Keppra 500 mg film-coated tablets

Type II: CCDS Update - Levetiracetam CCDS v8.0 – Cat B: Additional information regarding Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS.

Type II: CCDS Update - Levetiracetam CCDS v8.0 – Cat B: Additional information regarding Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS.

Var II - CCDS.v.5.0 - Neuroleptic Malignant Syndrome

Var II - CCDS.v.5.0 - Neuroleptic Malignant Syndrome

Update to recommend the same dosing for monotherapy and adjunctive therapy – PIL section 3

Update to recommend the same dosing for monotherapy and adjunctive therapy – SmPC Section 4.2

Addition of warning and adverse reaction of QT Prolongation – Section 2 & 4

Addition of warning and adverse reaction of QT Prolongation – Section 4.4 & 4.8

Addition of the warning and ADR on “Worsening Seizures”

Addition of the warning and ADR on “Worsening Seizures”

In section 4.4 of the SPC the following has been added:

Abnormal and aggressive behaviours

Levetiracetam may cause psychotic symptoms and behavioural abnormalities including irritability and aggressiveness. Patients treated with levetiracetam should be monitored for developing psychiatric signs suggesting important mood and/or personality changes. If such behaviours are noticed, treatment adaptation or gradual discontinuation should be considered. If discontinuation is considered, please refer to section 4.2.

In section 4 of the leaflet the following has been added:

Tell your doctor or pharmacist if any of the following side effects gets serious or last longer than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually, or if you or your family and friends notice important changes in mood or behaviour.

Pregnancy wording update, dysgeusia, pregnancy malformation update and gait disturbance

-        Section 6.3 Shelf Life (clarification / editorial / wording changes –  actual shelf life not changed).

-        Section 6.6 Special precautions for disposal and other handling (includes substantial changes to Instructions for reconstituting Actilyse).

-        Section 10 (Revision date updated).  The date of revision of the text has updated to align with the RMS approval dated 25Apr17.

Further to receipt of renewal approval, the following are updated:

Sections 1, 2 and 7 (with minor typographical changes)

Sections 3 (re appearance), 4.2, 4.3, 4.4, 4.6, 4.8, 4.9, 5.1, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6 and 9 (with significant changes)

Section 10 (revision date updated from August 2013 to March 2015) 

Section 4.3 Contraindications

This section has been updated to include warnings for latex and gentamicin.

This section has been updated to include additional anticoagulation statements.

Section 4.4 Special Warnings and Precautions for Use

This section has been updated to include warnings for latex and gentamicin.

This section has been updated to include additional anticoagulation statements.

Section 6.6 Special Precautions for Disposal and Other Handling

The section header has been updated to now read Special precautions for disposal and other handling i.e. … of a used medicinal product or waste materials derived from such medicinal product and … of the product have been deleted.

Section 10 Date of Revision of the Text

The date has been updated from October 2011 to August 2013.

Section 4.1 Therapeutic Indications

The final paragraph (regarding fibrinolytic treatment of acute ischaemic stroke) has had text both added to and deleted from.  The text … as early as possible …,

… 4.5 …, … after … and all that after … imaging techniques … is new.

Section 4.2 Posology and Method of Administration

The Acute ischaemic stroke sub-heading of this section has had both text added to and deleted from. 

The text … only …, … under the responsibility and follow-up of …, … trained and experienced …, and … neurovascular … is new in the first paragraph.

The text … as early as possible …, … 4.5 … and the complete final sentence of the third paragraph is new.

Section 4.3 Contraindications

The second paragraph of this section has been added as new text.

The first bullet point of the Additional contraindications in acute ischaemic stroke sub-heading has been amended.  The text … 4.5 …, … symptoms for which the …, … time … and … and could potentially be more than 4.5 hours ago (see section 5.1) has been added.

A new sub-heading entitled Use in elderly patients, together with corresponding text, has been added.

