Off-label prescription as a useful resource to fight COVID-19

Editor's note: Vera Lucia Raposo is an associate professor at the Faculty of Law of Macau University, China and an Auxiliary Professor at the Faculty of Law of Coimbra University, Portugal. The article reflects the author's opinions, and not necessarily the views of CGTN.

Off-label prescription refers to the use of a drug in different terms than the ones established in the marketing authorization (MA), that is, the approval issued by the competent drug authority - in China's case, the National Medical Products Administration. The MA allows the launching of a new drug into the market after a strict assessment of several materials (studies, results of clinical trials) presented by the drug manufacturer. No drug can be merchandised before having an MA, which settles the proper conditions to use the drug.

However, all around the world, drugs are systematically being prescribed outside the conditions of the respective MA. They are used for different types of patients (for instance, for children, when the drugs was only approved for adults), in a different method of administration (instead of an intravenous infusion, the drug is used in the form of eye drops), with a different dosage (2 ml per days instead of the approved 1 ml per day), or for a different medical condition (even though the drug was approved for hypertension, it is now being used for migraine headaches).

Off-label prescription is not necessarily illegal. Actually, it might even be required to meet the best standard of care in certain situations, such as when there is no drug specifically approved for the medical condition or when the duly approved drug is not effective any more for a given patient.

Nonetheless, it remains as a particularly risky practice. When we use a drug that was not specifically approved for that particular use (that is, when we use it off-label), we lack proper scientific evidences regarding the safety and efficiency of that use, which increases the risks of adverse drug effects and severe injuries for the patients. Moreover, off-label use frequently requires the manipulation of the drug (repacking the drug, solving it in a liquid, etc.), which increases the risks of contamination, even when performed in a sterile environment.

Therefore, though this practice should be accepted as good medical practice, it is imperative to have a regulation establishing the conditions for its legitimacy. But that hardly happens, and most countries lack a proper legal framework for off-label prescription. This question is particularly relevant nowadays because off-label drug use tends to increase during epidemics. Many epidemics involve new viruses, for which we do not have authorized drugs. Off-label drug use arises as a promising hope to cope with dramatic public health problems. For instance, during the SARS crisis, antibiotics were prescribed above the regular approved dosage (i.e., off-label) in order to manage the growing health crisis.

To counter the COVID-19 outbreak, off-label drug use emerges again as a valuable resource. The guidelines developed by Chinese experts, in accordance with the general rules of WHO Guideline Development and the WHO Rapid Advice Guideline, recommend that infected patients are to be treated with the drug Kaletra (a combination of lopinavir and ritonavir), originally approved for HIV. Very recently, the Chinese Ministry of Science and Technology announced that Chloroquine Phosphate, a drug approved for the treatment of malaria, was found to have curative effects on the novel coronavirus disease. Several other drugs are being suggested as therapeutic options, all within off-label drug use, combined with traditional Chinese medicine and experimental drugs.

Like the legal framework in many other jurisdictions, China still has some work to do in this field. And there are still doubts about the admissibility of off-label prescription under the current Chinese law. It is imperative to clarify whether off-label prescription is in accordance with the law, when can it be used, if and when can off-label drug use renders doctors accountable (medical liability), and under which conditions can pharmaceutical companies release information about off-label use of their drugs.

Epidemics present a challenge for everyone, doctors, scientists, governments, security forces, the community in general. Lawmakers are challenged to create laws adequate to these difficult times. Off-label drug use is one of the topics that requires legal attention.