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NSAIDs & Their Complications
Dr Mohammad Taraz
Clinical Pharmacist
September 2016
HISTORY
 Sodium salicylate
 The first NSAID (1763)
 GI toxicity (particularly dyspepsia)
 Phenylbutazone
 The first non-salicylate NSAID (1950)
 Also induces uricosuria; useful in ankylosing spondylitis & gout
 Bone marrow toxicity, particularly in women over the age of 60
 Indomethacin
 As a substitute for phenylbutazone (1960)
 There are now at least 20 different NSAIDs available for use in the USA.
Dr. Mohammad Taraz
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MECHANISM OF ACTION
Prostaglandin-mediated effects
Nonprostaglandin-mediated effects
 NSAIDs interfere with neutrophil-endothelial cell adherence by decreasing
the expression of L-selectins
 NSAIDs inhibit nuclear factor kappa B (NF-kB) dependent transcription in
vitro, resulting in inhibition of inducible nitric oxide synthetase (iNOS).
 The role of these non-prostaglandin mediated processes in clinical
inflammation remains unclear.
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Different NSAIDs have varying inhibitory potentials of the COX-1 & COX-2.
Selected NSAIDs & COX-2 Inhibitors
Salicylates
Acetylated: aspirin
Nonacetylated: trisalicylate, salsalate
Nonsalicylates (Based on COX-1/COX-2 selectivity ratio in vitro)
Nonselective (traditional) NSAIDs: ibuprofen, naproxen, tolmetin,
fenoprofen, sulindac, indomethacin, ketoprofen, ketorolac, piroxicam
Partially selective NSAIDs: etodolac, diclofenac, meloxicam, nabumetone,
celecoxib
Selective COX-2 inhibitors: rofecoxib, valdecoxib
Variability of response in adults
 There is a clear individual variation in response to NSAIDs; some patients
seem to respond better to one drug than to others.
 The risk of adverse events also seems to be variable among individual
drugs & patients.
 At equipotent doses, the clinical efficacy of the various NSAIDs in patient
populations is similar; in contrast, individual responses are highly
variable.
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 The differences in the effects of the various NSAIDs have been
ascribed to variations in one or more of the following:
 Mechanism of action
• Some NSAIDs are more potent inhibitors of PG synthesis, while others are
more effective in altering other nonprostaglandin mediated biologic events.
 Pharmacokinetics, pharmacodynamics, or metabolism
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 Observed variations in patient response may result in part from the
pharmacodynamics of a particular drug.
 Thus, it is believed that, if a patient fails an NSAID of one class, the
substitution of an NSAID of a different class is a reasonable therapeutic
option.
 Each attempt to achieve a response should probably last for about 2
weeks. The NSAID dose should be at the maximal antiinflammatory range.
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 Unfortunately, the same approach is not necessarily applicable to
patients who develop a toxic effect with one NSAID.
 Some toxicities are unique to particular classes of NSAIDs, while others
are related to the general mode of action of inhibition of PG synthesis.
 One such example is ARF due to renal vasoconstriction, which is mediated
by decreased production of vasodilator PGs & may be similar across
agents.
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Adverse Effects
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Gastrointestinal effects
Renal effects
Cardiovascular effects
Hepatic injury
Hematologic effects
Central nervous system
Musculoskeletal effects
Electrolyte complications
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Gastrointestinal Effects
 Nonselective NSAIDs have potentially important gastrointestinal adverse
effects, which include dyspepsia, peptic ulcer disease, & bleeding.
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Systemic vs Topical Effects
 Aspirin & many other NSAIDs are carboxylic acid derivatives. As a result, they are
not ionized at the acidic pH found in the gastric lumen & thus can be absorbed
across the gastric mucosa.
 Once the drug moves from the acidic environment of the gastric lumen into the
pH–neutral mucosa, the drug ionizes & is trapped temporarily in epithelial cells
where it may damage these cells.
 However, this "topical" epithelial injury by many NSAIDs does not appear to be of
prime importance in the pathogenesis of clinically important endpoints
(symptomatic ulcers).
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 The pathogenesis of symptomatic PUD caused by exposure to
NSAIDs is mainly a consequence of systemic (postabsorptive) inhibition of GI mucosal COX activity.
 Even IV or IM administration of aspirin or NSAIDs can cause
gastric or duodenal ulcers in animals & human.
