The Egyptian Pharmacovigilance Center (EPVC) Newsletter, May 2026 edition, presents critical safety information for healthcare professionals, including a major regulatory update on xylometazoline and oxymetazoline nasal decongestants, and a detailed local case safety report documenting severe neurotoxicity following colistimethate sodium administration in a patient with significant renal impairment.
Drug Safety Update – Xylometazoline / Oxymetazoline: Increased Risk of Rebound Congestion, Rhinitis Medicamentosa, and Tachyphylaxis with Overuse
1.1 Background and Therapeutic Context
Xylometazoline and oxymetazoline are sympathomimetic nasal decongestant sprays and drops used for the symptomatic relief of nasal and sinus congestion associated with the common cold, sinusitis, and allergic rhinitis in adults and children 6 years and above. They are also used for the treatment of flu symptoms in adults and children 12 years and above. These products are widely available over the counter from shops and pharmacies.
Xylometazoline is approved for use as a single active substance or in fixed-dose combinations with dexpanthenol and ipratropium bromide. Oxymetazoline is approved as a single active substance only.
1.2 The Safety Concern: Defining the Three Conditions
Reports of rebound congestion, rhinitis medicamentosa, and tachyphylaxis – especially with prolonged or extended use – prompted a formal safety review by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). The review was assessed by the Cardiovascular, Respiratory, Renal and Allergy Expert Advisory Group (CDRRA EAG) and the Pharmacovigilance Expert Advisory Group (PEAG) of the Commission on Human Medicines (CHM).
The three conditions are defined as follows:
| Condition | Description |
|---|---|
| Rebound Congestion | A temporary response in which nasal passages become more congested after the medication wears off, typically occurring with use beyond the recommended duration |
| Rhinitis Medicamentosa | The most serious of the three conditions. A chronic condition developing through prolonged use, characterised by severe nasal congestion with visible changes to the nasal mucosa and internal nasal structures. In severe, untreated cases, irreversible structural changes may require surgical intervention |
| Tachyphylaxis | An acute, rapid decrease in response to the drug after repeated administration, leading to rapid-onset tolerance. Effects become apparent after more than 5 days of continuous use, causing users to increase frequency and/or duration to achieve relief |
1.2.1 Pathophysiology of Rebound Congestion and Rhinitis Medicamentosa
Rhinitis medicamentosa (RM) is a drug-induced form of nonallergic rhinitis caused by prolonged or inappropriate use of topical nasal decongestants. Although these medications are effective in the short term, prolonged use can worsen nasal obstruction, cause mucosal oedema, and lead to dependence.
Mechanism: The pathophysiology of RM is complex and incompletely understood, but several mechanisms have been proposed:
Histological findings: The nasal mucosa in RM typically shows ciliary loss, damaged epithelium, infiltration of inflammatory cells, and oedema. The nasal mucosa may appear swollen and erythematous, with punctate bleeding and minimal mucus production.
1.3 Regulatory Action: Maximum Duration of Use Reduced
Following the safety review, the MHRA recommended the following updates to the Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL), and outer package labelling:
The MHRA advises that these medicines remain safe and effective when used as directed, and that packaging and patient information will be transitioning over the coming months to reflect the revised advice.
1.4 Literature and Evidence Supporting the Change
A study published in the BMJ (2026) reported that the MHRA updated its advice to clinicians and patients in response to recommendations from an expert advisory group saying that prolonged use of these sprays can lead to adverse side effects.
The MHRA noted that excessive use of the sprays can cause rebound congestion, a temporary swelling inside the nose that can lead to the chronic condition rhinitis medicamentosa, which causes severe nasal congestion and damage to tissues.
1.5 Key Messages for Patients and Healthcare Professionals
For Healthcare Professionals
For Patients
| Recommendation | Action |
|---|---|
| Short-term use | Only use these medicines for a short time (no more than 5 consecutive days) |
| Dose compliance | Do not exceed the daily recommended dose or minimum dosing interval |
| Recognising rebound | If the nose becomes blocked again after the medicine wears off, or other symptoms appear (runny nose, sneezing, itching), this may be a rebound effect—talk to a healthcare professional |
| Avoid combination use | Do not use xylometazoline or oxymetazoline together or with other oral/nasal decongestants |
| Seek medical advice | Contact a doctor if symptoms worsen or do not improve after 5 days |
1.6 Clinical Pearls on Rhinitis Medicamentosa Management
Effective management of rhinitis medicamentosa requires:
- Timely identification – Early recognition is crucial to prevent irreversible damage
- Patient education – Patients must understand the rebound phenomenon and the importance of discontinuation
- Discontinuation of the offending agent – The cornerstone of treatment
- Adjunctive therapies – Intranasal and oral corticosteroids can help reduce inflammation and speed recovery
Prognosis: With early recognition and treatment, patients typically recover within 3 months. In severe, untreated cases, irreversible structural changes may require surgical intervention. Stopping the nasal decongestant is the first-line treatment for RM. If necessary, intranasal glucocorticosteroids should be used to speed recovery.
