Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot directly be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to paroxetine capsules in the one 8-week Phase 2 randomized, placebo-controlled trial and the two Phase 3 randomized, placebo-controlled, 12-week and 24-week trials for the treatment of moderate to severe VMS [see Clinical Studies (14)]. In these trials, a total of 635 women were exposed to paroxetine capsules 7.5 mg administered orally once daily and 641 women received placebo. The majority of paroxetine capsule-treated patients were Caucasian (68%) and African American (30%), with a mean age of 55 years (range 40 to 73 years). Women with a history of suicidal ideation or suicidal behavior were excluded from these studies.

Adverse Reactions Leading to Study Discontinuation: A total of 4.7% of women taking paroxetine capsules discontinued from the clinical trials due to an adverse reaction, compared to 3.7% of women on placebo; the most frequent adverse reactions leading to discontinuation among paroxetine-treated women were: abdominal pain (0.3%), attention disturbances (0.3%), headache (0.3%), and suicidal ideation (0.3%).

Common Adverse Reactions: Overall, based on investigators’ determinations about what events were likely to be drug-related, about 20% of women treated with paroxetine capsules reported at least 1 adverse reaction in the three controlled studies. The most common adverse reactions (≥ 2% and more common among paroxetine capsule-treated women) reported in these studies were headache, fatigue/malaise/lethargy, and nausea/vomiting. Of these commonly reported adverse reactions, nausea occurred primarily within the first 4 weeks of treatment and fatigue occurred primarily within the first week of treatment, and decreased in frequency with continued therapy.

The adverse reactions that occurred in at least 2% of patients in the paroxetine capsule group and at a higher incidence than placebo are shown in Table 1 for the pooled Phase 2 and Phase 3 trials.

Table 1 Frequency of Adverse Reactions in the Phase 2 and Phase 3 Trials (≥ 2% and at a higher incidence than placebo)

Certain symptoms were seen more frequently in women at the time of discontinuation of paroxetine capsules compared to women discontinuing placebo, and have also been reported upon discontinuation of other formulations of paroxetine, particularly when abrupt. These include increased dreaming/nightmares, muscle cramps/spasms/twitching, headache, nervousness/anxiety, fatigue/tiredness, restless feeling in legs, and trouble sleeping/insomnia. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms with other formulations of paroxetine.

Serious Adverse Reactions: In the pooled Phase 2 and Phase 3 trials, three paroxetine capsule-treated patients reported a serious adverse reaction of suicidal ideation and one paroxetine capsule-treated patient reported a serious adverse reaction of suicide attempt. There were no serious adverse reactions of suicidal ideation or suicide attempt reported among the placebo-treated patients.