Oxycodone Drug Interactions and Effects

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Oxycodone is a potent prescription pain medication in the class of drugs known as opioid analgesics. It binds to specific brain and spinal cord receptors to reduce pain perception.

Like all medications, oxycodone can interact with other drugs, supplements, and herbs, which can affect its effectiveness and cause potentially harmful side effects.

Common Drug Interactions & Effects Associated With Oxycodone: 

  • Central Nervous System Depressants.
  • MAO Inhibitors.
  • Anticholinergic Drugs.
  • Serotonin Syndrome.
  • Adrenal Insufficiency.
  • Respiratory Depression.
  • Liver & Kidney Function.

It is important to always inform your healthcare provider about all medications, supplements, and herbs you are taking before starting oxycodone. Your healthcare provider can help you manage potential drug interactions and monitor you for side effects.

If you or someone you love has a substance use disorder, Guardian Recovery is available to help. We are dedicated to providing the most comprehensive and individualized medically monitored detox program. To learn more about our programs, contact us today.

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Types of Oxycodone Drug Interactions

Several types of drug interactions can occur when taking oxycodone:

  • Additive Effects – Oxycodone may interact with other medications to increase their effects or create a synergistic effect, which can be harmful. For example, taking oxycodone with alcohol or other CNS depressants can cause additive sedative effects.
  • Drug Displacement – Some drugs may displace oxycodone from their binding sites, increasing its concentration in the bloodstream and potentially leading to toxicity.
  • Metabolism Inhibition – Certain medications, such as cimetidine and fluoxetine, can inhibit the metabolism of oxycodone, leading to increased levels of the drug in the bloodstream and potentially increasing the risk of adverse effects.
  • Metabolism Induction – Other medications, such as rifampin and carbamazepine, can induce the metabolism of oxycodone, reducing its effectiveness and potentially leading to withdrawal symptoms.

What Are Drug Interactions?

Drug interactions occur when two or more medications, supplements, or herbs are taken together, and their effects are altered or intensified. These interactions can occur in several ways, affecting how the drug is metabolized, absorbed, or eliminated from the body. They can also affect how the drug works in the body, leading to unexpected side effects or reduced effectiveness.

Drug interactions can be classified into several categories: pharmacokinetic interactions, pharmacodynamic interactions, and additive effects. Pharmacokinetic interactions occur when one drug affects how another is absorbed, metabolized, or eliminated from the body.

Pharmacodynamic interactions occur when one drug affects how another works in the body. Additive effects occur when the combination of two or more medications has a more significant impact than the sum of their effects.

Drug interactions can be mild or severe, and some can be life-threatening. For example, drug interactions between opioids and sedatives can cause respiratory depression, a potentially fatal condition. Other drug interactions can lead to unexpected side effects, such as gastrointestinal upset, skin rashes, or dizziness.

Drugs Types That May Interact Negatively With Oxycodone

Several types of drugs can interact negatively with oxycodone. Some of the most common drug types that can interact with oxycodone are:

  • Other opioids.
  • Benzodiazepines.
  • Sedatives and sleeping pills.
  • Alcohol.
  • Monoamine oxidase inhibitors (MAOIs).
  • Selective serotonin reuptake inhibitors (SSRIs).
  • Muscle relaxants.
  • Antihistamines.
  • Anti-anxiety medications.
  • Anti-seizure medications.

CNS Depressants

CNS (central nervous system) depressants are a group of drugs that slow down brain activity, causing relaxation, sedation, and reduced brain function. Examples of CNS depressants include benzodiazepines, barbiturates, opioids, and alcohol. Oxycodone is also a CNS depressant, and when taken with other CNS depressants, it can increase the risk of respiratory depression, sedation, and overdose.

Taking oxycodone with other CNS depressants can enhance the sedative effects of both drugs, leading to extreme drowsiness, confusion, and impaired coordination. This can be particularly dangerous when driving or operating heavy machinery. In some cases, combining oxycodone and CNS depressants can cause respiratory depression, a potentially life-threatening condition where breathing slows down or stops.

