Pharmacology Watch

Medication Poisonings Are Increasing in Children

In this issue: Medication poisonings in children; rosuvastatin vs atorvastatin for atherosclerosis; saw palmetto for prostate symptoms; using atypical antipsychotics for off-label indications in adults; and FDA actions.

More medications, more poisonings

Medication poisonings among young children have increased in frequency in recent years despite safety measures to prevent them, according to a new study from Pediatrics. Researchers used patient records of more than 450,000 children 5 years old or younger from 2001-2008. The rate of poisoning increased by about a third during this time span compared to the prior decade. Child self-exposure was responsible 95% of the time with ingestion of prescription drugs causing more than half of the poisonings and more than 70% of significant injuries. The most dangerous drugs were opioids, sedative-hypnotics, and cardiovascular agents. The authors conclude that the number of children visiting emergency departments after medication exposure is increasing, with the majority of ingestions caused by children finding and ingesting medications by themselves. They suggest that efforts at poison-proofing homes with young children "may be a good, but insufficient, strategy." They further suggest that the increase in poisonings is in part due to the rise in number of medications in the environments of young children, with the number of adults taking medications, especially opioid medications, rising dramatically in the last 10 years. Other possible explanations include more siblings on medications, especially ADHD meds, as well as exposure to grandparents' homes where childproofing may not be as rigorous. They further conclude that current preventive efforts are inadequate and new measures, such as efforts targeting home medication safety (including storage of medications and child-resistant closures) and repackaging (such as blister packs and flow restrictors on liquid medications), should be considered. (Pediatrics published online September 16, 2011.)

Rosuvastatin no better than atorvastatin

Rosuvastatin is no better than atorvastatin in slowing progression of coronary atheroma, according to AstraZeneca, the manufacturer of rosuvastatin and sponsor of the study. Researchers compared rosuvastatin 40 mg to atorvastatin 80 mg in the Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin vs Atorvastatin (SATURN) trial. The primary efficacy endpoint was change from baseline in percent atheroma volume in a targeted coronary artery as assessed by intravascular ultrasound. After 104 weeks of treatment in some 1300 patients, there was a numerical greater reduction in favor of rosuvastatin, but the reduction did not reach statistical significance ( The full results will be presented at the American Heart Association meeting in November. The results come as a blow to the manufacturer of rosuvastatin (Crestor) who had hoped to gain a marketing advantage before the introduction of low-cost generic atorvastatin into the market, slated for December.

Saw palmetto for prostate symptoms

Saw palmetto is ineffective for treating lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH), even at higher doses, according to a new study. Previous studies have shown no benefit from saw palmetto, but researchers in this current study set out to test the efficacy of 2-3 times the normal daily dose on men over the age of 45 with significant LUTS. The main outcome was the difference in American Urologic Association Symptom Index score between baseline and week 72. Both saw palmetto and placebo led to an improvement in symptoms with a favorability toward placebo regardless of the dose of saw palmetto. Doses tested were a single 320 mg tablet per day with dose escalation to 2, then 3, tablets per day. The authors conclude that increasing doses of saw palmetto root extract did not lower LUTS more than placebo in men with BPH (JAMA 2011;306:1344-1351). This is the second rigorously controlled trial after the Saw Palmetto Treatment for Enlarged Prostates study (N Engl J Med 2006;354:557-566) to show no benefit from the supplement on LUTS in men with BPH.

Off-label use of atypical antipsychotics

Controversy surrounds the use of atypical antipsychotics for off-label indications in adults, especially the elderly with dementia. A new meta-analysis reviews the evidence of efficacy of these drugs for various off-label uses. Of more than 12,000 studies considered, 162 were included in the analysis. Drugs reviewed included risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), ziprasidone (Geodon), asenapine (Saphris), iloperidone (Fanapt), and paliperidone (Invega). For elderly patients with dementia, a small but statistically significant improvement in symptoms such as psychosis, mood alterations, and aggression were seen with aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, quetiapine was the most effective, while for obsessive-compulsive disorder, risperidone was associated with a 3.9 greater likelihood of favorable response, compared with placebo when used with antidepressants. There was no benefit seen with any of the drugs used in treating eating disorders, substance abuse, or insomnia, and only marginal benefit in personality disorders or posttraumatic stress disorder. All of these drugs have a boxed warning regarding increased mortality in elderly patients with dementia and increased risk of suicidality. Increased risk of death was seen in elderly patients with a number needed to harm (NNH) of 87. Also noted was increased risk of stroke, especially with risperidone (NNH = 53), extraparametal symptoms (NNH = 10 for olanzepine, NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). Weight gain was also a problem in non-elderly adults, particularly with olanzapine (incidence of more than 40%), while akathisia was more common with aripiprazole. Other common side effects included fatigue, sedation, and extrapyramidal symptoms. (JAMA 2011;306:1359-1369).

FDA actions

The FDA has issued a warning regarding the potential for arrhythmia associated with the anti-nausea drug ondansetron (Zofran). The drug should be avoided in patients with QT prolongation as they are at particular risk of developing torsade de pointes. Ondansetron should be used with caution in patients with congestive heart failure, bradyarrhythmias, those predisposed to low potassium or magnesium, and in those taking drugs that cause QT prolongation. These patients should have electrocardiogram monitoring if ondansetron is indicated. The FDA is requiring new labeling changes to reflect these warnings.

The FDA is reminding physicians and patients that epinephrine inhaler (Primatene Mist), the only over-the-counter inhaler for asthma, will be removed from the market on December 31. The withdrawal is due to an international ban on chlorofluorocarbon propellant. The FDA is recommending that physicians ask their patients with asthma if they use Primatene Mist and talk to them about prescription alternatives.

The FDA has approved infliximab (Remicade) to treat moderate-to-severe ulcerative colitis (UC) in children 6 years and older who have had inadequate response to conventional therapy. The drug is already approved for adults with UC. The approval was based on a randomized, open-label trial of 60 children ages 6 to 17 with moderate-to-severe UC. The drug carries a boxed warning for serious infections and cancer. Infliximab is manufactured by Janssen Biotech.

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) 262-5404. E-mail: