The Egyptian Pharmacovigilance Center (EPVC) Newsletter, August 2026 edition, presents critical safety information for healthcare professionals, including a class-wide safety update on GLP-1 receptor agonists and the risk of non-arteritic anterior ischaemic optic neuropathy (NAION), strengthened warnings on iatrogenic botulism following cosmetic use of botulinum toxin type A, a safety signal for nephrolithiasis associated with sertraline use, and a local case report on a drug administration error leading to skin necrosis and tissue breakdown. This article provides a comprehensive medical analysis of these updates, exploring the clinical presentation, pathophysiology, epidemiological evidence, regulatory actions, and practical recommendations for healthcare providers.
Section 1: Safety Update – GLP-1 Receptor Agonists and the Risk of Vision Loss
1.1 Background and Regulatory Context
The Therapeutic Goods Administration (TGA) of Australia has released a class-wide safety notice regarding glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications and a rare but serious eye condition: non-arteritic anterior ischaemic optic neuropathy (NAION). This advisory is particularly relevant given the widespread use of GLP-1 RAs in Egypt for treating type 2 diabetes and obesity, as well as similar actions already taken by the UK’s MHRA and ongoing evaluations by the EMA/PRAC .
1.2 What is Non-Arteritic Anterior Ischaemic Optic Neuropathy (NAION)?
NAION is a rare but serious condition characterised by sudden, painless vision loss, often associated with vascular risk factors. It is the most common cause of sudden optic nerve-related vision loss in adults over 50 years of age.
| Feature | Description |
|---|---|
| Definition | Ischaemic damage to the optic nerve head due to insufficient blood supply |
| Clinical presentation | Sudden, painless monocular vision loss; may be partial or complete |
| Risk factors | Small cup-to-disc ratio (“disc at risk”), diabetes, hypertension, hyperlipidaemia, obstructive sleep apnoea, increasing age |
| Prognosis | No treatment has been shown to improve visual acuity outcomes; may result in permanent visual impairment, including blindness |
| Mechanism | Changes in perfusion leading to venous dilation and congestion during relative hypoglycaemia |
The TGA described NAION as “a rare but serious condition that may result in permanent visual impairment, including blindness and no treatment has been shown to improve visual acuity outcomes” .
1.3 GLP-1 Receptor Agonists and NAION: The Evidence
The TGA’s class-wide safety update covers all GLP-1 RA medicines currently available in Australia, including semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), liraglutide (Saxenda), and dulaglutide (Trulicity) .
1.3.1 Epidemiological Data
1.3.2 Pathophysiological Mechanism
The association of NAION with small, crowded optic discs, optic disc oedema, and peripapillary exudation suggests that semaglutide-related NAION may result from changes in perfusion that lead to venous dilation and, presumably, to venous congestion during relative hypoglycaemia .
Additional proposed mechanisms include:
- Expression of GLP-1 receptors in the human optic nerve and GLP-1 RA-induced enhanced sympathetic nervous system activity influencing optic nerve head perfusion
- Rapid glycaemic reduction compromising retinal metabolism
- Potential effects on vascular regulation and blood flow dynamics
1.4 Regulatory Actions
The TGA has mandated a class-wide update to the Product Information (PI) and Consumer Medicine Information (CMI) for all GLP-1 RAs marketed in Australia. A new warning has been added under “Eye disorders” in the PI, advising that a sudden loss of vision should prompt urgent ophthalmological examination .
This follows:
- MHRA’s February 2026 drug safety update on semaglutide flagging the same risk
- EMA/PRAC review concluding NAION is a recognised risk associated with the class
- TGA’s first identification of a potential link in July 2024 after publication of a JAMA Ophthalmology study
1.5 Clinical Implications for Healthcare Professionals
| Implication | Action |
|---|---|
| Patient counselling | Inform patients about the rare but serious risk of vision loss; advise urgent ophthalmological examination if sudden vision loss occurs |
| Risk assessment | Identify patients at higher risk, including those with small cup-to-disc ratio, diabetes, hypertension, or obstructive sleep apnoea |
| Baseline eye examination | Consider baseline ophthalmological assessment, particularly for patients with risk factors |
| Monitoring | Maintain vigilance for visual symptoms during treatment |
| Risk communication | Emphasise that the absolute risk is low (2–18 additional cases per 100,000 users per year) but requires prompt action if symptoms occur |
Section 2: Safety Update – Iatrogenic Botulism Risk After Cosmetic Use of Botulinum Toxin Type A
2.1 Background and Regulatory Context
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-wide safety update on 15 July 2026, strengthening warnings for all botulinum toxin type A products following rare reports of iatrogenic botulism .
2.2 What is Iatrogenic Botulism?
Iatrogenic botulism is a rare but serious condition that occurs when the effect of botulinum toxin spreads beyond the intended injection site, affecting the nervous system.
