Contrave and Fentanyl Drug Interactions: Risks & Precautions

Combining medications can lead to unexpected and potentially dangerous interactions. Contrave and fentanyl drug interactions pose a significant risk due to the way these drugs affect the body. Contrave is used for chronic weight management, while fentanyl is a powerful opioid for pain relief. Because Contrave contains naltrexone, an opioid antagonist, taking it with fentanyl can result in opioid withdrawal, serious allergic reactions, and other severe health complications.

Understanding these risks and taking proper precautions is essential for anyone using either medication.

Key Takeaways

• Increased Risk of Severe Reactions – Taking Contrave with fentanyl may increase the risk of opioid withdrawal, irregular heartbeat, and serious skin reactions.
• Medical Supervision is Crucial – Patients receiving Contrave should consult a healthcare provider before taking other medicines, especially opioids.
• Potential for Dangerous Side Effects – The combination can lead to low blood sugar, suicidal thoughts, and serious allergic reactions.

What is Contrave?

Contrave (naltrexone bupropion) is a weight loss medication approved for chronic weight management in compatible obese adults and overweight adults with weight-related health conditions.

It combines two active ingredients: naltrexone, an opioid antagonist, and bupropion, an antidepressant used to treat depression and aid in smoking cessation.

How Contrave Works

The medicine affects the brain’s reward and appetite control centers to reduce cravings and regulate food intake.

Unlike some other drugs for weight loss, Contrave does not work by suppressing hunger alone but alters how the brain processes food-related pleasure and impulse control.

Contrave and Fentanyl Drug Interactions

Interaction Concern	Effect on the Body
Opioid Receptor Blockade	Naltrexone in Contrave blocks fentanyl’s effects, leading to sudden opioid withdrawal.
Precipitated Withdrawal	Can cause severe nausea, vomiting, sweating, irregular heartbeat, and high blood pressure.
Increased Overdose Risk	After naltrexone wears off, opioid receptors become hypersensitive, making fentanyl more potent and increasing the risk of respiratory depression or death.
Metabolism Alteration	Bupropion in Contrave affects liver enzymes, leading to unpredictable fentanyl levels, which may cause overdose or reduced pain relief.
Serious Side Effects	Risk of suicidal thoughts, serious allergic reactions, and irregular heartbeat when combined.

Dosage and Administration

Contrave is available as extended-release tablets and should be taken as prescribed by a healthcare provider. High fat meals can increase systemic exposure to bupropion, potentially leading to increased side effects.

Patients taking bupropion should be cautious, as this ingredient has been linked to an increased risk of seizures.

Potential Side Effects

Contrave use is associated with various side effects, including:

• High blood pressure and irregular heartbeat. This is even more likely in the case of Contrave and Amlodipine Drug Interactions.
• Flu-like symptoms, unusual tiredness, and skin rash
• Contrave constipation
• Serious allergic reaction, requiring emergency help
• Suicidal thoughts in patients with mental health conditions or psychiatric illness
• Low blood sugar, particularly in diabetic patients

For more information, see our guide on Contrave side effects and safety considerations for weight loss.

Patients using Contrave may face an increased risk of severe skin reactions, such as Stevens-Johnson syndrome.

“Contrave is an effective weight management tool for certain individuals, but patients must consider the increased risk of side effects, especially when combined with other medicines,” says Dr. Matthew Olesiak, Chief Medical Director at SANE MD. “Anyone using Contrave should be under the close supervision of a healthcare provider, particularly if they are on opioid analgesics or have heart conditions.”

See our comprehensive guide for more information on Contrave drug interactions.

What is Fentanyl?

Fentanyl is a potent opioid analgesic used to treat severe pain, typically in patients treated for cancer or post-surgical pain.

It is significantly stronger than morphine and can cause physical dependence when used long-term.

How Fentanyl Works

Fentanyl binds to opioid receptors in the brain, blocking pain signals and producing feelings of euphoria. This makes it highly effective but also increases the risk of addiction and opioid dependence.

