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Contrave

Last reviewed on RxList: 12/10/2018
Contrave Side Effects Center

Last reviewed on RxList 12/10/2018

Contrave (naltrexone HCl and bupropion HCl) Extended-release is a combination of an opioid antagonist and an antidepressant used as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m2 greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Common side effects of Contrave include:

Contrave is started at a low dose and gradually increased. A total daily dosage of two Contrave 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4. Contrave may interact with monoamine oxidase inhibitors (MAOIs), opioid-containing medicines (such as cough and cold remedies, antidiarrheal drugs, and opioid analgesics), antidepressants, antipsychotics, beta-blockers, antiarrhythmics, ticlopidine, clopidogrel, ritonavir, lopinavir, efavirenz, theophylline, corticosteroids, levodopa, amantadine, and alcohol. Tell your doctor all medications and supplements you use. Contrave is not recommended for use during pregnancy. It may harm a fetus. This drug passes into breast milk and is not recommended for use while breastfeeding. Withdrawal symptoms may occur if you suddenly stop taking this medication.

Our Contrave (naltrexone HCl and bupropion HCl) Extended-release Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Contrave Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

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 the rates observed in practice.

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. The majority of patients were treated with CONTRAVE 32 mg/360 mg total daily dose. In addition, some patients were treated with other combination daily doses including naltrexone up to 50 mg and bupropion up to 400 mg. All subjects received study drug in addition to diet and exercise counseling. One trial (N=793) evaluated patients participating in an intensive behavioral modification program and another trial (N= 505) evaluated patients with type 2 diabetes. 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). 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/m², and less than 2% with coronary artery disease. Dosing was initiated and increased weekly to reach the maintenance dose within 4 weeks.

In CONTRAVE clinical trials, 24% of subjects receiving CONTRAVE and 12% of subjects receiving placebo discontinued treatment because of an adverse event. The most frequent adverse reactions leading to discontinuation with CONTRAVE were nausea (6.3%), headache (1.7%) and vomiting (1.1%).

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.

Table 3: Adverse Reactions Reported by Obese or Overweight Patients With an Incidence (%) of at Least 2% Among Patients Treated with CONTRAVE and More Common than with Placebo

Adverse Reaction CONTRAVE 32 mg/360 mg
N=2545
%
Placebo
N=1515
%
Nausea 32.5 6.7
Constipation 19.2 7.2
Headache 17.6 10.4
Vomiting 10.7 2.9
Dizziness 9.9 3.4
Insomnia 9.2 5.9
Dry mouth 8.1 2.3
Diarrhea 7.1 5.2
Anxiety 4.2 2.8
Hot flush 4.2 1.2
Fatigue 4.0 3.4
Tremor 4.0 0.7
Upper abdominal pain 3.5 1.3
Viral gastroenteritis 3.5 2.6
Influenza 3.4 3.2
Tinnitus 3.3 0.6
Urinary tract infection 3.3 2.8
Hypertension 3.2 2.2
Abdominal pain 2.8 1.4
Hyperhidrosis 2.6 0.6
Irritability 2.6 1.8
Blood pressure increased 2.4 1.5
Dysgeusia 2.4 0.7
Rash 2.4 2.0
Muscle strain 2.2 1.7
Palpitations 2.1 0.9

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, feeling hot

Hepatobiliary Disorders: cholecystitis

Infections and Infestations: pneumonia, staphylococcal infection, kidney infection

Investigations: increased blood creatinine, increased hepatic enzymes, decreased hematocrit

Metabolism and Nutrition Disorders: dehydration

Musculoskeletal and Connective Tissue Disorders: intervertebral disc protrusion, jaw pain

Nervous System Disorders: disturbance in attention, lethargy, intention tremor, balance disorder, memory impairment, amnesia, mental impairment, presyncope

Psychiatric Disorders: abnormal dreams, nervousness, dissociation (feeling spacey), tension, agitation, mood swings

Renal and Urinary Disorders: micturition urgency

Reproductive System and Breast Disorders: vaginal hemorrhage, irregular menstruation, erectile dysfunction, vulvovaginal dryness

Skin and Subcutaneous Tissue Disorders: alopecia

Psychiatric And Sleep Disorders

In the one-year controlled trials of CONTRAVE, the proportion of patients reporting one or more adverse reactions related to psychiatric and sleep disorders was higher in the CONTRAVE 32/360 mg group than the placebo group (22.2% and 15.5%, respectively). 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). 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).

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). The most common cognitive-related adverse reactions were attention disorders (2.5% CONTRAVE, 0.6% placebo). 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). Dizziness was the primary reason for discontinuation for 0.9% and 0.3% of patients in the CONTRAVE and placebo groups, respectively.

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). 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. An in vitro drug-drug interaction study demonstrated that bupropion and its metabolites inhibit organic cation transporter 2 (OCT2), which is involved in the tubular secretion of creatinine, suggesting that the observed increase in serum creatinine may be the result of OCT2 inhibition.

Based on in vitro results and FDA guidance for Drug Interaction Studies, the ratios of the free (unbound) Cmax and IC50 value of bupropion and hydroxybupropion were well below 0.1 suggesting a drug-drug interaction between CONTRAVE and OCT2 substrate due to bupropion and hydroxybupropion is unlikely. The ratio for the threohydrobupropion and erythrohydrobupropion metabolite mixture was 0.29, suggesting a drug-drug interaction between CONTRAVE and OCT2 due to threohydrobupropion and erythrohydrobupropion is possible.

Postmarketing Experience

Additional adverse reactions have been identified during post approval use of CONTRAVE. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Read the entire FDA prescribing information for Contrave (Naltrexone HCl and Bupropion HCl Extended-Release Tablets)

Related Resources for Contrave

© Contrave Patient Information is supplied by Cerner Multum, Inc. and Contrave Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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