Last Updated on eMC 01-02-2017 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:30-11-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text



1.                      Marketing Authorisation holder

AstraZeneca UK Ltd

600 Capability Green,

Luton, LU1 3LU, UK.


Aspen Pharma Trading Limited

3016 Lake Drive,

Citywest Business Campus,

Dublin 24, Ireland

2.                      Marketing authorisation number(s)

PL 39699/0073 

 

PL 17901/0118

4.                      Date of revision of the text

November 2016 

 

20th February 2015

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling

Date of revision of text on the SPC:20-02-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 1 updated in line with QRD
Section 2 updated in line with QRD

Section 4.1 updated in line with QRD

Section 4.2 updated in line with QRD

Section 4.3 updated in line with QRD

Section 4.4 updated in line with QRD

Section 4.6 updated in line with QRD

Section 4.8 updated in line with QRD

Section 5.1 updated in line with QRD

Section 6.2 updated in line with QRD

Section 6.3 updated in line with QRD

Section 6.4 updated in line with QRD

Section 6.5 updated in line with QRD

Section 6.6 updated in line with QRD

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:18-09-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 5.1

Additional information regarding the onset and duration of action


Section 5.2

Additional information regarding the peak plasma concentrations.


Section 10

Date of revision updated to 18th September 2012

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:30-03-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4

 

New paragraph added after paragraph 3

 

Patients with cardiac insufficiency require special attention due to the risk of developing methaemoglobineamia (see section 4.8).

 

 

4th paragraph from end of section following wording added at end

 

(see sections 4.6 and 4.8).

 

 

Section 4.6

 

Paragraph 2 – following wording added to end of paragraph.

 

(see section 4.4).

 

 

Section 10

 

Date of revision changed to:   30th March 2012

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:10-12-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.2
remove reference to epidural use

Section 4.4 
with regards to chrondrolysis in patients receiving post-operative intra-articular continuous infusion of local anaesthetics.

Section 5.3 
with regards to carcinogenicity from preclinical toxicological studies of the metabolite o-toluidine.

 
Section 10
Date of revision of text: 10 December 2010

Reasons for adding or updating:

  • Change to section 6.1 - List of Excipients
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:19-08-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.1
additional text to include propyl parahydroxybenzoate (E216) as an additional preservative

Section 10
New revision date of text: 19 August 2010

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:25-03-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.3
Text changed from '3 years' to '2 years'

Section 10
25th March 2010

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:14-01-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Changes to Citanest 1% SPC

 

Section 4.8

New text to section:

 

“Undesirable effects

The adverse reaction profile for Citanest is similar to those of other amide local anaesthetics. Adverse reactions caused by the drug per se are difficult to distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia), events caused directly (e.g. nerve trauma) or indirectly (e.g. epidural abscess) by the needle puncture.

The adverse reactions considered at least possibly related to treatment with Citanest from clinical trials with related products and post-marketing experience are listed below by body system organ class and absolute frequency. Frequencies are defined as ‘very common’ (³1/10), ‘common’ (³1/100, <1/10), ‘uncommon’ (³1/1,000, <1/100), ‘rare’ (³1/10,000, <1/1,000), or ‘not known’ (cannot be estimated from the available data).

Table of Adverse Drug Reactions (ADRs)

System Organ Class

Frequency Classification

Adverse Drug Reaction

Blood and lymphatic system disorders

Rare

Methaemoglobinaemia (see below), cyanosis*

Immune system disorders

Rare

Allergic reactions (including urticaria, oedema, dyspnoea), anaphylactic reactions

Nervous system disorders

Common

Paraesthesia, dizziness

 

Uncommon

Signs and symptoms of CNS toxicity (see below)

 

Rare

Neuropathy, peripheral nerve injury

Eye disorders

Not known

Diplopia

Cardiac disorders

Common

Bradycardia

 

Rare

Cardiac arrest, cardiac arrhythmias

Vascular disorders

Very common

Hypotension**

 

Common

Hypertension

Respiratory disorders

Not known

Respiratory depression

Gastrointestinal disorders

Very common

Nausea**

 

Common

Vomiting**

*            In the presence of methaemoglobinaemia.

**         ADRs occur more frequently after epidural blocks.”

 

Section 10

14th January 2010

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:06-08-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



SmPC changes, Citanest 1%

 

Section 4.3 Contraindications

Changed to first paragraph, additional 2nd & 3rd paragraphs,

“Known hypersensitivity to anaesthetics of the amide type or to any of the excipients.

Hypersensitivity to methyl and/or propyl parahydroxybenzoate (methyl-/propyl paraben), or to their metabolite para-aminobenzoic acid (PABA).

Formulations of prilocaine containing parabens should be avoided in patients allergic to ester local anaesthetics or its metabolite PABA.”

 

Section 4.4

Change to heading.

“Special Warnings and precautions for use”

 

Deletion of paragraphs and additional 7th paragraph,

“Methaemoglobinaemia may occur at lower doses of prilocaine in patients suffering from anaemia, from congenital or acquired haemoglobinopathy (including methaemoglobinaemia), or in patients receiving concomitant therapy e.g. sulphonamides, known to cause such conditions. Infants are particularly susceptible, due to a lower activity of the enzyme which reduces methaemoglobin to haemoglobin. Hence prilocaine is not recommended for paracervical block (PCB) or pudendal block in the obstetric patient and in children under the age of 6 months.”

