Contrave and Hydromorphone Drug Interactions: A Risky Combo?

As more people turn to medications to manage weight and chronic pain, concerns about how these drugs may interact are becoming increasingly important. One such potential concern is the combination of Contrave and hydromorphone drug interactions.

Contrave, a prescription medication for chronic weight management in certain individuals, combines bupropion hydrochloride and naltrexone in extended-release tablets. If you’re wondering how long the effects of Contrave last, you can read more about how long Contrave stays in your system. Hydromorphone, on the other hand, is a powerful opioid analgesic used to treat moderate to severe pain. While both drugs serve distinct purposes, their interaction can pose serious health risks.

In this article, we’ll explore the pharmacology of both drugs, discuss the potential drug interactions, highlight risks such as the risk of seizures, opioid withdrawal symptoms, and high blood pressure, and offer guidance on what to discuss with your doctor before combining treatments.

Key Takeaways

• Combining Contrave and hydromorphone may increase the risk of serious health issues, including seizures, opioid withdrawal, and high blood pressure.
• Certain individuals, especially those with a seizure disorder, bipolar disorder, or severe hepatic impairment, face even greater risks.
• Always talk with your doctor before starting or adjusting medications to prevent adverse reactions and ensure your safety.

Understanding Contrave

Contrave is approved for use in certain obese or overweight patients who have an initial body mass index (BMI) of 30 kg/m2 or greater, or 27 kg/m2 with at least one weight-related condition like high blood pressure or Type 2 diabetes.  Contrave works for weight loss by combining two active ingredients:

• Bupropion hydrochloride, an antidepressant also used to treat depression and quit smoking.
• Naltrexone, an opioid antagonist commonly used to treat opioid dependence and alcohol use disorders.

Together, bupropion naltrexone targets brain pathways related to hunger and reward, supporting weight loss for compatible individuals when combined with a reduced-calorie diet and increased physical activity.

But like other weight loss drugs, taking Contrave is not without risks. The drug carries a boxed warning that alerts doctors to the potential for suicidal thoughts in some patients, especially during starting Contrave treatment or dose changes. It can also increase the risk of seizures, particularly in those with eating disorders, uncontrolled high blood pressure, or a seizure disorder.

Hydromorphone: What You Need to Know

Hydromorphone is a potent opioid used to manage moderate to severe pain. It is often prescribed after surgeries, for cancer pain, or for individuals with chronic pain conditions who are opioid-tolerant. Hydromorphone carries its own risk profile, including physical dependence, accidental overdose, and opioid withdrawal.

Importantly, naltrexone—one of the components of Contrave—blocks opioid receptors. When someone taking Contrave receives opioids like hydromorphone, the opioid’s effect can be reduced or entirely blocked. This can trigger opioid withdrawal symptoms in people dependent on opioids or cause inadequate pain control in those with no opioid dependence.

Why Contrave and Hydromorphone Don’t Mix

The combination of Contrave and hydromorphone is considered potentially dangerous due to how these drugs interact within the brain and body. Both medications have potent effects on the central nervous system, and their overlap can produce harmful outcomes.

Below are the key reasons why this mix should be approached with extreme caution:

1. Risk of Seizures

One of the most serious concerns when combining Contrave with hydromorphone is the heightened risk of seizures. Bupropion doses—a component of Contrave—are already known to reduce the seizure threshold, meaning they make seizures more likely, especially at higher doses or when taken by individuals with eating disorders, bipolar disorder, or a history of seizures.

Hydromorphone, as a powerful opioid, also affects the central nervous system and may further lower the brain’s seizure resistance.

When used together, the compounding effects can lead to a dangerously increased seizure risk, even in patients without a diagnosed seizure disorder. Those already predisposed to seizures are at especially high risk and must be monitored closely.

“Patients taking Contrave should be closely monitored when other central nervous system medications like opioids are added, due to changes in the seizure threshold,” says Dr. Matthew Olesiak, Chief Medical Director at SANE MD. “The interaction can become especially volatile if there are underlying neurological risk factors.”

