21 December 2023From the archive
Contrave
label of 6 April 202321 December 2023published 21 December 2023, reconstructed from the DailyMed archive
Adverse reactions
Added in this revision
- Added: The following adverse reactions are discussed in other sections of the labeling: Suicidal Behavior and Ideation Neuropsychiatric Adverse Events Seizures Increase in Blood Pressure and Heart Rate Allergic Reactions Angle-Closure Glaucoma
Removed in this revision
- Removed: The following adverse reactions are discussed in other sections of the labeling: Suicidal Behavior and Ideation Neuropsychiatric Adverse Events Seizures Increase in Blood Pressure and Heart Rate Allergic Reactions Angle-Closure Glaucoma Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect...
- Removed: CONTRAVE was evaluated for safety in five double-blind placebo controlled trials in 4,754 overweight or obese patients (3,239 patients treated with CONTRAVE and 1,515 patients treated with placebo) for a treatment period up to 56 weeks.
- Removed: The majority of patients were treated with CONTRAVE 32 mg/360 mg total daily dose.
- Removed: In addition, some patients were treated with other combination daily doses including naltrexone up to 50 mg and bupropion up to 400 mg.
- Removed: All subjects received study drug in addition to diet and exercise counseling.
- Removed: One trial (N=793) evaluated patients participating in an intensive behavioral modification program and another trial (N= 505) evaluated patients with type 2 diabetes.
- Removed: In these randomized, placebo-controlled trials, 2,545 patients received CONTRAVE 32 mg/360 mg for a mean treatment duration of 36 weeks (median, 56 weeks).
- Removed: Baseline patient characteristics included a mean age of 46 years, 82% women, 78% white, 25% with hypertension, 13% with type 2 diabetes, 56% with dyslipidemia, 25% with BMI greater than 40 kg/m 2, and less than 2% with coronary artery disease.
- Removed: Dosing was initiated and increased weekly to reach the maintenance dose within 4 weeks.
- Removed: In CONTRAVE clinical trials, 24% of subjects receiving CONTRAVE and 12% of subjects receiving placebo discontinued treatment because of an adverse event.
- Removed: The most frequent adverse reactions leading to discontinuation with CONTRAVE were nausea (6.3%), headache (1.7%) and vomiting (1.1%).
- Removed: Common Adverse Reactions Adverse reactions that were reported by greater than or equal to 2% of patients, and were more frequently reported by patients treated with CONTRAVE compared to placebo, are summarized in Table 3.
- Removed: Other Adverse Reactions The following additional adverse reactions were reported in less than 2% of patients treated with CONTRAVE but with an incidence at least twice that of placebo: Cardiac Disorders: tachycardia, myocardial infarction Ear and Labyrinth Disorders: vertigo, motion sickness Gastrointestinal Disorders: lower abdominal pain, eructation, lip swelling, hematochezia, hernia General Disorders and Administration Site Conditions: feeling jittery, feeling abnormal, asthenia, thirst,...
- Removed: These events were further categorized into sleep disorders (13.8% CONTRAVE, 8.4% placebo), depression (6.3% CONTRAVE, 5.9% placebo), and anxiety (6.1% CONTRAVE, 4.4% placebo).
- Removed: Patients who were 65 years or older experienced more psychiatric and sleep disorder adverse reactions in the CONTRAVE group (28.6%) compared to placebo (6.3%), although the sample size in this subgroup was small (56 CONTRAVE, 32 placebo); the majority of these events were insomnia (10.7% CONTRAVE, 3.1% placebo) and depression (7.1% CONTRAVE, 3.1% placebo).
- Removed: Neurocognitive Adverse Reactions Adverse reactions involving attention, dizziness, and syncope occurred more often in individuals randomized to CONTRAVE 32/360 mg group compared to placebo (15.0% and 5.5%, respectively).
- Removed: The most common cognitive-related adverse reactions were attention disorders (2.5% CONTRAVE, 0.6% placebo).
- Removed: Adverse reactions involving dizziness and syncope were more common in patients treated with CONTRAVE (10.6%) than in placebo-treated patients (3.6%); dizziness accounted for almost all of these reported events (10.4% CONTRAVE, 3.4% placebo).
- Removed: Dizziness was the primary reason for discontinuation for 0.9% and 0.3% of patients in the CONTRAVE and placebo groups, respectively.
- Removed: Increases in Serum Creatinine In the one-year controlled trials of CONTRAVE, larger mean increases in serum creatinine from baseline to trial endpoint were observed in the CONTRAVE group compared with the placebo group (0.07 mg/dL and 0.01 mg/dL, respectively) as well as from baseline to the maximum value during follow-up (0.15 mg/dL and 0.07 mg/dL, respectively).
- Removed: Increases in serum creatinine that exceeded the upper limit of normal and were also greater than or equal to 50% higher than baseline occurred in 0.6% of subjects receiving CONTRAVE compared to 0.1% receiving placebo.
- Removed: The observed increase in serum creatinine may be the result of OCT2 inhibition.
- Removed: Postmarketing Experience The following adverse reactions have been identified during post approval use of CONTRAVE.
- Removed: Because these 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.
- Removed: Loss of consciousness, malaise