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Contrave

  • Generic Name: naltrexone hcl and bupropion hcl extended-release tablets
  • Brand Name: Contrave
  • Drug Class: Opioid Antagonists

Contrave (Naltrexone HCl and Bupropion HCl Extended-Release Tablets) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Contrave Side Effects Center

What Is Contrave?

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).

What Are Side Effects of Contrave?

Common side effects of Contrave include:

Dosage for Contrave

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.

What Drugs, Substances, or Supplements Interact with Contrave?

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 During Pregnancy and Breastfeeding

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.

Additional Information

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.

 

Contrave Consumer Information

Get emergency medical help if you have signs of an allergic reaction: fever, swollen glands, mouth sores, muscle or joint pain; hives, rash or itching; chest pain, difficult breathing; swelling of your face, lips, tongue, or throat.

A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, severe drowsiness, or if you are hard to wake up.

Stop taking this medicine and call your doctor right away if you have:

  • severe headache, blurred vision, pounding in your neck or ears, fast heartbeats;
  • a seizure (convulsions);
  • blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • changes in mood or behavior--anxiety, depression, panic attacks, trouble sleeping, agitation, thoughts about suicide or hurting yourself;
  • a manic episode--racing thoughts, increased energy, unusual risk-taking behavior, extreme happiness, being irritable or talkative;
  • liver problems--upper stomach pain, tiredness, dark urine, jaundice (yellowing of the skin or eyes); or
  • severe skin reaction--fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling.

Older adults may be more likely to have certain side effects.

Common side effects may include:

  • nausea, vomiting, diarrhea, constipation;
  • headache, dizziness;
  • dry mouth; or
  • sleep problems (insomnia).

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.

Read the entire detailed patient monograph for Contrave (Naltrexone HCl and Bupropion HCl Extended-Release Tablets)

 

Contrave Professional Information

SIDE EFFECTS

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

  • Suicidal Behavior and Ideation [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
  • Neuropsychiatric Adverse Events [see WARNINGS AND PRECAUTIONS]
  • Seizures [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]
  • Increase in Blood Pressure and Heart Rate [see WARNINGS AND PRECAUTIONS]
  • Allergic Reactions [see WARNINGS AND PRECAUTIONS]
  • Angle-Closure Glaucoma [see WARNINGS AND PRECAUTIONS]

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 placebotreated 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. The observed increase in serum creatinine may be the result of OCT2 inhibition [see CLINICAL PHARMACOLOGY].

Postmarketing Experience

The following 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 not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Loss of consciousness, malaise

DRUG INTERACTIONS

Monoamine Oxidase Inhibitors (MAOI)

Concomitant use of MAOIs and bupropion is contraindicated. Bupropion inhibits the re-uptake of dopamine and norepinephrine and can increase the risk for hypertensive reactions when used concomitantly with drugs that also inhibit the re-uptake of dopamine or norepinephrine, including MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAOI phenelzine. At least 14 days should elapse between discontinuation of an MAOI and initiation of treatment with CONTRAVE. Conversely, at least 14 days should be allowed after stopping CONTRAVE before starting an MAOI [see CONTRAINDICATIONS].

Opioid Analgesics

Patients taking CONTRAVE may not fully benefit from treatment with opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations, and opioid analgesics. In patients requiring intermittent opiate treatment, CONTRAVE therapy should be temporarily discontinued and opiate dose should not be increased above the standard dose. CONTRAVE may be used with caution after chronic opioid use has been stopped for 7 to 10 days in order to prevent precipitation of withdrawal [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

During CONTRAVE clinical studies, the use of concomitant opioid or opioid-like medications, including analgesics or antitussives, were excluded.

Potential For CONTRAVE To Affect Other Drugs

Metabolized by CYP2D6

In a clinical study, CONTRAVE (32 mg naltrexone/360 mg bupropion) daily was coadministered with a 50 mg dose of metoprolol (a CYP2D6 substrate). CONTRAVE increased metoprolol AUC and Cmax by approximately 4- and 2-fold, respectively, relative to metoprolol alone. Similar clinical drug interactions resulting in increased pharmacokinetic exposure of CYP2D6 substrates have also been observed with bupropion as a single agent with desipramine or venlafaxine.

Coadministration of CONTRAVE with drugs that are metabolized by CYP2D6 isozyme including certain antidepressants (SSRIs and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If CONTRAVE is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need to decrease the dose of the original medication should be considered, particularly for those concomitant medications with a narrow therapeutic index [see CLINICAL PHARMACOLOGY].

Digoxin

Coadministration of CONTRAVE with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with CONTRAVE and digoxin [see CLINICAL PHARMACOLOGY].

Potential For Other Drugs To Affect CONTRAVE

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between CONTRAVE and drugs that are inhibitors or inducers of CYP2B6.

Inhibitors Of CYP2B6

Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. During concomitant use with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel), the CONTRAVE daily dose should not exceed two tablets (one tablet each morning and evening) [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Inducers Of CYP2B6

Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure and may reduce efficacy. Avoiding concomitant use with ritonavir, lopinavir, or efavirenz is recommended [see CLINICAL PHARMACOLOGY].

Drugs That Lower Seizure Threshold

Use extreme caution when coadministering CONTRAVE with other drugs that lower seizure threshold (e.g., antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses and increase the dose gradually. Concomitant use of other bupropioncontaining products is contraindicated [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Dopaminergic Drugs (Levodopa And Amantadine)

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution and monitor for such adverse reactions when administering CONTRAVE concomitantly with these drugs.

Use With Alcohol

In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion. The consumption of alcohol during treatment with CONTRAVE should be minimized or avoided.

Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. Falsepositive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

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

&Copy; 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.