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Risk Of Gastrointestinal Complications
Risk Factors for NSAID-Induced Ulcer & Ulcer-Related Upper GI Complicationsa
Established
Confirmed prior ulcer or ulcer-related complication
Age >65 years
Multiple NSAID use
High-dose NSAID use
Concomitant use of aspirin (including cardioprotective dosages [81–325
mg/day])
 Concomitant use of an anticoagulant, corticosteroid, oral
bisphosphonate, antiplatelet drugs (e,g. clopidogrel), or SSRI
 Selection of NSAID (selectivity of COX-1 vs. COX-2)
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Controversial
 H. pylori
 Alcohol consumption
 Cigarette smoking
aCombinations
of risk factors are additive.
15
 The use of a nonselective NSAIDs is linked to a 3- to 4-fold  in
upper GI complications while there is a 2- to 3-fold  with partially
& highly selective COX-2 inhibitors.
 The risk for NSAID-induced ulcer & related complications is dose
related, but ulcers can occur at any dosage, including low doses of
OTC NSAIDs.
 Upper GI events can occur at any time during treatment with an
NSAID, as the risk for complications is similar throughout treatment.
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 Age is an independent risk factor for NSAID-induced ulcers, as risk 
linearly with the age of the patient. The  incidence in older
patients may be explained by age-related changes in gastric
mucosal defense.
 The relative risk of GI bleeding increases up to 20-fold when NSAIDs
are taken concomitantly with anticoagulants (e.g., warfarin) & up
to 6-fold with the concurrent use of SSRIs.
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 When clopidogrel is taken in combination with ASA, an NSAID, or
an anticoagulant, the risk of GI bleeding is increased compared with
when these agents are taken alone.
 Even when prescribed as monotherapy, clopidogrel increases the
risk of rebleeding for patients with history of a bleeding ulcer.
 Corticosteroids do not  the ulcer risk when used alone, but the
risk is  2fold in corticosteroid users who are also taking concurrent
NSAIDs.
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 High risk
 History of complicated peptic ulcer disease
 Multiple (>2) risk factors (see below)
 Moderate risk (1 to 2 risk factors)
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Age >65 years
High dose NSAID therapy
A previous history of an uncomplicated ulcer
Concurrent use of aspirin (including low dose), corticosteroids, or
anticoagulants
 Low risk
 No risk factors
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Nonselective NSAIDs
 The following conclusions were reached in a meta-analysis of controlled
trials involving some of the most commonly prescribed NSAIDs:
 The risk of GI complications was highest with indomethacin followed
by naproxen, diclofenac , tolmetin, piroxicam, ibuprofen, &
meloxicam.
 Ketorolac is also associated with a high risk of GI toxicity, particularly
when used in higher doses, in older patients, & for > 5 days.
 One study found that ketorolac was 5.5 times more likely to cause GI
toxicity than other NSAIDs.
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Aspirin & GI ulcer
 Enteric-coated ASA may protect against the topical mucosal damage in
the stomach & minimize dyspepsia, but does not prevent an ulcer from
forming.
 Taking food, milk, or an antacid with ASA or NSAIDs may minimize
dyspepsia but does not prevent an ulcer.
 Even low-dose ASA (e.g., 81 mg/day) remains capable of causing an ulcer,
especially when used in conjunction with a NSAID.
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Selective COX-2 inhibitors
 Data suggest that COX-2 inhibitors are associated a reduced risk of
GI bleeding compared with nonselective NSAIDs but the risk is
increased compared with placebo.
 Thus, COX-2 inhibitors may be safer than conventional NSAIDs for
reduction in the risk of GI bleeding but are still associated with an
increased risk.
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Celecoxib with low dose aspirin
 Any potential gastroduodenal sparing effect with selective COX-2
inhibitors may be abrogated when they are used concurrently
with low dose aspirin therapy for primary or secondary prevention
of CVD.
 Thus, patients receiving both aspirin & a selective COX-2 inhibitor
may require prophylactic antiulcer therapy if they are at increased
risk for gastroduodenal toxicity.
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Primary Prevention
 Strategies to  the risk of NSAID ulcers & upper GI complications in
a patient taking a nonselective NSAID include:
 Cotherapy with a PPI or misoprostol or
 Use of a selective COX-2 inhibitor in place of the nonselective NSAID
 Strategies aimed at reducing the topical irritant effects of
nonselective NSAIDs, e.g., prodrugs, slow-release formulations, &
enteric-coated products, do not prevent ulcers or GI complications.
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 PPI Cotherapy
 PPI cotherapy reduces NSAID-related gastric & duodenal ulcer risk & is better
tolerated than misoprostol.
