This Friday, I write about two concepts in Pharmacovigilance.

Even if its a short to the point kind of article, these two concepts are important to understand for all PVG professionals and patients who take these medications alike.

Without further ado, lets jump right in!

Black box warning:

• A warning that appears on a prescription drug’s label and is designed to call attention to serious or life-threatening risks
• In the U.S., boxed warnings are ordinarily used to highlighted for prescribers one of the following situations:
• There is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life threatening or permanently disabling adverse reaction) that it is essential it be considered in assessing the risks and benefits of using the drug.
• There is a serious adverse reaction that can be prevented or reduced in severity by appropriate use of the drug (e.g., patient selection, careful monitoring, avoid certain concomitant therapy, addition of another drug or managing patient in a specific manner, avoiding use in a specific clinical situation)
• FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted.
• Infrequently, a boxed warning can also be used in other situations to highlight warning information that is especially important to the prescriber (e.g., reduced effectiveness in certain patient populations).

Inverted black triangle in the EU:

• In the European Union (EU), medicines that are being monitored particularly closely by regulatory authorities are labelled with a black inverted triangle (▼) in the product information.
• These medicines are described as being under ‘additional monitoring.’
• The European Medicines Agency (EMA) maintains a list of all medicines that are under additional monitoring in the EU.
• Medicines under additional monitoring have a black inverted triangle displayed in their package leaflet and in the information for healthcare professionals called the summary of product characteristics, together with a short sentence explaining what the triangle means.
• Additional monitoring icon: This medicinal product is subject to additional monitoring.
• The symbol does not appear on the outer packaging or labelling of medicines.
• Additional monitoring aims to enhance reporting of suspected adverse drug reactions for medicines for which the clinical evidence base is less well developed.
• The main goals are to collect information as early as possible to further inform the safe and effective use of these medicines and their benefit-risk profile when used in everyday medical practice.
• It does not mean that the medicine is unsafe.
• PRAC can add additional drugs.
• A medicine can be included on this list when it is approved for the first time or at any time during its life cycle.
• A medicine remains under additional monitoring for five years or until the PRAC decides to remove it from the list.
• Examples: Adalimumab, Rituximab, Enoxaparin, Cidofovir, Etanercept,

When are drugs kept under additional monitoring in the EU?

• Additional monitoring status is always applied to a medicine in the following cases:

1. It contains a new active substance authorized in the EU after 1 January 2011
2. It is a biological medicine, such as a vaccine or a medicine derived from plasma (blood), authorized in the EU after 1 January 2011.
3. It has been given a conditional approval (where the company that markets the medicine must provide more data about it) or approved under exceptional circumstances.
4. The company that markets the medicine is required to carry out additional studies, for instance, to provide more data on long-term use of the medicine or on a rare side effect seen during clinical trials.
5. It is authorized with specific obligations on the recording of suspected adverse drug reactions.
6. Other medicines can also be placed under additional monitoring, based on advice from PRAC.