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Pristiq (Desvenlafaxine Succinate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label;

  • Hypersensitivity [see Contraindications ( 4.1 )]
  • Effects on blood pressure [see Warnings and Precautions ( 5.3 )]
  • Abnormal bleeding [see Warnings and Precautions ( 5.4 )]
  • Mydriasis [see Warnings and Precautions ( 5.5 )]
  • Hypomania and mania [see Warnings and Precautions ( 5.6 )]
  • Serum cholesterol and triglyceride elevation [see Warnings and Precautions ( 5.8 )]
  • Seizure [see Warnings and Precautions ( 5.11 )]

Clinical Studies Experience

The most commonly observed adverse reactions in PRISTIQ treated MDD patients in short-term 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.

Adverse reactions reported as reasons for discontinuation of treatment

Combined across 8-week placebo-controlled pre-marketing studies for major depressive disorder, 12% of the 1,834 patients who received PRISTIQ (50-400 mg) discontinued treatment due to an adverse event, compared with 3% of the 1,116 placebo-treated patients in those studies. At the recommended dose of 50 mg, the discontinuation rate due to an adverse event 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 event was 8.7%.

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

Patient exposure

PRISTIQ was evaluated for safety in 3,292 patients diagnosed with major depressive disorder who participated in multiple-dose pre-marketing studies, representing 1,289 patient-years of exposure. Among these 3,292 PRISTIQ treated patients, 1,834 patients were exposed to PRISTIQ in 8-week, placebo-controlled studies at doses ranging from 50 to 400 mg/day. Out of the 1,834 patients, 687 PRISTIQ treated patients continued into a 10-month open-label study. Of the total 3,292 patients exposed to at least one dose of PRISTIQ, 1,070 were exposed to PRISTIQ for 6 months, representing 842 patient-years of exposure, and 274 were exposed for one year, representing 241 patient-years of exposure.

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

Common adverse reactions in placebo-controlled MDD studies

Table 3 shows the incidence of common adverse reactions that occurred in ≥ 2% of PRISTIQ treated MDD patients at any dose in the 8-week, placebo-controlled, fixed dose, pre-marketing clinical studies. In general, the adverse reactions were most frequent in the first week of treatment.

Table 3: Common Adverse Reactions: Percentage of Patients (≥ 2% in any Fixed-Dose Group) in MDD 8‑Week Placebo-Controlled Studiesa
 
Percentage of Patients Reporting Reaction
   
PRISTIQ

System Organ Class Preferred Term

Placebo

50 mg

100 mg

200 mg

400 mg

Cardiac disorders
   Palpitations 2 1 3 2 3
   Tachycardia 1 1 <1 1 2
   Blood pressure    increased 1 1 1 2 2

Gastrointestinal disorders
   Nausea 10 22 26 36 41
   Dry mouth 9 11 17 21 25
   Diarrhea 9 11 9 7 5
   Constipation 4 9 9 10 14
   Vomiting 3 3 4 6 9

General disorders and administration site conditions
   Fatigue 4 7 7 10 11
   Chills 1 1 <1 3 4
   Feeling jittery 1 1 2 3 3
   Asthenia 1 1 2 1 1

Metabolism and nutrition disorders
   Decreased    appetite 2 5 8 10 10
   Weight decreased 1 2 1 1 2

Nervous system disorders
   Dizziness 5 13 10 15 16
   Somnolence 4 4 9 12 12
   Headache 23 20 22 29 25
   Tremor 2 2 3 9 9
   Paraesthesia 1 2 2 1 3
   Disturbance in    attention <1 <1 1 2 1

Psychiatric disorders
   Insomnia 6 9 12 14 15
   Anxiety 2 3 5 4 4
   Nervousness 1 <1 1 2 2
   Irritability 1 2 2 2 2
   Abnormal dreams 1 2 3 2 4

Renal and urinary disorders
   Urinary hesitation 0 <1 1 2 2

Respiratory, thoracic and mediastinal disorders
   Yawning <1 1 1 4 3

Skin and subcutaneous tissue disorders
   Hyperhidrosis 4 10 11 18 21
   Rash <1 1 1 2 <1

Special Senses
   Vision blurred 1 3 4 4 4
   Mydriasis <1 2 2 6 6
   Tinnitus 1 2 1 1 2
   Dysgeusia 1 1 1 1 2

Vascular disorders
   Hot flush <1 1 1 2 2
a: Percentage based on the number of patients (placebo, n = 636; PRISTIQ 50 mg, n = 317; PRISTIQ 100 mg, n = 424; PRISTIQ 200 mg, n = 307; PRISTIQ 400 mg, n = 317).