Section 4.4 Special Warnings and Precautions for Use

A new first paragraph has been added to this section.

The sub-heading Additional special warnings and precautions in acute ischaemic stroke has had both text added to and deleted from.  The text … only …, … under the responsibility and follow-up of a … and … neurovascular … has been added.

A new third bullet point has been added to the Special warnings/conditions with a decreased benefit/risk ratio sub-heading.

A new penultimate paragraph (regarding data available from ECASS III) has been added to this section.

Section 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

The text … active substances which interfere with … has replaced the text … other agents inhibiting … in the second paragraph of this section.

Section 4.8 Undesirable Effects

The first paragraph of this section (regarding adverse reactions frequency and system organ class) has had text both added to and deleted from.

The text … and without any relevant increase in overall mortality and severe disability combined, i.e. mRS of 5 and 6 … has been added to the common category of the Haemorrhage sub-heading.

The text … ear haemorrhage … has been added to the uncommon category of the Haemorrhage sub-heading.

Section 4.9 Overdose

The text … severe bleeding results, the infusion of fresh frozen plasma or fresh blood is recommended and if necessary, synthetic antifibryinolytics may be administered … has been added to the first paragraph of this section.

Section 5.1 Pharmacodynamic Properties

The text … iv… and … s.c… has been replaced with the text … intravenous … and … subcutaneous … in the fourth paragraph of this section.

The Acute stroke sub-heading of this section has had both text added to and deleted from, including the addition of a new second paragraph regarding the ECASS III trial and the addition of a new third paragraph regarding the safety and efficacy of Actilyse for acute ischaemic stroke treatment.

Section 6.6 Special Precautions for Disposal and Other Handling

Minor editorial changes have been made to this section.

Section 10 Date of Revision of the Text

The date has been amended from November 2009 to October 2011.

Changes to section 4.2 - Posology and method of administration, Change to section 4.3 – Contraindications, Change to section 4.4 – Special warnings and special precautions for use, Change to section 4.5 – Interaction with other medicinal products and other forms of interaction, Change to section 4.8 – Undesirable effects.

Change details:

Section 4.2 Posology and method of administration.

The section on adjunctive therapy has been updated to incorporate current recommendations.  It now states “Antithrombotic adjunctive therapy is recommended according to the current international guidelines for the management of patients with ST-elevation myocardial infarction”

Section 4.3 Contraindications

Acitylase is contraindicated in cases where there is a high risk of haemorrhage in a number of situations; this now includes patients with a “significant bleeding disorder at present or within the past 6 months”.

An additional contraindication for use in acute myocardial infarction and acute pulmonary embolism was any history of stroke.  This has now been changed to include

“any known history of haemorrhagic stroke or stroke of unknown origin”

and “any known history of ischaemic stroke if transient ischaemic attack in the preceding 6 months, except current acute ischaemic stroke in the last 3 hours”.

Section 4.4 Special warnings and special precautions for use

This section now notes that the concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding.

Section 4.5 Interaction with other medicinal products and other forms of interaction

This section now notes that the concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding.

Section 4.8 – Undesirable effects

Corrections in the frequency classification of some undesirable effects.  The following effects have been reclassified from uncommon to common:

Respiratory tract haemorrhage (such as pharyngeal haemorrhage, epistaxis, haemoptysis)

Gastrointestinal haemorrhage (such as gastric haemorrhage, gastric ulcer haemorrhage, haemorrhage rectum, haematemesis, melaena, mouth haemorrhage)

As with other thrombolytic agents some cardiac disorders have been reported as sequelae of myocardial infarction and / or thrombolytic treatment. Reperfusion arrythmias are now classified as a very common undesirable effect.

Gastrointestinal disorders: Nausea and vomiting have been reclassified from a rare to a common undesirable effect.

The following effect has been added

Injury and poisoning and procedural complications:

rare:     fat embolism (cholesterol crystal embolisation), which may lead to corresponding consequences in the organs concerned