2. Opioid Withdrawal

Contrave contains naltrexone, an opioid receptor antagonist that blocks the effects of opioids in the brain. While this action is useful for supporting weight loss and treating opioid dependence, it presents a serious issue for anyone currently taking opioid medications like hydromorphone, morphine, hydrocodone, codeine, etc.

If naltrexone is taken by someone who is physically dependent on opioids—even if the last opioid dose was taken several hours ago—it can rapidly displace the opioid from the receptors, leading to symptoms of opioid withdrawal.

This withdrawal can be intense and sudden, with symptoms such as nausea, vomiting, sweating, tremors, anxiety, muscle aches, irritability, and insomnia. For those with chronic opioid use or opioid dependence, the experience can be medically dangerous and emotionally distressing.

Importantly, even low-dose or recent opioid use can result in these opioid withdrawal symptoms when combined with Contrave. Because naltrexone can remain active in the body for some time, knowing how long Contrave stays in your system can help patients and providers avoid unexpected withdrawal.

This makes it essential to talk with your doctor and fully disclose any recent or ongoing opioid use before starting Contrave treatment.

3. High Blood Pressure and Cardiovascular Strain

Another major concern is the increased risk of cardiovascular complications. Taking Contrave has been shown to cause elevations in blood pressure and heart rate due to its bupropion component, which influences the serotonergic neurotransmitter system and inhibits norepinephrine reuptake.

Hydromorphone, although a depressant, can cause fluctuations in cardiovascular function, including hypotension (low blood pressure) or rebound hypertension (high blood pressure), especially when pain levels are not properly managed.

When these medications are combined, they may create unpredictable blood pressure responses and place significant strain on the heart. This risk is particularly serious for individuals with uncontrolled high blood pressure, heart disease, or a history of chest pain or stroke. In worst-case scenarios, the combination could precipitate a cardiac event.

“We already know that bupropion inhibits norepinephrine reuptake, which can increase both heart rate and blood pressure,” explains Dr. Olesiak. “When you add opioids to the mix, you increase cardiovascular risk, especially if the patient has pre-existing risk factors.”

Even for those without diagnosed cardiovascular conditions, monitoring blood pressure during Contrave treatment becomes essential, especially when combined with other drugs that affect the heart.

Additional Red Flags

Suicidal Thoughts and Psychiatric Concerns

One of the most concerning side effects of taking Contrave is its potential to increase the risk of suicidal thoughts, especially during the early stages of treatment or when doses are changed. This risk is particularly elevated in younger adults, adolescents, and those with existing psychiatric conditions like bipolar disorder or major depressive disorder.

Bupropion, one of Contrave’s active ingredients, acts on neurotransmitters that regulate mood and behavior, which can sometimes lead to mental health destabilization in vulnerable individuals.

When combined with opioids like hydromorphone—known for their sedative and mood-altering properties—the potential for psychiatric side effects increases. This combination may worsen mood swings, emotional instability, and even lead to dangerous decision-making behavior.

Individuals with a personal or family history of psychiatric illness should be carefully evaluated before starting Contrave treatment and should talk with their doctor about any emerging mental health symptoms, including trouble sleeping, agitation, or dark thoughts.

Physical Dependence and Withdrawal

Both Contrave and hydromorphone can influence the brain’s reward and adaptation systems, although through very different mechanisms. Hydromorphone, as a narcotic analgesic, carries a high potential for physical dependence and can lead to withdrawal if suddenly discontinued.

Contrave, especially due to the bupropion doses, may also lead to withdrawal symptoms such as irritability, anxiety, and cravings if stopped abruptly—especially in patients who are also using it to quit smoking or treat depression.

When used together, these drugs can confuse the body’s adaptive responses, making withdrawal more intense or erratic. If a patient is already dependent on opioids and begins taking Contrave, the naltrexone component can precipitate acute opioid withdrawal symptoms, which are not only unpleasant but can be medically dangerous.

Gradual dose adjustments and close medical supervision are essential when stopping either drug, and patients should never discontinue without a clear tapering plan set by their provider.

