COX2 and the risk of cerebrovascular disease
COX-2 Inhibitors – The Basics
The cyclo-oxygenase 2 (COX-2) inhibitors are a form of drug in the class of medicines known as the non-steroidal anti-inflammatory drugs (NSAIDs). The COX-2 Inhibitors are a new form of NSAIDs that are considered to produce fewer gastro-intestinal side effects than the older non-selective drugs.
COX-2 inhibitor drugs include:
Celebrex (Celecoxib) Vioxx (Rofecoxib) Bextra (Valdecoxib)
The other COX-2 inhibitors being developed include:
Prexige (Lumiracoxib) Arcoxia (Etoricoxib)
Uses of COX-2 inhibitors
The COX-2 inhibitors have the following usage information highlighted:
Celebrex (Celecoxib) – Commonly prescribed for arthritis and other types of back pain. Vioxx (Rofecoxib) – Prescribed for pain relief from arthritis and back pain in various forms. Bextra (Valdecoxib) – Approved use for signs and symptoms of osteoarthritis and rheumatoid arthritis in adults and painful menstrual cramps.
Cerebrovascular Diseases – The Basics
Cerebrovascular disease (CVD) includes all disorders in which the area of the brain is transiently or permanently affected by ischemia or bleeding. One or more of the cerebral blood vessels are generally involved in the pathological process.
The incidence of cerebrovascular diseases is quite high in diabetic patients. The term is broadly used for any disease due to which the arteries in the brain or connected to the brain are affected. The cerebrovascular diseases can lead to a stroke or even a hemorrhagic stroke.
COX-2 Inhibitors and Cerebrovascular Diseases
In the last years, medical experts and officials have expressed concern over the cerebrovascular effects of certain COX-2 inhibitors.
According to a recent news release, Professor Gordon Duff, chairman of the British Committee on the Safety of Medicines, sent a notification to all the doctors in the United Kingdom in this context. The notification stated that patients with established ischemic heart disease or cerebrovascular disease who are being treated with any COX-2 inhibitors should be switched over to alternative (non COX-2 selective) treatments at the earliest convenience.
Another report by the Committee for Medicinal Products for Human Use (CHMP) recommended that the concerned products carry the following warnings:
- COX-2 inhibitors must not be used in patients with established ischemic heart disease and/or cerebrovascular disease or in patients with peripheral arterial disease.
- Physicians should exercise caution when prescribing COX-2 inhibitors to patients with risk factors for heart disease, such as hypertension, hyperlipidemia, diabetes, and smoking.
- The lowest effective dose for the shortest possible duration of treatment should be used, given the association between cardiovascular/cerebrovascular risk and exposure to COX-2 inhibitors.
- Hypersensitivity reactions and rare but serious and sometimes fatal skin reactions may occur; the majority of cases occur in the first month of use, and patients with a history of drug allergies may be at greater risk.
In another study, the serious adverse effects in the patients taking valdecoxib were quite high. These effects included cerebrovascular events, MIs, renal events and deaths.
The Regulations
A series of restrictions and special considerations were announced by the Food and Drug Administration (FDA) to regulate the use of these COX-2 inhibitors in light of the risk of cerebrovascular events.
In February 2005, an FDA release directed the Pfizer, Inc. to withdraw Bextra (valdexocib) from the market, as the overall risks factors were far more than the potential benefits of the drug.
In addition, the statement also directed Pfizer, Inc. to include a boxed warning in the Celebrex (celecoxib) label. Consequently, the Pfizer, Inc. agreed to suspend sales and marketing of Bextra in the US and work with the FDA on the boxed warning required on the packaging of Celebrex.
Finally, the FDA also issued supplemental request letters to sponsors of all COX-2 Inhibitors to revise the labeling for their products. The revised labeling or packaging insert is required to include a boxed warning highlighting the potential for increased risk of cardiovascular events and life-threatening gastrointestinal bleeding associated with their use.
After the withdrawal of Vioxx and Bextra from the market, Pfizer has now placed the following warning on Celebrex’s label:
Important Information: CELEBREX may increase the chance of a heart attack or stroke that can lead to death. It should not be used right before or after certain heart surgeries. Serious skin reactions or stomach problems such as bleeding can occur without warning and may cause death.
