The March 2026 issue of the Egyptian Pharmacovigilance Center (EPVC) newsletter presents important safety updates for healthcare professionals. Key topics include a label update on medicine‑induced Pisa syndrome (a rare neurological condition characterised by sustained lateral flexion of the spine) based on a review by the New Zealand regulatory authority (Medsafe). The newsletter also describes two local case reports of urinary incontinence associated with isotretinoin use, including a positive rechallenge, and discusses the implications for product labelling.
Additionally, EPVC reports on its “Pharmacovigilance: A Core Professional Skill” initiative, which delivered awareness lectures at three Egyptian pharmacy faculties. This article provides a detailed medical analysis of Pisa syndrome – its causes, pathogenesis, and management – and reviews the evidence linking isotretinoin to urological adverse effects, including urinary incontinence. Practical guidance for healthcare professionals on recognising and reporting these rare adverse drug reactions is also offered.
1. Introduction
The Egyptian Pharmacovigilance Center (EPVC) continues its mission to monitor the safety of pharmaceutical products and disseminate essential safety information to healthcare professionals. The March 2026 issue of the EPVC newsletter highlights:
- A label update from the New Zealand regulatory authority (Medsafe) regarding Pisa syndrome associated with donepezil and other medicines.
- Two local Individual Case Safety Reports (ICSRs) of urinary incontinence following isotretinoin use, with a positive rechallenge in one case.
- The launch of an educational initiative at Egyptian pharmacy faculties to raise pharmacovigilance awareness among students.
- Practical safety tips for medication use during fasting periods (e.g., Ramadan).
This article reviews these topics in depth, providing clinical context and evidence‑based recommendations.
2. Label Update: Medicine‑Induced Pisa Syndrome
2.1 What is Pisa Syndrome?
Pisa syndrome (also known as pleurosthotonus) is a rare neurological condition characterised by a sustained lateral flexion of the spine exceeding 10 degrees when the patient is upright. The abnormal posture resembles the Leaning Tower of Pisa, giving the syndrome its name. Patients may experience difficulty walking or standing up straight; some may be unaware that they are leaning.
2.2 Causes and Risk Factors
Pisa syndrome has a variety of causes, but it is most strongly associated with:
- Older age
- Female sex
- Neurodegenerative diseases (e.g., Parkinson’s disease, Alzheimer’s disease)
- Polypharmacy – particularly with antipsychotics and anticholinesterase inhibitors (especially with prolonged use or high doses)
2.3 Medicines Associated with Pisa Syndrome
A recent literature review found that anticholinesterase inhibitors and antipsychotics are the most frequently reported medicines associated with Pisa syndrome. The following table summarises the implicated drug classes and examples:
| Drug Class | Examples |
|---|---|
| Anticholinesterase inhibitors | Donepezil, rivastigmine, galantamine |
| Typical antipsychotics | Haloperidol, chlorpromazine, droperidol |
| Atypical antipsychotics | Quetiapine, risperidone, olanzapine, aripiprazole, clozapine, paliperidone, ziprasidone |
| Antidepressants | Amitriptyline, clomipramine, nortriptyline, mirtazapine, sertraline |
| Antiparkinsonian medicines | Levodopa, pramipexole, ropinirole |
| Mood stabilisers | Lithium |
| Anti‑seizure medicines | Valproate |
2.4 Pathophysiology
The exact mechanism of medicine‑induced Pisa syndrome is unknown. It is hypothesised to result from an imbalance between dopaminergic and cholinergic neurotransmitters, leading to dysfunction of postural control. Medicines associated with Pisa syndrome affect these neurotransmitter systems. For example, anticholinesterase inhibitors increase acetylcholine levels, while antipsychotics block dopamine receptors. The resulting imbalance may cause asymmetrical muscle tone and sustained lateral trunk flexion.
2.5 Clinical Presentation and Diagnosis
- Onset: The time between starting the medicine and symptom onset is unpredictable – it may occur weeks to months or even years after initiation.
- Symptoms: Persistent leaning to one side when standing or walking; patients may have difficulty maintaining an upright posture.
- Diagnosis: Clinical examination (measurement of lateral flexion angle). Other causes of postural abnormalities (e.g., scoliosis, vertebral fractures, Parkinsonian camptocormia) should be excluded.
2.6 Management
- Discontinuation or dose reduction of the offending medicine often leads to improvement or complete resolution, especially if the condition is recognised early.
- If the medicine is essential (e.g., donepezil for Alzheimer’s disease), switching to an alternative with a different pharmacological profile may be considered.
- Physical therapy and postural support can be helpful.
