During its September 2024 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended measures to minimize the serious consequences of known adverse reactions to the painkiller metamizole and made new recommendations to minimize the risk of meningioma from medications containing medroxyprogesterone acetate.
In addition, the PRAC also formulated new safety information for healthcare professionals (DHPC) for metamizole, medroxyprogesterone, and 5-fluorouracil.
Metamizole
Updated Product Information to Address Agranulocytosis Risks
The PRAC has recommended critical updates to product information regarding metamizole to raise awareness about the risk of agranulocytosis, a serious adverse reaction that can lead to fatal infections. Agranulocytosis is characterized by a significant drop in granulocytes, a type of white blood cell responsible for fighting infections. This condition may arise suddenly and can occur in patients at any point during treatment or shortly after discontinuation, regardless of prior tolerance to metamizole.
Metamizole is widely utilized across several EU nations for the treatment of moderate to severe pain and fever, with its specific uses varying by country—from alleviating pain post-surgery to managing discomfort associated with cancer.
Recognizing the importance of immediate intervention, the PRAC concluded that healthcare providers must be better equipped to detect the early signs of agranulocytosis. This includes being aware of patient-reported symptoms such as fever, chills, sore throat, or painful mouth lesions. Such information will empower both patients and healthcare professionals to act swiftly if these symptoms manifest.
As the only metamizole product authorized in Belgium, Novalgine will be one of the first to reflect these changes in its packaging and product information.
Medroxyprogesterone Acetate
Addressing the Increased Risk of Meningioma
The PRAC highlights an increased concern regarding the risk of developing meningiomas, a type of tumor that forms in the protective membranes of the brain and spinal cord, for patients on high doses of medroxyprogesterone acetate over prolonged periods. This risk is notably elevated in patients receiving doses equal to or exceeding 100 mg, particularly via injection or tablet forms.
Data revealed through epidemiological studies and medical literature cite a significant yet low absolute risk of meningiomas linked to the long-term use of this hormonal treatment. Hence, the EMA encourages healthcare providers to weigh the risk-versus-benefit scenario for patients requiring medroxyprogesterone acetate, especially when treating non-oncological conditions.
Notably, patients with a past history of meningioma or a current diagnosis should avoid high doses of medroxyprogesterone acetate unless absolutely necessary for oncological treatment. If a meningioma is identified during treatment, healthcare providers are advised to reassess the necessity of ongoing high-dose medication use.
Authorized medications in Belgium containing medroxyprogesterone acetate are marketed under various names, including:
- Sayana
- Depo-Provera
- Provera
New Safety Information for Healthcare Professionals
Metamizole: Key Recommendations Regarding Agranulocytosis
The PRAC will disseminate a direct healthcare professional communication (DHPC) to further inform prescribers, dispensers, and administrators of metamizole regarding the severe ramifications of agranulocytosis. This DHPC aims to enhance awareness about the risks and necessary preventative measures associated with this potentially fatal side effect.
Patients already on metamizole should be thoroughly educated on identifying early symptoms of agranulocytosis, such as:
- Fever
- Chills
- Sore throat
- Painful lesions in the mouth, nose, throat, or genital area
Furthermore, those experiencing symptoms or with concurrent antibiotic therapy—where agranulocytosis may present asymptomatically—are advised to seek immediate medical evaluations.
If agranulocytosis is suspected, healthcare providers should act swiftly by conducting a blood count, and treatment must cease until results are determined. A confirmed diagnosis should prevent re-initiation of metamizole therapy.
Medroxyprogesterone: Monitoring for Meningioma Symptoms
The new DHPC regarding medroxyprogesterone acetate reinforces the necessity of patient monitoring for potential meningioma symptoms during treatment, particularly in those on high doses. Symptoms to monitor for include:
- Vision changes
- Hearing issues
- Headaches
- Memory loss
- Weakness in limbs
5-Fluorouracil: Caution in Patients with Renal Impairment
As a cornerstone in cancer treatment protocols, 5-fluorouracil (5-FU) is utilized for diverse malignancies. However, caution is warranted concerning patients with renal impairments and variances in dihydropyrimidine dehydrogenase (DPD) enzyme activity, which governs 5-FU metabolism.
The PRAC approved an additional DHPC highlighting that blood uracil levels, when used to evaluate DPD phenotyping, may be misleading in the context of moderate-to-severe renal impairment, risking potential underdosing of critical treatments.
Healthcare professionals should remain vigilant in their assessments, considering dose adjustments for those found with complete or partial DPD deficiencies, ensuring they are not subject to avoidable toxicity.
| Medication | Indications | Adverse Effects |
|---|---|---|
| Metamizole | Pain & Fever Management | Agranulocytosis |
| Medroxyprogesterone Acetate | Hormonal Therapy | Meningioma |
| 5-Fluorouracil | Cancer Chemotherapy | DPD Deficiency Toxicity |
Once implemented, these DHPCs will be shared proactively with healthcare professionals and made accessible on official channels. Stakeholders can stay informed of numerous developments and updates via the EMA’s official website.
In summary, these significant recommendations aim to prioritize patient safety and ensure that healthcare professionals are equipped with the necessary tools and information to minimize risks associated with these medications.