SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Mepivacaine hydrochloride 20mg/ml solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

20 mg/ml:

Each ml contains Mepivacaine hydrochloride 20 mg.

Each 2 ml ampoule contains Mepivacaine hydrochloride 40 mg.

Each 5 ml ampoule contains Mepivacaine hydrochloride 100 mg.

Each 10 ml ampoule contains Mepivacaine hydrochloride 200 mg.

Each 20 ml vial contains Mepivacaine hydrochloride 400 mg.

Excipient with known effect:

Each ml of Mepivacaine 20 mg/ml solution for injection contains 0.12 mmol (2.8 mg) of sodium.

Each 2 ml ampoule of Mepivacaine 20 mg/ml solution for injection contains 0.24 mmol (5.6 mg) of sodium.

Each 5 ml ampoule of Mepivacaine 20 mg/ml solution for injection contains 0.60 mmol (14 mg) of sodium.

Each 10 ml ampoule of Mepivacaine 20 mg/ml solution for injection contains 1.2 mmol (28 mg) of sodium.

Each 20 ml vial of Mepivacaine 20 mg/ml solution for injection contains 2.4 mmol (56 mg) of sodium.

For the full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Solution for injection Clear, colourless solution.

The pH of solution is 5.5 - 6.5

20 mg/ml: Osmolality of solution is 300 -400 mOsmol/kg H2O

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Local anaesthesia by infiltration of the fingers, toes, ears, nose and penis and in other cases where adrenaline is considered contraindicated; peripheral nerve block; caudal anaesthesia and non-obstetric epidural anaesthesia.

4.2 Posology and method of administration

Posology

Mepivacaine should only be used by or under the supervision of physicians who are experienced in loco-regional anaesthesia techniques.

The form and concentration used vary according to the indication and the desired purpose, and the patient's age and disease status.

Adults and children over 15 years

The following table provides an overview of posologies for commonly used techniques. The physician's experience and knowledge of the patient's clinical condition are important when selecting the dose. When using prolonged blocks, by repeated administration, the risks of reaching toxic plasma concentrations or causing local neural trauma must be taken into consideration.

Mepivacaine hydrochloride 20 mg/ml solution for injection is not recommended for intercostal blocks in the absence of adrenalin.

The maximum recommended dose for single administration is:

-    ENT region: 200 mg mepivacaine hydrochloride (3 mg/kg body weight),

-    Epidural anaesthesia and peripheral blockades: 400 mg mepivacaine hydrochloride (6 mg/kg body weight),

-    Intercostal blockade: 300 mg mepivacaine hydrochloride (4 mg/kg body weight),

-    Plexus anaesthesia: 500 mg mepivacaine hydrochloride (7 mg/kg body weight).

1 ml Mepivacaine hydrochloride solution for injection contains 10 mg & 20 mg mepivacaine hydrochloride.

	Conc	Volume	Dose	Time to	Duration
	mg/ml	ml	mg	installation/ minutes	hours
Surgical Anaesthesia
Epidural lumbar anaesthesia*	20	10-15	200-300	-	-
	10	10-20	100-200	-	-
Epidural thoracic administration	10-20	5-12	50-240	10-20	1.5-2
Caudal block	10	20-30	200-300	15-30	1-1.5
	20	10-15	200-300	-	-
Neural blocks (small peripheral nerve and infiltration)
- infiltration	10	1-20	200	-	-
- digital block	10	1-5	10-50	2-5	1.5-2
- intercostal block (per segment)-	10	4	<400	3-5	1-2
maximum number of simultaneous neural blocks must be a maximum of 10			(Cumulati ve dose of each of the injections)
- peribulbar block	20	5-7.5	100-150	3-5	1.5-2

Pudendal block (on each side)	10	7-10	70-100	-	-
Retrobulbar block	20	3	60	-	-
Major peripheral neural block
- paracervical block (on each side)*	10	5-10	50-100	3-5	1-1.5
- Brachial plexus block	20	3-5	60-100	-	-
- axiliary	10	25-35	250-350	-	-
- supraclavicular, interscalene and	10	30-40	300-400	15-30	1.5-2
subclavicular perivascular
- sciatic nerve block	20	15-20	300-400	15-30	2-3
- Femoral block or block of fascia iliaca	10	10-20	100-200	-	-
* Not recommended during la	bor