Misoprostol Cotherapy
 Misoprostol  the risk of NSAID-induced gastric & duodenal ulcers.
 Initially, the recommended dosage was 200 mcg QID, but diarrhea &
abdominal cramping limited its use. A dosage of 200 mcg TID is comparable
in efficacy & should be used in patients unable to tolerate the higher dose.
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 H2-Receptor Antagonist Cotherapy
 Standard H2RA dosages (e.g., famotidine 40 mg/day) are effective in  NSAIDrelated DU but not GU.
 Higher dosages (e.g., famotidine 40 mg BID, ranitidine 300 mg BID) may
reduce the risk of GU & DU.
 The H2RAs are not recommended as prophylactic cotherapy because it is
likely that they are not as effective as the PPIs or misoprostol in preventing
NSAID-induced GU & related GI complications.
 An H2RA, however, may be used to relieve NSAID-related dyspepsia.
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 The approved doses of drugs in patients taking nonselective
NSAIDs include :
 Misoprostol (200 µg QID)
 Lansoprazole (15 or 30 mg daily)
 Esomeprazole (20 or 40 mg daily)
 Although not all PPIs have received FDA approval, they
probably all have similar effectiveness.
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Secondary Prevention
With continued NSAID therapy
 Considered together studies suggest that patients with gastroduodenal ulcers or
numerous erosions who must continue NSAID therapy should be treated with a
PPI for as long as the NSAID or aspirin is used.
 Omeprazole was found to be superior to ranitidine & misoprostol in maintaining
remission.
 Combination therapy with omeprazole & misoprostol did not appear to be more
effective than omeprazole alone. However, in this study, a low, possibly
suboptimal dose of misoprostol was used.
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 When COX-2 inhibitors were first introduced, these agents appeared to
hold promise as an alternative to traditional NSAIDs in preventing
recurrent PUD in individuals who required ongoing antiinflammatory
therapy. However, the relative risk reduction in GI bleeding associated
with these agents appears to be modest at best.
 Replacing a COX-2 inhibitor for the nonselective NSAID in patients with
NSAID-related ulcer disease should not be chosen over PPI maintenance
therapy.
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With continued low-dose aspirin
 Patients with low-dose aspirin(75 to 325 mg/day) have an increased risk of GI
bleeding, which must be weighed against a possible increase in mortality.
 Patients who have had a bleeding ulcer while taking low-dose aspirin therapy
should be treated with a PPI (rather than an H2-blocker), along with H. pylori
eradication if they test positive for H. pylori.
 There are no compelling data that suggest that any of the available PPIs are
more effective than another.
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Treatment
 If a patient develops an ulcer while on a NSAID or low-dose aspirin, the
NSAID or low-dose aspirin should be stopped if at all possible &
traditional ulcer therapy with a PPI or an H2 antagonist started.
 PPIs are generally preferred because they are associated with more
rapid ulcer healing.
 For patients who must remain on low-dose aspirin or NSAID therapy,
randomized trials have shown that ulcer healing occurs more rapidly with
a PPI than an H2 antagonist, misoprostol, or sucralfate.
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 Treatment with a PPI is generally continued for 4 to 8 weeks,
depending on the ulcer location (duodenal or gastric), the
original ulcer size & the severity of the initial clinical
presentation.
 Maintenance therapy is indicated in patients who remain on
or resume NSAID treatment.
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RENAL EFFECTS
 NSAID can induce two different forms of AKI:
 Hemodynamically-mediated
 Acute interstitial nephritis, Nephrotic syndrome
 The former & perhaps the latter are directly related to the
reduction in PG synthesis induced by the NSAID.
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Hemodynamically-mediated AKI
 Acute kidney injury can occur with any NSAID.
 The selective COX-2 inhibitors also may precipitate AKI in certain patients.
 There has been concern that ketorolac might have greater nephrotoxic potential
than other NSAIDs.
 There is suggestive evidence that some nonselective NSAIDs have a lower
nephrotoxic potential than others. Low-dose aspirin (studied at
approximately 40 mg per day), low-dose OTC ibuprofen, & perhaps
sulindac appear to be safer; one proposed mechanism is relative sparing
of renal PG synthesis.
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Acute Interstitial Nephritis &
Nephrotic Syndrome
 Affected patients typically present with hematuria, pyuria, white cell
casts, proteinuria, & an acute rise in the SrCr.
 The full picture of an allergic reaction — fever, rash, eosinophilia, &
eosinophiluria — is typically absent but one or more of these findings may
be present.
