Contrave side effects and how to avoid them

Common Contrave side effects include nausea, constipation, and headache

By Stephanie Melby, Pharm.D. | May 4, 2023

Contrave (naltrexone/bupropion) extended-release tablet is a brand-name medication used for weight management in certain adults who are overweight or obese. This medication is intended to be used alongside a reduced-calorie diet and increased physical activity to help lose weight. Contrave is used in adults with an initial body mass index (BMI) of ≥30 or in adults with an initial BMI of ≥27 plus at least one weight-related health condition (such as Type 2 diabetes mellitus, high blood pressure, or high cholesterol). Contrave works to reduce food intake by targeting two areas of the brain, the mesolimbic reward system and the hypothalamus. In these areas, Contrave regulates feelings of pleasure when eating to help control cravings and curb hunger. This medication is typically not used first for weight loss management as it has cardiovascular safety issues and a higher risk of side effects than other weight loss medications.

Common side effects of Contrave

Like other weight loss drugs, Contrave has many common side effects. The most common side effects include nausea, headache, and constipation. According to clinical trial data, 24% of patients receiving Contrave discontinued treatment because of an adverse event as they could not tolerate the weight loss medicine.

Other common side effects of Contrave include the following:

Vomiting
Dizziness
Insomnia
Dry mouth
Diarrhea
Increase in blood pressure
Increase in heart rate
Anxiety
Hot flush
Fatigue
Tremor
Abdominal pain
Stomach virus
Influenza
Ringing in ears
Urinary tract infection
Excessive sweating
Irritability
Altered taste
Rash
Muscle strain
Heart palpitations

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Serious side effects of Contrave

Contrave has several serious side effects, including a Boxed Warning for suicidal thoughts and behaviors. Serious side effects of Contrave include the following:

Neuropsychiatric disorders
Homicidal ideation
Suicidality
Depression exacerbation
Hypersensitivity reaction
Stevens-Johnson syndrome (a serious disorder of the skin)
Erythema multiforme (skin reaction)
Anaphylaxis
Liver toxicity
Heart attack
Severe high blood pressure
Seizures
Angle-closure glaucoma

Nausea

Nausea is the most common side effect of Contrave and happens to about 1/3 of people taking it. Clinical trial data shows the most frequent side effect leading to discontinuation is nausea. Along with nausea, other gastrointestinal (GI) side effects are common with Contrave, such as vomiting. Generally, nausea and other GI side effects are temporary and resolve quickly. Some tips for managing nausea include drinking plenty of water and eating a small amount of food with Contrave (such as dry toast). If symptoms do not improve, it is best to consult with the healthcare team and decide if an over-the-counter (OTC) anti-nausea medication is appropriate.

Constipation

Constipation is the second most common side effect of Contrave and happens to about 19% of people taking it. Clinical trial data doesn’t show that constipation is one of the top reasons for discontinuation, but people may find this side effect intolerable. Like the other GI side effects common with Contrave, constipation is generally temporary and resolves quickly. While taking Contrave, it is best to stay hydrated and drink plenty of water to help “get things moving” again, as water is important for digestion. If symptoms do not improve, it is best to consult a provider and decide if an OTC constipation medicine is necessary. However, worsening constipation with severe abdominal pain could indicate a more serious health condition and immediate medical attention is required.

Headache

Aside from GI side effects, a headache is the next most common side effect of Contrave and happens in about 18% of people. Clinical trial data shows a small number of people discontinue Contrave due to headaches (about 2%). This side effect is typically short-term. While taking Contrave, it is best to stay hydrated and drink plenty of water, which can help manage this side effect. If headache symptoms do not improve or become more severe, seek medical attention as this could be a sign of a more serious problem, such as a hypertensive event (dangerously high blood pressure).

Insomnia

Some people taking Contrave may have trouble falling asleep, staying asleep, or getting good quality sleep. Insomnia is another common side effect of Contrave and happens in about 9% of people. Taking Contrave around bedtime may lead to a greater chance of this side effect happening. Some tips for avoiding or managing insomnia include taking the evening Contrave dose before dinner and practicing good sleep hygiene. If symptoms do not improve, it is best to consult with the healthcare team and decide if an OTC or prescription sleep aid is appropriate.

How soon do Contrave side effects start?

People who start taking Contrave may experience side effects at the start of treatment. Typically, Contrave is started at a low dose and gradually increased to the standard dose over the course of one month. Gradually increasing the dose can help prevent or lessen the severity of side effects. The most common side effects that may happen when starting Contrave include GI-related effects like nausea, vomiting, and constipation.