The dosage for epidural anaesthesia must be calculated on the basis of age; for the lumbar region, the following values are a guide:

- 5-year-olds:	0.5 ml/segment
- 10-year-olds:	0.9 ml/segment
- 15-year-olds:	1.3 ml/segment
- 20-year-olds:	1.5 ml/segment
- 40-year-olds:	1.3 ml/segment
- 60-year-olds:	1.0 ml/segment
- 80-year-olds:	0.7 ml/segment

Smaller doses must in general be used in patients in impaired general condition.

In patients with certain pre-existing conditions (vascular occlusion, arteriosclerosis or nerve damage due to diabetes) the dose must be reduced by a third.

Elevated plasma levels can occur in patients with impaired hepatic or renal function, in particular after repeated use. In these cases a lower dose range is likewise recommended.

Children aged between 1 and 15 years

For children the dosages must be calculated on an individual basis, taking into account age and weight. The maximum dose is mepivacaine hydrochloride 5 mg per kg body weight. Individual differences are possible. For overweight children, a gradual dose reduction is often necessary; the dose should be based on ideal weight.

Use of Mepivacaine hydrochloride solution for injection in neonates should be avoided due to the reduced metabolism of the active substance in the liver.

Chil dren aged 1-15 years	Concentr ation mg/mL	Vol ume mL/ kg	Do se mg /kg	Ti m e to in st all at io n mi ns	Dura tion hours
Caud	10	0.5	5	10	1-2
al				-
anae				15
sthes
ia

Instructions for use

The total dose should be injected slowly or fractionated at an increasing dose, while at the same time closely monitoring the vital functions of the patient with constant verbal contact. When administering an epidural dose a prior test dose is recommended. Accidental intravascular injection can be recognised by the specific toxicity symptoms. Accidental intrathecal injection is recognised by the signs of spinal blockade. If toxic symptoms occur, the injection must be halted immediately.

Mepivacaine hydrochloride solution for injection is injected into the space around the spinal cord for targeted anaesthesia of individual nerves (epidural nerve block).

To anaesthetise tissue, Mepivacaine hydrochloride solution for injection is injected into a localised area of tissue (infiltration anaesthesia). To anaesthetise individual nerves (peripheral nerve block), for pain therapy and sympathetic nerve blockade, Mepivacaine hydrochloride solution for injection is applied locally following targeted puncture, depending on anatomical considerations.

Mepivacaine hydrochloride solution for injection should be used only by those with the relevant knowledge of successfully conducting the relevant anaesthetic procedure.

As a general rule, low concentration solutions are applied in continuous administration (drip).

Repeated use of this medicinal product can result in loss of efficacy due to rapid development of tolerance to the drug (tachyphylaxis).

Method of administration

The method of administration of Mepivacaine varies according to the procedure of infiltration anaesthesia perineural anaesthesia and epidural anaesthesia.

4.3    Contraindications

•    hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

•    severe disturbances of the cardiac conduction system.

•    acute decompensated heart failure.

•    paracervical anaesthesia in obstetrics.

•    Intravascular injections

In addition, the special contraindications for epidural anaesthesia must be taken into account, such as:

•    uncorrected hypovolaemia

•    elevated intracranial pressure

•    Acute active CNS disease such as meningitis, tumours, poliomyelitis and intracranial bleeding, seizures or uncontrolled epilepsy

•    Spinal stenosis, active spinal disease (such as spondylitis, tuberculosis and tumour) and spinal trauma (such as fracture)

•    Septicaemia

•    Pernicious anaemia combined with degenerative changes in the spinal cord

•    Infection at the injection site

•    Coagulation disorder or anticoagulant treatment (except low-dose heparin) Cardiogenic or hypovolaemic shock

4.4    Special warnings and precautions for use

Before using the local anaesthetic, it is essential to ensure that resuscitation equipment (e.g. to maintain the airway and administer oxygen) and emergency medication to treat toxic reactions are immediately available.

Mepivacaine hydrochloride solution for injection must be used only with particular caution in

•    renal or liver diseases,

•    vascular occlusion,

•    arteriosclerosis,

•    nerve damage caused by diabetes mellitus,

Mepivacaine hydrochloride solution for injection should be used in patients with acute porphyria only if strictly indicated, as Mepivacaine hydrochloride solution for injection can trigger porphyria. Appropriate precautions should be taken in all patients with porphyria.

Chondrolysis was reported in post-marketing surveillance in patients who had received continuous intra-articular infusions of local anaesthetics post-operatively. In the majority of cases the shoulder joint was involved. Mepivacaine hydrochloride solution for injection is not authorised for continuous intra-articular infusions.

The following points should be noted in order to avoid undesirable effects:

•    An intravenous access for an infusion (volume replacement) should be placed in patients who are at risk and when using high doses.

•    In general a vasoconstrictor should not be added to the therapy.

•    The patient should be correctly positioned.

•    Blood pressure, pulse/ECG and the size of the pupils should be monitored.

•    General and special contraindications as well as interactions with other medicinal products must be noted.

•    Have a lipidic emulsion available to administer in the event of intoxication with clinical symptoms of neurotoxicity or cardiotoxicity.

It must be noted that an increased haemorrhagic tendency is generally to be expected during treatment with drugs that inhibit blood coagulation (anticoagulants such as heparin), non-steroidal anti-rheumatic drugs or plasma substitutes. In addition, inadvertent vascular injury in the course of pain therapy can result in severe bleeding. If necessary, the bleeding time and the activated partial thromboplastin time (aPTT) should be determined, a Quick test performed and the platelet count checked. In patients who are at risk, these tests should also be carried out in patients receiving low-dose heparin prophylaxis (precautionary treatment with the anticoagulant heparin at a low dose) before the use of Mepivacaine hydrochloride solution for injection.

Anaesthesia in patients who are receiving concomitant precautionary treatment to prevent thromboses (thrombosis prophylaxis) with low-molecular-weight heparin should be undertaken only with special caution.

Retrobulbar injections may rarely reach the cranial subarachnoid space and cause, for example, temporary blindness, cardiovascular collapse, apnea and convulsion, these symptoms must be treated immediately.

Retro and peribulbar injections of local anaesthetics may cause some risk of patients ocular muscle dysfunction. The main causes are traumatic nerve injury and/ or local toxic effect on muscles and nerves. The scale of such tissue damage is due to trauma size, the local anesthetics concentration and duration of tissue exposure to local anesthetics. For this reason, the lowest effective dose should be chosen.

Epidural anaesthesia may lead to hypotension and bradycardia. The risk can be reduced by intravenous administration of crystalloid or colloidal liquid. Hypotension should be treated immediately, for example ephedrine 5-10 mg intravenously, repeated necessary.

Mepivacaine hydrochloride solution for injection is not recommended for paracervical block in childbirth or epidural anaesthesia for caesarean section. Placental transfer is relatively large, and fetuses and newborns have a slower metabolism than adults, increasing the risk of toxic symptoms.

Some patients require special attention, even though regional anaesthesia is frequently indicated in such patients:

•    elderly patients (sudden arterial hypotension is one of the complications possible in epidural anaesthesia),

•    patients with advanced hepatic or severe renal dysfunction,

•    patients in weakened general condition at risk of reduced hepatic blood flow

•    patients with partial or complete heart block, since local anaesthetics can suppress myocardial conduction.

Use in the head and neck region is more hazardous, since the risk of central nervous system intoxication symptoms is increased.

For small surgical procedure, then more short term anaesthesia is desired.

Each ml of Mepivacaine 10 mg/ml solution for injection contains 0.14 mmol (3.2 mg) of sodium.

Each 10 ml ampoule of Mepivacaine 10 mg/ml solution for injection contains 1.4 mmol (32 mg) of sodium.

Each 20 ml vial of Mepivacaine 10 mg/ml solution for injection contains 2.8 mmol (64 mg) of sodium.

Take into account in individuals on a strict low-salt diet.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of vascoconstrictors prolongs the duration of effect of Mepivacaine hydrochloride solution for injection.

