6.1. Report from the June 2021 PRAC meeting
The EMA reported from the PRAC meeting held from 7 to 10 June 2021.
6.2. Periodic Safety Update Reports (PSUR)
6.2.1. PRAC recommendations on PSUSAs for CMDh position16.2.1.1. Baclofen (oral) - PSUSA/00000294/202009
The CMDh, having considered the PSUR on the basis of the PRAC recommendation and the PRAC assessment report, agreed by consensus on the variation of the marketing
authorisations of medicinal products containing baclofen (oral).
1 Subject to adoption via written procedure in advance of the meeting. For discussion/adoption at the plenary if comments are received during written procedure.
6.2.1.2. Hydroxyzine chloride / hydroxyzine pamoate and all fixed combination, hydroxyzine - PSUSA/00001696/202011
The CMDh, having considered the PSUR on the basis of the PRAC recommendation and the PRAC assessment report, agreed by consensus on the variation of the marketing
authorisations of medicinal products containing hydroxyzine chloride / hydroxyzine pamoate and all fixed combination, hydroxyzine.
PRAC noted that information related to the risk of hypotonia, movement disorders including extrapyramidal disorders, clonic movements, CNS depression, neonatal hypoxic conditions, and urinary retention in neonates whose mothers received hydroxyzine during late
pregnancy and/or labour is not always included in sections 4.6 of the Summary of Product Characteristics and the corresponding PL section of hydroxyzine containing medicinal products.
Therefore, PRAC recommends that the following wording is included in product information of hydroxyzine containing products, if similar information is not already included in their product information:
Summary of Product Characteristics Section 4.6
In neonates whose mothers received <product> during late pregnancy and/or labour, the following events were observed immediately or only a few hours after birth: hypotonia, movement disorders including extrapyramidal disorders, clonic movements, CNS depression, neonatal hypoxic conditions, or urinary retention.
Package leaflet Section 2
The following symptoms may occur in newborn babies of mothers that have used
<product> during late pregnancy and/or labour, they were observed immediately or only a few hours after birth: shaking, muscle stiffness and/or weakness, breathing problems and urinary retention (withholding/retaining urine).
The MAHs should submit a variation to the relevant national competent authorities within 2 months to update their product information as proposed above, if similar information is not already included in their product information.
6.2.1.3. Perindopril - PSUSA/00002354/202010
The CMDh, having considered the PSUR on the basis of the PRAC recommendation and the PRAC assessment report, agreed by consensus on the variation of the marketing
authorisations of medicinal products containing perindopril.
In the framework of the PSUSA on perindopril, the PRAC noted that perindopril is also authorised in fixed dose combination (FDC) products. The PRAC considered that the risk of Syndrome of Inappropriate Anti Diuretic Hormone secretion (SIADH), depression, flushing, anuria and oliguria as well as a change in frequency for acute renal failure in patients with hypertension, stable coronary artery disease or symptomatic heart failure, would also be relevant to be included in fixed dose combinations of perindopril as these FDCs have the same pharmaceutical form, strengths and similar indications of perindopril as single
substance. The adverse reactions should be included in the SmPC section 4.8 for perindopril even if already included for another active substance in the same FDC product.
The same timelines as for the present PSUSA on perindopril would apply in accordance with the CMDh guidance on implementing variations.
6.2.1.4. Polystyrene sulfonate - PSUSA/00002472/202010
The CMDh, having considered the PSUR on the basis of the PRAC recommendation and the PRAC assessment report, agreed by consensus on the variation of the marketing
authorisations of medicinal products containing polystyrene sulfonate.
As part of the PSUSA, the frequency of PSUR submission has been revised from 8 years to 1 year. The MAHs of products referred to in Articles 10(1), 10a, 14, 16a of Directive
2001/83/EC as amended are going to be included in the next PSUSA and are asked to provide in the next PSUR a thorough and critical benefit/risk evaluation, considering available efficacy evidence and up-to date evidence of serious gastrointestinal risks associated with the use of polystyrene sulfonate products together with the evaluation of the effectiveness of current routine risk minimisation measures in place. Discussion about accuracy of information presented in the PI with respect to the target population (indication, contraindication, dosage recommendation, treatment duration, recommendation for
electrolytes monitoring, etc.) should be provided and PI update should be proposed if needed.
6.2.2. Information on PRAC recommendations for PSUSAs for maintenance
6.2.2.1. Desogestrel / ethinylestradiol - PSUSA/00000967/202009
In the framework of the PSUSA on desogestrel / ethinylestradiol, the PRAC noted that inconsistent information related with angioedema is included in section(s) 4.4 and 4.8 of the Summary of Product Characteristics and in sections 2 and 4 of the Package Leaflet of all ethinylestradiol containing medicinal products (single agent and in fixed dose
combinations).
Therefore, PRAC recommends that the following is included in the product information of all ethinylestradiol containing medicinal products:
Summary of product characteristics A warning should be added/revised as follows:
Section 4.4
Exogenous estrogens may induce or exacerbate symptoms of hereditary and acquired angioedema.
