The World Health Organization (WHO) Pharmaceuticals Newsletter No. 1, 2026, provides a critical compilation of regulatory safety information on medicinal products from national pharmacovigilance centres worldwide and the WHO Advisory Committee on Safety of Medicinal Products (ACSoMP). This article presents a detailed summary of recent safety findings, regulatory actions, and emerging safety signals for a wide range of medicinal products, including antineoplastics, vaccines, antidiabetics, and others.
Key topics include new adverse reactions for bosutinib, bortezomib, and cefazolin; updated warnings for GLP-1 receptor agonists regarding pancreatitis, NAION, and altered skin sensations; removal of suicidal ideation warnings for GLP-1 RAs; restrictions on chikungunya vaccine in older adults; and ACSoMP recommendations on paracetamol in pregnancy, topiramate teratogenicity, and NAION as a potential safety signal.
1. Introduction
The WHO Pharmaceuticals Newsletter is a periodic publication that disseminates regulatory information on the safety of medicinal products. It is based on communications received from WHO’s network of national pharmacovigilance centres, specialized bulletins, journals, and partners. Issue No. 1 of 2026 includes a wide range of safety updates from regulatory authorities across Europe, the Americas, Asia, and the Middle East, as well as a feature summary of the twenty-fourth meeting of the WHO Advisory Committee on Safety of Medicinal Products (ACSoMP), held in November 2025.
2. Regulatory Matters: Key Safety Updates by Drug
2.1 Bosutinib – Risk of Cutaneous Vasculitis (Europe)
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended updating the product information for bosutinib (Bosulif®), a tyrosine kinase inhibitor used in chronic myelogenous leukaemia, to include cutaneous vasculitis as an adverse reaction. The condition is considered “uncommon” (affecting up to 1 in 100 people), manifesting as skin rash or bruising. Patients should be advised to contact their doctor if these symptoms occur.
2.2 Bortezomib – Risk of DRESS (Canada)
Health Canada reviewed 29 international cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients treated with bortezomib, an antineoplastic for multiple myeloma and mantle cell lymphoma. While confounders existed, 27 cases were possibly linked to bortezomib, including one death. The product safety information will be updated accordingly.
2.3 Carbidopa/Levodopa – Vitamin B6 Deficiency and Seizures (USA)
The FDA requires a new warning for all carbidopa/levodopa products (Sinemet, Duopa, Rytary, Vyalev). A safety review identified 14 cases of seizures linked to vitamin B6 deficiency, including focal onset and status epilepticus. High levodopa doses (>1,000 mg daily) deplete vitamin B6; carbidopa exacerbates functional loss. Clinicians should evaluate baseline vitamin B6 levels and supplement as needed. Seizures may not respond to standard anticonvulsants but often resolve with vitamin B6.
2.4 Carbimazole – Risk of Agranulocytosis (India)
India’s CDSCO and IPC have requested that carbimazole prescribing information be updated to include agranulocytosis as a serious adverse reaction, based on ICSR assessments from the National Coordination Centre for Pharmacovigilance.
2.5 Cefazolin – Kounis Syndrome (Europe)
PRAC has requested MAHs to update cefazolin product information to add Kounis syndrome – cardiovascular symptoms secondary to an allergic/hypersensitive reaction causing coronary artery constriction, potentially leading to myocardial infarction. Patients should stop the drug immediately if they experience breathing problems or chest pain.
2.6 Cetirizine and Levocetirizine – Severe Itching After Discontinuation (Pakistan)
Following a US FDA warning, Pakistan’s DRAP has issued a safety alert regarding severe pruritus after stopping long-term use of these antihistamines. The itching typically occurs within days of discontinuation after months or years of daily use, in patients without prior such symptoms. Healthcare professionals should discuss this risk with patients using these drugs chronically.
2.7 Chikungunya Vaccine (Live Attenuated) – Aseptic Meningitis and Restrictions
Europe (EMA): PRAC updated product information to include aseptic meningitis, observed in young adults, as a known adverse effect. Previously, reports predominantly involved elderly or multimorbid patients.
United Kingdom (MHRA): Additional restrictions introduced: vaccine no longer recommended for adults aged ≥60 years; contraindicated in individuals of any age with hypertension, cardiovascular disease, diabetes mellitus, or chronic kidney disease. A comprehensive benefit-risk assessment must be conducted before vaccination.
2.8 Colchicine – Drug-Drug Interactions (Japan)
Japan’s MHLW/PMDA updated colchicine product information to include a contraindication for patients with renal or hepatic impairment who are also taking strong CYP3A4 inhibitors (e.g., clarithromycin, ritonavir) or P-glycoprotein inhibitors (e.g., cyclosporine). Concomitant use significantly increases colchicine plasma concentration, leading to severe toxicity including pancytopenia.