Monoamine Oxidase Inhibitors (MAOIS)

Monoamine oxidase inhibitors (MAOIs) are a medication used to treat depression, anxiety, and other mental health conditions. MAOIs work by blocking the action of monoamine oxidase, an enzyme that breaks down neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain. This leads to an increase in the levels of these neurotransmitters, which can improve mood and reduce symptoms of depression.

When oxycodone is taken with MAOIs, it can increase the levels of oxycodone in the blood, increasing the risk of side effects and overdose. This is because MAOIs inhibit the enzymes in the liver that break down oxycodone, leading to a buildup of the drug in the bloodstream. The increased levels of oxycodone in the blood can lead to respiratory depression, sedation, and other serious side effects.

Anticholinergic Drugs

Anticholinergic drugs are a class of medications that block the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. They commonly treat conditions such as allergies, asthma, motion sickness, and gastrointestinal disorders. Some examples of anticholinergic drugs include diphenhydramine (Benadryl), tolterodine (Detrol), and oxybutynin (Ditropan).

When taken with oxycodone, anticholinergic drugs can increase the risk of side effects such as constipation, dry mouth, blurred vision, and urinary retention. This is because anticholinergic drugs reduce the activity of the parasympathetic nervous system, which is responsible for maintaining normal bodily functions such as digestion and urination. Oxycodone, on the other hand, can also cause constipation and urinary retention as side effects.

CYP3A4 Inhibitors

CYP3A4 inhibitors are a class of medications that inhibit the activity of the CYP3A4 enzyme in the liver, which is responsible for metabolizing many drugs, including oxycodone. Examples of CYP3A4 inhibitors include ketoconazole, erythromycin, and grapefruit juice.

When taken with oxycodone, CYP3A4 inhibitors can slow the metabolism of oxycodone in the liver, leading to an increase in the levels of oxycodone in the bloodstream. This can increase the risk of side effects and overdose and prolong the duration of the drug’s effects.

Serotonin-norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of medications used to treat depression, anxiety, and other mental health conditions. SNRIs work by increasing the levels of serotonin and norepinephrine in the brain, which can improve mood and reduce symptoms of depression.

When taken with oxycodone, SNRIs can increase the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, fever, muscle rigidity, and seizures. Serotonin syndrome can occur when the serotonin levels in the brain become too high, and oxycodone can also increase serotonin levels.

Antifungal Medications

Antifungal medications treat fungal infections like candidiasis, aspergillosis, and cryptococcosis. Some examples of antifungal medications include fluconazole, itraconazole, and ketoconazole.

When taken with oxycodone, antifungal medications can slow down the metabolism of oxycodone in the liver, leading to an increase in the levels of oxycodone in the bloodstream. This can increase the risk of side effects and overdose and prolong the duration of the drug’s effects.


Benzodiazepines are a class of medications commonly used to treat anxiety, insomnia, and other mental health conditions. Examples of benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin), and diazepam (Valium).

When taken with oxycodone, benzodiazepines can increase the risk of respiratory depression, a potentially life-threatening condition characterized by slow or shallow breathing. Both benzodiazepines and oxycodone can cause respiratory depression as side effects, and when taken together, the risk of this side effect increases.

Opioid Antagonists

Opioid antagonists are a class of medications used to reverse the effects of opioids, such as oxycodone, in the body. Examples of opioid antagonists include naloxone, naltrexone, and methylnaltrexone.

When taken with oxycodone, opioid antagonists can reduce or block the effects of oxycodone, which may be desirable in some situations, such as in cases of opioid overdose or addiction treatment. However, taking opioid antagonists with oxycodone can also reduce the effectiveness of oxycodone for pain relief.


Alcohol and oxycodone are both central nervous system (CNS) depressants. Using them together can lead to serious health risks, including respiratory depression, coma, and even death. Drinking alcohol can enhance the sedative effects of oxycodone. Therefore, it is not recommended to combine alcohol and oxycodone.

