Vraylar (Page 3 of 11)

5. 7 Metabolic Changes

Atypical antipsychotic drugs, including VRAYLAR, have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. There have been reports of hyperglycemia in patients treated with VRAYLAR. Although all drugs in the class to date have been shown to produce some metabolic changes, each drug has its own specific risk profile.

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication and monitor periodically during long-term treatment.

Schizophrenia

In the 6-week, placebo-controlled trials of adult patients with schizophrenia, the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) and borderline (≥100 and <126 mg/dL) to high were similar in patients treated with VRAYLAR and placebo. In the long-term, open-label schizophrenia studies, 4% patients with normal hemoglobin A1c baseline values developed elevated levels (≥ 6.5%).

Bipolar Disorder

In six placebo-controlled trials up to 8-weeks of adult patients with bipolar disorder (mania or depression), the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) and borderline (≥100 and <126 mg/dL) to high were similar in patients treated with VRAYLAR and placebo. In the long-term, open-label bipolar disorder studies, 4% patients with normal hemoglobin A1c baseline values developed elevated levels (≥ 6.5%).

Adjunctive Treatment of Major Depressive Disorder

In two 6-week placebo-controlled trials of adult patients with major depressive disorder, the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL) was greatest in the VRAYLAR 3 mg per day + antidepressant therapy arm (3.2%) compared with those taking VRAYLAR 1.5 mg per day + antidepressant therapy (2%) or those placebo-treated (1.3%). The proportion of patients with shifts from normal to borderline (≥100 and <126 mg/dL) or from borderline to high were similar in patients treated with VRAYLAR and placebo. In a long-term, open-label adjunctive treatment of MDD study, 7% patients with normal hemoglobin A1c baseline values developed elevated levels (> 6%).

In one 8-week placebo-controlled trial of adult patients with major depressive disorder, the changes from baseline to end of the trial in fasting glucose were similar among the VRAYLAR and placebo + antidepressant therapy treatment groups. During the 8-week trial, serum insulin levels increased by 12 pmol/L in the VRAYLAR 1 mg to 2 mg per day group, 20 pmol/L in the VRAYLAR 2 mg to 4.5 mg per day group, and 8.5 pmol/L in the placebo group.

Dyslipidemia

Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Schizophrenia

In the 6-week, placebo-controlled trials of adult patients with schizophrenia, the proportion of patients with shifts in fasting total cholesterol, LDL, HDL, and triglycerides were similar in patients treated with VRAYLAR and placebo.

Bipolar Disorder

In six placebo-controlled trials up to 8-weeks of adult patients with bipolar disorder (mania or depression), the proportion of patients with shifts in fasting total cholesterol, LDL, HDL, and triglycerides were similar in patients treated with VRAYLAR and placebo.

Adjunctive Treatment of Major Depressive Disorder

In two 6-week placebo-controlled trials of adult patients with major depressive disorder, the proportion of patients with shifts in total cholesterol, fasting LDL, HDL, and fasting triglycerides were similar in patients treated with VRAYLAR and placebo.

Weight Gain

Weight gain has been observed with use of atypical antipsychotics, including VRAYLAR. Monitor weight at baseline and frequently thereafter. Tables 2, 3, 4, and 5 show the change in body weight occurring from baseline to endpoint in 6-week trials of schizophrenia, 3-week bipolar mania trials, 6-week and 8-week bipolar depression trials, and 6-week and 8-week trials of adjunctive treatment for major depressive disorder, respectively.

Table 2. Change in Body Weight (kg) in 6-Week Schizophrenia Trials
VRAYLAR *
Placebo(N=573) 1.5 — 3 mg/day(N=512) 4.5 — 6mg/day(N=570) 9 — 12 mg/day(N=203)
Mean Change at Endpoint +0.3 +0.8 +1 +1
Proportion of Patients with Weight Increase (≥7%) 5% 8% 8% 17%

*Data shown by modal daily dose, defined as most frequently administered dose per patient⸰The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

In long-term, uncontrolled trials with VRAYLAR in schizophrenia, the mean changes from baseline in weight at 12, 24, and 48 weeks were 1.2 kg, 1.7 kg, and 2.5 kg, respectively.

Table 3. Change in Body Weight (kg) in 3-Week Bipolar Mania Trials
VRAYLAR *
Placebo(N=439) 3 — 6mg/day(N=259) 9 — 12 mg/day(N=360)
Mean Change at Endpoint +0.2 +0.5 +0.6
Proportion of Patients with Weight Increase (≥7%) 2% 1% 3%

*Data shown by modal daily dose, defined as most frequently administered dose per patient⸰The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

Table 4. Change in Body Weight (kg) in two 6-Week and one 8-Week Bipolar Depression Trials
VRAYLAR
Placebo 1.5 mg/day 3 mg/day
(N=463) (N=467) (N=465)
Mean Change at Endpoint -0.1 +0.7 +0.4
Proportion of Patients with Weight Increase (≥7%) 1% 3% 3%
Table 5. Change in Body Weight (kg) in two 6-Week and one 8-Week Adjunctive Treatment for Major Depressive Disorder Trials
VRAYLAR
6-week Trials Placebo +ADT 1.5 mg/day +ADT 3 mg/day +ADT
(N=503) (N=502) (N=503)
Mean Change at Endpoint +0.2 +0.7 +0.7
Proportion of Patients with Weight Increase (≥7%) 1% 2% 2%
8-week Trial Placebo +ADT(N=266) 1 to 2 mg/day + ADT(N=273) 2 to 4.5 mg/day + ADT (N=273)
Mean Change at Endpoint 0 +0.9 +0.9
Proportion of Patients with Weight Increase (≥7%) 2% 2% 3%

In the long-term, open-label adjunctive treatment of MDD trial, 2 patients (0.6%) discontinued due to weight increase. VRAYLAR was associated with mean change from baseline in weight of 1.7 kg at Week 26. In the long-term, open-label adjunctive treatment of MDD trial, 19% of patients demonstrated a ≥7% increase in body weight, and 5% demonstrated a ≥7% decrease in body weight.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.