2.9 Cytarabine – Palmar-Plantar Erythrodysesthesia (Saudi Arabia)
The SFDA requested that cytarabine SmPC be updated to include palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome). A signal review identified 224 local and global case reports; causality assessment of 25 high-completeness cases found 20 possibly linked.
2.10 Datopotamab Deruxtecan – Anaphylactic Reaction (Europe)
PRAC recommended updating product information to include anaphylactic reaction as a potential adverse effect. Serious allergic reactions can be life-threatening; infusion must be discontinued immediately if anaphylaxis occurs.
2.11 Dimethyl Fumarate – Gastrointestinal Events (Canada)
Health Canada updated the Canadian Product Monograph to include warnings for gastrointestinal perforation, ulceration, haemorrhage, and obstruction. A safety review of 22 international cases found 18 possibly linked to the drug.
2.12 Empagliflozin – Fournier’s Gangrene Without Diabetes (New Zealand)
Medsafe updated safety information to warn of Fournier’s gangrene (necrotising fasciitis of the perineum) in patients without type 2 diabetes. As of December 2025, 44 case reports were associated with empagliflozin, two in patients with heart failure. Patients should seek urgent medical attention for genital/perineal pain, redness, or swelling with fever.
2.13 Epcoritamab – Hypogammaglobulinemia (Europe)
PRAC recommended that epcoritamab (Tepkinly®) product information list hypogammaglobulinemia as a “very common” adverse reaction (>1 in 10 patients). Immunoglobulin levels should be monitored before and during treatment.
2.14 Erdafitinib – Growth Acceleration and Epiphysiolysis (Europe)
PRAC requested that erdafitinib (Balversa®) product information include growth acceleration and epiphysiolysis of the femoral head as undesirable effects, observed in off-label paediatric use. Paediatric patients receiving the drug (outside authorised indication) may experience accelerated growth or irregular hip joint growth/damage.
2.15 Ferzolinetant – Drug-Induced Liver Injury (Ireland)
The HPRA announced that ferzolinetant (Veoza®) product information has been updated to include drug-induced liver injury. Liver function tests must be performed prior to initiation and monitored regularly, especially during the first three months. The drug should not be started if baseline liver enzymes exceed specified levels.
2.16 GLP-1 Receptor Agonists and Dual GIP/GLP-1 Agonists – Multiple Safety Updates
2.16.1 Removal of Suicidal Ideation Warnings (USA)
The FDA requested removal of warnings regarding suicidal ideation and behaviour from GLP-1 RA labels (liraglutide, semaglutide, tirzepatide). A comprehensive review (91 placebo-controlled trials, 107,910 patients) found no increased risk. A retrospective cohort study of over 2 million patients also showed no increased risk of intentional self-harm compared to SGLT2 inhibitors.
2.16.2 Alignment of Warnings (Australia)
The TGA aligned product warnings across the GLP-1 RA class. While evidence does not support a causal association with suicidal behaviours, harmonised wording now advises monitoring patients for emergence or worsening of depression and suicidal thoughts.
2.16.3 Severe Acute Pancreatitis (UK)
The MHRA updated product information to include rare reports of necrotising and fatal pancreatitis. Between 2007 and October 2025, the MHRA received 1,296 Yellow Card reports of various forms of pancreatitis, including 24 necrotising and 19 fatal cases. If pancreatitis is suspected, treatment should be discontinued immediately and not restarted if confirmed.
2.16.4 Altered Skin Sensations (New Zealand)
Medsafe highlighted that GLP-1 agonists (semaglutide, tirzepatide) are associated with dysaesthesia and allodynia. In clinical trials, altered skin sensations were reported in 2.1% of semaglutide patients vs. 1.2% placebo. Healthcare professionals should consider these medications as a possible cause of abnormal skin sensitivity.
2.16.5 Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) – Semaglutide (UK)
The MHRA announced that semaglutide product information will include NAION as a risk. A European review suggested approximately a two-fold increase in relative risk, corresponding to roughly one additional case per 100,000 treated patients per year. Patients experiencing sudden vision loss should be referred urgently to an ophthalmologist.
2.16.6 Reduced Effectiveness of Oral Contraceptives – Tirzepatide (Australia)
The TGA updated tirzepatide product information to advise patients using oral hormonal contraceptives to switch to non-oral methods or add a barrier method during treatment initiation and dose escalation phases. At least one case report of pregnancy while on oral contraceptives has been received.
2.17 Idecabtagene Vicleucel – Progressive Multifocal Leukoencephalopathy (Japan)
MHLW/PMDA revised the package insert to include PML as a clinically significant adverse reaction. Healthcare professionals should monitor for new or worsening neurological symptoms and perform CSF testing and MRI if PML is suspected.