Toxic synergy has been described for centrally-acting analgesics and ether.

Combinations of various local anaesthetics result in additive effects in the cardiovascular system and CNS.

In patients simultaneously receiving other local anaesthetics or structurally related substances (e.g. anti-arrhythmics such as mexiletine), Mepivacaine hydrochloride solution for injection must be used with particular caution, as the undesirable effects are additive in these cases.

No studies of the interactions between mepivacaine and Class III anti-arrhythmics (e.g. amiodarone) have been conducted, but caution is advised in this case also. Patients who are being treated with Class III anti-arrhythmics (e.g. amiodarone) should be kept under strict observation with ECG monitoring, as the cardiac effects can be additive.

The effect of non-depolarising muscle relaxants is prolonged by Mepivacaine hydrochloride solution for injection.

4.6 Fertility, pregnancy and lactation

Pregnancy

On the basis of long-standing use, anaesthetics of the mepivacaine type are considered to be reasonably safe for use on pregnant women.

Retrospective studies of pregnant women receiving local anaesthetics for emergency surgery early in pregnancy have not shown that local anaesthetics cause birth defects. However, no controlled studies have been carried out in pregnant women.

Moreover, inadequately investigated animal reproduction studies have been performed with mepivacaine (see section 5.3). Therefore, caution should be taken before administering this anaesthetic during early pregnancy.

One possible complication of using Mepivacaine hydrochloride solution for injection in obstetrics is the occurrence of arterial hypotension in the mother.

Following paracervical blockade with mepivacaine hydrochloride during parturition, symptoms of intoxication were observed in the neonates: frequently bradycardia (20 to 30% in foetuses with no risk factors, 60% in fetuses with risk factors), in some instances tonic-clonic seizures, respiratory arrest, hypotension, mydriasis with absent reaction to light. The use of paracervical blockade in obstetrics is therefore contraindicated. For pharmacokinetic reasons (risk of systemic accumulation) mepivacaine hydrochloride is not the drug of choice for epidural anaesthesia in obstetrics.

Mepivacaine hydrochloride solution for injection crosses the placenta by means of simple diffusion. The ratio of embryofetal blood concentration to maternal blood concentration is 0.46:2.9.

Breast-feeding

It is not known whether local anaesthetics are excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when mepivacaine is administered to a nursing woman. Should administration be necessary during lactation, breast-feeding can be resumed approximately 24 hours after the end of treatment.

4.7 Effects on ability to drive and use machines

Depending on the dose and route of administration mepivacaine have a transient effect on mobility and coordination (see section 4.2).

When Mepivacaine hydrochloride solution for injection is used, the doctor must decide in each individual case whether the patient can drive or use machines.

4.8 Undesirable effects

The possible undesirable effects after use of Mepivacaine hydrochloride solution for injection largely correspond to those of other local anaesthetics of the amide type. Undesirable effects caused by the medicinal products itself are difficult to distinguish from the physiological effects of nerve blockade (e.g. drop in blood pressure, bradycardia). They are also difficult to distinguish from the consequences of the puncture, either direct (e.g. nerve damage) or indirect (e.g. abscess at the administration site).

In addition, any abnormal absorption characteristics or disturbances of metabolism in the liver or disturbances in excretion via the kidneys must be considered as a possible cause of undesirable effects.

The stated frequencies of undesirable effects have been based on the following categories:

Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000) and Very rare (<1/10,000), not known (cannot be estimated from the available data).

MedDRA system organ class	Adverse reaction
Immune system disorders
Rare	allergic reactions anaphylactic shock
Nervous system disorders
Common	paresthesia
	dizziness
Uncommon	signs and symptoms of CNS toxicity (convulsions, tingling in the mouth area,
	numbness of the tongue, auditory and visual disturbances, loss of consciousness, tremor, tinnitus, speech disturbances, suppression of CNS function, light-headedness)
Rare	neuropathy peripheral nerve injury arachnoiditis
Eye disorders
Rare	diplopia
Cardiac disorders
Common	bradycardia
Rare	cardiac arrest
	cardiac arrhythmia
Vascular disorders
	hypotension*
Common	hypertension
Respiratory, thoracic and mediastinal disorders
Rare	respiratory depression

Gastrointestinal disorders

	nausea*
Common	vomiting*

* These undesirable effects occur more frequently after epidural anaesthesia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Inadvertent intravenous administration can trigger systemic effects immediately (within seconds or within a few minutes). In the event of overdose the systemic toxicity occurs later (15 to 60 minutes after injection) which is attributable to the slower increase in concentration of the local anaesthetic in the blood.