Forms of Fentanyl

Fentanyl is available in multiple dosage forms, including:

• Patches
• Injections
• Lozenges
• Nasal sprays

Risks and Side Effects

Fentanyl can cause severe respiratory depression, leading to life-threatening complications.

Additional side effects include:

• Low blood pressure and irregular heartbeat
• Flu-like symptoms, unusual tiredness, and skin reactions
• Serious allergic reaction and serious skin reactions
• Withdrawal symptoms if stopped suddenly

Contrave and Fentanyl Drug Interactions

Taking Contrave and fentanyl together is not recommended due to significant and potentially life-threatening risks. The primary concern stems from naltrexone, one of Contrave’s key ingredients, which functions as an opioid antagonist.

This means it actively blocks opioid receptors in the brain, preventing fentanyl from producing its typical pain-relieving and euphoric effects. The same risk applies to ALL opioid medications. Please see our guide on Contrave and Codeine drug interactions.

How Naltrexone in Contrave Interferes with Fentanyl

When fentanyl is taken by someone on Contrave, the naltrexone component binds to the same opioid receptors, effectively blocking fentanyl’s action. This can lead to precipitated opioid withdrawal, a condition that occurs when opioids are suddenly removed from the system, leading to severe and rapid withdrawal symptoms.

Unlike traditional opioid withdrawal, which occurs gradually as the drug leaves the body, precipitated withdrawal happens suddenly and intensely due to opioid receptor blockade.

Symptoms of Opioid Withdrawal Triggered by Contrave

Patients who take fentanyl while on Contrave may experience withdrawal symptoms such as:

• Severe nausea, vomiting, and sweating – The body reacts to the sudden loss of opioid activation, triggering gastrointestinal distress and excessive sweating.
• Irregular heartbeat and high blood pressure – The abrupt shift in the body’s neurochemical balance can strain the cardiovascular system, leading to dangerous fluctuations in heart rate and blood pressure.
• Flu-like symptoms and unusual tiredness – Withdrawal can cause extreme fatigue, body aches, chills, and fever-like symptoms.
• Suicidal thoughts in patients with bipolar disorder or psychiatric illness – Opioid withdrawal can severely impact mental health, especially in individuals already dealing with mood disorders.

Increased Risk of Overdose After Naltrexone Use

Another serious concern is the increased risk of overdose if fentanyl is taken after Contrave. The combined medicine effects of Contrave and fentanyl can increase the risk of overdose, especially if opioids are taken after naltrexone has blocked their effects.

Once naltrexone wears off, opioid receptors may become hypersensitive, meaning a previously tolerated dose of fentanyl could become dangerously potent. This can result in severe respiratory depression, unconsciousness, or even death. This risk is especially high because fentanyl is 50-100 times more potent than morphine and even small amounts can cause fatal overdoses.

Patients taking Contrave should be aware of these risks and consult their healthcare provider before using any opioid medications.

How Contrave Alters Fentanyl’s Metabolism

Apart from opioid receptor blockade, Contrave’s bupropion component also affects the metabolism of certain medicines, including opioids. Bupropion inhibits enzymes in the liver that break down drugs, meaning it can alter how fentanyl is processed in the body. This can result in:

• Unpredictable drug levels – Some individuals may experience either a weakened or prolonged fentanyl effect.
• Heightened risk of respiratory depression – If fentanyl levels rise unexpectedly, it can lead to dangerous breathing difficulties, the primary cause of opioid overdose deaths.

Importance of Medical Supervision

Due to these risks, individuals taking Contrave should consult their healthcare provider before using fentanyl or other opioid analgesics.

Patients receiving Contrave for weight loss or chronic weight management should disclose any past or current opioid use to their doctor to avoid dangerous interactions.

“Many people don’t realize that taking Contrave while on opioid analgesics like fentanyl can result in sudden opioid withdrawal, which can be dangerous,” says Dr. Matthew Olesiak, Chief Medical Director at SANE MD. “It’s critical to speak with a healthcare provider before combining these certain medicines, as doing so can increase the risk of severe health consequences.”

Precautions and Recommendations

If you are taking Contrave or considering it for weight loss, it is important to take proper precautions to avoid serious health risks, especially when using other medicines like fentanyl.