2.18 Isotretinoin – Updated Prescribing Guidance (UK) and Sacroiliitis (Canada)
United Kingdom: The requirement for a second independent prescriber for patients under 18 has been removed to reduce treatment delays. Alternative measures include an updated “acknowledgement of risk” form, a mandatory clinical audit (2026), and a patient information video. Monitoring for mental health and sexual function adverse effects remains essential.
Canada: Health Canada updated isotretinoin product information to include sacroiliitis as a potential adverse reaction. Healthcare professionals should be alert to back pain or joint stiffness.
2.19 Levamisole – Withdrawal from EU Market (Europe)
PRAC recommended that all levamisole-containing medicines be removed from the EU market due to the risk of leukoencephalopathy, a rare but devastating brain condition that may occur after a single dose, with onset from one day to several months after treatment.
2.20 Lubiprostone – Ischemic Colitis and Anaphylaxis (Japan)
MHLW/PMDA updated the package insert to include ischemic colitis and anaphylaxis. Patients should discontinue the drug and seek medical attention if they experience severe abdominal pain, bloody stools, or hypersensitivity symptoms.
2.21 Pegylated Liposomal Doxorubicin – Renal-Limited Thrombotic Microangiopathy (Europe)
PRAC requested MAHs to amend product information to include renal-limited thrombotic microangiopathy (clogging of very small blood vessels in the kidneys) as an adverse effect, based on case reports from EudraVigilance and literature.
2.22 Triazolam – Contraindication with Ceritinib (Japan)
Triazolam is now contraindicated for co-administration with ceritinib, as ceritinib inhibits CYP3A4 metabolism of triazolam, significantly increasing its blood concentrations and sedative effects.
2.23 Vitamin B6 – Peripheral Neuropathy Risk (Australia)
The TGA reclassified products providing >100 mg of vitamin B6 daily as pharmacist-only medicines. All products containing >10 mg of vitamin B6 must include a prominent warning about peripheral neuropathy. The TGA has recorded 250 reports of neuropathy associated with vitamin B6, occurring even at daily doses <50 mg.
2.24 Zoledronic Acid – Use in Elderly Patients (New Zealand)
Medsafe issued a clinical reminder that elderly patients (≥65 years) are at increased risk of acute phase reactions (fever, myalgia, arthralgia occurring within three days of infusion) and renal impairment. Adequate hydration and renal function assessment before each dose are essential.
3. Safety of Medicinal Products: Emerging Signals
3.1 Atomoxetine – Risk of Gynaecomastia (New Zealand)
Medsafe is investigating the risk of gynaecomastia (male breast enlargement) with atomoxetine, an ADHD medication. A case report of a 36-year-old male following dose increase prompted the investigation. Gynaecomastia is not currently listed in the product information, and Medsafe has placed the concern on its Medicines Monitoring scheme.
3.2 Dulaglutide – Sleep Disorders (Saudi Arabia)
The SFDA identified a safety signal for sleep disorders associated with dulaglutide. A review identified 104 global ICSRs; causality assessment found one case “probably” linked and two “possibly” linked. The SFDA is evaluating regulatory actions.
3.3 GLP-1 Analogues – Reminder of Safety Aspects (Ireland)
The HPRA issued a reminder regarding:
- NAION with semaglutide: advise patients to seek immediate ophthalmological examination for sudden vision changes.
- Aspiration risk during anaesthesia due to delayed gastric emptying.
- Acute pancreatitis: discontinue treatment if suspected.
- Pregnancy: GLP-1 analogues are generally not recommended or contraindicated during pregnancy.
3.4 Liraglutide – Hepatocellular Carcinoma Signal (Saudi Arabia)
The SFDA posted an alert for a safety signal of hepatocellular carcinoma (HCC) associated with liraglutide. A review identified 29 global ICSRs; three cases showed a possible association. One published study supported a possible link. The SFDA is evaluating regulatory actions.
3.5 Onasemnogene Abeparvovec – Pneumonia (Saudi Arabia)
The SFDA identified a safety signal for pneumonia associated with this gene therapy for spinal muscular atrophy. A review identified 97 global case reports; 14 of 19 high-completeness cases were possibly linked. Healthcare professionals should remain vigilant for signs of pneumonia.
4. Feature: Summary of Recommendations from the 24th ACSoMP Meeting (November 2025)
The WHO Advisory Committee on Safety of Medicinal Products (ACSoMP) held its twenty-fourth meeting in November 2025. Key discussions and recommendations are summarised below.
4.1 Moxidectin – Treatment of Onchocerciasis
The Committee reviewed safety data for moxidectin, used for onchocerciasis (river blindness). It recommended establishing pregnancy exposure registries or leveraging existing registries to follow up moxidectin exposures and pregnancy outcomes. Research needs include repeated annual dosing safety, pregnancy and lactation outcomes, drug-drug interactions with other neglected tropical disease medicines, and safety in vulnerable groups (children, elderly).
