McKenna's Pharmacology for Nursing, 2e

248

P A R T 3  Drugs acting on the immune system

TABLE 16.2

DRUGS IN FOCUS Non-steroidal anti-inflammatory drugs (NSAIDs) and related agents (continued)

Drug name

Dosage/route

Usual indications

etoricoxib (Arcoxia)

30 mg/day PO up to maximum 60mg/day PO Treatment of osteoarthritis, gouty arthritis, acute pain

paracoxib (Dynastat) Related agent paracetamol (Panadol, Panamax, Dymadon, Febridol and others)

40 mg IM or IV as single dose

Postoperative pain

Adults and children over 12 years: one to two tablets every 4–6 hours with water Maximum of eight tablets in 24 hours Maximum daily dose: 4000 mg Children 7 to 12 years: Half to one tablet every 4–6 hours with water Maximum of four tablets in 24 hours For Adults: Do not use for more than a few days at a time, except on medical advice For children ages 7–17: Do not use for more than 48 hours, except on medical advice

Relief of pain and fever in a variety of situations

The evidence

BOX 16.4

Cyclooxygenase-2 inhibitors In late 2004, Merck voluntarily withdrew their

believed that the benefits of marketing the drug did not outweigh the potential risks for using the drug. Celecoxib (Celebrex) remains on the market.The APC study (Adenoma Prevention with Celecoxib) did show a two- to threefold increase in CV events among people using the drug compared with a placebo over 33 months. There did seem to be a dose correlation, with more events in the group using a higher dose. A nearly identical study, the PreSAP trial (Prevention of Spontaneous Adenomatous Polyps), showed no increase in CV events in the group using celecoxib. A small study, the ADAPT (Alzheimer’s Disease Anti-inflammatory PreventionTrial), did not appear to show an increase in CV events in the people in that study. The media helped to fuel a real concern about the safety of any anti-inflammatory medication.The questions remain: Were the CV events related to dosage, length of drug use, or the underlying conditions of the people being studied?Were the CV events a direct effect of the COX-2 inhibitor?Would these same events have occurred if the drug were used at the dosages approved and for the approved length of time? More long-term, controlled studies are needed to answer these questions. In the meantime, the FDA has recommended that valdecoxib and rofecoxib stay off the market until appropriate guidelines and controls are in place for their return; that all NSAIDs’ packaging information include warnings that there is potential risk for increased CV events as well as the risk of GI bleeding, and that healthcare providers use caution in recommending these drugs to anyone with an established CV risk; that all prescription NSAIDs be contraindicated in people immediately after CABG surgery; and that the prescribing information for celecoxib include a black-box warning referencing the available data about increased CV risk.Two new COX-2 inhibitors being studied, lumiracoxib and etoricoxib, will be carefully reviewed for data on the incidence of increased CV events before they will be considered for approval.

cyclooxygenase-2 (COX-2) inhibitor, rofecoxib (Vioxx), from the market following release of a midstudy finding that the use of the drug over an 18-month period led to a significant increase in cardiovascular (CV) mortality in those taking the drug compared with a placebo group. The study, called the APPROVe study (Adenomatous Polyp Prevention on Vioxx), was targeted at testing whether the blocking of such growth factors as angiogenesis could decrease cancer risk in a specific population.The study participants took 25 mg of Vioxx each day for 18 months (the halfway point in the study) when the finding of increased CV events was announced and the study was stopped.The CV outcomes were not noted earlier than 18 months. Interestingly, other studies, including a 4-year study of the effects on Alzheimer’s disease, did not show a significant difference in CV events between the placebo and drug groups.Yet, in the VIGOR (Vioxx Gastrointestinal Outcomes Research) study, in which rofecoxib was compared with naproxen (another NSAID) for 12 months, increased CV events were noted in the rofecoxib group after only 2 months. The US Food and Drug Administration (FDA) formed a committee to study the COX-2 inhibitors and then all of the NSAIDs on the market to see if there were any problems in oversight of drug safety and to make recommendations about the future use of these drugs. Valdecoxib (Bextra) was withdrawn from the market at FDA request after the committee reviewed data. A small study did show an increase in CV events, including death, when Bextra was used immediately in postoperative people recovering from coronary artery bypass graft (CABG) surgery.The drug was not proven to be especially more effective than other NSAIDs for relieving pain, and already had a black-box warning about the increased possibility of severe skin reactions, including Stevens– Johnson syndrome. With those facts in mind and the possibility of a COX-2 link to increased CV events, the FDA