December 28, 2009 — A review article published in the December 15 issue of the American Family Physician offers recommendations for prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) in the primary care setting.
"...NSAIDs are commonly used to treat inflammation, pain, and fever by decreasing prostaglandin synthesis through blockage of the cyclooxygenase (COX) enzyme," write Amanda Risser, MD, MPH, from Oregon Health and Science University in Portland, and colleagues. "The two major isoforms of COX (COX-1 and COX-2) are inhibited by nonselective NSAIDs. COX-2 is also inhibited by selective NSAIDs. All nonselective NSAIDs inhibit platelet aggregation through inhibition of COX-1 and the thromboxane A2 (TXA2) pathway."
Although NSAIDs are in widespread use, there are accompanying risks, including significant upper gastrointestinal (GI) tract bleeding (particularly in older persons), risks in those receiving anticoagulant therapy, and risks in patients with a history of upper GI tract bleeding associated with NSAID use.
Dyspepsia, abdominal pain, GI discomfort, and GI bleeding may be reduced by combining the NSAID with a proton pump inhibitor (PPI) or histamine H2 blocker.
Despite the cardioprotective qualities of aspirin, other NSAIDs may have adverse cardiac effects, including worsening of congestive heart failure, increase in blood pressure, myocardial infarction, and ischemia. The risk for myocardial infarction is increased with COX-2 inhibitors, although celecoxib, which is the only COX-2 inhibitor still available in the United States, is somewhat safer regarding cardiovascular effects.
NSAIDs should not be used in patients with cirrhotic liver diseases because such patients are at greater risk of bleeding and for kidney failure. However, NSAIDs rarely cause hepatic damage, and any hepatic effects are usually reversible. NSAIDs with more potential for hepatic problems include sulindac and diclofenac.
Caution is advised when NSAIDs are prescribed in the setting of anticoagulant therapy, platelet dysfunction, or immediately before surgery.
Central nervous system adverse effects of NSAIDs may include aseptic meningitis, psychosis, and tinnitus. NSAIDs may also trigger or exacerbate asthma.
In patients with asthma, especially those with nasal polyps or recurrent sinusitis, NSAIDs and aspirin should be avoided.
During the last 6 to 8 weeks of pregnancy, NSAIDs should be avoided to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and antiplatelet activity causing maternal and fetal complications.
However, most NSAIDs are likely safe in pregnancy.
In breast-feeding women, ibuprofen, indomethacin, and naproxen can be safely used. Parents should be educated regarding correct NSAID dosing and storage in childproof containers to prevent accidental NSAID overdose in children.
Key Recommendations
Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:
Physicians should consider prescribing PPIs, double-dose histamine H2 blockers, or misoprostol with NSAIDs for persons who must take NSAIDs, although they have had an NSAID-associated ulcer. Celecoxib may also be used alone in these patients, but this drug should be avoided in patients at increased risk for myocardial infarction. Women who might become pregnant should not take misoprostol (level of evidence, C). Two systematic reviews describe the use of NSAIDs in this setting for the prevention of endoscopic ulcers.
For prevention of acute renal failure, NSAIDs should be avoided whenever possible in patients with preexisting kidney disease, congestive heart failure, or cirrhosis (level of evidence, C, based on a literature review and a summary of consensus guidelines).
For patients at risk for renal failure, and in those taking angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, physicians should consider monitoring serum creatinine levels after prescribing treatment with NSAIDs (level of evidence, C, based on a summary of consensus guidelines).
In patients taking anticoagulants, NSAIDs and aspirin should be avoided if possible. An increase in international normalized ratio (INR) should be expected if concurrent use of NSAIDs and anticoagulants is required. These patients should have appropriate INR monitoring, dosage adjustments of warfarin, and GI prophylaxis (level of evidence, C, based on a systematic review).
In breast-feeding women, ibuprofen, indomethacin, and naproxen can be safely used (level of evidence, C, based on a consensus guideline).
Editorial: Increased Cardiovascular Concerns
In an accompanying editorial, Gunnar H. Gislason, MD, PhD, from Copenhagen University Hospital Gentofte in Copenhagen, Denmark, describes increased concerns regarding the cardiovascular safety profile of NSAIDs, which have come to light during the last decade. Although these concerns were first recognized for COX-2 inhibitors, increased cardiovascular risk associated with nonselective NSAIDs has recently been identified.
Because there will always be groups of patients with pain conditions who must take NSAIDs, there is a need to focus on the balance between risk and benefit before NSAID therapy is started.
"This is especially important in persons with established cardiovascular disease in whom alternative pain treatment with lower cardiac risk (e.g., acetaminophen, weak opiates) should always be the first choice,
" Dr. Gislason writes. "In persons needing NSAID treatment, NSAIDs with the highest COX-1 selectivity (e.g., naproxen, ibuprofen, aspirin) should be preferred and used in the lowest dosages and for the shortest durations possible. For stronger analgesic effect, a combination with other types of analgesics should be considered."
As supplements to analgesic therapy, Dr. Gislason also recommends considering nonpharmacologic treatment, such as physiotherapy and physical exercise.
