The AEMPS periodically publishes a report prepared from suspected adverse reactions reported with treatments used in Covidien-19 and the most relevant findings. The Pharmacovigilance Center of Catalonia participates in the case-monitoring working group and in the preparation of reports. We thank the notifiers for their collaboration in generating knowledge in the context of the current pandemic.
The AEMPS updates again the information on potential therapeutic strategies and others under investigation.
Baricitinib (JAK kinase inhibitor) and anakinra (IL-1 receptor antagonist) are included among potential therapeutic strategies. These drugs may be used outside their authorized indications, but their use in clinical trials is recommended to generate knowledge.
It is recalled that there is no solid evidence of efficacy for any of the treatments being used, and the importance of reporting suspected adverse reactions.
During coronavirus pandemia, different publications have emerged discussing benefits and risks of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) in COVID-19 patients.
A recent publication of a retrospective observational study shows the influence of these two drug groups on the mortality of patients with COVID-19. A total of 1128 hypertensive patients of nine hospitals from the Chinese Province of Hubei was studied. The objective was to determine the mortality for all-causes, depending on whether they took these drugs or not.
Results show that patients who took ACE inhibitors or ARBs had lower mortality than those who did not take it, including when confounding factors or the use of other antihypertensive drugs are controlled.
In the discussion, authors comment that they cannot rule out that those results may not be influenced by uncontrolled confounding factors, or other methodological limitations of the study.
Further studies will need to be awaited to confirm or refute this finding.
Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 https://doi.org/10.1161/CIRCRESAHA.120.317134
AEMPS updates information on potential therapeutic strategies and others under investigation.
Ruxolitinib (JAK kinase inhibitor) and siltuximab (IL-6 inhibitor) are among the potential therapeutic strategies. Access for patients with COVID-19 infection will be through clinical trial and compassionate use.
The use of tocilizumab is recommended at an earlier stage of the disease and a second tocilizumab infusion may be considered.
As for hydroxychloroquine, the recommended 5-day regimen may be extended up to a maximum of 10 days depending on severity.
Dr. Joan-Ramon Laporte, in an interview by Frank Barat, talks about the type of medicine that people should take, hydroxychloroquine "magic drug", the role of pharmaceutical companies in the midst of a crisis and the fact of that "the sacred cows of clinical research are still there"
It reports on issues related to medications to treat COVID-19, with other treatments already taken by patients, ongoing clinical investigations and alerts of illegal and counterfeit products.
In addition to unproven efficacy on COVID-19, both chloroquine and hydroxychloroquine have serious adverse effects, especially at high doses or in combination with other medicinal products. In no case should they be used without medical supervision.
It recommends that they be used preferably in the context of clinical trials or according to established protocols.
The Center of Evidence-Based Medicine (CEBM) has published a note in which it is expressed in relation to the potential beneficial effect of ACEI and ARA II in the prevention and treatment of the effects of COVID-19.
Considering the few studies carried out so far and taking into account the mechanism of action of these drugs and the mechanism by which SARS-COV-2 supposedly enters cells, the relationship between the possible benefits and risks of inhibiting RCT-1 or blocking angiotensin receptors in these patients is unclear.
Until further evidence comes from clinical trials, it does not seem reasonable to use these drugs for the treatment of COVID-19.
In the case of patients with cardiovascular disease, affected by COVID-19, decisions will have to be individualized, taking into account the clinic and hemodynamic status of each patient.
The most difficult cases are those of patients with severe hypertension or chronic heart failure, in which their condition can deteriorate rapidly by withdrawing drugs that act on the renin-angiotensin-aldosterone system. The recommendation presents a decision algorithm in these patients, according to the risk of infection.
Merck S.L., according to the AEMPS, reported that a new formulation of Eutirox® tablets will be available from April 2020. The formulation change affects the excipients: lactose is removed and mannitol and citric acid are incorporated.