Below are critical safety steps to follow:

1. Inform Your Healthcare Provider About All Medications

Always inform your healthcare provider about any prescription, over-the-counter, or herbal supplements you are taking. This includes other antidepressants, opioid analgesics, tricyclic antidepressants, and systemic corticosteroids. Certain medicines can interfere with Contrave’s effectiveness, increase the risk of seizures, or cause serious allergic reactions.

Additionally, missed doses of Contrave should not be doubled, as this could raise the risk of seizures and adverse reactions.

2. Avoid Alcoholic Beverages

Drinking alcoholic beverages while taking Contrave can increase the risk of serious allergic reactions, irregular heartbeat, and low blood sugar. Alcohol use disorder is also a concern, as bupropion, one of Contrave’s ingredients, has been associated with an increased risk of suicidal thoughts and mental health conditions in certain individuals.

Those who drink alcohol regularly should discuss their consumption with a healthcare provider before starting Contrave.

3. Never Stop Taking Fentanyl Abruptly if You Are Opioid-Dependent

If you are opioid-dependent, do not stop fentanyl suddenly while on Contrave, as this can potentially lead to severe opioid withdrawal symptoms. This may include flu-like symptoms, unusual tiredness, increased heart rate, and dangerously high blood pressure.

Any dose reduction or changes in opioid use should be done under medical supervision to prevent withdrawal complications.

4. Monitor for Serious Skin Reactions

Some individuals may develop serious skin reactions, such as skin rash, hives, or life-threatening allergic reactions. If you notice skin irritation, blistering, or flu-like symptoms accompanying a rash, seek medical attention immediately.

Patients on systemic corticosteroids should be particularly cautious, as they may have an altered immune response to skin reactions.

5. Monitor Blood Sugar Levels, Especially for Diabetic Patients

Patients receiving Contrave for chronic weight management and those with diabetes should closely monitor their blood sugar levels. Since Contrave can lead to low blood sugar, adjustments to diabetes medications or dietary plans may be necessary.

Maintaining a reduced-calorie diet and discussing any symptoms of low blood sugar with a healthcare provider is recommended.

6. Watch for Mental Health Changes

Since Contrave contains bupropion, it can affect mental health conditions, particularly in those with bipolar disorder, psychiatric illness, or major depressive disorder. Be vigilant for warning signs such as increased suicidal thoughts, unusual tiredness or fatigue, severe mood swings or agitation, irrational behavior or increased anxiety. Monitoring mental health changes is also crucial if you’re taking Contrave and Prozac together, as drug interactions can be particularly severe.

If you experience any of these symptoms, seek emergency help or consult your healthcare provider immediately.

7. Avoid High-Fat Meals When Taking Contrave

High-fat meals can increase the absorption of naltrexone bupropion, leading to a higher risk of side effects like nausea, dizziness, and irregular heartbeat.

To minimize risks, take Contrave’s extended-release tablets with a light or moderate meal instead of a heavy one.

8. Special Considerations for Pregnant and Breastfeeding Women

Women who are pregnant or breastfeeding should not take Contrave, as its ingredients can pass into breast milk and may cause harm to a newborn. If you are planning to become pregnant or are nursing, consult a healthcare professional about safer weight management alternatives.

9. Be Aware of Potential Drug Interactions

Contrave interacts with certain medicines, including other antidepressants (such as SSRIs, SNRIs, and tricyclic antidepressants), smoking cessation drugs, opioid analgesics, which can lead to opioid withdrawal. (Patients must discontinue opioids 7 to 10 days before initiating Contrave and should understand how long Contrave stays in their system to prevent interactions and to avoid withdrawal symptoms), over-the-counter medications and supplements, and other weight loss medications, which may have overlapping effects.

Consult your healthcare provider before adding or stopping any medication to avoid dangerous interactions.

10. Know When to Seek Emergency Help

Seek emergency help if you experience life-threatening symptoms such as severe allergic reaction (swelling of the face, lips, or throat, heart attack symptoms (chest pain, shortness of breath, or arm pain), severe suicidal thoughts or unusual behavior changes, seizures or loss of consciousness. Following these precautions and recommendations can significantly reduce the increased risk of serious side effects when using Contrave.

