TABLE 4.

Safety Concerns Regarding Pediatric Free Samples Distributed in the United States in 2004

Medication Name and Use	Weighted No. of US Children Receiving Sample	Warning	Safety Concerns
Strattera (atomoxetine),  psychostimulant	226 055	Black box warning  added in 2005a	Suicidal ideation in children and adolescents. Strattera increased the risk of suicidal ideation  in short-term studies with children or adolescents with attention-deficit/hyperactivity  disorder. Patients who start therapy should be monitored closely for suicidality (suicidal  thinking and behavior), clinical worsening, or unusual changes in behavior. Families and  caregivers should be advised of the need for close observation and communication with  the prescriber. Strattera is approved for use for attention-deficit/hyperactivity disorder in  pediatric and adult patients but not major depressive disorder
			Also, a medication guide is to be distributed with each prescription
Elidel (pimecrolimus), topical  immunosuppressant	137 618	Black box warning  added in 2006a	Long-term safety of topical calcineurin inhibitors has not been established. Although a  causal relationship has not been established, rare cases of malignancy (eg, skin and  lymphoma) have been reported in patients treated with topical calcineurin inhibitors,  including Elidel cream. Continuous long-term use of topical calcineurin inhibitors,  including Elidel, in any age group should be avoided, and application should be limited  to areas of involvement with atopic dermatitis. Elidel cream is not indicated for use in  children <2 y of age
			Also, a recommendation for use as a second-line treatment was added to the indications  section. A medication guide is to be distributed with each prescription
Advair Diskus (fluticasone/  salmeterol inhaled),  inhaled steroid and long-  acting β-receptor agonist	77 997	Black box warning  as of 2004	Small but significant increase in asthma-related deaths in patients receiving salmeterol vs  placebo. Risk may be greater for black patients, compared with white patientsb
		Revisions to black  box warning  added in 2006a	Long-acting β2-adrenergic receptor agonists such as salmeterol may increase the risk of  asthma-related death. When treating patients with asthma, physicians should prescribe  Advair Diskus only for patients who do not have adequate control with other asthma-  controller medications or whose disease severity clearly warrants initiation of treatment  with 2 maintenance therapies
Adderall/Adderall XR  (amphetamine/  dextroamphetamine and  its extended-release  form), stimulant	62 483	Black box warning  as of 2004	Amphetamines have a high potential for abuse. Administration for prolonged periods may  lead to drug dependence. There is a possibility of subjects obtaining amphetamines for  nontherapeutic use or distribution to others. The drugs should be prescribed or  dispensed sparingly
		Revision to black  box warning  added in 2005a	Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events
		Schedule II  controlled  substance
Lexapro (escitalopram;  Forest, New York, NY)  antidepressantc	46 601	Black box warning  added in 2005a	Not approved for use in pediatric patients. Suicidality in children and adolescents.  Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-  term studies with children and adolescents with major depressive disorder and other  psychiatric disorders. Patients who start therapy should be observed closely for clinical  worsening, suicidality, or unusual changes in behavior. Families and caregivers should be  advised of the need for close observation and communication with the prescriber
Paxil/Paxil CR (paroxetine  and its continuous-release  form; Glaxo Smith Kline,  Brentford, United  Kingdom),  antidepressantc	21 695
Ritalin (methylphenidate;  Basel, Switzerland),  stimulantc	5689	Black box warning  before 2004	Drug dependence. Ritalin should be given cautiously to emotionally unstable patients, such  as those with a history of drug dependence or alcoholism; such patients may increase  dosage on their own initiative. Chronically abusive use can lead to marked tolerance and  psychic dependence, with varying degrees of abnormal behavior. Frank psychotic  episodes can occur, especially with parenteral abuse. Careful supervision is required  during drug withdrawal; severe depression and chronic overactivity can be unmasked
		Warning added in  2006 (not black  box)	Serious cardiovascular events. Sudden death was reported in association with central  nervous system stimulant treatment at usual doses in children and adolescents with  structural cardiac abnormalities or other serious heart problems
		Schedule II  controlled  substance

Data were obtained from the Physicians’ Desk Reference and the Food and Drug Administration Web site (www.fda.gov). Information on black box warnings was taken from medication labels.

^aDates refer to the date the Food and Drug Administration approved the black box warning or revision. These warnings typically appear in the Physicians’ Desk Reference the following year.

^bBeginning in 2006, the possible risk difference for black patients was no longer emphasized in the black box warning but was discussed in the warning section.

^cNot among the top 15 samples given to children.