The European Medicines Agency has reviewed the risks associated with the
use of heparin medicinal products contaminated with oversulphated
chondroitin sulphate (OSCS). Heparins are used to prevent and treat
blood clots. They are used widely in patients who could have, or have
had a heart attack, in patients who have undergone major surgery, or
patients on dialysis.
The Agency’s Committee for Medicinal Products for Human Use (CHMP)
concluded that:
– OSCS has been found in unfractionated (standard) and
low-molecular-weight heparin;
– there is a link between contamination with high levels of OSCS and
serious side effects seen in some patients who have received
contaminated standard heparin. All batches of affected standard heparin
have been identified by regulatory authorities worldwide and removed
from the market;
– low levels of OSCS have also been identified in some batches of the
low-molecular-weight heparin enoxaparin. However, no similar side
effects have been observed when enoxaparin has been used. A total
removal of contaminated enoxaparin from the market in countries where it
is used would lead to a shortage of supply and patients would not be
able to continue their treatment.
The Committee concluded that doctors can continue to use enoxaparin with
low levels of OSCS to treat patients temporarily until the situation is
resolved. However, a series of measures should be put in place to
minimise the risk of side effects. These include:
– avoiding intravenous or intra-arterial administration of enoxaparin;
– monitoring patients closely for signs of allergic reactions. Patients
should receive anti-allergy treatments if reactions occur;
– as a precautionary measure, avoiding administration to pregnant women
if alternative products or uncontaminated enoxaparin are available.
The CHMP also looked at long-term approaches to minimise the possibility
of future contamination. It recommended any inspection of the heparin
supply-chain requires a coordinated approach between European and
international partners and that modifications to the existing legal and
regulatory framework for strengthening the supply-chain control should
be explored with the European Commission;
Specific tests for OSCS and other possible contaminants should be
included in the heparin monographs in the European Pharmacopoeia.
Heparin medicines are authorised at the level of the Member States.
Country-specific advice and information on stocks and potential
shortages are available in all affected Member States.
Notes
1. More information is available in a
question-and-answer document.
2. The review was initiated by Germany under Article 5(3) of Regulation
(EC) No 726/2004 following detection of a contaminant in a limited
number of batches in some Member States of the European Union.
European Medicines Agency