Updated: January 27, 2026
Prolate Drug Interactions: What to Avoid and What to Tell Your Doctor
Author
Peter Daggett
ChatGPT
Claude
Gemini
Overview
Prolate (oxycodone/acetaminophen) has serious drug interactions that can be life-threatening. Learn what medications to avoid and what you must tell your doctor.
Is Prolate in stock near you?
Medfinder checks real pharmacy inventory — start a search and we'll find Prolate near you.
Prolate (oxycodone hydrochloride and acetaminophen) is a powerful medication with several serious drug interactions. Some of these interactions can be life-threatening. This guide covers the most important interactions to know — including medications, supplements, foods, and alcohol — and what you absolutely must tell your doctor before starting Prolate.
The Most Dangerous Interaction: CNS Depressants
The FDA requires a black box warning for Prolate about the combined use of opioids with benzodiazepines and other central nervous system (CNS) depressants. This combination can cause profound sedation, respiratory depression, coma, and death.
CNS depressants that interact dangerously with Prolate include:
Benzodiazepines: alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin) — commonly prescribed for anxiety and panic disorders
Sleep medications: zolpidem (Ambien), eszopiclone (Lunesta), zaleplon (Sonata)
Muscle relaxants: cyclobenzaprine (Flexeril), carisoprodol (Soma), methocarbamol
Gabapentinoids: gabapentin (Neurontin), pregabalin (Lyrica) — increasingly combined with opioids, which significantly increases overdose risk
Antipsychotics: quetiapine (Seroquel), olanzapine (Zyprexa), and others — increase sedation and respiratory depression risk
Other opioids: combining Prolate with any other opioid significantly increases overdose risk
Check live stock now.
Alcohol: Never Mix with Prolate
Alcohol is doubly dangerous with Prolate. It acts as a CNS depressant (compounding oxycodone's respiratory depression risk) AND increases the liver toxicity risk from acetaminophen. Even moderate alcohol consumption can significantly increase acetaminophen-induced liver damage. Do not drink alcohol at all while taking Prolate.
CYP3A4 Inhibitors — Increase Oxycodone Levels
Oxycodone is metabolized by the liver enzyme CYP3A4. Drugs that inhibit this enzyme cause oxycodone to build up in the blood, potentially to dangerous levels. Common CYP3A4 inhibitors to watch for:
Azole antifungals: fluconazole (Diflucan), ketoconazole, itraconazole
Macrolide antibiotics: erythromycin, clarithromycin (but NOT azithromycin, which has minimal CYP3A4 effect)
HIV protease inhibitors: ritonavir, lopinavir — strong CYP3A4 inhibitors that can dramatically increase oxycodone blood levels
Grapefruit juice: Inhibits intestinal CYP3A4 and can increase oxycodone absorption. Avoid grapefruit and grapefruit juice while taking Prolate.
CYP3A4 Inducers — Decrease Oxycodone Levels
Drugs that induce (speed up) CYP3A4 cause oxycodone to be metabolized faster, potentially reducing pain relief or causing withdrawal-like symptoms:
Rifampin (antibiotic used for tuberculosis)
Carbamazepine (Tegretol — seizure medication)
Phenytoin (Dilantin — seizure medication)
St. John's Wort (herbal supplement — a significant CYP3A4 inducer)
Serotonergic Drugs — Risk of Serotonin Syndrome
Combining opioids with drugs that affect serotonin can cause serotonin syndrome — a potentially life-threatening condition characterized by agitation, high fever, rapid heart rate, and muscle rigidity. Drugs that interact this way include:
SSRIs: fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro)
SNRIs: venlafaxine (Effexor), duloxetine (Cymbalta)
TCAs: amitriptyline, nortriptyline
MAOIs: phenelzine, tranylcypromine, selegiline, linezolid — CONTRAINDICATED within 14 days of MAOI use
Other Acetaminophen Sources
Because Prolate already contains 300mg of acetaminophen per tablet, be very careful about taking any other acetaminophen-containing products simultaneously. Common hidden sources of APAP:
Tylenol (regular or extra strength)
Cold and flu medications (NyQuil, DayQuil, Theraflu)
Sleep aids containing diphenhydramine and APAP (ZzzQuil)
Other opioid combination products that also contain APAP
For information on what side effects to watch for while on Prolate, see our post on Prolate side effects. If you need help finding Prolate at a pharmacy near you,
medfinder contacts pharmacies near you to find which ones have it in stock.
Frequently Asked Questions
Ibuprofen and Prolate are generally safe to take together, and some providers recommend NSAIDs alongside opioids for better multimodal pain control. However, ibuprofen has its own risks (GI bleeding, kidney effects, cardiovascular effects), so check with your doctor first — especially if you have kidney disease, stomach ulcers, or heart disease.
No. Alcohol should be strictly avoided while taking Prolate. Alcohol acts as a CNS depressant that compounds oxycodone's respiratory depression risk, and it also significantly increases the risk of liver damage from the acetaminophen component. Even moderate drinking can be dangerous.
Only under close medical supervision. Combining gabapentin (or pregabalin) with opioids like Prolate significantly increases the risk of respiratory depression and overdose. The FDA has required black box warnings about this combination. If you take both, your doctor should closely monitor your breathing and sedation levels.
Grapefruit and grapefruit juice should be avoided while taking Prolate. Grapefruit inhibits the CYP3A4 enzyme in the intestine, which can significantly increase oxycodone absorption and blood levels — potentially leading to dangerous oversedation or respiratory depression.
Medfinder Editorial Standards
Medfinder's mission is to ensure every patient gets access to the medications they need. We are committed to providing trustworthy, evidence-based information to help you make informed health decisions.
Read our editorial standardsPatients searching for Prolate also looked for:
More about Prolate
Why Is Prolate So Hard to Find? [Explained for 2026]
How to Find Prolate in Stock Near You (Tools + Tips for 2026)
Alternatives to Prolate If You Can't Fill Your Prescription
Prolate Shortage Update: What Patients Need to Know in 2026
Prolate Shortage: What Providers and Prescribers Need to Know in 2026
How to Help Your Patients Find Prolate in Stock: A Provider's Guide
39,049 have already found their meds with Medfinder.
Start your search today.
Your information is private and never shared.