2.3 Epidemiological Data
2.4 Regulatory Actions
The MHRA has worked with manufacturers to update the Summary of Product Characteristics (SmPC) and Patient Information Leaflet (PIL) for all UK-authorised botulinum toxin type A products to more clearly highlight the risk of iatrogenic botulism .
Key advice for healthcare professionals:
- Cases of iatrogenic botulism have been rarely reported following therapeutic or cosmetic use of botulinum toxin products
- Symptoms typically occur between 4 and 8 days but can take up to 4 weeks to develop
- Risks may be increased in patients with underlying disorders, use of high doses, off-label use, or use of counterfeit/unauthorised products
- Advise patients to seek immediate medical attention if symptoms occur
- Ensure the botulinum toxin product is authorised for use and follow product-specific guidance
2.5 Clinical Implications for Healthcare Professionals
| Implication | Action |
|---|---|
| Product verification | Ensure only licensed, authorised botulinum toxin products are used |
| Patient selection | Assess for risk factors including underlying neurological disorders and history of dysphagia |
| Dose and site adherence | Use recommended doses and approved injection sites only |
| Patient education | Inform patients about symptoms of iatrogenic botulism and the need to seek immediate medical attention |
| Multidisciplinary management | Involve critical care and neurology teams if botulism is suspected |
| Antitoxin availability | Heptavalent botulinum antitoxin (HBAT) should be available; it neutralises circulating toxin but does not reverse established neuromuscular blockade |
Section 3: Safety Signal – Potential Risk of Nephrolithiasis Associated with Sertraline Use
3.1 Background
The Safety Signals Management Unit within the Egyptian Pharmaceutical Vigilance General Administration (PVGA) identified and evaluated reports of nephrolithiasis (kidney stones) in patients taking sertraline to assess a potential causal link and potential risk factors.
3.2 What is Nephrolithiasis?
Nephrolithiasis is a common condition characterised by the formation of urinary stones, often presenting with haematuria and abdominal, flank, or groin pain. It affects approximately 1 in 11 individuals during their lifetime. Stone formation is related to reduced urine volume or increased excretion of stone-forming substances, including calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calcium-containing stones account for 60–80% of cases, followed by struvite (10–15%), uric acid (5–10%), cystine (1%), and other rare stone types, including drug-induced calculi.
3.3 Methodology and Results
A quantitative signal of significant disproportionate reporting (SDR) between nephrolithiasis and sertraline was identified, with a total of 66 case reports retrieved from the WHO global database (VigiBase) up to 08/02/2026. A case series causality assessment using the Bradford Hill criteria method was conducted, alongside a review of scientific literature.
| Parameter | Finding |
|---|---|
| Total cases | 66 |
| Gender | 32 females, 30 males, 4 unknown |
| Mean age | 44.4 years |
| Physician-confirmed | 31.8% |
| Countries reporting | 11 countries |
| Median time to onset | 55 days for acute renal colic |
| Doses in Egyptian cases | 100–150 mg/day |
3.4 Pathophysiological Mechanism
Published evidence suggests that serotonergic modulation associated with SSRIs may increase sympathetic activity while reducing parasympathetic control of bladder emptying. This may increase post-void residual urine volume and contribute to urinary retention, potentially creating conditions conducive to urinary stone formation and subsequent nephrolithiasis.
Serotonin in the lower urinary tract can exert inhibitory effects on the bladder, probably mediated by 5-HT1 receptors. Furthermore, serotonin can increase central sympathetic activity .
Urinary disorders listed in the local PI and EU SmPC, including pollakiuria, urinary retention, polyuria, and nocturia, provide additional biological plausibility for a potential association between sertraline and nephrolithiasis.
3.5 Conclusion and Recommendations
The weighted available evidence from the case series analysis and published literature supports a potential safety signal of nephrolithiasis associated with sertraline and the SSRI group, possibly secondary to drug-induced urinary retention and voiding dysfunction.
The PVGA has imposed risk-minimisation measures to enhance healthcare professionals’ awareness of the potential risk of nephrolithiasis associated with sertraline and other SSRIs, to facilitate early recognition, appropriate clinical assessment, timely management, and prompt reporting of suspected cases, particularly in patients receiving long-term therapy, higher doses, or those with predisposing risk factors.
| Implication | Action |
|---|---|
| Awareness | Consider nephrolithiasis in patients on sertraline presenting with flank pain, haematuria, or urinary symptoms |
| Risk assessment | Evaluate for predisposing risk factors including dehydration, personal/family history of stones, and urinary retention |
| Monitoring | Monitor for urinary symptoms, particularly in patients on long-term therapy or higher doses |
| Management | Ensure adequate hydration; consider alternative antidepressants if recurrent stones occur |
| Reporting | Report any suspected cases to the PVGA |
Section 4: Local Case Safety Report – Drug Administration Error Leading to Skin Necrosis and Tissue Breakdown
4.1 Case Summary
The Cairo Regional Pharmacovigilance Center received an Individual Case Safety Report concerning a 21-year-old male patient who presented to the Emergency Room with disturbed consciousness and hepatic encephalopathy. The patient began receiving an intravenous dose of ceftriaxone (2 g once daily) on May 16, 2026, to treat spontaneous bacterial peritonitis.