 

Additional 9th paragraph,

“Preservative containing solutions i.e. those supplied in multi-dose vials should not be used for intrathecal or epidural anaesthesia, intraocular or retrobulbar injections or in doses of more than 15 ml for other types of blockades.”

Section 4.8 Undesirable effects

Additional sub-headings,

Acute systemic toxicity

Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system (CVS). Such reactions are caused by high blood concentrations of a local anaesthetic, which may appear due to (accidental) intravascular injection, overdose or exceptionally rapid absorption from highly vascularised areas (see section 4.4). CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drug, both quantitatively and qualitatively.

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscular twitching or tremors are more serious and precede the onset of generalized convulsions. These signs must not be mistaken for neurotic behaviour. Unconsciousness and grand mal convulsions may follow which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with respiration and possible loss of functional airways. In severe cases apnoea may occur. Acidosis, hyperkalaemia, hypocalcaemia and hypoxia increase and extend the toxic effects of local anaesthetics.

Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the drug have been injected.

Cardiovascular system toxicity may be seen in severe cases and is generally preceded by signs of toxicity in the central nervous system. In patients under heavy sedation or receiving a general anaesthetic, prodromal CNS symptoms may be absent. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics, but in rare cases cardiac arrest has occurred without prodromal CNS effects.

In children, early signs of local anaesthetic toxicity may be difficult to detect in cases where the block is given during general anaesthesia.

Treatment of acute toxicity

If signs of acute systemic toxicity appear, injections of the local anaesthetic should be stopped immediately and CNS symptoms (convulsion, CNS depression) must promptly be treated with appropriate airway/respiratory support and the administration of anticonvulsant drugs.

If circulatory arrest should occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.

If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressor, chronotropic and or inotropic agents should be considered. Children should be given doses commensurate with age and weight.

Methaemoglobinaemia

Methaemoglobinaemia may occur after the administration of prilocaine. The repeated administration of prilocaine, even in relatively small doses, can lead to clinically overt methaemoglobinaemia (cyanosis). Prilocaine is therefore not recommended for continuous techniques of regional anaesthesia.

Methaemoglobin has risen to clinically significant levels in patients receiving high doses of prilocaine. Cyanosis occurs when the methaemoglobin concentration in the blood reaches 1–2 g/100 ml (6–12% of the normal haemoglobin concentration). The reduction in oxygen-carrying capacity due to the administration of prilocaine in normal patients is marginal; hence the methaemoglobinaemia is usually symptomless. However, in severely anaemic patients it may cause hypoxaemia. It is important to rule out other more serious causes of cyanosis such as acute hypoxaemia and/or heart failure.

In neonates and small infants there is an increased risk of development of methaemoglobinaemia (see sections 4.2 and 4.4).

Note: Even low concentrations of methaemoglobin may interfere with pulse oximetry readings, indicating a false, low oxygen saturation.

Treatment of methaemoglobinaemia

If clinical methaemoglobinaemia occurs, it can be rapidly treated by a single intravenous injection of a 1% methylene blue solution, 1 mg/kg body weight, over a 5-minute period. Cyanosis will disappear in about 15 minutes. This dose should not be repeated as methylene blue in high concentrations acts as a haemoglobin oxidant.”

Section 4.9 Overdose

New paragraph,

Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of overdose, systemic toxicity appears later (15–60 minutes after injection) due to the slower increase in local anaesthetic blood concentration (see section 4.8 Acute systemic toxicity and Treatment of acute systemic toxicity).”

Section 5.2 Pharmacokinetic properties

Additional last paragraph,

“In the liver, prilocaine is primarily metabolised by amide hydrolysis to orthotoluidine and N-propylamine. O-Toluidine is subsequently hydroxylated to 2-amino-3-hydroxytoluene and 2-amino-5-hydroxytoluene, metabolites with long half-lives that tend to accumulate and are believed to be responsible for the occurrence of methaemoglobinaemia.”

Section 10, Date of Revision of the Text

“6th August 2009”

 

 

 

 

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:19-08-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4

 

Additional new text 4th and 5th paragraphs

Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive (see section 4.5).

Citanest solution for injection is possibly porphyrinogenic and should only be prescribed to patients with acute porphyria when no safer alternative is available. Appropriate precautions should be taken in case of vulnerable patients.

 

 

Section 4.7

Change of text:

Depending on dosage Besides the direct anaesthetic effect, local anaesthetics may have a very mild effect on mental function and co-ordination even in the absence of overt CNS toxicity, and may temporarily impair locomotion and alertness co-ordination.

 

Section 10

Date of revision of text: 19 August 2008

Reasons for adding or updating:

  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.9 - Overdose

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 4 - Special Precautions for Storage
  • Correction of spelling/typing errors

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 8 - MA number
  • Change to section 9 - Date of Renewal of Authorisation
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Reasons for adding or updating:

  • No reasons supplied