Section 4.8
Text in the tabulated list of adverse reactions in the SOC Immune system disorders should be added/revised as follows:
Exacerbation of symptoms of hereditary and acquired angioedema. (Frequency
‘Unknown’) Package leaflet
2. What you need to know before you use [brand name]
Tell your doctor if any of the following conditions apply to you.
If the condition develops or gets worse while you use [trade name], you should also tell your doctor.
- If you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives potentially with difficulty breathing contact a doctor immediately. Products containing estrogens may cause or worsen the symptoms of hereditary and acquired angioedema.
4. Possible side effects Serious side effects
Contact a doctor immediately if you experience any of the following symptoms of angioedema: swollen face, tongue and/or throat and/or difficulty swallowing or hives potentially with difficulty breathing (see also section “Warnings and precautions”).
6.2.2.2. Tetrabenazine - PSUSA/00002911/202010
In the framework of the PSUSA on tetrabenazine, the PRAC noted that inconsistent information related to the risk of depression and suicidality and overdose is included in sections 4.4, 4.8 and 4.9 of the Summary of Product Characteristics and in sections 2, 3 and 4 of the Package Leaflet of tetrabenazine containing medicinal products.
Therefore, PRAC recommends that the following is included in all product information of concerned products:
Summary of Product Characteristics Section 4.4
Depression/Suicidality
Tetrabenazine may cause depression or worsen pre-existing depression. Cases of suicidal ideation and behaviour have been reported in patients taking the product. Particular caution should be exercised in treating patients with a history of depression or prior suicide
attempts or ideation (see also section 4.3).
Patients should be closely monitored for the emergence of such adverse events and patients and their caregivers should be informed of the risks and instructed to report any concerns to their doctor immediately.
If depression or suicidal ideation occurs it may be controlled by reducing the dose of tetrabenazine and/or initiating antidepressant therapy. If depression suicidal ideation is profound, or persists, discontinuation of tetrabenazine and initiation of antidepressant therapy should be considered.
Section 4.8
The following adverse reactions should be added under the SOC Psychiatric disorders with a frequency of very rare:
- Suicidal ideation - Suicide attempt Section 4.9
Symptoms associated with overdoses of tetrabenazine may include acute dystonia, oculogyric crisis, nausea, vomiting, diarrhoea, sweating, hypotension, confusion, hallucinations, hypothermia, sedation, rubor and tremor.
Treatment should consist of those general measures employed in the management of overdosage with any CNS-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing
overdosage, the possibility of multiple drug involvement should always be considered. The physician should consider contacting a poison control centre on the treatment of any overdose.
Package Leaflet
Section 2. What you need to know before you take [Product]
Warnings and precautions
Talk to your doctor or pharmacist before taking [Product]
• If you have been diagnosed with depression or have thought about or tried to commit suicide.
• If you have ever had depression Section 3. How to take [Product]
If you take more [Product] than you should
If you take too many tablets or someone else accidentally takes your medicine, contact your doctor, pharmacist, or nearest hospital straight away. Symptoms of overdose include
uncontrollable muscle spasms affecting the eyes, head, neck and body, uncontrolled rolling of the eyes, excessive eye blinking, nausea, vomiting, diarrhoea, sweating, dizziness, feeling cold, confusion, hallucinations, drowsiness, redness/inflammation, and tremor.
Section 4. Possible side-effects
Please seek advice immediately or go to your emergency department if you experience the following side effects:
Very Common (may affect more than 1 in 10 people)
• [Product] can cause depression, which can, in some people, lead to thoughts of committing suicide. If you feel down or very sad you may be starting to become depressed and you should tell your doctor about this change.
Very Rare (may affect up to 1 in 10,000 people)
• If you have tried to commit suicide.
• If you have intentionally hurt yourself or if you have started to think about intentionally hurting yourself.
Affected MAHs are requested to submit the appropriate variations to the relevant national competent authorities within 2 months.
6.2.3. Information on PRAC recommendations for PSUSAs for CAPs/NAPs or CAPs None
6.2.4. Outcomes of informal PSUR work sharing procedures / Chair
The CMDh adopted the outcome of the informal PSUR work sharing procedure on Edarclor (azilsartan medoxomil/chlortalidone).
The SmAR will be published on the CMDh website (Action: EMA).
6.2.5. PSUSA Lead Member State appointment
The CMDh appointed the lead Member States for single assessment of PSURs for NAPs to be started in June 2022. The appointed lead member states will be published in the EURD list.
6.2.6. PSUSA Follow-up procedures
None
6.3. Results of post-authorisation safety studies (PASS) imposed in the MA (in accordance with Art. 107q)
26.3.1. PRAC recommendations on PASS results for CMDh position
None
6.4. Lists
6.4.1. Union Reference Date list
The CMDh noted the update of the Union Reference Date list.
6.4.2. List of medicinal products under additional monitoring
The CMDh noted the update of the list of medicinal products under additional monitoring.
6.5. Information from Member States on actions for nationally authorised products related to safety
None
6.6. Other topics related to pharmacovigilance
None