Table 7.

Communicated signals with suggested mechanisms for risk group susceptibility

Communicated signal	Mechanisms for risk group susceptibility suggested in signal
Hepatitis with ceftriaxone in patients 75 years and older [18]	Elderly patients have a longer elimination half-life of ceftriaxone than young adults, which may increase the risk of hepatotoxicity, as raised liver enzymes is a known adverse drug reaction
Myoclonus with levofloxacin in patients 75 years and older [19]	Elderly patients with risk factors for myoclonus such as renal impairment and CNS conditions may predispose to the event
Anaphylactic shock with omalizumab in females [20]	Females suggested to be more sensitive to anaphylactic reactions, possibly attributable to oestradiol
Deep vein thrombosis and pulmonary embolism with aflibercept in males [21]	Multiple lines of evidence suggest a gender influence on the amount of circulating VEGF, with females having higher serum levels than males. A hypothesis would be that females have a higher concentration of un-antagonised VEGF at the same doses of aflibercept than males (although a subgroup analysis in clinical development did not reveal any “clinical relevant” influence of gender on plasma concentrations of free aflibercept or aflibercept–VGEF complex)
Gynaecomastia with esomeprazole in obese adults [22]	Obesity is associated with increased oestrogen due to extragonadal conversion of androgen by tissue aromatase, and omeprazole known to be associated with gynaecomastia due to inhibition of CYP3A4, which is responsible for catabolism of oestradiol
Hypoglycaemia with selegiline in underweight adults [23]	Underweight is a risk factor of hypoglycaemia and may present an additive effect to the known ability of the drug to cause the reaction
Palpitations with glibenclamide in the Asian population [24]	Glibenclamide is metabolised by CYP2D6, of which specific polymorphisms (*2 and *3), common in Asian populations, lead to poor metabolisation. Palpitations may be an adrenergic response to hypoglycaemia secondary to poor metabolism of glibenclamide

CNS central nervous system, VEGF vascular endothelial growth factor