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Common Side Effects of Oxycodone Interactions

Oxycodone is a potent opioid pain medication that can cause various side effects. The severity of side effects can depend on multiple factors, such as the individual’s age, medical history, and overall health. In addition, oxycodone can interact with other medications, which may increase the risk and severity of side effects. Some of the common side effects of oxycodone interactions include:

  • Respiratory Depression – Oxycodone can depress breathing, especially when combined with other respiratory depressants such as alcohol or benzodiazepines.
  • Sedation – Oxycodone can cause drowsiness, dizziness, and confusion, mainly when used with other medications that have sedative effects.
  • Nausea & Vomiting – These side effects are common with opioids and can be worsened by interactions with other medications, such as anti-nausea drugs.
  • Constipation – Opioids can cause constipation, which certain medications, such as antihistamines and antispasmodics, may worsen.
  • Low Blood Pressure – Oxycodone can cause a drop in blood pressure, especially when combined with medications used to treat high blood pressure.
  • Cognitive Impairment – Oxycodone can impair cognitive function, primarily when used with other medications that affect brain function, such as antidepressants and antipsychotics.
  • Increased Risk of Falls – Oxycodone can cause dizziness, weakness, and other side effects that may increase the risk of falls, particularly in older adults.

How to Prevent Negative Drug Interactions

Preventing negative drug interactions with oxycodone is crucial for ensuring the safe and effective use of the medication. Here are some tips to help avoid adverse drug interactions with oxycodone.

Steps to Prevent Negative Drug Interactions With Oxycodone: 

  • Inform your doctor and pharmacist of all medications, supplements, and herbal remedies you are currently taking.
  • Follow your doctor’s instructions carefully when taking oxycodone.
  • Avoid drinking alcohol while taking oxycodone, as it can increase the risk of side effects such as drowsiness and respiratory depression.
  • Do not take oxycodone with other medications that can cause sedation or respiratory depression, such as benzodiazepines, sleeping pills, or tranquilizers, unless specifically instructed by your doctor.
  • If you are taking any medications that can affect liver function, such as some antibiotics or antifungal medications, inform your doctor, as oxycodone is metabolized in the liver, which may increase the risk of side effects.
  • Inform your doctor of any medical conditions that may interact with oxycodone, such as kidney or liver disease, heart disease, or respiratory problems.
  • If you experience any unusual or concerning side effects while taking oxycodone, inform your doctor immediately.

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At Guardian Recovery, we remain dedicated to providing our clients with a comprehensive program of oxycodone detox that focuses on much more than physical stabilization. In addition to emphasizing physical recovery, we tackle mental, emotional, and spiritual well-being. While prioritizing a safe and pain-free cocaine withdrawal, we offer individualgroup, and family therapy sessions, case management services, relapse prevention training, and aftercare planning.

Contact us today if you or your loved one is ready to begin an entirely new way of life and commit to long-term recovery. As soon as you call, we start developing a plan of action that begins with an initial pre-assessment. This assessment helps us determine the most appropriate level of care for each unique case. We identify potential coverage options if our medically monitored detox program is a good fit. We work closely with most major regional and national insurance providers. Contact us today for a free, no-obligation insurance benefit check.


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Reviewed professionally for accuracy by:

Ryan Soave


Ryan Soave brings deep experience as a Licensed Mental Health Counselor, certified trauma therapist, program developer, and research consultant for Huberman Lab at Stanford University Department of Neurobiology. Post-graduation from Wake Forest University, Ryan quickly discovered his acumen for the business world. After almost a decade of successful entrepreneurship and world traveling, he encountered a wave of personal and spiritual challenges; he felt a calling for something more. Ryan returned to school and completed his Master’s Degree in Mental Health Counseling. When he started working with those suffering from addiction and PTSD, he found his passion. He has never looked back.

Written by:

Cayla Clark

Cayla Clark

Cayla Clark grew up in Santa Barbara, CA and graduated from UCLA with a degree in playwriting. Since then she has been writing on addiction recovery and psychology full-time, and has found a home as part of the Guardian Recovery team.

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