Sexual function adverse reactions

Table 4 shows the incidence of sexual function adverse reactions that occurred in ≥ 2% of PRISTIQ treated MDD patients in any fixed-dose group (8-week, placebo-controlled, fixed and flexible-dose, pre-marketing clinical studies).

Table 4: Sexual Function Disorders: Adverse Reactions (≥ 2% in Mena or Womenb in any PRISTIQ Group) During the On-Therapy Period
   
PRISTIQ

System Organ Class Preferred Term

Placebo

50 mg

100 mg

200 mg

400 mg
a: Percentage based on the number of men (placebo, n = 239; PRISTIQ 50 mg, n = 108; PRISTIQ 100 mg, n = 157; PRISTIQ 200 mg, n = 131; PRISTIQ 400 mg, n = 154).

b: Percentage based on the number of women (placebo, n = 397; PRISTIQ 50 mg, n = 209; PRISTIQ 100 mg, n = 267; PRISTIQ 200 mg, n = 176; PRISTIQ 400 mg, n = 163).


    Men only
     Anorgasmia 0 0 3 5 8
     Libido      decreased 1 4 5 6 3
     Orgasm
     abnormal
0 0 1 2 3
     Ejaculation
     delayed
<1 1 5 7 6
     Erectile
     dysfunction
1 3 6 8 11
     Ejaculation
     disorder
0 0 1 2 5
     Ejaculation
     failure
0 1 0 2 2
     Sexual
     dysfunction
0 1 0 0 2

     Women only
     Anorgasmia 0 1 1 0 3

Other adverse reactions observed in pre-marketing clinical studies

Other infrequent adverse reactions, not described elsewhere in section 6.1, occurring at an incidence of < 2% in MDD patients treated with PRISTIQ were:

Immune system disorders – Hypersensitivity.

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

Nervous system disorders – Convulsion, syncope, extrapyramidal disorder.

Musculoskeletal and connective tissue disorders – Musculoskeletal stiffness.

Psychiatric disorders – Depersonalization, hypomania.

Respiratory, thoracic and mediastinal disorders – Epistaxis.

Vascular disorders – Orthostatic hypotension.

In clinical studies, there were uncommon reports of ischemic cardiac adverse events, 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 [see Warnings and Precautions ( 5.7 )].

Discontinuation events

Adverse events reported in association with abrupt discontinuation, dose reduction or tapering of treatment in MDD clinical studies at a rate of ≥ 5% include: dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, abnormal dreams, fatigue, and hyperhidrosis. In general, discontinuation events occurred more frequently with longer duration of therapy [see Dosage and Administration ( 2.4) and Warnings and Precautions ( 5.9 )].

Laboratory, ECG and vital sign changes observed in MDD clinical studies

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

Lipids

Elevations in fasting serum total cholesterol, LDL (low density lipoproteins) cholesterol, and triglycerides occurred in the controlled studies. Some of these abnormalities were considered potentially clinically significant [see Warnings and Precautions ( 5.8 )].

The percentage of patients who exceeded a predetermined threshold value is shown in Table 5.

Table 5: Incidence (%) of Patients With Lipid Abnormalities of Potential Clinical Significance*
   
PRISTIQ
 
Placebo

50 mg

100 mg

200 mg

400 mg
Total Cholesterol
*(Increase of ≥ 50 mg/dl and an absolute value of ≥ 261 mg/dl)
2 3 4 4 10
LDL Cholesterol
*(Increase ≥ 50 mg/dl and an absolute value of ≥ 190 mg/dl)
0 1 0 1 2
Triglycerides, fasting
*(Fasting: ≥ 327 mg/dl)
3 2 1 4 6

Proteinuria

Proteinuria, greater than or equal to trace, was observed in the fixed-dose controlled studies (see Table 6). This proteinuria was not associated with increases in BUN or creatinine and was generally transient.

