E-DRUG: Moving towards a new definition of essential medicines? (5)
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Dear All,
As an advocate of the concept of WHO Essential Medicines List from my
formative years in Pakistan in the late 80s, I share some of the concerns
raised by Dr. Manikandan. I don't have full knowledge or background of the
discussions that resulted in new additions to the EML. However, I would
like to talk about drugs for the treatment of multi-drug resistant
tuberculosis (MDR-TB) that have been added to the list.
The following are the main recommendations of the Expert Committee
regarding addition of anti-tuberculosis drugs in the Model Lists:
"For the treatment of multi-drug resistant tuberculosis (MDR-TB),
extensively drug resistant tuberculosis (XDR) and pre-XDR, the Expert
Committee recommended the addition of bedaquiline, delamanid and linezolid
to the complementary list, and the addition of terizodone
(as an alternative to cycloserine) to the core list. Similarly, linezolid
and terizidone were recommended for the EMLc. *The Committee supports the
use of these medicines recommended in WHO guidelines, with careful
selection of patients, close monitoring to control adverse events and
active pharmacovigilance.* The Committee also recommended the addition of
rifapentine to the core list of EML and EMLc for the treatment of latent TB
infection."
I have highlighted the sentence above which describes the way these TB
drugs should be used:
1. Careful selection of patients
2. Close monitoring to control adverse events, and
3. Active pharmacovigilance
We all know that the treatment of MDR-TB poses a special challenge with the
existing therapy. No one can deny the urgent need for newer medicines with
shorter courses and better safety profile. Let's see what are the options
for a patient with MDR-TB, long course (upto 24 months) of treatment with
drugs which are known to have dangerous side effects; which can result in
lack of adherence; protracted illness; permanent disability; and
potentially death because of treatment failure. The alternative is to try
the shorter regimens of the new or repurposed TB drugs which have not be
tested well but offer some hope. We absolutely need Phase III trials to
better understand the safety and efficacy of the newer drugs.
We know that the US FDA granted bedaquiline a “fast track” approval and by
law the company has to conduct a confirmatory trial that can bring some
clarity to the question of excess deaths observed in the bedaquiline arm in
the pivotal trial. However, the results of this confirmatory trial is not
required until 2022. Given the high risk benefit ratio of bedaquiline based
on the current evidence, I agree with the WHO interim guidance
recommendation that Cohort Event Monitoring (CEM) provides the most
complete and comprehensive data and is therefore the recommended approach
to active pharmacovigilance for introduction of bedaquiline (and
delamanid). Let’s hope that relevant individuals belonging to the National
Tuberculosis Control Program and the national medicine regulatory
authorities in countries where newer anti-TB drugs are introduced receive
adequate training in active pharmacovigilance.
Best wishes,
Rizwan
Syed Rizwanuddin Ahmad, MD, MPH, FISPE, FCP
Pharmacovigilance Consultant with a Special Interest to Strengthen
National Medicines Regulatory Authorities in Resource-limited Settings
Ex-Consultant/Safety Reviewer, U.S. FDA (1998-2013)
Associate Professor (adjunct), Rutgers School of Public Health, NJ, USA
Assistant Professor (adjunct), Georgetown University School of Medicine,
Washington, DC, USA
www.drugsafetyconsultant.com
Stronger Regulatory Systems - Safer Drugs
drugsafetyconsultant@gmail.com