Always work closely with a healthcare provider to ensure the safest approach to weight management and medication use.

Frequently Asked Questions (FAQ)

When taking Contrave or fentanyl, it is essential to understand potential drug interactions and safety concerns.

Below are common questions regarding the risks and precautions associated with these medications.

1. Can you take Contrave with opioids?

You should not take Contrave with opioids. Contrave contains naltrexone, an opioid antagonist, which blocks the effects of opioids and can cause sudden opioid withdrawal if opioids are still in your system. This can lead to severe withdrawal symptoms such as nausea, vomiting, irregular heartbeat, flu-like symptoms, and high blood pressure.

If you are currently using opioids and want to start Contrave, you must consult your healthcare provider about safely discontinuing opioids first.

2. What medications should not be taken with fentanyl?

Fentanyl interacts with multiple medications, potentially leading to severe side effects, including respiratory depression, irregular heartbeat, and increased risk of overdose. Medications to avoid while taking fentanyl include opioid antagonists like naltrexone (found in Contrave), other opioid analgesics, tricyclic antidepressants, certain sedatives (benzodiazepines, barbiturates, or muscle relaxants), and systemic corticosteroids.

Combining fentanyl with these drugs can increase the risk of life-threatening side effects. Always inform your healthcare provider of any medications you take before starting fentanyl.

3. What medications should you avoid while taking Contrave?

Several medicines should not be taken with Contrave, including opioids, antidepressants (such as SSRIs, SNRIs, and tricyclic antidepressants), seizure medications, and over-the-counter stimulant-based weight loss medications. Opioids should be avoided due to naltrexone’s opioid-blocking effects, which can lead to opioid withdrawal.

Additionally, Contrave contains bupropion, which can lower the seizure threshold, increasing the risk of seizures when combined with other stimulant medications or alcohol. Always check with your healthcare provider before adding or discontinuing any medications while on Contrave.

4. Does naltrexone affect fentanyl?

Naltrexone directly affects fentanyl by blocking its opioid receptors, preventing it from providing pain relief or causing euphoria. This is because naltrexone is an opioid antagonist, meaning it reverses or negates the effects of opioids like fentanyl. If someone taking fentanyl takes naltrexone suddenly, it can lead to immediate opioid withdrawal, causing intense flu-like symptoms, irregular heartbeat, and dangerously high blood pressure.

Additionally, taking fentanyl after stopping naltrexone can increase the risk of overdose, as the body becomes more sensitive to opioids once the antagonist effect wears off.

5. What happens if you take opioids with Contrave?

If you take opioids with Contrave, you may experience opioid withdrawal, as naltrexone in Contrave blocks opioid receptors, preventing opioids from working. This can cause severe nausea, sweating, vomiting, high blood pressure, and flu-like symptoms. Additionally, using opioids after Contrave wears off can lead to a higher risk of overdose, as opioid receptors may become hypersensitive after being blocked.

If you are currently taking opioids and want to start Contrave, consult a healthcare provider to safely transition off opioids first.

Conclusion

The interaction between Contrave and fentanyl presents serious health risks, including opioid withdrawal, increased risk of overdose, irregular heartbeat, and serious allergic reactions. Because Contrave contains naltrexone, an opioid antagonist, it blocks the effects of fentanyl, which can trigger sudden and severe withdrawal symptoms. Additionally, taking fentanyl after Contrave has worn off can increase the risk of overdose, as opioid receptors become more sensitive.

Patients considering Contrave for weight management should carefully review their medical history and any current medications with their healthcare provider. Those using opioids for pain management must take extra precautions to avoid harmful interactions. Other medicines, including antidepressants, seizure medications, and certain weight loss drugs, may also pose risks when combined with Contrave.

Understanding the potential dangers and drug interactions associated with these medications is essential for making informed health decisions. If you are currently on Contrave or fentanyl, or plan to start either, consult your healthcare provider to ensure safe and effective treatment while minimizing risks.