Arostanil Adverse Reactions

Exemestane was generally well tolerated across all clinical studies conducted with exemestane at a standard dose of 25 mg/day undesirable effects were usually mild to moderate.
The withdrawal rate due to adverse events was 7.4% in patients with early breast cancer receiving adjuvant treatment with exemestane following initial adjuvant tamoxifen therapy. The most commonly reported adverse reactions were hot flushes (22%), arthralgia (18%) and fatigue (16%).
The withdrawal rate due to adverse events was 2.8% in the overall patient population with advanced breast cancer. The most commonly reported adverse reactions were hot flushes (14%) and nausea (12%).
Most adverse reactions can be attributed to the normal pharmacological sequoias of oestrogen deprivation (e.g. hot flushes).
The reported adverse reactions are listed below by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from available data). (See Table 2.)

Click on icon to see table/diagram/image

Blood and lymphatic system disorders: In patients with advanced breast cancer, thrombocytopenia and leucopenia have been rarely reported. An occasional decrease in lymphocytes has been observed in approximately 20% of patients receiving exemestane, particularly in patients with pre-existing lymphopenia; however, mean lymphocyte values in these patients did not change significantly over time and no corresponding increase in viral infections was observed. These effects have not been observed in patients treated in early breast cancer studies.
Hepatobiliary disorders: Elevation of liver function test parameters, including enzymes, bilirubin and alkaline phosphatase, has been observed.
The table below presents the frequency of pre-specified adverse events and illnesses in the early breast cancer study (IES), irrespective of causality, reported in patients receiving trial therapy and up to 30 days after cessation of trial therapy. (See Table 3.)

Click on icon to see table/diagram/image

In the IES study, the frequency of ischaemic cardiac events in the exemestane and tamoxifen treatment arms was 4.5% versus 4.2%, respectively. No significant difference was noted for any individual cardiovascular event, including hypertension (9.9% versus 8.4%), myocardial infarction (0.6% versus 0.2%) and cardiac failure (1.1% versus 0.7%).
In the IES study, exemestane was associated with a greater incidence of hypercholesterolaemia compared with tamoxifen (3.7% vs. 2.1%).
In a separate double-blind, randomised study of postmenopausal women with early breast cancer at low risk treated with exemestane (N=73) or placebo (N=73) for 24 months, exemestane was associated with an average 7-9% mean reduction in plasma HDL-cholesterol, versus a 1% increase on placebo. There was also a 5-6% reduction in apolipoprotein A1 in the exemestane group versus 0-2% for placebo. The effect on the other lipid parameters analysed (total cholesterol, LDL cholesterol, triglycerides, apolipoprotein-B and lipoproteins) was very similar in the two treatment groups. The clinical significance of these results is unclear.
In the IES study, gastric ulcer was observed at a higher frequency in the exemestane arm compared to tamoxifen (0.7% versus <0.1%). The majority of patients on exemestane with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history.
Adverse reactions from post-marketing experience: Hepatobiliary disorders: hepatitis, cholestatic hepatitis.
Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.