Table 6: Incidence (%) of Patients with Proteinuria in the Fixed-dose Clinical Studies
   
PRISTIQ
 
Placebo

50 mg

100 mg

200 mg

400 mg
Proteinuria 4 6 8 5 7

ECG changes

Electrocardiograms were obtained from 1,492 PRISTIQ treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between PRISTIQ treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval.

Vital sign changes

Table 7 summarizes the changes that were observed in placebo-controlled, short-term, pre-marketing studies with PRISTIQ in patients with MDD (doses 50 to 400 mg).

Table 7: Mean Changes in Vital Signs at Final on Therapy for All Short-term, Fixed-dose Controlled Studies
   
PRISTIQ
 
Placebo

50 mg

100 mg

200 mg

400 mg

Blood pressure
Supine systolic bp (mm Hg) -1.4 1.2 2.0 2.5 2.1
Supine diastolic bp (mm Hg) -0.6 0.7 0.8 1.8 2.3

Pulse rate
Supine pulse (bpm) -0.3 1.3 1.3 0.9 4.1

Weight (kg)
0.0 -0.4 -0.6 -0.9 -1.1

At the final on-therapy assessment in the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to PRISTIQ during the initial 12-week, open-label phase, there was no statistical difference in mean weight change between PRISTIQ and placebo-treated patients.

Orthostatic hypotension

In the short-term, placebo-controlled clinical studies with doses of 50-400 mg, systolic orthostatic hypotension (decrease ≥ 30 mm Hg from supine to standing position) occurred more frequently in patients ≥ 65 years of age receiving PRISTIQ (8.0%, 7/87) versus placebo (2.5%, 1/40), compared to patients < 65 years of age receiving PRISTIQ (0.9%, 18/1,937) versus placebo (0.7%, 8/1,218).

Adverse Reactions Identified During Post-Approval Use

The following adverse reaction has been identified during post-approval use of PRISTIQ. Because post-approval 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:

Skin and subcutaneous tissue disorders – Angioedema.

Adverse Reactions Reported With Other SNRIs

Although the following are not considered adverse reactions for PRISTIQ, they are adverse reactions for other SNRIs and may also occur with PRISTIQ: gastrointestinal bleeding, hallucinations, photosensitivity reactions and severe cutaneous reactions (such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, and/or erythema multiforme).



REPORTS OF SUSPECTED PRISTIQ SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Pristiq. The information is not vetted and should not be considered as verified clinical evidence.

Possible Pristiq side effects / adverse reactions in 78 year old male

Reported by a consumer/non-health professional from Brazil on 2011-10-04

Patient: 78 year old male

Reactions: Nephrolithiasis, Drug Effect Decreased

Suspect drug(s):
Pristiq

Other drugs received by patient: Clindamycin



Possible Pristiq side effects / adverse reactions in 35 year old female

Reported by a physician from Colombia on 2011-10-07

Patient: 35 year old female

Reactions: Anaphylactic Reaction

Adverse event resulted in: life threatening event

Suspect drug(s):
Pristiq



Possible Pristiq side effects / adverse reactions in 65 year old male

Reported by a pharmacist from Australia on 2011-10-07

Patient: 65 year old male

Reactions: Wrong Technique in Drug Usage Process, Chest Discomfort, Dyspnoea, Drug Ineffective, Chest Pain

Adverse event resulted in: hospitalization

Suspect drug(s):
Pristiq
    Dosage: 12.5 mg, 1x/day in the morning

Pristiq
    Dosage: 25 mg, 1x/day in the morning
    Indication: Depression
    Start date: 2010-03-01

Other drugs received by patient: Atorvastatin; Tamsulosin; Perindopril Arginine; Coumadin; Pantoprazole; Acetylsalicylic Acid; Sotalol; Metformin HCL



See index of all Pristiq side effect reports >>

Drug label data at the top of this Page last updated: 2011-01-17

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