The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) met from 1-4 September 2025. Their role: monitor the safety of medicines in the EU, assess risk signals, recommend actions, and ensure the benefit/risk of drugs remains favorable.
Here are the key takeaways from the meeting, plus deeper insight into why they matter.
Key Decisions & Updates
Here are the primary safety updates PRAC discussed and the outcomes or next steps:
- Safety Review of Levamisole
- Levamisole is a drug used in some EU countries to treat parasitic worm (helminth) infections in adults and children. European Medicines Agency (EMA)
- New reports have emerged of leukoencephalopathy, a serious neurological condition affecting the brain’s white matter. In at least one reported case, the use of levamisole led to death. European Medicines Agency (EMA)
- PRAC has initiated a full review of levamisole medicines for this risk. The review will examine whether the product information needs updating, or whether regulatory actions (variation, suspension, withdrawal) are warranted. European Medicines Agency (EMA)
- Warning about Caspofungin + Polyacrylonitrile (PAN) Membranes in CRRT
- Caspofungin is an antifungal given by IV infusion for serious fungal infections. European Medicines Agency (EMA)
- Continuous Renal Replacement Therapy (CRRT) uses membranes to filter blood; some of these are made from polyacrylonitrile. Laboratory data suggest that PAN membranes bind caspofungin—i.e., they may reduce its effectiveness. European Medicines Agency (EMA)
- PRAC endorsed a Direct Healthcare Professional Communication (DHPC) warning: in patients undergoing CRRT with PAN membranes, healthcare providers should consider using a different membrane or alternative antifungal. European Medicines Agency (EMA)
- Updated Monitoring Recommendations for Crysvita (burosumab)
- Crysvita is used for treating X-linked hypophosphataemia, among other related bone disorders. European Medicines Agency (EMA)
- Reports included severe hypercalcaemia (very high blood calcium) especially in certain vulnerable patient groups (e.g. those with pre-existing issues like hyperparathyroidism). European Medicines Agency (EMA)
- PRAC recommends blood calcium be measured before treatment starts, and then at 1-2 weeks after starting or dose change, then periodically (every six months in general; more frequent in young children). Also monitor parathyroid hormone levels. European Medicines Agency (EMA)
- Remsima (infliximab) Intravenous Formulation Contraindicated in Hereditary Fructose Intolerance (HFI)
- A new IV formulation of Remsima (a biosimilar to infliximab) contains sorbitol, which is unsafe for people with HFI. Even small amounts of sorbitol IV in people with HFI can lead to severe adverse effects (hypoglycaemia, liver failure, kidney failure, etc.). European Medicines Agency (EMA)
- PRAC recommends that healthcare professionals check for HFI before administering this new form; product info and reminder cards will be updated accordingly. European Medicines Agency (EMA)
- Restriction of Tegretol (carbamazepine 100 mg/5 mL suspension) in Neonates
- The oral suspension contains propylene glycol as an excipient. Neonates (both term and preterm) have immature liver and kidney function, making them less able to eliminate propylene glycol. This raises risk of accumulation and toxicity (metabolic acidosis, renal dysfunction, etc.). European Medicines Agency (EMA)
- PRAC recommends restricting use of this formulation in neonates (below certain ages), unless no alternative is available and expected benefits outweigh risks. Also that monitoring (osmolarity, anion gap, etc.) be done. European Medicines Agency (EMA)
Why These Updates Matter: Broader Impacts
Beyond the specific drug-by-drug news, these topics underscore several broader themes in pharmacovigilance and patient safety.
1. Improved Detection of Rare but Severe Risks
Some of the risks (like leukoencephalopathy from levamisole, or hypercalcaemia from Crysvita) are not everyday side effects. They’re serious, potentially rare, and they may only emerge with long-term real-world use or in particular patient sub-groups. The fact that PRAC is hitting them early means better protection for patients.
2. The Importance of Monitoring and Managing Excipient Risks
We tend to focus on active ingredients, but excipients (sorbitol, propylene glycol, membrane materials) can have serious effects—especially in vulnerable populations (neonates, patients with metabolic or renal issues). These updates reinforce that excipients are not always inert or “just fillers.”
3. Communication & Guidance for Healthcare Professionals
When PRAC endorses DHPCs (direct communications), that’s critical. It means doctors, nurses, pharmacists across the EU will get clear guidance about what to do differently right away (e.g. selecting different membranes, adjusting monitoring schedules). Good risk mitigation depends on this.
4. Benefit-Risk Balances Are Dynamic
A medicine’s safety profile is not “locked in” at the time of approval. As more data (post-market, from literature, spontaneous reports) accumulate, benefit-risk can shift—sometimes a small risk emerges that changes how a drug is used, who gets it, or what monitoring is required. These PRAC actions show how regulators adapt to new evidence.
5. Patient-Specific Considerations
Several of the updates emphasize that not all patients are the same. For example:
- Neonates have different physiology and risk than older children/adults.
- Patients with hereditary conditions (like HFI) may respond differently.
- Comorbidities (renal impairment, hyperparathyroidism, etc.) can magnify risk.
Additional Thoughts & Context
Here are some extra points that help understand the full picture.
- Levamisole History: Levamisole is not a newcomer; the drug has been in use for decades. It has a known history of neurological adverse effects, including reports of leukoencephalopathy. However, recent data triggered more concern and prompted a focused review. This shows continuous safety monitoring works—even for older, “well-known” medicines. European Medicines Agency (EMA)
- Clinical Impact in ICU Settings: The caspofungin + PAN membrane issue is especially relevant in the ICU. Critically ill patients often depend on CRRT; if an antifungal is less effective because of membrane binding, infections could worsen. That has real mortality implications.
- Regulatory Harmonization and Label Updates: For many of these actions, the medical product’s label (product information) or package insert will need updating. Healthcare providers across different EU Member States will need to adapt practices—monitoring schedules, pre-treatment screening, etc.
- Implementation Challenges: Some of the recommendations require infrastructure: ability to measure calcium/PTH levels, availability of alternative membranes or formulations, clinician awareness. In some regions, lab or healthcare access constraints might slow adoption.
- International Relevance: Even if you are outside the EU, many drugs used globally are the same or similar. Regulatory decisions in the EU often influence policy elsewhere or prompt local regulators to reevaluate their own data.
What Healthcare Professionals & Patients Should Do
If you’re a doctor, pharmacist, or patient, here’s what to watch out for or act upon:
- For levamisole: Be alert for neurological symptoms in patients taking this drug; consider warning patients to report symptoms like confusion, weakness, speech/vision impairment. Monitor literature or regulatory updates for whether medicine is suspended or label changed.
- For caspofungin + CRRT: If you treat critically ill patients on CRRT, check the type of membrane used. If it’s PAN, consider switching or using alternative antifungals. Monitor therapeutic outcomes.
- For Crysvita: If prescribing for bone disorders, set up baseline calcium and PTH measurements. After dosing or adjusting, monitor more frequently. Be extra careful in children and patients with risk factors (like renal impairment, hyperparathyroidism).
- For Remsima IV formulation: Screen for hereditary fructose intolerance before using the new IV form. Ensure patients (or their caregivers) are aware of this risk.
- For Tegretol suspension in neonates: Use alternative formulations if possible; avoid use in very young neonates when there are safer alternatives. Monitor for signs of toxicity if use is unavoidable.
- Across all cases: stay current with updates to product labels / regulatory communications; check for DHPCs; ensure your prescribing and patient counseling reflects the latest risk recommendations.
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