2.7 Regulatory Action in New Zealand
Medsafe reviewed the risk of Pisa syndrome with donepezil and concluded that there is sufficient evidence to support an association. Sponsors have been requested to update donepezil data sheets with this adverse effect. In Egypt, healthcare professionals should be aware of this rare but recognisable and often reversible condition.
3. Local Case Safety Report: Urinary Incontinence with Isotretinoin
3.1 Case Summaries
The Cairo Regional Pharmacovigilance Center received two ICSRs involving adult female patients (aged 19 and 24 years) who developed suspected adverse reactions associated with oral isotretinoin used for severe acne.
| Parameter | Case 1 | Case 2 |
|---|---|---|
| Age | 19 years | 24 years |
| Reactions | Urinary incontinence, postictal state, disturbance of consciousness, sialorrhoea, viral encephalitis | Urinary incontinence |
| Diagnostic findings | CSF supported viral encephalitis; other investigations largely unremarkable | Largely unremarkable |
| Seriousness | Prolonged hospitalisation | Significant disability affecting quality of life |
| Dechallenge | Improvement/recovery after isotretinoin discontinuation | Improvement/recovery after discontinuation |
| Rechallenge | Not reported | Performed – urinary incontinence recurred (positive rechallenge) |
| Concomitant medications | Topical medications reported | None reported |
3.2 Isotretinoin: Background and Mechanism
Isotretinoin is an oral retinoid indicated for severe forms of acne (nodular or conglobate acne, or acne at risk of permanent scarring) resistant to standard therapy with systemic antibacterials and topical treatment.
Mechanism of action (from the Summary of Product Characteristics – SmPC):
- Isotretinoin suppresses sebaceous gland activity and reduces the size of the sebaceous glands.
- It has a dermal anti‑inflammatory effect.
- It inhibits sebocyte proliferation and normalises differentiation of the pilosebaceous unit.
- Reduced sebum production limits colonisation by Propionibacterium acnes.
Posology: Isotretinoin should only be prescribed by or under the supervision of physicians experienced in systemic retinoid therapy, who fully understand the risks and monitoring requirements (including pregnancy prevention).
3.3 Isotretinoin and Urinary Incontinence – Evidence
Current labelling: According to the SmPC, isotretinoin may cause glomerulonephritis as a very rare adverse drug reaction, but urinary incontinence is not listed.
Global database evidence: A search of the global VigiBase (using VigiLyze) identified 38 reports of urinary incontinence associated with isotretinoin, including 2 reports from Egypt.
Published case report: A case published in an Elsevier journal described a 29‑year‑old male who developed overactive bladder shortly after starting isotretinoin. Urodynamics revealed no detrusor overactivity. Symptoms did not resolve entirely after discontinuation, suggesting that retinoid effects on the urinary tract may be under‑recognised. Animal studies have shown that isotretinoin directly affects cystometric parameters.
Conclusion from EPVC: Although urinary incontinence is not currently listed in the product labelling, the receipt of two serious local reports – including one with a positive rechallenge – together with supportive global database reports, suggests that a potential association cannot be excluded. Healthcare professionals should be vigilant for similar reports.
3.4 Recommendations for Healthcare Professionals
| Recommendation | Details |
|---|---|
| Prescribing indications | Isotretinoin must be prescribed strictly for approved indications (severe acne unresponsive to standard therapy). |
| Prescriber expertise | Treatment must be initiated and supervised by physicians experienced in systemic retinoid therapy. |
| Baseline assessment | Conduct a thorough medical history, paying particular attention to neurological disorders and urinary tract conditions. |
| Patient education | Advise patients to report new‑onset urinary symptoms (urgency, leakage, incontinence), neurological symptoms (confusion, altered consciousness, seizures), or any other adverse reactions. |
| Reporting | Ensure that any suspected drug‑related adverse events are promptly documented and submitted to the Pharmaceutical Vigilance General Administration (PVGA, formerly EPVC) for continuous safety monitoring. |
4. EPVC Educational Initiative: “Pharmacovigilance: A Core Professional Skill for Pharmacists”
4.1 Objectives of the Initiative
EPVC launched an initiative aimed at:
- Preparing a generation of graduates from medical faculties who possess adequate awareness of the importance of pharmacovigilance and its role within the healthcare system.
- Providing opportunities for the new generation to participate in raising awareness about pharmacovigilance and how to monitor and report adverse drug reactions.
- Promoting community integration and strengthening a culture of positive and active participation in serving society.
4.2 Implementation
The initiative was launched through three field visits to faculties of pharmacy at:
- Port Said University
- Damanhour University
- Pharos University in Alexandria
4.3 Content of Lectures
Three introductory awareness lectures were delivered, covering six topics about the pharmacovigilance landscape in Egypt and globally (PV Landscape). Specific lectures included:
- “Pharmacovigilance: A Core Professional Skill for Pharmacists and Its Role in Protecting Society”
- Principles of pharmacovigilance
- Reporting channels and methods for detecting adverse drug reactions
4.4 Attendance
The events were attended by 186 participants from faculty deans, academic staff, teaching assistants, and students, reflecting the academic interest in supporting and strengthening pharmacovigilance concepts among students.
