Attention Deficit Hyperactivity Disorder (ADHD) medications and risk of priapism

HSA would like to draw the attention of healthcare professionals to rare overseas reports of prolonged and painful erections (priapism) associated with the use of Attention Deficit Hyperactivity Disorder (ADHD) medications, namely methylphenidate and atomoxetine. The occurrence of this adverse event in relation to changes in dosage appeared to be inconsistent. Some cases occurred subsequent to an increase in methylphenidate dose, whereas others developed during periods of drug withdrawal (i.e. drug holidays or after discontinuation of treatment).

Methylphenidate and atomoxetine are both licensed locally for the treatment of ADHD. Methylphenidate is a central nervous system stimulant registered locally under the brand names Concerta® (Johnson & Johnson Pte Ltd), Ritalin® (Novartis (Singapore) Pte Ltd) and Rubifen® (Zyfas Medical Co). Atomoxetine (Strattera®, Eli Lilly (Singapore) Pte Ltd) is a selective norepinephrine reuptake inhibitor.

Published overseas case reports of priapism

Several case reports of priapism associated with methylphenidate have been reported in the literature.^1-4 In one article, a 12-year-old Caucasian boy was reported to have experienced prolonged and painful erections unaccompanied by sexual excitation for two years.¹ During these two years, he was treated with a starting dose of 18mg of methylphenidate which was subsequently increased to 36mg. The unwanted erections abated after methylphenidate was gradually reduced and subsequently stopped. In another case, the opposite effect was seen, where priapism occurred with missed doses. The 16-year-old boy, who was prescribed 54mg of extended-release methylphenidate daily for one year would experience priapism lasting for up to 24 hours whenever he missed a dose of his medication and the event would resolve after the drug was taken.³ The mechanism of priapism associated with methylphenidate has not been understood but may be associated with methylphenidate's influence on multiple neurotransmitters.¹

Review by the US Food and Drug Administration (FDA)

In December 2013, the US FDA issued a safety communication to warn of rare but serious cases of priapism associated with the use of methylphenidate.⁵ This signal followed a safety review conducted by the FDA which took into consideration data from the FDA Adverse Event Reporting System and published literature. From 1997 to 2012, a total of 15 cases of priapism associated with methylphenidate were reported. The median age of these patients was 12.5 years (range 8 to 33 years). Of these cases, there were four patients who reported priapism following the withdrawal of methylphenidate and a few who reported the event after an increase in the drug dosage. In some patients, the event resolved after methylphenidate was restarted. There were cases where patients had to be hospitalised for treatment, including two patients who required surgical interventions such as shunt placement and needle aspiration of the corpus cavernosum.

In the safety communication, FDA similarly cautioned healthcare professionals that atomoxetine has also been associated with priapism. In fact, priapism appears to be more common with atomoxetine than methylphenidate and hence precautions on potential risk of priapism should be taken into consideration when patients are switched from methylphenidate to atomoxetine.

HSA’s advisory

HSA has not received any local adverse reaction reports of priapism or sexual dysfunction associated with the use of methylphenidate or atomoxetine.

Healthcare professionals are advised to take into consideration the potential risk of priapism when prescribing methylphenidate or atomoxetine, or when switching their patients from methylphenidate to atomoxetine. Informing male patients and their caregivers about the risk of developing priapism and the signs and symptoms to look out for may help promote seeking of timely medical attention if priapism develops.

HSA is working with the companies to strengthen the package inserts of methylphenidate and atomoxetine products to include information on the risk of priapism. Healthcare professionals are encouraged to report local adverse reactions of priapism or sexual dysfunction associated with ADHD medications to the Vigilance Branch of HSA.

References

1. Turk J Pediatr 2010; 52: 430-4

2. J Pediatr Urol 2013; 9: e1-2

3. http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v16n3-eng.php#a3

4. J Pediatr 2004; 144: 675-6

5. http://www.fda.gov/Drugs/DrugSafety/ucm375796.htm