During its July 2021 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded a safety signal of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane around the heart) with COVID-19 vaccines Comirnaty and Spikevax and has recommended that people who have previously had capillary leak syndrome must not be vaccinated with COVID-19 vaccine Janssen.
Comirnaty and Spikevax: possible link to very rare cases of myocarditis and pericarditis
EMA’s safety committee (PRAC) has concluded that myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane around the heart) can occur in very rare cases following vaccination with the COVID-19 vaccines Comirnaty (Pfizer/BioNTech) and Spikevax (previously known as COVID-19 Vaccine Moderna).
The Committee therefore recommends listing myocarditis and pericarditis as new side effects in the product information for these vaccines, together with a warning to raise awareness among healthcare professionals and people taking these vaccines.
Myocarditis and pericarditis are inflammatory conditions of the heart. Symptoms can vary but often include breathlessness, a forceful heartbeat that may be irregular (palpitations), and chest pain.
In reaching its conclusion, the Committee took into consideration all currently available evidence.
This included an in-depth review of 145 cases of myocarditis in the European Economic Area (EEA) among people who received Comirnaty and 19 cases among people who received Spikevax. PRAC also reviewed reports of 138 cases of pericarditis following the use of Comirnaty and 19 cases following the use of Spikevax. As of 31 May 2021, around 177 million doses of Comirnaty and 20 million doses of Spikevax had been given in the EEA.
In addition the PRAC also looked into cases received worldwide.
The Committee concluded that the cases primarily occurred within fourteen days after vaccination, more often after the second dose and in younger adult men. In five cases that occurred in the EEA, people died. They were either of advanced age or had concomitant diseases. Available data suggest that the course of myocarditis and pericarditis following vaccination is similar to the typical course of these conditions, usually improving with rest or treatment.
Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. They should tell people receiving these vaccines to seek immediate medical attention if symptoms indicative of myocarditis or pericarditis occur. These include breathlessness, a forceful heartbeat that may be irregular and chest pain.
Healthcare professionals should consult applicable guidance and/or consult specialists (e.g. cardiologists) to diagnose and treat these conditions.
At this point in time, no causal relationship with myocarditis or pericarditis could be established with two other COVID-19 vaccines authorised in the EEA, COVID-19 Vaccine Janssen and Vaxzevria, and the Committee has requested additional data from the companies marketing these vaccines.
EMA confirms that the benefits of all authorised COVID-19 vaccines continue to outweigh their risks, given the risk of COVID-19 illness and related complications and as scientific evidence shows that they reduce deaths and hospitalisations due to COVID-19.
As for all vaccines, EMA will continue to monitor the vaccines’ safety and effectiveness and provide the public with the latest information, particularly as more adolescents and young adults are vaccinated and more second doses are given. The agency will take necessary action if any new safety issues are identified.
Information for the general public
- Very rare cases of myocarditis and pericarditis (inflammatory conditions of the heart) have occurred in people who received Comirnaty and Spikevax (formerly COVID-19 Vaccine Moderna).
- The chance of these conditions occurring is very low, but you should be aware of the symptoms so that you can get prompt medical treatment to help recovery and avoid complications.
- You must seek medical attention immediately if you have the following symptoms after vaccination:
- breathlessness;
- a forceful heartbeat that may be irregular;
- chest pain.
- Speak to your healthcare professional or contact your relevant national health authority if you have any questions about the rollout of the vaccines in your country.
Information for healthcare professionals
Following a review of very rare cases of myocarditis and pericarditis in people who received Comirnaty and Spikevax (formerly COVID-19 Vaccine Moderna), healthcare professionals should:
- be alert to the signs and symptoms of myocarditis and pericarditis in people who have had these vaccines;
- tell people receiving the vaccine that they must seek immediate medical attention if they have the following symptoms suggestive of myocarditis and pericarditis after vaccination: (acute and persisting) chest pain, palpitations or shortness of breath. People with myocarditis or pericarditis may require specialist treatment;
- consult applicable guidance and/or consult specialists (e.g. cardiologists) to diagnose and treat these conditions.
The product information will be updated to include myocarditis and pericarditis as side effects with unknown frequency.
A direct healthcare professional communication (DHPC) will be sent in due course to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website.
EMA advises against use of COVID-19 Vaccine Janssen in people with history of capillary leak syndrome
EMA’s safety committee (PRAC) has recommended that people who have previously had capillary leak syndrome must not be vaccinated with COVID-19 Vaccine Janssen. The Committee also recommended that capillary leak syndrome should be added to the product information as a new side effect of the vaccine, together with a warning to raise awareness among healthcare professionals and patients of this risk.
The Committee reviewed three cases of capillary leak syndrome in people who had received COVID-19 Vaccine Janssen, which occurred within two days of vaccination. One of those affected had a history of capillary leak syndrome and two of them subsequently died. As of 21 June 2021, more than 18 million doses of COVID-19 Vaccine Janssen had been administered worldwide.