How long do Contrave side effects last?

Generally, most side effects of Contrave are temporary and resolve quickly as the body adjusts to the new medication, like nausea and other GI side effects. However, if a side effect continues to be bothersome or becomes more severe, it’s best to consult with a healthcare provider for medical advice.

What are the long-term side effects of Contrave?

Once Contrave has been stopped, related side effects should cease. However, some possible disease-related concerns could persist, such as liver problems, kidney problems, or narrow-angle glaucoma.

Contrave contraindications

Certain people should not take Contrave as it could cause serious harm. The groups of people who have contraindications to Contrave include:

Uncontrolled hypertension (high blood pressure)
Seizure disorder or a history of seizures
Use of other bupropion-containing products including Aplenzin, Forfivo XL, Wellbutrin SR, and Wellbutrin XL
Bulimia or anorexia nervosa, which increase the risk of seizure
Chronic opioid or opiate agonist (e.g., methadone) or partial agonists (e.g., buprenorphine) use, or acute opiate withdrawal
Anyone undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
Concomitant administration of monoamine oxidase inhibitors (MAOI); at least 14 days should elapse between discontinuation of MAOI and initiation of treatment with Contrave
Allergy/history of allergic reaction to bupropion or naltrexone

Pregnancy and nursing

Medications for weight loss therapy are not recommended during pregnancy or for women who are breastfeeding. Due to the potential for fetal harm associated with weight loss during pregnancy, Contrave should be discontinued once pregnancy is detected.

Children

The Food and Drug Administration (FDA) has not approved the use of Contrave for anyone under 18. Contrave is not recommended for use in children.

Contrave warnings

Contrave has a Boxed Warning, the most severe type of warning mandated by the FDA, for suicidal thoughts and behavior. This risk should be considered and discussed with the provider before starting therapy with Contrave. The Suicide and Crisis Lifeline provides support 24/7 via 9-8-8, a toll-free hotline.

Some health conditions may get worse or cause serious side effects in people taking Contrave, so treatment will require more careful monitoring:

Older adults
Kidney problems
Liver problems
Bipolar disorder
Diabetes mellitus
Cardiovascular disease
Narrow-angle glaucoma
Psychiatric disorders

Recalls

A drug recall is the most effective way to protect the public from a defective or potentially harmful product. There have not been any recent Contrave recalls.

Abuse and dependence

In clinical studies, there was no evidence of abuse or dependence associated with Contrave. However, there are reports of bupropion (an ingredient in Contrave) being abused by inhaling or injecting dissolved tablets, leading to life-threatening seizures.

Overdose

Taking too much Contrave can lead to an overdose and result in serious problems, including seizures, convulsions, coma, respiratory failure, and death. Immediate emergency medical care is required if an overdose is suspected. Other symptoms of a Contrave overdose include:

Racing heart
Loss of consciousness
Hallucinations
Irregular heartbeat
Hyperactive reflexes
Stiff or rigid muscles

The maximum dosage of Contrave is 4 tablets a day (naltrexone 32 mg/bupropion 360). Each tablet contains 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride.

Contrave interactions

Taking Contrave with certain drugs may cause a dangerous drug interaction. Contrave should not be taken with or used with caution in the following:

Monoamine oxidase inhibitors (MAOIs): Examples include isocarboxazid, phenelzine, transdermal selegiline, and tranylcypromine can increase the risk for hypertensive reactions.
Drugs that are metabolized by CYP2D6 isozyme: Examples include certain antidepressants (SSRIs and many tricyclics), antipsychotics (such as haloperidol, risperidone, and thioridazine), beta blockers (such as metoprolol), and Type 1C antiarrhythmics (such as propafenone and flecainide).
Opioid analgesics: People taking Contrave may not fully benefit from treatment with opioid-containing medicines.
Dopaminergic drugs: Medications such as levodopa and amantadine can increase the chance of CNS toxicity.
Consuming alcohol or caffeine: Alcohol or caffeine may increase the adverse effects including a greater chance of seizures and alcohol tolerance may decrease during treatment.
Drugs that lower the seizure threshold: Examples include antipsychotics, antidepressants, theophylline, or systemic corticosteroids.