Local Case Safety Report – Neurotoxicity After Usage of Colistimethate Sodium
2.1 Case Summary
The regional pharmacovigilance centre in Cairo received a case report involving a 45-year-old female patient with a history of recurrent urinary tract infections (UTIs) and cystitis. Her medical history was significant for a left nephrectomy performed 12 years prior due to left renal atrophy. Over the past six months, her UTIs persisted despite multiple courses of various antibiotics, prompting her physician to order a urine culture and prescribe intravenous colistimethate sodium.
Following the administration of a single 9 million IU loading dose, the patient acutely developed severe neurotoxicity characterised by:
- Numbness in her lips, tongue, face, hands, and feet
- Dyspnoea
- Sudden inability to stand or walk
This adverse drug reaction required an extended hospital stay; however, the patient fully recovered after the medication was permanently discontinued.
2.2 Background: Colistimethate Sodium
Colistimethate sodium is a polymyxin antibiotic indicated for the management of acute and chronic infections caused by susceptible strains of specific Gram-negative bacilli, particularly infections associated with sensitive strains of Pseudomonas aeruginosa. Parenteral colistimethate may be initiated in severe infections suspected to result from Gram-negative organisms and may also be utilised for the treatment of infections caused by susceptible Gram-negative pathogenic bacilli.
The Revival of Colistin: The increasing prevalence of multi-drug-resistant (MDR) Gram-negative pathogens in intensive care units and the shortage of new antibiotics have led to the re-evaluation of colistin. Colistin had gone into disrepute in the early 1970s because of numerous reports of adverse renal and neurological effects. The renewed interest in colistin has also revived the discussion about its toxicity.
2.3 Mechanism of Action
Colistin is a multicomponent polypeptide antibiotic comprised of colistins A and B.
Primary Mechanism: The initial interaction of colistin with the bacterial membrane is mediated by electrostatic attraction between the cationic polypeptide structure of colistin and the anionic lipopolysaccharides present in the outer membrane of Gram-negative bacteria. This interaction disrupts membrane integrity, increases cell envelope permeability, and results in leakage of intracellular contents, ultimately leading to bacterial cell death.
Alternative Mechanisms: Intracellular activity whereby colistin may induce precipitation of ribosomes and other cytoplasmic constituents has also been proposed. Nevertheless, the precise mechanism of action has not been fully elucidated and remains incompletely understood.
2.4 Mechanism of Neurotoxicity
The neurotoxic effects of colistin are believed to result from non-competitive presynaptic neuromuscular blockade leading to inhibition of acetylcholine release. This can result in:
| Manifestation | Description |
|---|---|
| Paresthesias | Facial and peripheral numbness, tingling |
| Muscle weakness | Including respiratory muscle weakness |
| Ataxia | Loss of coordination |
| Confusion/psychotic reactions | Altered mental status |
| Seizures | In severe cases |
| Neuromuscular blockade | Can lead to apnea and acute respiratory failure |
Key Point: Neurotoxicity has been reported more frequently in females and in patients with renal impairment or Myasthenia gravis.
2.5 Risk Factors and Literature Findings
2.5.1 Renal Impairment: The Most Significant Risk Factor
Colistin (administered as colistimethate sodium, CMS) is primarily eliminated via renal excretion. In patients with impaired renal function, maintaining efficacy while reducing nephrotoxicity requires:
- Individualised dose reduction
- Prolonged dosing intervals
- Where available, therapeutic drug monitoring
Evidence from the literature:
- A study comparing polymyxin B with colistimethate sodium (CMS) found that among 147 patients included in neurotoxicity analysis, 13 of 77 patients with polymyxin B and 1 of 70 with CMS had neurotoxic adverse events, mainly paresthesias. All events were reversible after drug discontinuation.
- Among 290 patients included in nephrotoxicity analysis, the incidence of acute kidney injury (AKI) was 44.7% and 40.0% for polymyxin B and CMS, respectively. AKI was reversible in 91.6% of patients with CMS and 79% with polymyxin B after drug withdrawal.
- Older age, higher baseline serum creatinine, and the use of at least two nephrotoxic drugs were independent factors associated with AKI.
2.5.2 Published Case Reports
| Case | Details |
| Seizures in a patient on haemodialysis | 47-year-old hypertensive female with CKD-5 on colistimethate sodium 1 million units IV once daily developed paresthesias and seizures on the 12th day of therapy |
| Acute respiratory failure | 31-year-old female with paraplegia developed acute respiratory failure requiring mechanical ventilation 6 days after initiation of IV colistimethate; extubated within 24 hours of discontinuation |
| Paediatric fatality | A previously well 4-year-old child died following administration of ten times the recommended dosage of colistimethate sodium |
2.5.3 Reported Neurological Manifestations
According to the literature, the most frequently reported adverse effects associated with colistin therapy are nephrotoxicity and neurotoxicity. Neurological manifestations may include:
2.6 Labelled Information
According to the Summary of Product Characteristics (SmPC), the risk of neurotoxicity is addressed under several sections:
Section 4.4: Special Warnings and Precautions for Use
- Elevated serum concentrations of colistimethate sodium, which may occur due to overdose or failure to appropriately adjust the dose in patients with renal impairment, have been associated with neurotoxic reactions including facial paresthesia, muscle weakness, vertigo, slurred speech, vasomotor instability, visual disturbances, confusion, psychotic reactions, and apnea.