 Spontaneous recovery generally occurs within weeks to a few months
after therapy is discontinued.
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 All NSAIDS should be terminated in patients suspected of having NSAIDinduced acute interstitial nephritis. Since topically administered NSAIDs
can be systemically absorbed, such therapy should also be terminated.
 There is no definitive evidence that corticosteroid therapy is beneficial in
this setting. However, a course of prednisone may be considered in
patients whose renal failure persists > 1 to 2 weeks after the NSAID has
been discontinued.
 Such patients should avoid the subsequent administration of NSAIDs.
Relapse may occur with rechallenge.
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CARDIOVASCULAR EFFECTS
 NSAIDs have a variety of effects on the cardiovascular system.
 Interference with the beneficial antiplatelet activity of aspirin
 An increase in cardiovascular events
 Exacerbation of heart failure
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Interference with Aspirin
 The beneficial antiplatelet effects of aspirin for secondary or primary
prevention of CVD result from irreversible acetylation of the active site of
COX in platelets; these effects may be attenuated by prior or ongoing
administration of some nonselective NSAIDs, including ibuprofen & naproxen.
 Thus, regular NSAID use should be avoided, if possible, in patients taking
low-dose aspirin for cardiovascular protection.
 In patients who require NSAIDs on an occasional short-term basis, we suggest
that aspirin be taken at least 2 h before the NSAID, although the data are
limited.
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Effect On Cardiovascular Risk
 The effect of NSAID therapy on cardiovascular risk has been
evaluated with both the nonselective & COX-2 selective
NSAIDs; medications within both NSAID classes appear to
increase such risk.
 The degree of COX-2 selectivity, even among nonselective
NSAIDs, may be related to the level of risk.
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 Naproxen appears to be the safest with respect to such risk,
although an increased risk of MI or stroke with naproxen use
has also been reported.
 Several COX-2 selective inhibitors (eg, rofecoxib) have been
withdrawn from the market because of an increased risk of
ischemic cardiovascular events.
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Exacerbation Of Heart Disease
 Use of NSAIDs may cause worsening of HF & an increased risk of new
events, including MI, in patients with established heart disease.
 If NSAIDs are required, they should be used at the lowest effective dose &
for the shortest duration necessary for the given indication.
 We suggest naproxen for patients with known CVD or increased CV
risk who require treatment with a nonselective NSAID, when an
equivalent therapeutic intervention is not available.
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Elevation In Blood Pressure
 All NSAIDs in doses adequate to reduce inflammation & pain can increase
BP in both normotensive & hypertensive individuals. The average rise in
BP is 3/2 mmHg but varies considerably.
 These effects may contribute to the increase in cardiovascular risk
associated with the selective COX-2 inhibitors.
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Consensus Statements & Guidelines
 High GI/high CV risk: should not receive NSAIDs, including COX-2 inhibitors
 High GI/low CV risk: should receive a COX-2 inhibitor PLUS a PPI or misoprostol
 Moderate GI/low CV risk: should receive a COX-2 inhibitor alone or a conventional
NSAID PLUS a PPI or misoprostol.
 Moderate GI/high CV risk: should receive naproxen PLUS a PPI or misoprostol
 Low GI/high CV risk: should receive naproxen PLUS a PPI or misoprostol
 Low GI/low CV risk: can receive a conventional NSAID alone, although the "least
ulcerogenic NSAID at the lowest effective dose" is recommended.
 All patients regardless of risk who are about to start long-term traditional NSAID
therapy should be considered for testing for H. pylori & treated if positive.
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HEPATIC INJURY
 Elevations of serum aminotransferases are commonly associated with
NSAID use; however, liver failure is quite rare.
 Sulindac was the only NSAID with a substantially greater risk than that of
the overall NSAID group; However, the liver injury associated with
sulindac & the other NSAIDs was generally mild & reversible.
 Diclofenac has been reported to cause clinical hepatitis. Introduction of
another class of NSAID in many of these patients appeared to be safe.
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 Hepatotoxicity is rare, & the cost-effectiveness of monitoring serum
transaminase levels is uncertain.
 However, if the aminotransferases are noted to rise to > 3 times the
upper limit of normal, if there is a fall in serum albumin (suggestive of a
synthetic defect induced by the drug), or if the INR is prolonged, NSAID
toxicity should be suspected, & the potentially offending agent should be
discontinued.
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HEMATOLOGIC EFFECTS
 Some of the early NSAIDs (eg, phenylbutazone and, to a lesser degree,
indomethacin) have been associated with an increased risk for bone
marrow failure (ie, aplastic anemia).