A plasma concentration of 5 to 6 micrograms mepivacaine hydrochloride per ml is regarded as the critical threshold dose.

Acute systemic toxicity

Systemic toxic reactions mainly affect the CNS and the cardiovascular system. Such reactions are triggered by high plasma concentrations of local anaesthetic which can occur as a result of inadvertent intravenous administration, overdose or unusually rapid absorption in areas with a high density of blood vessels.

The signs of an overdose can be classed in two qualitatively distinct groups of symptoms, and according to their intensity:

Central nervous system symptoms

The first symptoms are usually light-headedness, paraesthesia in the region of the mouth, a feeling of numbness in the tongue, excessively acute hearing, ringing in the ears and visual disturbances. Speech disturbances, muscle twitching or tremor are more serious and precede a generalised seizure. Such signs must not be misinterpreted as neurotic behaviour. Loss of consciousness and grand mal seizures can then follow, generally lasting between several seconds and a few minutes. Hypoxia and an excessively high level of carbonic acid in the blood immediately follow the seizures, and are attributable to the increased muscle activity in conjunction with respiratory disturbances. In severe cases respiratory arrest can occur. Acidosis, hyperkalaemia, hypocalcaemia and hypoxia potentiate and prolong the toxic effects of local anaesthetics.

The regression and resolution of central nervous symptoms is attributable to redistribution of the local anaesthetic with its removal from the CNS and its subsequent metabolism and excretion. Regeneration can occur rapidly unless large quantities have been administered.

Cardiovascular symptoms

Cardiovascular toxicity can occur in severe cases. The signs of toxic symptoms in the central nervous system generally precede the toxic cardiovascular effects. This does not however apply if the patient is under general anaesthetic or is deeply sedated with drugs such as benzodiazepines or barbiturates.

Hypotension, bradycardia, arrhythmias and even cardiac arrest can occur due to the high systemic concentration of local anaesthetics. In rare cases cardiac arrest has occurred without prior CNS effects.

Treatment of acute systemic toxicity

If signs of acute systemic toxicity occur, administration of the local anaesthetic must be halted immediately. Symptoms affecting the CNS (seizures, CNS depression) must be treated immediately by appropriate maintenance of the airway/breathing and by administering an anticonvulsant.

In the event of cardiac arrest, the customary emergency medicine procedures must be carried out. A constant optimised supply of oxygen, ventilation and circulatory support as well as treatment of acidosis are vital.

In the event of cardiovascular depression (low blood pressure, bradycardia) appropriate treatment with intravenous fluids, vasopressors, chronotropic and/or inotropic drugs should be considered. Children should be given doses appropriate to their age and weight.

A lipidic emulsion must be administered in the event of intoxication when clinical symptoms of neurotoxicity or cardiotoxicity are observed.

Centrally acting analeptics are contraindicated in intoxication by local anaesthetics.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Local anaesthetics of the amide type

ATC code: N01BB03

Mepivacaine hydrochloride is a local anaesthetic of the amide type with rapid onset of effect and reversible blockade of vegetative, sensory and motor nerve fibres as well as cardiac conduction. It is assumed that its effect is due to the blocking of sodium channels in the nerve membrane. Mepivacaine hydrochloride solution has a pH of 5.5 to 6.5 and a pKa value of 7.6. The ratio of dissociated to lipid-soluble base is determined by the pH of the tissues.

The active substance is diffused initially by the nerve membrane to the nerve fibre in the alkaline form, but becomes effective as a mepivacaine cation only after reprotonation. Where pH values are low, e.g. in tissue with inflammatory changes, only small amounts are available in alkaline form, and so adequate anaesthesia cannot be achieved.

The motor blockade does not outlast the analgesia.

