Non-steroidal anti inflammatory drugs (NSAIDs) are used by millions of patients. They act by inhibiting the enzyme cyclooxygenase (COX) which facilitates the formation of prostaglandins and thromboxane. The enzyme has two forms: COX-1 and COX-2. They mediate inflammation and pain by simulating prostaglandin synthesis. All the NSAIDs available in the US save one inhibit both COX 1 and 2. Thus, they also impair clotting by blocking thromboxane formation. Hence, prolonged use is associated with bleeding, most importantly in the head and GI tract.
The sole exception is celecoxib which inhibits only the COX-2 enzyme. Accordingly, it is much less likely to cause bleeding. There used to be another COX-2 inhibitor available here – Vioxx, but it was forced off the market in a convulsion of deranged thought by a vocal, but poorly informed segment of the medical community.
As the specific COX inhibitors did not affect thromboxane formation it was felt that somehow clotting formation would be enhanced and thus Vioxx was accused of facilitating coronary thrombosis and stroke. Rigorous analysis of pertinent data failed to show such an effect, but Vioxx was withdrawn nevertheless. This left celecoxib as the only specific COX-2 antagonist on the market. It has a therapeutic profile identical to that of Vioxx. If the latter was dangerous enough to prohibit than so was the former. But medicine is no more rational than the rest of human activity and celecoxib was left standing. All the COX inhibitors are given in the figure below.
Having gotten this ancient history off my chest, let’s turn to NSAIDs and pregnancy. The FDA on Oct 15 issued a Drug Safety Communication, excerpts are below.
The U.S. Food and Drug Administration (FDA) is warning that use of nonsteroidal anti-inflammatory drugs (NSAIDs) around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications. NSAIDs are commonly used to relieve pain and reduce fevers. They include medicines such as aspirin, ibuprofen, naproxen, diclofenac, and celecoxib. After around 20 weeks of pregnancy, the unborn babies’ kidneys produce most of the amniotic fluid, so kidney problems can lead to low levels of this fluid. Amniotic fluid provides a protective cushion and helps the unborn babies’ lungs, digestive system, and muscles develop…
Pregnant women should not use NSAIDs at 20 weeks or later unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby. Talk with your health care professional about the benefits and risks of these medicines during pregnancy before using them, especially at 20 weeks or later.
It is not clear how common this effect on fetal kidneys is, but it appears to be an infrequent complication. Renal side effects of NSAIDs in children and adults are infrequent, but are serious when they occur. The two most observed kidney disorders caused by NSAIDs are interstitial nephritis and nephrotic syndrome, though as stated they are not common.
NSAIDs are very effective at relieving chronic pain, such as that secondary to osteoarthritis. Of course, the population with osteoarthritis is usually at an age beyond that of child bearing. Because of its decreased likelihood of inducing bleeding, celecoxib is best prescribed for long term use.
The full text of the FDA advisory is below.