 Although phenylbutazone is rarely used, neutropenia & antiplatelet
effects can be induced by any of the NSAIDs.
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 For most NSAIDs, platelet function normalizes within 3 days of
discontinuation, suggesting that NSAIDs should generally be
discontinued at least 3 days before surgery.
 In healthy individuals receiving ibuprofen for one week, platelet function
appears to return to normal within 24 h after the last dose; thus,
ibuprofen can be stopped 24 h prior to surgery.
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 Aspirin irreversibly inhibits platelet COX, & platelets lack the machinery to
produce new COX. Thus, if aspirin is discontinued preoperatively, patients
should stop aspirin for at least 1 week prior to a planned surgical
procedure to allow the body to generate new platelets that have not
been exposed to aspirin.
 Highly selective inhibitors of the COX-2 have little or no
effect on the platelet, since COX-2 activity has not been found in
platelets.
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CENTRAL NERVOUS SYSTEM
 Psychosis & cognitive impairment:
 Are more prevalent in older patients, particularly with the use of
indomethacin. Thus, indomethacin should be prescribed judiciously in
geriatric patients, with close attention to mental status changes.
 Tinnitus:
 Is a common problem in patients who are prescribed high doses of
salicylates. Although it can occur with all of the available NSAIDs, it is less
commonly seen among non-salicylate NSAIDs. Tinnitus is typically reversible
upon cessation of drug therapy & is a good warning sign to identify those
patients who are developing high blood levels of the drug.
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MUSCULOSKELETAL EFFECTS
Possible effect on fracture healing
 A causal relationship has not been proven, & the effect of these drugs on
fracture healing in humans is uncertain.
Possible effect on tendon injury
 Animal studies suggest a theoretical adverse impact of some NSAIDs (both
nonselective & COX-2 selective) on healing from tendon & ligament injuries for
which NSAIDs are often used. However, there are no published human data
demonstrating such effects.
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ELECTROLYTE COMPLICATIONS
 In the setting of effective volume depletion, NSAIDs can produce a
variety of complications related to renal dysfunction, each of which is
reversible with discontinuation of therapy.
 These include hyperkalemia, hyponatremia, & edema. These
complications are mediated in part by reductions in the secretion of renin
& aldosterone & by increased activity of ADH.
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Drug interactions
 NSAIDs can interact with numerous drugs:
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Anticoagulants
antiplatelet agents
Antihypertensives
Diuretics
Glucocorticoids
Lithium
SSRIs
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Acetaminophen
 Initial dose per day (mg)
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PO: <2600
IV: <2600
 Usual analgesic dose and interval
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PO: 325 to 1000 mg every 4 to 6 h
IV: 650 mg every 4 h or 1000 mg ever 6 h, or 15 mg/kg every 6 h for patients Wt <50 kg
 Maximum dose per day (mg)
 4000
 4000; maximal daily dose 75 mg/kg if <50 kg
 Role in therapy


PO: Treatment of mild pain and minor febrile conditions. Lacks significant antiinflammatory effect.
IV: Short term treatment of mild to moderate acute pain and febrile conditions when oral
administration is not available and as an adjunct to opiate analgesics for the treatment of
moderate to severe pain.
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Aspirin
 Initial dose per day (mg)
• PO: 2600
 Usual analgesic dose and interval
• PO: 325 to 650 mg every 4 to 6 h
 Maximum dose per day (mg)
• 4000
 Role in therapy
 Now used infrequently for treatment of chronic pain and inflammation due to
its association with severe gastropathy. Unlike other NSAIDs, irreversibly
inhibits platelet function for platelet life (7 to 10 days) .
Dr. Mohammad Taraz
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Ibuprofen
 Initial dose per day (mg)
 PO: 1600
 IV: 1600
 Usual analgesic dose and interval
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PO: 400 mg every 4 to 6 h
IV: 400 to 800 mg every 6 h
 Maximum dose per day (mg)
 3200 acute, 2400 chronic
 3200 (acute)
 Role in therapy


PO: Treatment of mild to moderate pain, minor fever and acute or chronic inflammatory
conditions. Reversibly inhibits platelet function and increases bleeding time. Can alter
cardioprotective effect of low dose aspirin.
