Pharmacology Watch
Dual Antiplatelet Therapy? Consider H2 Blockers, not PPIs
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In this issue: Clopidogrel and proton pump inhibitors; adverse events with tamsulosin after cataract surgery; new guidelines for persistent pain in the elderly; and FDA Actions.
PPIs and clopidogrel—Bad combination
Proton pump inhibitors (PPIs) should not be combined with clopidogrel (Plavix®) based on the results of a study presented at the Society for Cardiovascular Angiography and Interventions (SCAI) in May. PPIs, such as esomeprazole (Nexium®), omeprazole (Prilosec®), lansoprazole (Prevacid®), and pantoprazole (Protonix®), are frequently prescribed with clopidogrel to prevent GI complications and bleeding. Some guideline groups actually recommend the combination routinely, and as a result more than 50% of people on clopidogrel are currently on a PPI as well. In the study presented to the SCAI, 16,690 patients were evaluated who took clopidogrel for a year after coronary stenting. Patients taking the combination of a PPI and clopidogrel experienced a 50% increase in the combined risk of hospitalization for heart attack, stroke, unstable angina, or repeat revascularization compared to those on clopidogrel alone. The overall rate for combined events was 17.9% for clopidogrel alone, 24.3% for lansoprazole, 24.9% for esomeprazole, 25.1% for omeprazole, and 29.2% for pantoprazole. Patients enrolled in the study took PPIs for an average of 9 months. The SCAI points out that while this is the largest trial to date to examine the interaction between PPIs and clopidogrel, other smaller studies have indicated similar findings. It is theorized that the mechanism is mediated by PPIs blocking the conversion of the prodrug clopdogrel to its active metabolite, which has antiplatelet activity. Currently, SCAI is recommending more research, but in the meantime health care providers who are treating post-stent patients on dual antiplatelet therapy should consider prescribing an H2 blocker, such as ranitidine (Zantac®), famotidine (Pepcid®), or cimetidine (Tagamet®), instead of a PPI. The full statement can be found at www.SCAI.org.
Tamsulosin increases cataract complications
Men who take tamsulosin (Flomax®) within 2 weeks of cataract surgery are at higher risk of serious eye complications according to a new study. Tamsulosin is commonly used to treat symptoms of benign prostatic hyperplasia (BPH) in older men, the same demographic that commonly requires cataract surgery. Researchers from Canada reviewed the records of 3550 patients who had recent exposure (within 2 weeks) to tamsulosin and 7426 patients who had recent exposure to other α-blockers from the database of more than 96,000 men who had cataract surgery between 2002 and 2007. Adverse events were significantly more common among men with recent tamsulosin exposure (7.5% vs 2.7%), but were not associated with recent exposure to other α-blockers (7.5% vs 8.0%) or to exposure to tamsulosin more than 2 weeks prior to surgery. The number needed to harm was 255 for recent exposure to tamsulosin. Complications after cataract surgery included floppy iris syndrome, retinal detachment, loss of lens or fragments, and endophthalmitis (JAMA 2009;301:1991-1996). It is postulated that tamsulosin, a selective α-blocker, targets receptors in the bladder and iris. An accompanying editorial suggests that "the data on the risk of this complication should be reassessed to determine whether a "black box" warning should be issued to caution the ophthalmic surgeon and the general public (men in particular) of danger to the eye of taking a1-adrenergic blocking agents before cataract surgery" (JAMA 2009;301:2044-2055).
New guidelines for persistent pain in elderly
The American Geriatrics Society has updated its "Pharmacological Management of Persistent Pain in Older Persons" guideline first published 11 years ago and last updated in 2002. The most dramatic change in the guideline is the new recommendation that NSAIDs (both nonselective NSAIDs and COX-2 inhibitors) should be considered only with "extreme caution" in older adults in whom other safer therapies have failed. Absolute contraindications for NSAIDs include chronic kidney disease and heart failure, and relative contraindications include hypertension, H. pylori infection, history of peptic ulcer disease, and concomitant use of corticosteroids or SSRIs. If a nonselective NSAID must be used in older persons or if a COX-2 inhibitor is given with aspirin, a proton pump inhibitor or misoprostol should also be used for gastrointestinal protection. The guideline further recommends that all patients on a nonselective NSAIDs or COX-2 inhibitor should be routinely assessed for gastrointestinal and renal toxicity, hypertension, heart failure, and other side effects. Acetaminophen should be considered as "initial and ongoing pharmacotherapy in the treatment of persistent pain," particularly for musculoskeletal pain. Opioids may be considered in all patients with moderate-to-severe pain or diminished quality of life due to pain. Patients with fibromyalgia or neuropathic pain are candidates for adjuvant analgesics. The full guideline is available at www.americangeriatrics.org.
FDA Actions
Two topical testosterone gel products must carry boxed warnings on their labeling after an FDA ruling that the gels may cause adverse effects in children who are inadvertently exposed by contact with adults who are using the products. Testosterone gel is approved for use in men with low testosterone levels and is applied to the shoulders and abdomen. The gels are also occasionally used for off-label indications in women. The FDA has received reports of several cases of secondary exposure in children, and more cases are under review. Exposed children showed signs of enlargement of the genitalia, premature development of pubic hair, advanced bone age, increased libido, and aggressive behavior. The FDA recommends that adults wash their hands after application of the gel, cover the application site with clothing, and wash thoroughly where any skin to skin contact may occur. The products affected by the boxed warning include AndroGel® 1% and Testim® 1%.
The FDA has approved a new atypical antipsychotic drug for treatment of schizophrenia. Iloperidone (Pantheon, Inc.) will carry the same boxed warning as other atypical antipsychotics regarding the increased risk of death associated with dementia-related psychosis. Iloperidone will be marketed as Fanapt™.
The FDA is warning consumers to immediately stop using Hydroxycut dietary supplements marketed for weight loss, as fat burners, as energy enhancers, as low-carb diet aids, and diuretics. Hydroxycut products have been associated with a number of serious liver injuries including jaundice and elevated liver enzymes, liver damage requiring liver transplant, and liver failure. Other health problems include seizures, cardiovascular disorders, and rhabdomyolysis. One death has been reported. Iovate Health Sciences is recalling 14 products under the Hydroxycut brand.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: [email protected].
Clopidogrel and proton pump inhibitors; adverse events with tamsulosin after cataract surgery; new guidelines for persistent pain in the elderly; and FDA Actions.Subscribe Now for Access
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