The suspected drug was injected over the course of two minutes after being diluted in 20 mL of normal saline. Following a single dose, the patient developed skin disintegration and necrosis. The suspected medication was stopped, but the reaction outcome was “not recovered.”
4.2 Background
4.2.1 Ceftriaxone
Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity. Its bactericidal activity results from inhibiting cell-wall synthesis by binding to penicillin-binding proteins.
4.2.2 Spontaneous Bacterial Peritonitis (SBP)
SBP is the infection of ascitic fluid in the absence of any intra-abdominal, surgically treatable source of infection.
4.2.3 Skin Necrosis
Skin necrosis is characterised by transmural necrosis affecting the epidermis, dermis, and possibly the subcutis. It is infrequently diagnosed as a primary lesion and most commonly occurs secondary to damage of the epidermis.
4.3 Labelled Information
According to the Summary of Product Characteristics (SmPC) of ceftriaxone, the posology and method of administration states that ceftriaxone can be administered by:
| Route | Recommended Administration |
|---|---|
| Intravenous infusion | Over at least 30 minutes (preferred route) |
| Slow intravenous injection | Over 5 minutes |
The SmPC also states that severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome) have been reported in association with ceftriaxone treatment.
4.4 Discussion
This case represents a medication administration error—the ceftriaxone was administered over 2 minutes instead of the recommended 30 minutes (infusion) or 5 minutes (slow injection). The concentration of ceftriaxone was 100 mg/mL (2 g in 20 mL), which exceeds the concentration threshold of >400 mg/mL associated with skin necrosis in bolus injection .
Literature evidence supports this association:
- A French national pharmacovigilance database analysis identified 10 cases of subcutaneous necrosis with ceftriaxone, mainly at doses of 2 g
- The median time to onset of skin necrosis was 4 days
- In an animal model, local tissue response was remarkably reduced when the same ceftriaxone dose was administered in a larger volume
4.5 Recommendations for Healthcare Professionals
| Recommendation | Action |
|---|---|
| Adherence to administration guidelines | Administer ceftriaxone strictly according to the approved route and rate of administration (infusion over ≥30 minutes or slow injection over 5 minutes) |
| Concentration awareness | Avoid high-concentration bolus injections |
| IV access verification | Ensure secure IV access and verify patency before and during administration |
| Prompt recognition | Stop administration immediately if extravasation or significant injection-site symptoms are suspected |
| Documentation | Assess and document suspected tissue injury promptly |
| Differential diagnosis | Distinguish local injection-site injury from severe cutaneous adverse reactions |
| Monitoring | Monitor patients for serious cutaneous reactions during ceftriaxone treatment |
| Reporting | Report suspected adverse reactions, including administration-related events, to the General Administration of Pharmaceutical Vigilance (PVGA) |
EPVC Tips – Protect Your Kidney from Medicine Overuse
The EPVC newsletter emphasises that too much medicine can hurt your kidneys. Some medicines, especially certain painkillers, can affect kidney function when used too often, in high doses, or for a long time.
Key messages for patients:
| Recommendation | Action |
|---|---|
| Follow the recommended dose and duration | Always adhere to prescribed dosing and duration |
| Avoid repeated painkiller use | Do not take painkillers repeatedly without medical advice |
| Avoid duplicate active ingredients | Do not take several medicines containing the same active ingredient |
| Maintain hydration | Drink enough fluids unless advised to restrict them |
| Consult healthcare professionals | Ask your doctor or pharmacist before using medicines if you have kidney problems or take several medicines |
Clinical Takeaways and Conclusions
Key Messages from the August 2026 Issue
| Topic | Key Takeaway |
|---|---|
| GLP-1 RAs and NAION | Class-wide safety update; sudden vision loss should prompt urgent ophthalmological examination; absolute risk is low (2–18 additional cases per 100,000 users per year) |
| Iatrogenic botulism | Strengthened warnings for all botulinum toxin type A products; symptoms can occur up to 4 weeks after treatment; patients should seek immediate medical attention if symptoms develop |
| Sertraline and nephrolithiasis | Potential safety signal of kidney stones associated with sertraline use, possibly secondary to drug-induced urinary retention and voiding dysfunction; monitor patients on long-term therapy |
| Ceftriaxone administration error | Adherence to the recommended method of administration is essential to prevent skin necrosis and tissue breakdown |
