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NSAIDS - DARE TO COMPARE - RxFiles

NSAIDsDARE TO COMPARETheRxFilesTheRxFilesTheRxFilesThe RxFilesJuly 1997 vProduced by the Community Drug Utilization Program,a Saskatoon District Health/St. Paul's Hospital programfunded by Saskatchewan Health. For more information checkour website or, contact Loren Regier C/O Pharmacy Department, Saskatoon City Hospital, 701 Queen St. Saskatoon, SK S7K 0M7, Ph (306)655-8506,Fax (306)655-8804; Email have come a long way from the days of willowbark. Today salicylates and non-steroidal anti-inflammatory drugs ( NSAIDS ) comprise one of thelargest and most commonly prescribed groups ofdrugs In Saskatchewan, over 20different agents are available, accounting for morethan 300,000 prescriptions and over $7 million insales each year (Saskatchewan Health-Drug Plandata 1996).

NSAIDs DARE TO COMPARE TheRxFiles July 1997 v Produced by the Community Drug Utilization Program, a Saskatoon District Health/St. Paul's Hospital program funded by Saskatchewan Health. For more information check

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Transcription of NSAIDS - DARE TO COMPARE - RxFiles

1 NSAIDsDARE TO COMPARETheRxFilesTheRxFilesTheRxFilesThe RxFilesJuly 1997 vProduced by the Community Drug Utilization Program,a Saskatoon District Health/St. Paul's Hospital programfunded by Saskatchewan Health. For more information checkour website or, contact Loren Regier C/O Pharmacy Department, Saskatoon City Hospital, 701 Queen St. Saskatoon, SK S7K 0M7, Ph (306)655-8506,Fax (306)655-8804; Email have come a long way from the days of willowbark. Today salicylates and non-steroidal anti-inflammatory drugs ( NSAIDS ) comprise one of thelargest and most commonly prescribed groups ofdrugs In Saskatchewan, over 20different agents are available, accounting for morethan 300,000 prescriptions and over $7 million insales each year (Saskatchewan Health-Drug Plandata 1996).

2 Despite the wide selection, NSAID sare more alike than different. Although they dodiffer in chemical structure, pharmacokinetics, andto some degree pharmacodynamics, they sharesimilar mechanisms of action, efficacy, and work by inhibiting cyclooxygenase (COX)and subsequent prostaglandin synthesis as well asby other less understood mechanisms. Incomparative studies between NSAIDS , no clinicallysignificant differences in efficacy have Wide variability in patients response maybe due to differences in pain threshold, diseaseseverity, cyclooxygenase configuration, and otherfactors. Since there is no method of predicting whowill respond to which NSAID, initial selection isempiric.

3 About 60% of patients will respond to aspecific NSAID; non-responders are just as likelyto respond to an alternate agent particularly if it isfrom a different chemical of analgesia occurs rapidly with all NSAIDS ,usually within one hour. In recent years, moreexpensive, fast-acting formulations of someNSAIDs have been introduced. They are morequickly absorbed, and have a more immediate onset. While this may be advantageous in somehighly acute situations, the benefit beyond theinitial dose and in treatment of chronic pain isdoubtful. In addition, anti-inflammatory activityoften requires aHighlights All NSAIDS have similar efficacy and sideeffect profiles In low risk patients, Ibuprofen and naproxenmay be first choice agents because they areeffective, well tolerated and inexpensive Acetaminophen is the recommended first lineagent for osteoarthritis Misoprostol is the only approved agent forprophylaxis of NSAID-induced ulcers and isrecommended in high risk patients if NSAIDS cannot be or more to become established.

4 For thisreason, an adequate trial of 1-2 weeks should beallowed before increasing the dose or changing toanother NSAID. Combining NSAIDS is notrecommended as it has no additive analgesic effectand increases risk of (Toradol ) is sometimes mistaken for ananalgesic superior to the NSAIDS since it is oftencompared with the opiates. In reality, its analgesiais similar to ibuprofen and its anti-inflammatoryeffects are poor compared with other Itsonly advantage is that it is available in injectableform which can be used in situations where oralNSAIDs are excluded (eg. acute post-op period).ADVERSE EFFECTSNSAIDs cause a variety of side effects includingnausea, diarrhea, constipation, dizziness, headache,confusion, edema, rash, and pruritis.

