PRISTIQ^®Adverse Reactions (desvenlafaxine succinate)

Patient Exposure

PRISTIQ was evaluated for safety in 8,394 patients diagnosed with major depressive disorder who participated in multiple-dose pre-marketing studies, representing 2,784 patient-years of exposure. Of the total 8,394 patients exposed to at least one dose of PRISTIQ; 2,116 were exposed to PRISTIQ for 6 months, representing 1,658 patient-years of exposure, and 421 were exposed for one year, representing 416 patient-years of exposure.

Adverse Reactions Reported as Reasons for Discontinuation of Treatment

In the pre-marketing pooled 8-week placebo-controlled studies in patients with MDD, 1,834 patients were exposed to PRISTIQ (50 to 400 mg). Of the 1,834 patients, 12% discontinued treatment due to an adverse reaction, compared with 3% of the 1,116 placebo-treated patients. At the recommended dose of 50 mg, the discontinuation rate due to an adverse reaction for PRISTIQ (4.1%) was similar to the rate for placebo (3.8%). For the 100 mg dose of PRISTIQ the discontinuation rate due to an adverse reaction was 8.7%.

The most common adverse reactions leading to discontinuation in at least 2% and at a rate greater than placebo of the PRISTIQ treated patients in the short-term studies, up to 8 weeks, were: nausea (4%); dizziness, headache and vomiting (2% each). In a longer-term study, up to 9 months, the most common was vomiting (2%).

Common Adverse Reactions in Placebo-Controlled MDD Studies

The most commonly observed adverse reactions in PRISTIQ treated MDD patients in pre-marketing pooled 8-week, placebo-controlled, fixed-dose studies (incidence ≥ 5% and at least twice the rate of placebo in the 50 or 100 mg dose groups) were: nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and specific male sexual function disorders.

Table 2 shows the incidence of common adverse reactions that occurred in ≥ 2% of PRISTIQ treated MDD patients and twice the rate of placebo at any dose in the pre-marketing pooled 8-week, placebo-controlled, fixed dose clinical studies.

Sexual Function Adverse Reactions

Table 3 shows the incidence of sexual function adverse reactions that occurred in ≥ 2% of PRISTIQ treated MDD patients in any fixed-dose group (pre-marketing pooled 8-week, placebo-controlled, fixed -dose, clinical studies) [see Warnings and Precautions (5.11)].

Other Adverse Reactions Observed in Premarketing and Postmarketing Clinical Studies

Other infrequent adverse reactions, not described elsewhere in the label, occurring at an incidence of < 2% in MDD patients treated with PRISTIQ were:

Cardiac disorders – Tachycardia.

General disorders and administration site conditions – Asthenia.

Investigations – Weight increased, liver function test abnormal, blood prolactin increased.

Musculoskeletal and connective tissue disorders – Musculoskeletal stiffness.

Nervous system disorders –Syncope, convulsion, dystonia.

Psychiatric disorders – Depersonalization, bruxism.

Renal and urinary disorders – Urinary retention.

Skin and subcutaneous tissue disorders – Rash, alopecia, photosensitivity reaction, angioedema.

In clinical studies, there were uncommon reports of ischemic cardiac adverse reactions, including myocardial ischemia, myocardial infarction, and coronary occlusion requiring revascularization; these patients had multiple underlying cardiac risk factors. More patients experienced these events during PRISTIQ treatment as compared to placebo.

Laboratory, ECG and Vital Sign Changes Observed in MDD Clinical Studies

The following changes were observed in pre-marketing placebo-controlled, short-term MDD studies with PRISTIQ.