4.2 Paracetamol During Pregnancy and Potential Association with Autism in Offspring
ACSoMP reviewed WHO’s approach to evaluating the possible association between paracetamol use in pregnancy and autism spectrum disorder (ASD) and attention deficit-hyperactivity disorder (ADHD). Key conclusions:
- No robust evidence supports a causal link between paracetamol use in pregnancy and ASD/ADHD.
- Existing studies have methodological limitations; many are of poor quality and not conducted according to accepted scientific standards for pharmacoepidemiology.
- The risks of untreated pain and fever in pregnancy must be considered.
- Alternative analgesics (NSAIDs, opioids) have known serious risks for the fetus and neonate.
- Communications must clearly explain the rarity and uncertainty, emphasising that pregnant women should not be driven towards more dangerous alternatives.
- WHO was encouraged to perform a living systematic review with clearly defined PICO questions addressing timing, dose, duration, and frequency of exposure.
- Robust post-marketing surveillance for medicines used in pregnancy and breastfeeding is essential.
4.3 Teratogenic Concerns of Topiramate and Updates on Sodium Valproate
ACSoMP reviewed whether maternal topiramate use justifies a unique ICD-11 classification for neurodevelopmental disorders. While topiramate is associated with increased risk of oral clefts, evidence for neurodevelopmental disorders remains conflicting and less robust than for valproate. The Committee does not recommend proceeding with ICD coding for topiramate-related neurodevelopmental disorders at this point, as evidence is insufficient and inconclusive. Monitoring should continue.
4.4 Adverse Drug Reactions Causality Assessment
ACSoMP discussed the development of a standardised methodology for causality assessment that integrates assessment of adverse reactions, medication errors, and substandard or falsified products. Members expressed broad interest but noted challenges: obtaining detailed data may be difficult due to data-privacy laws, and the tool must be appropriate for countries of all socioeconomic statuses.
4.5 Safety Surveillance of Lenacapavir and Cabotegravir in Pregnant and Breastfeeding Women
Current safety data for long-acting cabotegravir and lenacapavir as PrEP are reassuring, but more data are needed to detect rare adverse birth outcomes. ACSoMP recommended:
- Post-marketing surveillance in pregnancy, including pregnancy exposure registries in high-prevalence settings.
- Reporting of pregnancy exposures to the Antiretroviral Pregnancy Registry.
- Longer-term follow-up of infants exposed in utero.
- Risk minimisation efforts for inappropriate administration or incorrect dosing schedules (given the long half-life of these medicines) – the WHO database VigiBase contains reports indicating these risks.
- Increased collaboration between WHO teams to support maternal and newborn health safety monitoring.
4.6 NAION as a Potential Class Effect of GLP-1 Receptor Agonists
ACSoMP confirmed that NAION is a safety signal driven primarily by semaglutide data; a class effect among all GLP-1 RAs cannot yet be determined. The association with semaglutide cannot be ruled out despite lack of a plausible biological mechanism. Key recommendations:
- Clear communication must be integrated into the rollout campaign accompanying the WHO guideline on GLP-1 therapies for obesity, including warnings on counterfeit use and misuse.
- Messaging must explain the rarity and potential irreversibility of NAION, encourage patients to report sudden vision changes promptly, and reinforce shared decision-making.
- Research must address evidence gaps: mechanistic studies, stratified analyses to identify at-risk populations, and improved case detection in specialised databases.
- It is currently unknown whether stopping the medicine prevents progression of NAION.
5. Call for Submissions
WHO invites national medical products regulatory authorities to submit the latest information on safety and regulatory actions on medicinal products from their countries. Short reports on pharmacovigilance events or achievements are also welcome. Submissions should be sent to pvsupport@who.int.
6. Conclusion
The WHO Pharmaceuticals Newsletter No. 1, 2026, provides a wealth of critical safety information for healthcare professionals and regulators. Key themes include:
- Increased vigilance for cardiovascular and hypersensitivity reactions (cefazolin, bosutinib, bortezomib).
- Expanding safety profiles of GLP-1 receptor agonists, including pancreatitis, NAION, altered skin sensations, and potential drug interactions with oral contraceptives, while removing unsupported warnings (suicidal ideation).
- Specific safety concerns for vulnerable populations: elderly (zoledronic acid), children (chikungunya vaccine restrictions, erdafitinib growth effects), pregnant women (paracetamol, topiramate, lenacapavir/cabotegravir).
- Ongoing monitoring of rare but serious events such as Fournier’s gangrene (empagliflozin), PML (idecabtagene vicleucel), and leukoencephalopathy (levamisole).
- ACSoMP’s critical guidance on paracetamol in pregnancy (no robust causal link to ASD/ADHD), topiramate (no ICD code for neurodevelopmental disorders yet), and NAION (signal driven by semaglutide).
