains neuromuscular block between 89% and 99% for
prolonged periods.
During stable anesthesia with isoflurane or enflurane, the need for a
reduction in the infusion rate by up to 40% should be considered. One study has shown that the infusion rate of mivacurium must be reduced by 50% with sevoflurane. With halothane
smaller reductions in the infusion rate may be necessary.
Spontaneous recovery, after infusion with MIVACRON, is independent of the duration
of the infusion and comparable to the recovery required after the administration of single doses.
Continuous infusion of MIVACRON has not been associated with the development of tachyphylaxis or
accumulation of the neuromuscular blocker.
MIVACRON, in a 2 mg/ml solution, can be used undiluted in infusion.
MIVACRON is compatible with the following infusion fluids:

• Sodium Chloride solution (0.9% w/v)
• Glucose solution (5% w/v)
• Sodium Chloride (0.18% w/v) and Glucose (4% w/v) solution
• Ringer Lactate solution, United States Pharmacopeia (USP).

When diluted with the solutions mentioned above, in a ratio of 1 to 3 (equal to 0.5 mg/ml),
MIVACRON has been shown to be chemically and physically stable for at least 48
hours at 30°C. However, since the product does not contain antibacterial preservatives, it is
recommended that dilution take place immediately before use, that administration begin
as soon as possible and that the remaining solution be discarded.

Use in children between 2 and 12 years of age
In children between 2 and 12 years of age, compared to adults, MIVACRON has a higher ED (0.1
mg/kg), a faster onset of neuromuscular block, a shorter clinical effect and a
faster spontaneous recovery.
The recommended initial bolus ranges from 0.1 mg/kg to 0.2 mg/kg administered in 5-15 seconds.
When a dose of 0.2 mg/kg is administered during stable narcotic anesthesia or with
halothane, a clinically effective block with an average duration of 9 minutes is produced. For
tracheal intubation, a dose of 0.20 mg/kg is recommended. Maximum block is reached
approximately 2 minutes after the administration of this dose and good to excellent intubation conditions are reached within these times.
Maintenance doses are generally needed more frequently in children than
in adults. Available data suggest that a subsequent dose of 0.1 mg/kg allows
further 6-9 minutes of clinically effective block during narcotic anesthesia or with halothane.
Children usually require a higher infusion rate than adults.
For children between 2 and 12 years of age, the average dose during narcotic anesthesia or with halothane is
13-14 micrograms/kg/min (approximately 0.8 mg/kg/hour) [range of 5-31
micrograms/kg/min (approximately 0.3-1.9 mg/kg/hour)].
The neuromuscular block of mivacurium is potentiated by inhalational agents. One study has
shown that the infusion rate of mivacurium must be reduced by 70% with
sevoflurane in children from 2 to 12 years of age.
Once spontaneous recovery has begun, it is completed in approximately 10 minutes.

Use in children under 2 years of age
Until further information is available, no dosage recommendations can be made for children under 2 years of age.

Infants and children under 2 months of age
The safety and efficacy of mivacurium chloride in neonates and infants under 2 months of age has not been established. No dosage recommendations can be made.

Elderly
In elderly patients receiving single bolus doses of MIVACRON, the time of onset,
duration of action and recovery phase are prolonged by 20-30% compared to younger
individuals.
These patients may require a reduction in the infusion rate, or smaller and less
frequent maintenance boluses.

Use in patients with cardiovascular disease
In patients with significant cardiovascular pathology, the initial dose of MIVACRON should
be administered over more than 60 seconds.

MIVACRON has been administered in this way, with minimal hemodynamic effects, in

patients undergoing aortocoronary bypass or valve replacement.

Use in patients with reduced renal function
In patients with severe renal insufficiency, the clinically effective duration of block after
administration of 0.15 mg/kg of MIVACRON is approximately 1.5 times that of
subjects with normal renal function. Consequently, the dose must be adjusted
according to the clinical response of the individual patient.
In patients with acute or chronic renal insufficiency, a prolonged and more intense
neuromuscular block may also occur following the reduction of plasma levels of
cholinesterase (see section 4.4 Special warnings and precautions for use).