5. EPVC Safety Tips: Safe Fasting and Medication Use
The newsletter includes practical advice for patients who fast (e.g., during Ramadan):
| Advice | Explanation |
|---|---|
| Do not stop or change medicines without consulting a healthcare professional | May lead to reduced effectiveness or unwanted adverse reactions. |
| Adjust medication schedules | When appropriate, medications may be timed to coincide with the fasting schedule (e.g., at Iftar and Suhoor). |
| Take medicines with food if required | Some medicines should be taken with food to avoid stomach irritation. |
| Monitor for dehydration and hypoglycaemia | Fasting may increase the risk of dehydration (especially with diuretics) or low blood sugar (with antidiabetic agents). |
| Seek medical advice before fasting | Patients using blood sugar‑lowering agents should monitor their glucose closely and consult their doctor. |
| Report unusual symptoms | Dizziness, severe weakness, or fainting should be reported to a healthcare provider and, if suspected as an ADR, reported to EPVC. |
Key message: Maintaining safe medication use during fasting helps ensure both effective treatment and patient safety.
6. How to Report Adverse Drug Reactions to EPVC
Healthcare professionals and the public can report suspected adverse reactions to the Egyptian Drug Authority (EDA) through:
- Email: pv.followup@edaeqypt.gov.eg
- Hotline: 15301
- Website: EDA website
- Alternative: Report through a pharmacy, product distributor, or company hotline – they are required to forward reports to EDA.
Why your report matters: Every report contributes to the safety of medicines and patients worldwide.
7. Clinical Implications and Practical Guidance
7.1 Recognising Medicine‑Induced Pisa Syndrome
| Step | Action |
|---|---|
| Maintain high suspicion | In patients on anticholinesterase inhibitors (especially donepezil) or antipsychotics who develop a sustained lateral lean. |
| Review medication history | Note duration of treatment and any recent dose changes. |
| Measure lateral flexion | More than 10 degrees when upright supports the diagnosis. |
| Exclude other causes | Scoliosis, vertebral fractures, Parkinsonian postural abnormalities. |
| Manage | Consider dose reduction or discontinuation; if the drug is essential, try switching to an alternative. |
| Report | Notify EPVC to help characterise this rare ADR. |
7.2 Isotretinoin and Urinary Incontinence – What to Do
| Scenario | Action |
|---|---|
| Patient on isotretinoin reports new‑onset urinary urgency, leakage, or incontinence | Assess for other causes (urinary tract infection, neurological conditions). If no alternative cause is found, consider isotretinoin as a possible cause. |
| Severe or disabling symptoms | Discontinue isotretinoin and monitor for improvement (dechallenge). |
| Symptoms recur on rechallenge | This strongly supports a causal association; avoid re‑exposure. |
| Report the case | Submit an ICSR to EPVC, including details of dechallenge/rechallenge. |
7.3 Promoting Pharmacovigilance Education
EPVC’s initiative to visit pharmacy faculties is a model for integrating pharmacovigilance into undergraduate curricula. Key elements include:
- Practical skills: How to recognise and report ADRs.
- Systems knowledge: Understanding national and global PV frameworks (EDA, WHO PIDM, VigiBase).
- Professional identity: PV as a core competency for pharmacists.
8. Conclusion
The March 2026 EPVC newsletter provides critical safety information for healthcare professionals in Egypt and beyond. Key takeaways include:
- Pisa syndrome – a rare, reversible neurological condition associated with anticholinesterase inhibitors (especially donepezil) and antipsychotics. Clinicians should suspect medicine‑induced Pisa syndrome in patients presenting with sustained lateral spinal flexion.
- Isotretinoin and urinary incontinence – two local ICSRs, including one with a positive rechallenge, together with 38 global VigiBase reports, suggest a potential association not currently listed in the product labelling. Healthcare professionals should be vigilant for urological adverse effects in patients taking isotretinoin and report suspected cases.
- Pharmacovigilance education – EPVC’s initiative at pharmacy faculties reached 186 participants, fostering awareness of ADR reporting and patient safety among future pharmacists.
- Safe fasting – Patients should not alter their medication regimens without medical advice; prescribers should proactively counsel patients who fast.
By staying vigilant and actively participating in pharmacovigilance activities, healthcare professionals can help ensure safer use of medicines for all patients, including those receiving isotretinoin or donepezil, and contribute to the global knowledge base through EPVC reporting.