- Patients should be carefully monitored for signs of overdose, particularly perioral and peripheral paresthesia.
- Renal impairment may increase the risk of apnea and neuromuscular blockade.
- The concomitant administration of intravenous colistimethate sodium with agents known to possess nephrotoxic or neurotoxic potential should be approached with extreme caution. Concurrent use with other neurotoxic and/or nephrotoxic medicinal products, especially aminoglycosides such as Gentamicin, Amikacin, Netilmicin, and Tobramycin, should preferably be avoided.
Section 4.7: Effects on Ability to Drive and Use Machines
- Parenteral administration of colistimethate sodium may result in neurotoxic effects such as dizziness, confusion, and visual disturbances. Patients should therefore be advised not to drive or operate machinery if such symptoms occur.
Section 4.8: Undesirable Effects
- Neurological adverse events have been reported in up to 27% of patients with Cystic fibrosis receiving colistimethate sodium. These reactions are generally mild in severity and usually resolve during treatment or shortly after discontinuation.
2.7 Clinical Implications and Recommendations for Healthcare Professionals
EPVC Tips – “Right Medicine, Right Patient, Right Dose, Right Duration”
The EPVC newsletter emphasises that overuse of medicines can increase the risk of adverse drug reactions, drug resistance, dependence, and treatment failure.
4.1 For Healthcare Professionals
| Recommendation | Action |
|---|---|
| Clinical indication | Use medicines only when clinically indicated |
| Dose and duration | Follow the recommended dose and duration |
| Avoid unnecessary use | Avoid unnecessary antibiotics, painkillers, and supplements |
| Patient education | Educate patients not to self-medicate or share medicines |
| Prescription monitoring | Monitor repeated prescriptions for signs of misuse or duplication |
| ADR reporting | Report suspected adverse reactions or medication overuse issues |
“By working together, we can ensure medications remain safe and effective tools for improving health.”
Call for ADR Reporting
5.1 Why Your Report Matters
The EPVC newsletter emphasises that every report counts when it comes to the safety of medicines and patients worldwide.
5.2 How to Report in Egypt
Healthcare professionals and patients can report adverse drug reactions to the Egyptian Drug Authority (EDA) through multiple channels:
| Method | Contact Information |
|---|---|
| pv.followup@edaegypt.gov.eg | |
| Hotline | 15301 |
| Fax | +202-23610497 |
| Address | 21 Abd El Aziz AlSoud Street, El-Manial, Cairo, Egypt, PO Box: 11451 |
| Online reporting | EDA website |
| Alternative | Report through your pharmacy, product distributor, or company hotline—they are required to forward it to EDA |
5.3 Additional Resources
| Resource | Access |
|---|---|
| EDA website | All medicine-related news, updates, and alerts |
| EPVC Newsletters and DHPCs | Available on EDA website |
| Alerts regarding counterfeit/falsified products | Released by Central Administration of Operations |
References
- Egyptian Pharmacovigilance Center. EPVC Newsletter, Issue 196. Cairo: Egyptian Drug Authority; May 2026.
- Medicines and Healthcare Products Regulatory Agency (UK). Recommended use of some nasal decongestant sprays limited to five days by UK regulator. London: MHRA; 30 April 2026.
- Medicines and Healthcare Products Regulatory Agency (UK). Drug Safety Update – April 2026. London: MHRA; 2026.
- BMJ. Limit use of nasal decongestant sprays to five days, UK regulator says. BMJ 2026;393:s849.
- British Society for Allergy and Clinical Immunology (BSACI). Recommended use of some nasal decongestant sprays limited to five days by UK regulator. 2026.
- StatPearls. Rhinitis Medicamentosa. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026.
- Aysert-Yildiz P, et al. Polymyxin B vs. colistin: the comparison of neurotoxic and nephrotoxic effects of the two polymyxins. BMC Infect Dis. 2024;24(1):862.
- Convulsions in a critically ill patient on hemodialysis: Possible role of low dose colistin. J Anaesthesiol Clin Pharmacol. 2014;30(3):415-418.
- Intravenous colistin-induced acute respiratory failure: A case report and a review of literature. Int J Crit Illn Inj Sci. 2014;4(3):266-270.
- PAGB statement on nasal decongestant sprays updated guidance. PAGB; 30 April 2026.