Other Drug Interactions

Can Contrave interact with other medications? Unfortunately, the answer is “yes.” Many patients taking Contrave are also managing other health conditions like diabetes, hypertension, or anxiety—and are therefore often on multiple medications. This increases the chances of certain drug interactions with Contrave, particularly when combining over-the-counter drugs, other medications, or even herbal remedies. Some drugs may increase the risk of side effects by affecting liver enzymes that process Contrave, while others might alter its efficacy or trigger unpredictable reactions.

For example, decongestants can elevate blood pressure, increasing the danger of hypertension in patients already at risk. Antidepressants like Effexor and Prozac, stimulants like Ritalin and caffeine, or antipsychotics may enhance central nervous system stimulation, raising the risk of seizures or mood disturbances. Even some dietary supplements marketed for weight loss may interfere with bupropion naltrexone.

These overlapping effects can be unpredictable—and potentially dangerous—when multiple medications are used together, especially without close monitoring.

According to a 2023 study published in Medicina, 85.3% of patients taking two or more medications simultaneously had at least one potential drug-drug interaction. Similarly, a 2014 study in PLOS ONE found that 70% of elderly patients engaged in polypharmacy, with over 10% experiencing adverse drug reactions.

Always provide a full list of medications and supplements to your healthcare provider and talk with your doctor before starting Contrave in a polypharmacy context.

High-Fat Meals

Food intake—specifically high-fat meals—can significantly influence how Contrave is absorbed. Research has shown that consuming a high-fat meal can increase bupropion exposure, potentially raising serum drug levels and intensifying side effects. This elevated exposure further lowers the seizure threshold, which is already compromised in patients on Contrave.

When opioids like hydromorphone are introduced, the overlapping effects on the central nervous system can compound these risks, making side effects like dizziness, sedation, or confusion more likely.

Patients should be advised to take Contrave with a low-fat meal or on an empty stomach to reduce risk. The medication guide also warns against high-fat food intake during Contrave treatment, especially when patients are also using other drugs that impact the central nervous system.

Allergic Reactions and Skin Rash

Although rare, allergic reactions can occur with Contrave, ranging from mild skin rash to more serious reactions involving swelling, difficulty breathing, or hives. These reactions are more likely when the immune system is activated by multiple other drugs, especially those known to trigger histamine release. Combining Contrave with hydromorphone—which can also cause histamine-related side effects—may amplify the risk of an allergic response.

​Clinical data and post-marketing reports have documented instances of allergic reactions, including skin rashes, among patients using the bupropion/naltrexone combination therapy. According to the FDA product monograph for Contrave (the brand name for bupropion/naltrexone), common dermatologic adverse reactions (occurring in 1% to 10% of patients) include hyperhidrosis and rash, while uncommon reactions (0.1% to 1%) encompass alopecia.

Patients with a history of medication allergies should, therefore, be cautious and talk with their doctor about their history before taking Contrave. Any new skin changes, itching, or respiratory symptoms should be reported immediately to prevent serious adverse reactions.

Who’s Most at Risk?

Some individuals face a significantly increased risk of complications when taking Contrave alongside opioids or other medications.

You may be in a higher-risk category if you:

• Have a seizure disorder or a history of seizures: Your risk of experiencing a seizure is already elevated, and Contrave can further reduce your seizure threshold.
• Are taking other CNS stimulants or sedatives: This includes medications for ADHD, sleep disorders, anxiety, or mood stabilization. These can interact with bupropion or hydromorphone and amplify side effects.
• Have bipolar disorder or psychiatric conditions: The mood-modulating effects of both drugs can trigger suicidal thoughts, manic episodes, or emotional instability.
• Have uncontrolled high blood pressure: Contrave is known to raise blood pressure. When paired with opioids or other medications, this can heighten your risk of cardiovascular complications.
• Are pregnant or breastfeeding: Both bupropion and naltrexone may pass into breast milk, and their effects on infants have not been fully established. Pregnant or nursing patients should avoid Contrave unless clearly needed and prescribed under careful supervision.
• Are already dependent on opioids: Taking Contrave while using opioids like hydromorphone can trigger sudden and severe opioid withdrawal symptoms, which can be medically dangerous.

