541791
research-article2014
AOPXXX10.1177/1060028014541791Annals of PharmacotherapyEiland et al
Review Article
Priapism Associated With the Use of Stimulant Medications and Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Children
Annals of Pharmacotherapy 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014541791 aop.sagepub.com
Lea S. Eiland, PharmD, BCPS, FASHP1, Edward A. Bell, PharmD, BCPS2, and John Erramouspe, PharmD, MS3
Abstract Objective:To review the association of priapism with stimulant medications and atomoxetine commonly used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Data Sources: A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. Google Scholar, Scopus, and the Food and Drug Administration (FDA) Web site were also searched. References from identified literature were also reviewed. Study Selection and Data Extraction: All identified literature focused on ADHD treatment. Literature regarding priapism caused by methylphenidate, amphetamines, and atomoxetine were included. Data Synthesis: Stimulant medications and atomoxetine have been linked to the occurrence of priapism in children. Specifically, methylphenidate has been implicated in a recent FDA safety announcement warning as a result of 15 case reports (mean age = 12.5 years), and thus, the drug label and medication guides have been updated to reflect this concern. Prolonged erections and priapism occurred with immediate- and long-acting products, dose increases, and drug withdrawal periods. Priapism has also occurred in 4 patients taking amphetamines and one 11-year-old patient taking atomoxetine for ADHD. Conclusions: Priapism has been associated with stimulants, amphetamines, and atomoxetine use for ADHD in children. Providers and health care practitioners should educate male patients prescribed these ADHD medications as well as caregivers regarding the signs, symptoms, and complications with priapism. Discontinuation and evaluation of the medication is warranted if this adverse drug reaction occurs. Depending on the priapism subtype, other products may be initiated or medications not associated with priapism may be utilized. Keywords amphetamine, atomoxetine, attention deficit disorder with hyperactivity, methylphenidate, priapism
Introduction Priapism is defined as a persistent male erection that lasts for at least 4 hours and is unrelated to sexual stimulation or desire.1 There are 3 subtypes of priapism: ischemic, nonischemic, and stuttering. Ischemic is described as venoocclusive with low flow, whereas nonischemic is arterial with high flow. Stuttering is characterized by intermittent painful erections with periods of detumescence. Low-flow priapism is painful and examination reveals a rigid erection whereas high-flow priapism is painless and the penis is not fully rigid. Priapism in the pediatric population is rare. The most common etiologies are sickle cell disease, malignancy, or trauma.1 Sickle cell disease and leukemia primarily result in low-flow priapism, whereas high-flow priapism usually results from perineal or penile trauma. Stuttering priapism
has historically been used as a term for the recurrent erections in patients with sickle cell disease.2 Priapism caused by low flow is a urological emergency in order to prevent permanent erectile dysfunction, fibrosis, and impotence. High-flow priapism does not require immediate intervention. A challenge with priapism in the pediatric population is that many children, especially those who are prepubertal, may not be aware of the concern or may be embarrassed to tell a caregiver or health care provider. 1
Auburn University Harrison School of Pharmacy, Huntsville, AL, USA Drake University College of Pharmacy, Des Moines, IA, USA 3 Idaho State University College of Pharmacy, Pocatello, ID, USA 2
Corresponding Author: Lea S. Eiland, Auburn University Harrison School of Pharmacy, UAB/ Pediatrics 301 Governors Dr, Huntsville, AL 35803, USA. Email: [email protected]
Downloaded from aop.sagepub.com at Aston University - FAST on August 25, 2014
2
Annals of Pharmacotherapy
Medications are also implicated as causes of priapism. α-Adrenergic receptor antagonists, anticoagulants, antidepressants, antipsychotics, antihypertensives, hormones, and recreational drugs have all been noted as causative agents.2 In December of 2013, the US Food and Drug Administration (FDA) issued a safety announcement warning of the potential of priapism caused by the use of methylphenidate.3 Methylphenidate is a stimulant that is commonly used to treat attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult populations. In the warning, the FDA also cautioned practitioners on switching patients to atomoxetine for ADHD treatment because it has also been associated with priapism in young children, teenagers, and adults. Finally, they warned about inconclusive evidence linking priapism to amphetamine products. Because these 3 medications are common agents for the treatment of ADHD in children, an evaluation of the literature was conducted to review the association of priapism with stimulant medications and atomoxetine.
Data Sources and Selection A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. References identified from the literature search were also reviewed. Additionally, the FDA’s Web site, Google Scholar, and Scopus were searched. All identified literature that was focused on these ADHD treatment medications and potential cases of priapism, primarily case reports, were included in the review. Literature regarding priapism solely caused by non-ADHD medications and those not in English were excluded. Additionally, no literature was identified for α-agonists causing priapism. Therefore, they are not discussed in this article.