"Epidemiologic studies have demonstrated extensive use of prescription NSAIDs in the general population, as well as in persons with established cardiac disease," Dr. Gislason concludes.
"Also, in many countries, NSAIDs are sold without a prescription, expert advice, limits on their use, or information on potential adverse effects. This indicates the need for reevaluation of current treatment strategies regarding NSAID use and the misconception that NSAIDs are harmless for everyone."
The review authors and editorialist have disclosed no relevant financial relationships.
Am Fam Physician. 2009;80:1371-1378. Abstract
Clinical Context
NSAIDs are commonly used to treat inflammation, pain, and fever by blockage of the COX enzyme, and there is limited evidence to support differences in effectiveness for pain treatment when comparing NSAIDs.
The likelihood of adverse effects increases with duration of use and dose.
However, the adverse effect profile of the different NSAIDs may differ. For example, aspirin is used for primary prevention of coronary and cardiovascular conditions such as stroke because of its antiplatelet effects, whereas COX-2 inhibitors have little antiplatelet effect.
This is a review of the adverse effects of NSAIDs and precautions needed to minimize risk when NSAIDs are prescribed. Adverse effects occur mainly in the GI, cardiovascular, hepatic, renal, hematologic, nervous, and respiratory systems.
Study Highlights
Taking drug holidays or using intermittent dosing may be strategies to reduce the risks associated with NSAID use.
Dyspepsia and GI discomfort occur in 10% to 20% of persons taking NSAIDs, but dyspeptic symptoms do not correlate well with clinically significant ulcers.
GI adverse effects are increased with age and comorbidity.
The 1-year risk of serious GI bleeding from long-term NSAID use ranges from 1 in 2100 adults younger than 45 years to 1 in 110 older than 75 years.
Risk for death for the 2 groups ranges from 1 in 12,353 to 1 in 647 adults, respectively.
Concomitant anticoagulant use increases the risk by 5 to 6 times.
In those with a history of bleeding ulcers, the risk is 5% in 6 months, even with the use of COX-2 inhibitors or nonselective NSAIDs with a PPI.
Eradication of Helicobacter pylori only minimally decreases the rate of peptic ulcer in persons taking NSAIDs.
Taking misoprostol with an NSAID reduces ulcer-related complications but is contraindicated in pregnancy (category X) and has undesirable GI effects.
Use of PPIs or double-dose antihistamines with NSAIDs decreases the rate of endoscopically diagnosed ulcers.
Although low-dose aspirin has been shown to reduce the risk for coronary artery and cerebrovascular disease, other NSAIDs are associated with an increased risk for worsening congestive heart failure, increased blood pressure, and adverse cardiovascular events.
Blood pressure increases by 5 mm Hg, whereas use of nonselective NSAIDs and some COX-2 inhibitors also increases blood pressure.
COX-2 inhibitors have been implicated in the risk for myocardial infarction, although celecoxib may be safer than the others.
COX-2 inhibitors should be avoided in persons at risk for cardiovascular events, who should consider a nonselective NSAID with misoprostol or a PPI for GI protection instead.
Sulindac and diclofenac are associated with a higher rate of hepatic dysfunction than other NSAIDs, but clinically significant events are rare.
Idiosyncratic liver toxicity may occur in those with hepatitis C or underlying liver impairment.
NSAIDs should be avoided in persons with preexisting renal disease, congestive heart failure, or cirrhosis to prevent renal failure.
It is unclear whether monitoring renal function in those with renal risk who are taking NSAIDs reduces morbidity or mortality rates.
In high-risk persons with recent myocardial infarction or stent placement, aspirin should be continued before and after surgery.
In those with bleeding risk, aspirin and other NSAIDs may be withheld before surgery for 5 elimination half-lives (eg, 7 - 10 days before surgery for aspirin and 2 days for ibuprofen).
Aspirin should be avoided in those for whom benefits do not outweigh risks.
In persons taking anticoagulants, INR monitoring is required when using NSAIDs, and GI prophylaxis should be prescribed.
Central nervous system effects are rare and occur mainly in elderly persons, including tinnitus, cognitive changes, confusion, and depression.
Indomethacin has been associated with psychosis, whereas aseptic meningitis has been seen with lupus in those taking ibuprofen or naproxen.
Bronchoconstriction has been associated with NSAID use, especially in those with underlying respiratory disease such as asthma.
NSAIDs are not teratogenic in humans, and the American Academy of Pediatrics considers ibuprofen, indomethacin, and naproxen safe in breast-feeding women.
NSAID use close to term in pregnant women is associated with prolonged labor or gestation, blood loss and anemia, and increased risk of neonatal bleeding.
Low-dose aspirin is considered safe during pregnancy and lactation.
Clinical Implications
The risk of GI bleeding with NSAID use is increased with age, duration of use, comorbidities, anticoagulant use, and a history of bleeding ulcers.
Other systemic adverse effects associated with NSAID use include those affecting the cardiovascular, hepatic, renal, hematologic, nervous, hematologic, and respiratory systems.
Dato' Dr. Ismail Yaacob
Medical Director/Consultant Physician
Kedah Medical Centre
No comments:
Post a Comment