IV: Short term treatment of mild to moderate acute pain and febrile conditions when oral
administration is not available
Dr. Mohammad Taraz
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Naproxen
 Initial dose per day (mg)
• 500 once
 Usual analgesic dose and interval
• 250 mg every 8 h or 500 mg every 12 h
 Maximum dose per day (mg)
• 1250 acute, 1000 chronic
 Role in therapy
 Treatment of mild to moderate pain, minor fever and acute and chronic inflammatory
conditions. In the treatment of rheumatologic disorders, total daily dose may be
increased to a maximum of 1500 mg when needed for added effect.
 Reversibly inhibits platelet function and increases bleeding time. Can alter
cardioprotective effect of low dose aspirin.
 Appears to have the greatest relative cardiovascular safety profile among
nonselective COX-2 inhibitors.
Dr. Mohammad Taraz
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Diclofenac
 Initial dose per day (mg)
• 75 or 100 mg once
 Usual analgesic dose and interval
• 50 mg every 8 h
 Maximum dose per day (mg)
• 150 mg
 Role in therapy
 For treatment of mild to moderate pain and acute or chronic inflammation.
Dr. Mohammad Taraz
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Tolmetin
 Initial dose per day (mg)
• 600
 Usual analgesic dose and interval
• 400 to 600 mg every 8 h
 Maximum dose per day (mg)
• 1800
 Role in therapy
For treatment of chronic pain and inflammation, OA and RA.
Dr. Mohammad Taraz
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Sulindac
 Initial dose per day (mg)
• 300
 Usual analgesic dose and interval
• 150 to 200 mg every 12 h
 Maximum dose per day (mg)
• 400
 Role in therapy
 For treatment of acute and chronic pain and inflammatory conditions.
 More frequently implicated in hepatotoxicity than other NSAIDs.
Dr. Mohammad Taraz
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Indomethacin
 Initial dose per day (mg)
• 75
 Usual analgesic dose and interval
• 25 to 50 mg every 8 to 12 h
• Controlled release: 75 mg every 12 h
 Maximum dose per day (mg)
• 150
 Role in therapy
 An alternate, non first-line option for treatment of mild to moderate pain and
acute or chronic inflammatory conditions.
 GI and CNS adverse effects may be more frequent or severe than with
other NSAIDs.
Dr. Mohammad Taraz
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Ketorolac (IV and IM)
 Initial dose per day (mg)
• <65 yrs 60 mg IV or IM once
• ≥65 yrs 30 mg IV or IM once
 Usual analgesic dose and interval
• <65 yrs 15 to 30 mg every 6 h
• ≥65 yrs 15 mg every 6 h
 Maximum dose per day (mg)
• <65 yrs 120
• ≥65 yrs 60
 Role in therapy
 Short term treatment of moderate acute pain when oral administration of
an NSAID is not available and as an adjunct to other analgesics for the
treatment of moderate to severe postoperative pain. Risk of gastropathy is
increased when use exceeds 5 days.
Dr. Mohammad Taraz
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Meloxicam
 Initial dose per day (mg)
• 7.5
 Usual analgesic dose and interval
• 7.5 to 15 mg every 24 h
 Maximum dose per day (mg)
• 15
 Role in therapy
 For treatment of chronic pain and inflammation, osteo- and rheumatoid arthritis. Once
daily dosing may be useful.
 While reported to be selective for COX-2 at lower dose of 7.5 mg, overall adverse
effects are similar to other NSAIDs.
Dr. Mohammad Taraz
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Piroxicam
 Initial dose per day (mg)
• 10
 Usual analgesic dose and interval
• 10 to 20 mg every 24 h
 Maximum dose per day (mg)
• 20
 Role in therapy
 An alternate, non first-line option for treatment of chronic pain and inflammation
poorly responsive to other NSAIDs. Comparatively high incidence of gastropathy
in daily dose above 20 mg and in older adults.
Dr. Mohammad Taraz
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Mefenamic acid
 Initial dose per day (mg)
• 500 once
 Usual analgesic dose and interval
• 250 mg every 6 h
 Maximum dose per day (mg)
• 1000
 Role in therapy
 For acute pain and dysmenorrhea. Anti-inflammatory efficacy is
comparatively low.
Dr. Mohammad Taraz
64
Celecoxib
 Initial dose per day (mg)
• 400 once
 Usual analgesic dose and interval
• 200 mg daily or 100 mg every 12 h
 Maximum dose per day (mg)
• 400
 Role in therapy
 An option for patients requiring chronic NSAID treatment who may be at risk
for gastropathy. No effect on platelet function. Dosage above 200 mg daily
associated with increased cardiovascular risk.
Dr. Mohammad Taraz
65