Another Drug Safety Withdrawal - The Opioid Dependence Drug Levomethadyl (ORLAAM)

Quietly on September 2, 2003, Roxane Laboratories of Columbus, OH announced it was discontinuing production of levomethadyl (ORLAAM), a drug used to treat opioid (narcotic) dependence, because of reports of severe adverse drug reactions.

Levomethadyl is now the twelfth drug approved in the U.S. since 1992 that was subsequently withdrawn from the market for safety reasons.

The European Agency for the Evaluation of Medicinal Products (EMEA) announced on April 19, 2001 that marketing of this drug had been suspended in European countries. This was more than two years before the announcement of the FDA’s action.

Levomethadyl causes QTc interval prolongation. The QTc interval is the length of time it takes the large chambers of the heart (ventricles) to electrically discharge and recharge. A prolongation of the QTc interval can lead to cardiac arrythmias (heart rhythm disturbances) such as torsade de pointes and other life-threatening arrhythmias. The QTc interval is measured by an electrocardiogram (EKG or ECG) in milliseconds (msec-thousandths of a second). The subscript “c” indicates that the QT interval has been corrected for the patient’s heart rate. Torsade de pointes is a French phrase that means “twisted point,” describing the appearance of this type of rhythm disturbance on the EKG tracing.

Ten cases of life-threatening heart rhythm disturbances associated with the use of levomethadyl have been reported to European authorities since July 1, 1997.

Since the introduction of levomethadyl in the U.S. in 1995, there have been increasing reports of severe cardiac-related adverse events, including QT interval prolongation (15 reports), torsade de pointes (8 reports) and cardiac arrest (6 reports). Other cardiac-related adverse events have also been reported, including arrhythmias, syncope (fainting), and angina (chest pain). Extensive changes, including additional warnings and contraindications, were made to the U.S. professional product labeling, or package insert, for the drug in April 2001.

Roxane Laboratories is advising that levomethadyl will be unavailable shortly after the beginning of 2004 and that no new patients should be started on the drug. Patients currently using levomethadyl should be started on other treatments as soon as possible. Other drugs approved by the Food and Drug Administration (FDA) for the management of opiate dependence are methadone (DOLOPHINE) and buprenorphine (SUBOXONE, SUBUTEX).

In the past decade there have been an unprecedented number of drug safety withdrawals in the U.S. (12 to be exact), of which levomethadyl is the latest. We have written on numerous occasions that drugs are coming on the market in this country that are less safe, and in some cases less effective, than drugs already available.

There appear to be several reasons for this unfortunate situation. First was the passage of the Prescription Drug User Fee Act (PDUFA) in 1992 that allowed the FDA to charge drug companies to review new drugs for approval. The re-authorization of PDUFA in 1997 brought with it stringent performance criteria for the agency, all aimed at making the drug approval process predictable and more streamlined for drug companies. The new income to the FDA from this change in the law could be used only for funding the drug approval process, nothing else.

Industry money has fundamentally changed the relationship between the FDA and the drug industry. The industry, not the American public, has become the FDA’s primary client. This change in relationship appears to have resulted in the FDA being pressured to approve new drugs, drugs that we do not think would have come on the market in this country 15 years ago.

There is one more very important factor contributing to the recent spate of drug safety recalls: failure of Congress over the last dozen years to hold meaningful public oversight hearings on the FDA’s drug approval process. There was a time in which, when a drug came off the market for safety reasons, its approval and the circumstances that led to its withdrawal would be reconstructed in careful detail. Lessons were learned and attempts were made not to make the same mistakes twice.

Now, nothing has been learned from the lives of people injured or killed from these 14 withdrawn drugs. Congress must once again fulfill its vital role in drug safety.

What You Can Do

You should contact the prescribing physician as soon as possible if you or a member of your family is now taking levomethadyl.

Do not discontinue the use of levomethadyl (ORLAAM) without medical supervision.