Literature Evaluation Methylphenidate On December 17, 2013, the FDA published a Drug Safety Communication on priapism associated with methylphenidate.3 This announcement indicated that the labeling of methylphenidate products and their patient Medication Guides had been changed to reflect this adverse effect. The FDA’s review of reported cases from 1997 to 2012 includes 15 male participants, mostly 4 to 6 hours. Thus, it can be argued that some of the suspected methylphenidateinduced adverse effects described above may not truly be defined as priapism. Nonpainful erections with a duration of
research-article2014
AOPXXX10.1177/1060028014541791Annals of PharmacotherapyEiland et al
Review Article
Priapism Associated With the Use of Stimulant Medications and Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Children
Annals of Pharmacotherapy 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014541791 aop.sagepub.com
Lea S. Eiland, PharmD, BCPS, FASHP1, Edward A. Bell, PharmD, BCPS2, and John Erramouspe, PharmD, MS3
Abstract Objective:To review the association of priapism with stimulant medications and atomoxetine commonly used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Data Sources: A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. Google Scholar, Scopus, and the Food and Drug Administration (FDA) Web site were also searched. References from identified literature were also reviewed. Study Selection and Data Extraction: All identified literature focused on ADHD treatment. Literature regarding priapism caused by methylphenidate, amphetamines, and atomoxetine were included. Data Synthesis: Stimulant medications and atomoxetine have been linked to the occurrence of priapism in children. Specifically, methylphenidate has been implicated in a recent FDA safety announcement warning as a result of 15 case reports (mean age = 12.5 years), and thus, the drug label and medication guides have been updated to reflect this concern. Prolonged erections and priapism occurred with immediate- and long-acting products, dose increases, and drug withdrawal periods. Priapism has also occurred in 4 patients taking amphetamines and one 11-year-old patient taking atomoxetine for ADHD. Conclusions: Priapism has been associated with stimulants, amphetamines, and atomoxetine use for ADHD in children. Providers and health care practitioners should educate male patients prescribed these ADHD medications as well as caregivers regarding the signs, symptoms, and complications with priapism. Discontinuation and evaluation of the medication is warranted if this adverse drug reaction occurs. Depending on the priapism subtype, other products may be initiated or medications not associated with priapism may be utilized. Keywords amphetamine, atomoxetine, attention deficit disorder with hyperactivity, methylphenidate, priapism
Introduction Priapism is defined as a persistent male erection that lasts for at least 4 hours and is unrelated to sexual stimulation or desire.1 There are 3 subtypes of priapism: ischemic, nonischemic, and stuttering. Ischemic is described as venoocclusive with low flow, whereas nonischemic is arterial with high flow. Stuttering is characterized by intermittent painful erections with periods of detumescence. Low-flow priapism is painful and examination reveals a rigid erection whereas high-flow priapism is painless and the penis is not fully rigid. Priapism in the pediatric population is rare. The most common etiologies are sickle cell disease, malignancy, or trauma.1 Sickle cell disease and leukemia primarily result in low-flow priapism, whereas high-flow priapism usually results from perineal or penile trauma. Stuttering priapism
has historically been used as a term for the recurrent erections in patients with sickle cell disease.2 Priapism caused by low flow is a urological emergency in order to prevent permanent erectile dysfunction, fibrosis, and impotence. High-flow priapism does not require immediate intervention. A challenge with priapism in the pediatric population is that many children, especially those who are prepubertal, may not be aware of the concern or may be embarrassed to tell a caregiver or health care provider. 1
Auburn University Harrison School of Pharmacy, Huntsville, AL, USA Drake University College of Pharmacy, Des Moines, IA, USA 3 Idaho State University College of Pharmacy, Pocatello, ID, USA 2
Corresponding Author: Lea S. Eiland, Auburn University Harrison School of Pharmacy, UAB/ Pediatrics 301 Governors Dr, Huntsville, AL 35803, USA. Email: [email protected]
Downloaded from aop.sagepub.com at Aston University - FAST on August 25, 2014
2
Annals of Pharmacotherapy
Medications are also implicated as causes of priapism. α-Adrenergic receptor antagonists, anticoagulants, antidepressants, antipsychotics, antihypertensives, hormones, and recreational drugs have all been noted as causative agents.2 In December of 2013, the US Food and Drug Administration (FDA) issued a safety announcement warning of the potential of priapism caused by the use of methylphenidate.3 Methylphenidate is a stimulant that is commonly used to treat attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult populations. In the warning, the FDA also cautioned practitioners on switching patients to atomoxetine for ADHD treatment because it has also been associated with priapism in young children, teenagers, and adults. Finally, they warned about inconclusive evidence linking priapism to amphetamine products. Because these 3 medications are common agents for the treatment of ADHD in children, an evaluation of the literature was conducted to review the association of priapism with stimulant medications and atomoxetine.
Data Sources and Selection A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. References identified from the literature search were also reviewed. Additionally, the FDA’s Web site, Google Scholar, and Scopus were searched. All identified literature that was focused on these ADHD treatment medications and potential cases of priapism, primarily case reports, were included in the review. Literature regarding priapism solely caused by non-ADHD medications and those not in English were excluded. Additionally, no literature was identified for α-agonists causing priapism. Therefore, they are not discussed in this article.
Literature Evaluation Methylphenidate On December 17, 2013, the FDA published a Drug Safety Communication on priapism associated with methylphenidate.3 This announcement indicated that the labeling of methylphenidate products and their patient Medication Guides had been changed to reflect this adverse effect. The FDA’s review of reported cases from 1997 to 2012 includes 15 male participants, mostly 4 to 6 hours. Thus, it can be argued that some of the suspected methylphenidateinduced adverse effects described above may not truly be defined as priapism. Nonpainful erections with a duration of