5.2 Pharmacokinetic properties

Absorption

The rate of absorption is dependent on the dose and route of administration. The absorption from the epidural route is biphasic, where peak plasma concentrations reach after 15-20 minutes. When epidural and branchial blockage the peak plasma concentrations are 0.75-1.0 microgram/ml per 100 mg. Intercostals blockage gives the highest peak plasma concentration, about 1.6 microgram/ml per 100 mg.

Distribution

The volume of distribution at steady state is about 84 liters and plasma protein binding is approximately 75%. Binding essentially occurs to alpha 1-acid glycoprotein.

Mepivacaine crosses the placenta by simple distribution and the plasma concentration of unbound mepivacaine will be the same in the mother and the fetus. Total plasma concentration will be lower in the fetus which has a lower protein binding with a foetal/maternal blood ratio of about 70%.

Biotransformation

Mepivacaine is metabolized almost entirely in the liver via hydroxylation and conjugation. Clearance is therefore dependant on the hepatic blood flow and activity of metabolizing enzymes. The hepatic extraction ratio is 0.5.

Only 4% is excreted unchanged in the urine. Total plasma clearance is 0.8 l/min and the elimination half life is 1.9 hours. In the new-born, half-life is 3-5 times longer than in adults.

5.3 Preclinical safety data

Local toxicity

Studies of the local toxicity of mepivacaine in various animal species gave no indications of irreversible tissue damage.

Chronic toxicity

Investigations of sub-chronic toxicity due to local application of mepivacaine in animals (rabbit, monkey, rat) revealed no signs of muscle fibre atrophy or other lesions.

In repeated dose toxicity studies, inflammatory changes were observed at the injection site following subcutaneous application of mepivacaine over a period of 21 days in rats.

Monkeys were treated with mepivacaine 18 times over a period of 21 days with 3-5 or 4-8 mg/kg body weight (with and without a vasoconstrictor). No effect on body weight or haematological parameters was observed. There were no pathological changes.

Mutagenic and carcinogenic potential

Studies to date of genetic toxicology have shown no indications of a clinically relevant risk.

No long-term studies of the carcinogenic potential of mepivacaine are available.

Reproductive toxicity

Embryotoxicity studies with mepivacaine hydrochloride were performed in two species, but these studies do not meet current standards. Macroscopically visible malformations and skeletal malformations were not observed in the offspring. Because of the small number of maternal animals per group and the absence of visceral investigations of the offspring, however, a teratogenic risk cannot be excluded. In addition there are neither studies of the possible effects of mepivacaine hydrochloride on the fertility of the parent generation nor on postnatal development following prenatal and postnatal exposure of the offspring.

When mepivacaine was administered during parturition (epidural anaesthesia), fetal depression, fetal intoxication manifestations, reduced muscle tone and reduced muscle strength were reported in the first 8 hours after birth.

Fetal bradycardia and deaths have been reported in connection with the use of mepivacaine for paracervical blockade.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium chloride

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Water for injections

6.2    Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3    Shelf life

2 years

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

Do not freeze.

6.5    Nature and contents of container

Type I glass ampoules and Type I glass vials with rubber stopper and flip-off seal.

Mepivacaine 20 mg/ml solution for injection:

•    2 ml green band ampoules are supplied in packs of 1 and 5 ampoules

•    5 ml red band ampoules are supplied in packs of 1, 5, 10 and 50 ampoules

•    10 ml green band ampoules are supplied in packs of 1 and 5 ampoules

•    20 ml vials with chlorobutyl rubber stopper and lavender flip-off seal are supplied in packs of 1, 5 and 10 vials

The ampoules are available in blister/ tray pack.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Use immediately after opening.

Only clear solutions practically free from particles should be used.

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

The solution for injection is intended for single withdrawal and use only and must be used immediately after opening the ampoule or vial. Any unused solution must be discarded.

7 MARKETING AUTHORISATION HOLDER

Accord Healthcare Limited Sage House

319, Pinner Road, North Harrow Middlesex HA1 4HF United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 20075/0449

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

06/06/2016

10    DATE OF REVISION OF THE TEXT

06/06/2016