Use in patients with reduced hepatic function
In patients with severe hepatic insufficiency, the clinically effective duration of block after
administration of 0.15 mg/kg of MIVACRON is approximately tripled compared to
subjects with normal hepatic function. This increase in duration is correlated with the
notably reduced activity of plasma cholinesterases observed in these patients.
Consequently, the dose must be adjusted according to the clinical response of the individual
patient.

Use in patients with reduced plasma cholinesterase activity
MIVACRON is metabolized by plasma cholinesterases. Plasma activity of these
enzymes may be decreased by the presence of genetic abnormalities (for example patients
heterozygous or homozygous for the gene of atypical plasma cholinesterases), and in various
pathological conditions (see 4.4 Special warnings and precautions for use) and by the
administration of certain drugs (see 4.5 Interactions with other medicines and other forms
of interaction). The possibility of a prolongation of the neuromuscular block, after
administration of MIVACRON, must be considered in patients who present a
reduction in plasma cholinesterase activity.
Mild reductions in plasma cholinesterases (i.e. within 20% of the lower limit of normal
values) are not associated with clinically significant effects on the duration of the block.
(See sections 4.3 and 4.4 for information on homozygous and heterozygous patients).

Use in obese patients
In obese patients (with a weight more than 30% above their ideal weight), the initial dose of
MIVACRON should be calculated based on ideal weight and not on actual weight.

Use in burned patients
Burned patients may develop resistance to non-depolarizing neuromuscular blocking agents and
therefore require higher doses of the drug. However, these patients may also present a
reduction in plasma cholinesterase activity, which requires a lower dose.
Consequently, burned patients should be administered a test dose of 0.015-
0.020 mg/kg of MIVACRON, followed by the appropriate dose assessed by monitoring the
neuromuscular block through a peripheral nerve stimulator.

Monitoring
As with other neuromuscular blocking agents, monitoring of
neuromuscular function is recommended during the use of MIVACRON, in order to assess in each
patient the dose necessary for an adequate neuromuscular block.
With MIVACRON, no significant weakening of the “train-of-four” is observed during the onset
of the clinical effect. It is often possible to intubate the trachea before complete abolition
of the “train-of-four” response of the thumb adductor muscle.
Overdosage
Signs and symptoms
The main effect of an overdose with neuromuscular blocking agents is prolonged muscle
paralysis and its consequences.
However, the risk of hemodynamic adverse effects, especially a reduction in
systemic blood pressure, may increase.

Treatment
In these cases, it is essential to maintain airway patency and practice positive pressure
assisted ventilation until adequate spontaneous breathing has been restored.
Complete sedation may be necessary as the state of consciousness is not altered.
Recovery may be accelerated by the administration of anticholinesterase agents,
accompanied by atropine or glycopyrrolate, administered as soon as signs of
spontaneous recovery are evident.
Cardiovascular support may be helpful by placing the patient in the correct position and
administering fluids or vasopressors.
Special precautions for disposal and handling
Compatibility with some drugs commonly used in the peri-
operative setting, provided as acidic solutions, has been demonstrated.
If these drugs are infused with the same needle or cannula used for
MIVACRON ,and compatibility has not been demonstrated, it is recommended, after the
administration of each drug, to flush the line with saline solution.
Since the MIVACRON packages do not contain antibacterial preservatives, it is
recommended that it be used under totally aseptic conditions and that any dilution take place
immediately before use. Any solution not used in opened vials must be discarded.
MIVACRON is compatible with the following infusion fluids:

• glucose solution (5% w/v)
• Sodium Chloride solution (0.9% w/v)
• Sodium Chloride solution (0.18% w/v) and glucose (4% w/v) Ringer Lactate solution (USP) When diluted with the solutions above, in a ratio of 1 to 3 (equal to 0.5 mg/ml), MIVACRON has been shown to be chemically and physically stable for at least 48 hours at 30°C. However, since the product does not contain antibacterial preservatives, dilution is recommended immediately before use, administration should start as soon as possible and the remaining solution should be discarded.