Despite the fact that the change only affects excipients, as it is a drug with a narrow therapeutic margin (levothyroxine), it is necessary to be aware of potential thyroid imbalances. It is recommended to extreme clinical control and, in the case of suggestive symptoms, to carry out analytical control of patients, especially those affected by thyroid cancer, cardiovascular diseases, pregnant women, children and the elderly, who switch to the new formulation.
This change comes at a time of health emergency and the necessary circuits will have to be established to guarantee the care, follow-up and safety of patients who start taking the new formulation.
You can consult the communication and the patient information sheet at: sinaem.agemed.es
The Liverpool Drug Interaction Group has published information on interactions between
medications that are being used to treat COVID-19 and commonly used medications, such as pain
relievers, anticoagulants, antibiotics, antidepressants, antipsychotics, antidiabetics, etc.
That they can be of help in the treatment of these patients in the current situation.
This is a summary table and another with more details, which describe the possible interactions and consequences in each case. They are accompanied by a document indicating how the risk of interaction has been evaluated.
We recommend periodically accessing so that the documents are updated with new information. covid19-druginteractions.org
You can also follow them on Twitter @covidDDIs
The European Medicines Agency (@EMA_News), the European Commission (@EU_Commission) and the
Network of Drug Agencies (#HMA) update the guide for the development of clinical trials related to
Version 2, of March 27, 2020, expands aspects related to informed consent, security and methodological, among others.
You can consult the document Guidance clinical trials covid19 and follow future updates in the EMA news section coronavirus disease COVID-19.
During this pandemic the opportunity to find new effective treatments to treat Covidien-19 should not be missed. The use of potentially useful drugs (chloroquine, hydroxychloroquine, azithromycin, lopinavir-ritonavir, favipiravir, remdesivir, ribavirin, interferon, anti-IL-6 inhibitors) used in an unauthorized indication (off-label use) or for compassionate use it can exaggerate the benefits and minimize toxicity (even known). If there is no control group, it becomes more difficult to obtain new knowledge.
NEJM. Lopinavir + ritonavir clinical trial versus placebo (199 severe patients with COVID19). It does not improve the mortality rate or the length of hospital stay.
There are methodological limitations, due to the urgency of the situation. It will be necessary to continue studying whether to add other antiretrovirals may give better results. www.doi.org/10.1056/NEJMoa2001282
Spanish summary at: sietes.org
Chloroquine, hydroxychloroquine and azithromycin are drugs that increase the QT interval and increase the risk of severe ventricular arrhythmias.
The appearance of ventricular arrhythmias, of the type "torsades de pointes", increases when the QTc exceeds the 500 milliseconds.
- The situation may be exacerbated if there is hypokalemia or more than one drug is used that prolongs the QT interval.
- The risk also increases in case of bradycardia (<55 bpm)
These circumstances are often found in patients affected by SARS-CoV-2.
For this reason it is advisable to monitor with the ECG and, whenever possible, correct it hypokalemia (potassium should be maintained between 4 and 4.5 mmol/L), before giving chloroquine or hydroxychloroquine, alone or in combination with azithromycin.
- The QT must be kept below 480 ms
- If QT is between 480 and 500 milliseconds, the patient should be closely monitored for assess the appearance of bradycardia or ventricular extrasystoles
- If a QT greater than 500 ms is confirmed, specialist intervention is required. Decrease the dose of the drugs or withdraw them and closely monitor the patient up to the normalization of the episode.
See the full recommendation at:
If you suspect adverse effects of these drugs on patients with Covidien-19, report them to www.targetagroga.cat. Share information and generate knowledge among all.
The data provided by the study by Gautret et al. The favorable use of the combination of hydroxychloroquine and azithromycin in patients with COVID-19 is still too preliminary and does not allow recommending the systematic administration of this combination. Among other methodological limitations, only 6 patients received the combination and presented a marked suppression of the viral load. https://doi.org/10.1016/j.ijantimicag.2020.105949
In case of use, the risk of serious adverse reactions and reactions such as QT interval arrhythmias must be taken into account.
In order to maximize patient benefits, urgency must not make us lose our prudence.