Capillary leak syndrome is a very rare, serious condition that causes fluid leakage from small blood vessels (capillaries), resulting in swelling mainly in the arms and legs, low blood pressure, thickening of the blood and low blood levels of albumin (an important blood protein).
Healthcare professionals should be aware of the signs and symptoms of capillary leak syndrome and of its risk of recurrence in people who have previously been diagnosed with the condition.
People who have been vaccinated with COVID-19 Vaccine Janssen should seek immediate medical assistance if they experience rapid swelling of the arms and legs or sudden weight gain in the days following vaccination. These symptoms are often associated with feeling faint (due to low blood pressure).
PRAC will continue to monitor for cases of the condition and will take any further actions necessary. The Committee has also asked Janssen, the company marketing the vaccine, for further information about a possible mechanism for the development of capillary leak syndrome following vaccination.
As for all vaccines, EMA will continue to monitor the vaccine’s safety and effectiveness and provide the public with the latest information.
A similar review was recently finalised for another COVID-19 vaccine, Vaxzevria (previously COVID-19 Vaccine AstraZeneca).
Information for the public
- A very small number of cases of capillary leak syndrome have occurred in people who received COVID-19 Vaccine Janssen.
- You must not have this vaccine if you have previously experienced capillary leak syndrome.
- Capillary leak syndrome is a serious condition. The chance of the condition occurring is very low, but you should still be aware of the symptoms so that you can get prompt medical treatment to help recovery and avoid complications.
- You must seek medical attention immediately if you have the following symptoms in the days after vaccination, which may occur together with feeling faint (due to low blood pressure):
- rapid swelling of the arms and legs;
- sudden weight gain.
- Speak to your healthcare professional or contact your relevant national health authority if you have any questions about the rollout of the vaccine in your country.
Information for healthcare professionals
- EMA has reviewed cases of capillary leak syndrome in people who received COVID-19 Vaccine Janssen.
- Healthcare professionals must not give this vaccine to anyone who has a history of capillary leak syndrome.
- Capillary leak syndrome is a very rare, serious condition, which can be fatal if untreated. It causes fluid leakage from the capillaries, resulting in oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia.
- Healthcare professionals should be aware of the risk of recurrence of capillary leak syndrome in people who have previously experienced the condition.
- Healthcare professionals should be aware of the signs and symptoms of capillary leak syndrome. Patients with an acute episode of capillary leak syndrome following vaccination require prompt treatment and may require continuous specialist monitoring and intensive supportive therapy.
- Healthcare professionals should tell people receiving the vaccine that they must seek medical attention if they have the following symptoms in the days after vaccination, which may be associated with feeling faint (due to low blood pressure):
- oedema in the extremities;
- sudden weight gain.
- The product information will be updated to include a contraindication in people with a history of capillary leak syndrome. The condition will also be listed as a side effect with an unknown frequency.
A direct healthcare professional communication (DHPC) will be sent in due course to healthcare professionals prescribing, dispensing or administering the vaccine. The DHPC will also be published on a dedicated page on the EMA website.
EMA finds no evidence linking viral vector in Zynteglo to blood cancer
EMA’s safety committee (PRAC) has concluded that there is no evidence Zynteglo causes a blood cancer known as acute myeloid leukaemia (AML).
Zynteglo, a gene therapy for the blood disorder beta thalassaemia, uses a viral vector (or modified virus) to deliver a working gene into the patient’s blood cells.
The PRAC reviewed two cases of AML in patients treated with an investigational medicine, bb1111, in a clinical trial for sickle cell disease. Although there have been no reports of AML with Zynteglo, both medicines use the same viral vector and there was a concern that the vector may be implicated in the development of the cancer (insertional oncogenesis).
The review found that the viral vector was unlikely to be the cause. In one of the patients, the viral vector was not present in the cancer cells, and in the other patient it was present at a site (VAMP4) that does not appear to be involved in cancer development.
After examining all the evidence, the PRAC concluded that more plausible explanations for the AML cases included the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of blood cancer in people with sickle cell disease.
Patients having Zynteglo treatment for beta thalassaemia also need conditioning treatment to clear out their bone marrow cells. Healthcare professionals should therefore explicitly inform patients receiving Zynteglo of the increased risk of blood cancers from medicines used in conditioning treatments.
The PRAC has also updated its recommendations for monitoring patients. Healthcare professionals should now check their patients for signs of blood cancers at least once a year for 15 years. The previous recommendation was for healthcare professionals to check for signs of cancer once a year.
The Committee, which worked closely with experts from the Committee for Advanced Therapies (CAT), concluded that the benefits of Zynteglo continue to outweigh its risks. As for all medicines, the PRAC will monitor any new data on its safety and update advice for patients and healthcare professionals when necessary.