Safe Use Guidelines

Talk With Your Doctor

Before taking Contrave, always talk with your doctor, especially if you’re already taking opioids. It’s essential to disclose all medications, including over-the-counter drugs, herbal supplements, and other medications, to prevent Contrave interactions.

Start Low, Go Slow

This approach helps monitor patients for any worsening side effects or new symptoms. Gradual titration, especially when starting Contrave treatment, can help reduce the risk of seizures and ensure tolerability.

Avoid Alcohol

Drinking alcohol while taking Contrave can lower the seizure threshold and amplify central nervous system effects. Patients who suddenly stop drinking alcohol are at even greater risk.

Follow the Medication Guide

Always read the FDA-approved medication guide and follow the instructions carefully. Note the importance of not skipping your scheduled dose or taking more than your next scheduled dose.

Frequently Asked Questions (FAQs)

Combining weight loss medications like Contrave with pain relievers—especially opioids—raises important safety questions. Whether you’re managing chronic pain, post-surgical discomfort, or simply need a temporary painkiller, it’s crucial to understand the potential interactions and risks.

Below are answers to commonly asked questions about taking Contrave with opioids and other pain medications.

1. Can I take Contrave with HYDROcodone?

It is generally not recommended to take Contrave with hydrocodone or any opioid medication. Contrave contains naltrexone, an opioid receptor blocker, which can interfere with the effects of hydrocodone. This interaction can lead to reduced pain relief or even trigger sudden opioid withdrawal symptoms in individuals who are physically dependent on opioids.

Always talk with your doctor before combining these medications.

2. Can you take hydromorphone with bupropion?

Caution is advised when taking hydromorphone with bupropion. Both drugs can affect the central nervous system and may increase the risk of seizures, especially in those with a seizure disorder or bipolar disorder. Additionally, bupropion may intensify the effects of opioids or interfere with pain perception.

Always talk with your doctor if you’re prescribed both medications to determine the safest approach.

3. Can you take Contrave with opioids?

No, taking Contrave with opioids is not considered safe without medical supervision. The naltrexone in Contrave can block opioid effects and cause opioid withdrawal, even if the opioid was taken hours earlier. This interaction can be physically distressing and potentially dangerous.

Patients who need pain management with opioids should talk with their doctor before starting or continuing Contrave.

4. What medications should not be taken with Contrave?

Several types of medications can cause harmful Contrave interactions. These include opioids, such as hydrocodone, monoamine oxidase inhibitors (MAOIs), other antidepressants, and medications that lower the seizure threshold, such as antipsychotics or stimulants. Drugs that affect blood pressure, insulin or oral diabetes medications (due to the risk of low blood sugar), and over-the-counter drugs like decongestants can also pose risks.

Always provide your doctor with a full list of other drugs you’re taking, including supplements and herbals.

5. Can you take painkillers with Contrave?

Non-opioid painkillers like acetaminophen (Tylenol) or ibuprofen (Advil) are typically safe to use with Contrave, but opioid-based painkillers are not. Because Contrave blocks opioid receptors, combining it with opioids may result in ineffective pain relief or trigger opioid withdrawal symptoms.

If you’re in pain, talk with your doctor to find safe alternatives that won’t interfere with your Contrave treatment or increase health risks.

Final Thoughts

When used as prescribed, both Contrave and hydromorphone can provide therapeutic benefits. However, Contrave and hydromorphone drug interactions are not something to overlook. From opioid withdrawal symptoms and high blood pressure to risk of seizures and suicidal thoughts, the combination can be dangerous, especially without professional oversight.

Taking Contrave alongside opioids like hydromorphone should be avoided unless under direct medical supervision. Whether you’re pursuing clinically meaningful weight loss or managing pain, your health depends on open communication.

Always talk with your doctor to weigh risks, manage side effects, and choose the safest path forward.

Disclaimer: This article is intended for informational purposes only. It does not substitute professional medical advice, diagnosis, or treatment.

Sources

PLOS One

Medicina

FDA