Specific drugs that are contraindicated with Contrave include:

Seizure medications: Including brivaracetam, carbamazepine, cenobamate, clobazam, clonazepam, clorazepate, diazepam, eslicarbazepine acetate, ethosuximide, felbamate, fenfluramine, fosphenytoin, gabapentin, ganaxolone, lacosamide, lamotrigine, levetiracetam, lorazepam, methsuximide, midazolam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproic acid, vigabatrin, zonisamide.
Analgesics: Including buprenorphine, butorphanol, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, tapentadol, tramadol.
Antidepressants: Including bupropion, isocarboxazid, phenelzine, selegiline transdermal, and tranylcypromine.
Miscellaneous: Including acetazolamide, cannabidiol, eliglustat, linezolid, methylene blue injection, opium, pimozide, and thioridazine.

How to avoid Contrave side effects

While some Contrave side effects are common, there are tips for avoiding and minimizing side effects.

1. Take Contrave as directed

Follow the instructions given by a healthcare professional that is written on the prescription label. Contrave dosing should be increased slowly over the course of one month according to a specific schedule. Gradually increasing the dose can help prevent or lessen the severity of side effects. Take tablets whole and do not cut, chew, or crush them. A helpful dosing tip is to take the morning dose with breakfast and the evening dose before dinner.

People with kidney or liver impairment or those taking certain other medications may need to follow a different dosing schedule. Do not take more tablets than the directions say (the maximum dose is 4 tablets a day).

2. Tell the healthcare provider about all medical conditions

Increased side effects can be avoided by informing the healthcare provider about all medical conditions. Some of the conditions that impact the use of Contrave include:

Seizure disorder or a history of seizures
Past or present eating disorders, especially anorexia or bulimia
Any history of suicide, depression, or other mental illness
Any history of mania, hypomania, or bipolar disorder
Drinking alcohol or using illicit drugs
Heart disease, high blood pressure, or recent heart attack
Diabetes
Liver problems
Kidney problems
Pregnancy or plans to become pregnant
Breastfeeding or plans to breastfeed

3. Tell the healthcare provider about all medications

Along with sharing all medical conditions, the healthcare provider should be made aware of all medications being taken including prescription drugs, over-the-counter drugs, and dietary supplements. This can help avoid dangerous drug interactions that may increase adverse events.

4. Drink plenty of water

To help avoid and lessen the side effects of Contrave, it is best to drink plenty of water and stay hydrated. This can help with common side effects including nausea, headache, and constipation.

5. Do not take Contrave with high-fat meals

Taking Contrave with high-fat meals may increase the risk of seizures. Because there is an increased chance of seizures while taking Contrave, it is best to minimize other risk factors including alcohol and caffeine.

6. Monitor body weight loss

While an effective weight loss medication, Contrave can usually be discontinued once a person’s weight loss is <4% to 5% of baseline after 3 months. Once Contrave has been stopped, a healthy diet and regular physical activity can be continued to manage weight.

How to treat side effects of Contrave

Most of the side effects of Contrave are temporary and resolve quickly as the body adjusts to the new medication, like nausea and other GI side effects. However, there are some tips to help treat side effects and lessen the severity if they are bothersome. If a side effect continues and becomes more severe, it’s best to consult with a healthcare provider.

Nausea treatment

As the most common side effect, it is likely that people taking Contrave will experience nausea. To help with nausea, it’s important to drink plenty of water and eat a small amount of food with Contrave (such as dry toast). If symptoms do not improve, it is best to consult with a healthcare provider and decide if an OTC anti-nausea medication (such as Dramamine or Pepto Bismol) is appropriate.

Constipation treatment

As another common GI side effect, drinking plenty of water and staying hydrated can help treat constipation associated with Contrave. Hydrating can help “get things moving” again, as water is vital for digestion. If symptoms do not improve, it is best to consult a provider and decide if an OTC constipation medicine (such as Senna or Dulcolax) is necessary.

Headache treatment

Some headaches can be successfully treated with OTC pain reliever medications such as Tylenol (acetaminophen), Advil or Motrin (ibuprofen), or Aleve (naproxen). Similar to the treatment of some GI side effects, staying hydrated and drinking plenty of water can also help treat headaches. Some other useful techniques include resting in a darkened room or placing a cold pack on the forehead.

Insomnia treatment

Trouble sleeping, like difficulty falling asleep and staying asleep or getting good quality sleep, can be a bothersome side effect of Contrave. Taking the evening dose of Contrave before dinner and practicing good sleep hygiene can help treat insomnia. If symptoms do not improve, it is best to consult a healthcare provider and decide if an OTC sleep aid (such as melatonin or Unisom) or prescription sleep aid is appropriate.

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