On March 29th, the French Journal Officiel published a decree authorizing “off-label” prescriptions of Rivotril® until April 15, 2020, that is, prescribed for conditions that have not received marketing authorization. It will be dispensed as an injection on an outpatient basis in the context of the Covid-19 epidemic.
This decree allows local pharmacies to dispense this drug for patients with COVID-19, or those suspected of being infected, if their clinical condition requires it, with a prescription specifying “Off-label Prescription for Covid-19”.
The purpose is clearly to allow doctors a treatment for their patients who have acute respiratory distress at the end of their life. This drug is usually prescribed as a sedative, according to the recommendations of the “SFAP” (French Society for Accompaniment and Palliative Care) which updated its informational leaflets for doctors due to the current pandemic.
This drug belongs to the class of benzodiazepines, such as midazolam, Valium® (diazepam), Narcozep®, Lexomil®, Xanax®, Rohypnol® (flunitrazepam) or Tranxene® (clorazepate). Rivotril® (clonazepam), like those other molecules, has diverse effects on the patient depending on the dose dispensed: sedative effect against anxiety, hypnotic effect (to induce sleep, or coma) or anticonvulsant effect (to treat epilepsy, for which it received marketing authorization).
Just as the previously mentioned drugs, the effect of Rivotril® varies depending on the dose administered, particularly it causes respiratory depression.
Rivotril®‘s long half-life (time necessary for eliminating half of concentration after administration) is both beneficial (it avoids lengthy perfusions) and also a disadvantage because patients’ differences make it difficult to adjust the dosage for the objective sought. Furthermore, the additional use of other drugs such as those belonging to the morphine class can potentiate the effect of Rivotril®.
Modifying the specific marketing authorization for this drug shows the present shortage of sedatives such as midazolam, or diazepam, with well-known properties. This emphasizes the need to use Rivotril® as an anxiolytic and palliative care but not for euthanasia.
Rivotril® can be administered by subcutaneous injection twice a day. Since its half-life is considerably longer (30 to 40 hours) compared to midazolam (2 hours half-life), Rivotril® is of easier use for caregivers for it can be administered without perfusions, with a mere injection regularly renewed. Thus however, Rivotril® doses are less adjustable that midazolam.
Allowing Rivotril® to be prescribed off-label as an injection, on an outpatient basis follows the same logic as off-label prescriptions of midazolam for implementing sedation, (as the French Health Ministry announced last February). However, the authorization only applies to Covid-19 patients, with acute respiratory distress (asphyxia), and who are not to be ressuscitated.
Therefore, Rivotril® is efficacious and apparently easy to use, although clearly labeled as being contraindicated in cases of “severe respiratory failure”. Thus, these extended authorizations may greatly increase the risk of euthanasia since the caregivers who use Rivotril® may not have proper training or experience, and may lack team-work. The collegial dimension for implementing such palliative care in private practice or in nursing homes and medico-social establishments could also indeed be called into question.
On March 26, Alliance VITA relayed several caregivers’warning about the dangers of “transitory and exceptional” protocols and the dangers of hastily implementing palliative care for respiratory distress, without adequately attempting to treat patients beforehand.
The March 28th decree specifies that when prescribing off-label pharmaceutics, “the doctor should comply with the transitory and exceptional protocols to treat dyspnea” as well as “provide palliative care of respiratory distress, according to the French Society for Accompaniment and Palliative Care (“SFAP”) and as posted on its website.”
Alliance VITA reminds us that although palliative care is a precious necessity, it also requires appropriate training. The role of palliative care is not to compensate the lack or abandonment of necessary treatment by categorizing patients as “at the end-of-life” when they should have access to curative therapy. Therefore, Alliance VITA association warns against possible transgressions by misusing a drug, either voluntarily or involuntarily, to cause euthanasia. Alliance VITA also underlines the importance of not basing therapeutic decisions uniquely on the age of a patient who remains personally concerned.
To put a break on the risks of serious drift, Alliance VITA has proposed a 24/7 on-call national or regional service for geriatricians and experienced palliative care doctors, instead of expecting lone practitioners to “comply” with pre-established protocols. Any emergency prescriptions of Rivotril® for cases of Covid-19, in accordance with the new decree, would be submitted to their approval. The collegial decision-making and availability of medical supplies then have to be anticipated.
Given the complex situations caregivers are facing, Alliance VITA’s SOS End-of-life listening service, has created an informational web space dedicated to the caregivers. It aims at offering those who wish it an opportunity to take a step back through exchanges with other caregivers. This service has been opened in cooperation with the VITA network of caregivers among other structures.