5 They can alsocause more serious toxicities such as gastro-intestinal (GI) ulceration/bleeding, hematologicdisturbances, bronchospasm, angioedema, renaldysfunction, and hepatotoxicity. Many of these arerelated to NSAID inhibition of prostaglandinsynthesis other than at the desired site of salicylates are weak inhibitors ofprostaglandin synthesis and are less apt to causeadverse allergic, gastric, renal, or antiplatelet differences in toxicity between NSAID smust be interpreted in light of different utilizationpatterns and interpatient side effects are most common. Thepropionic acid derivatives such as ibuprofen andnaproxen are generally better tolerated than otherNSAIDs.

6 Enteric coated (EC) products may reducecomplaints of stomach upset but do not appear toreduce the incidence of GI ulceration. Injectableketorolac, suppository formulations, and pro-drugswhich are activated after absorption from the GI tractalso do not eliminate the problem of gastric Development of more selective COX-2inhibitors such as nabumetone and etodolac thatpreferentially inhibit cyclooxygenase at sites ofinflammation rather than in the internal organs mayhold some promise. However, long-term studies arelacking to validate claims of reduced GI GI complications may be more closely relatedto dose and duration of therapy than to any Since risk is greatest at the high end ofdosing ranges and during the first 3-6 months, dosesand duration should be minimized as much astherapeutically should be avoided in patients at high riskfor GI complications (Tables 1,2).

7 However if theiruse cannot be avoided, addition of a prophylacticagent to reduce ulceration is is the only agent approved for theprevention of NSAID induced ulcers. Misoprostolhas been shown to significantly reduce the incidenceof both gastric and duodenal ulcers in NSAID misoprostol may cause GI side effects suchas diarrhea, a gradual dosage titration may help toimprove patient tolerance and compliance. Acombination of misoprostol and ibuprofen was foundto cause a lower incidence of endoscopic ulcers thanthe selective COX-2 agent, H2blockers (eg. ranitidine), omeprazole, and sucralfateare not indicated for the prevention of NSAID induced gastric failure may result when NSAIDS are used inpatients whose kidney perfusion is dependent onlocal prostaglandin production.

8 Sulindac wasthought to have a renal sparing effect but it appearsto be only marginally safer and cannot be prescribedwithout The COX-2 inhibitors may prove tobe less toxic but supporting data is lacking. NSAID sshould be avoided in those at high risk ofnephrotoxicity (Table 3).A recent review of NSAID utilization patterns inSaskatchewan revealed that a significant number ofpatients have concomitant prescriptions for H2blockers, ACE inhibitors, diuretics, and multipleNSAIDs .12 This raises the concern that high riskpatients may be receiving inappropriate most notable difference among NSAIDS is prices vary considerably, ranging fromless than $10 a month for ibuprofen to more than$100 for high dose etodolac.

9 The cost of treatingNSAID-related complications has additional impacton the health care system. Treatment of GI problemsalone is estimated to add over 40% to the cost ofarthritis Newer, more expensive agents do notguarantee safer, more effective treatment, and in themajority of cases do not offer significant advantagesover previously available NSAIDS . Ibuprofen andnaproxen are recommended as first line agents asthey are effective, inexpensive, and generally well-tolerated in low risk CONSIDERATIONS Consider non-pharmacologic treament ( , weight loss, hot/cold therapy) Consider using acetaminophen before NSAIDS inosteoarthritis (eg. acetaminophen in doses of up to4 g/day is highly effective, well tolerated, and saferthan NSAIDS in osteoarthritis, and should beconsidered the drug of choice)14 Try less expensive agents first (eg.)

10 Ibuprofen,naproxen) when an NSAID is indicated Use the lowest effective dose and as short aduration as possible without compromising care Allow 1-2 weeks before increasing dose orchanging agents Avoid combinations of NSAIDS Avoid NSAIDS if possible in patients at high risk ofGI or renal complicationsWe wish to acknowledge those who have assisted in the development andreview of this newsletter: Dr. Z. Tymchak (FM), Dr. P. Peloso (Rheum.),Dr. J. Richardson (Pharm.), and the CDUP Advisory Loren D. Regier BSP,BA; Sharon L. Downey BSPThe Rx Files: NSAIDS - Dare to CompareSupplementary ChartsTable 1 Risk Groupsfor NSAID Induced Ulcers*15 Age: >65 years Previous GI History: Recent Peptic Ulcer Disease Previous GI Bleed Coexisting Significant Disease Cardiovascular Hepatic or Renal Impairment Concomitant Therapy with: Corticosteroids (eg.


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