Percocet Drug Interactions: Can Xanax Or Tramadol Be Taken With It?

Last Updated: June 24, 2020

Authored by Roger Weiss, MD

Reviewed by Michael Espelin APRN

The efficacy of Percocet medication in relieving severe pain is remarkable. However, its users have to worry about its interactions with other drugs. However, if an individual uses this painkiller with other opioids or medications like SSRI antidepressants, even if they have been prescribed, the result can be lethal. This is why it is essential to understand the risks associated with Percocet drug interactions. Read on to explore more information about the interactions of Percocet with other medications.

Percocet and Antidepressants

The presence of acetaminophen in Percocet counteracts the efficacy of the serotonergic antidepressants. If they both stay in the system, they can lead to bleeding in the gastric mucosa. This can eventually lead to death. Some of the antidepressants that person using painkillers have to be extremely careful with are the following:

Percocet and Zoloft Interactions

Zoloft and Percocet interactions can put the person using them at a severe risk causing extreme sedation or depressed respiration. The study published by NCBI reports that coadministration of sertraline and oxycodone may also cause a serotonin syndrome severe tremor and visual hallucinations. A patient should stay away from Zoloft and Percocet during pregnancy or breastfeeding.

Percocet Interactions with Ambien

Some people are combining Percocet and Ambien to stimulate sleep, but they may become dependent on them with time. Also, NIH recorded some cases of the recreational use of  Ambien and Percocet to get high, relaxed, and euphoric; some even take them with alcohol to get drunk faster. The risks of taking these two together include:

  • Having heightened drowsiness Young woman with asthma attack
  • Increased fatigue
  • Slurred speech
  • Confusion
  • Malaise
  • Respiratory difficulty
  • Decreased mental alertness

Xanax And Percocet Combination

FDA expert Dr. Leana Wen said: “Nearly one in three unintentional overdose deaths from prescription opioids also involve benzodiazepines.” This combination can make a person extremely sleepy or depressed. It can easily cause overdose also.

Valium And Percocet

The combination of Valium and Percocet, as well as, Diazepam and Ativan, has a lesser severity when it comes to withdrawal contrary to Percocet and Xanax (Alprazolam) mix.

How Percocet interacts with Neuropathy Drugs?

Combining Percocet And Weed

Percocet and cannabis are synonymous as marijuana has been shown to relieve pain in cancer patients as well as people living with AIDS. Nonetheless, if weed is taken with Percocet 7,5/325 or stronger, it can lead to severe CNS depression. When smoked together, they can affect breathing and increase the heart rate as well.
Other neuropathy drugs Percocet interacts with are:

Tramadol and Percocet Interactions

Tramadol and Percocet can both be addictive, and withdrawal symptoms may be experienced in people trying to stop it. The challenge is that they are both useful in relieving severe pain, but since they work differently, having both in one’s system is risky. Even two painkillers with a similar mechanism of actions, such as Vicodin and Percocet, is risky to take together.

Gabapentin and Percocet Interactions

Studies have shown that surgeons favor Gabapentin and opioids for postoperative pain. The acetaminophen component in the painkiller can be administered with Gabapentin without any complications, but one should notify the physician if any other drug has been taken already. People who overdose on GABA analogs were mostly found abusing opioids at the same time.
Some of the adverse effects that may harm one’s health, as a result of opioid and neuropathic drugs being mixed up together in the body system, are:

  • HepatotoxicityStressed businessman having severe headache
  • Increased chances of bleeding from the gastric ulcers
  • Hemorrhage in the digestive tract
  • Depression of the central nervous system
  • Severe sedation
  • Uncontrollable hemorrhaging during surgical procedures
  • Localized death of the intranasal septum and palatal structure

Opioid Pain Medication and Antihistamines

Opioid drugs, inhibits CYP450 2D6, causing retention of antihistamines that are not metabolized in the cells. Percocet and Darvocet both contain acetaminophen. Some patients may not realize that they are taking an additional amount of paracetamol when using other drugs. Significant amounts of paracetamol or acetaminophen present in the drug have been known to cause acute liver failure. Hepatic failure can occur when more than eight acetaminophen tablets of 500mg stay in the system for a 24-hour period.
Whether it is taken purely or it gets into the system from its combination with another drug, it poses a severe threat to the body. Therefore, taking painkillers with antihistamines significantly poses a danger to one’s life.

Percocet and Benadryl Interactions

Another combination that can be life-threatening is Benadryl or diphenhydramine, which can be found in sleep-inducing drugs and common cold medications. Benadryl and Percocet should not be used together because they can lead to loss of cognitive functions. This combo can cause coma or death, from respiratory compromise.

Percocet Interactions with Other Substances

Combining Percocet and Cocaine

Cases of nasal inhalation of grounded Percocet and cocaine have resulted in necrosis of the intranasal palatal and septal structures. The nasal sinus is supplied with a lot of blood vessels, that is why these crushed medications get in the blood faster. The blood then carries the drug into the brain. Since Percocet and cocaine were being inhaled overtime forcefully, they gradually compromise the integrity of the nasal septum, sinuses, and soft palate.

Combination of Percocet and Alcohol

Presence of alcohol and Percocet drug in the system increases the chances of addiction, sedation, liver failure, overdose, and death. Staying away from alcohol is not so easy even more as ethanol is present in some drugs. For instance, alcohol is present in sertraline oral concentrate making it dangerous to stay in the system when taking opioid as well.

St. John’s Wort and Percocet interactions

People experiencing depressions are known to use over-the-counter drugs like St. John’s Wort. However, the pain usually accompanies depression as comorbidities, and when Percocet is used, the two drugs react. When taken together, St. John’s Wort causes a faster clearance of the oxycodone present in the painkiller rendering the latter less effective. The perceived inefficiency of the painkiller may lead to individuals increasing the doses or the frequency of taking the drug, which may lead to hepatotoxicity, nausea, or vomiting.

Substances Percocet Should Not Be Taken With

If a patient just got a Percocet prescription, it is advisable to check this list and notice all substances interactions with can be harmful during the painkiller treatment:

  • Alcohol
  • Anesthetics
  • Antihistamines
  • Antipsychotics
  • “azole” antifungal medications
  • Baclofen
  • Barbiturates
  • Benzodiazepines
  • Bosentan
  • Bupropion
  • Buspirone
  • Butorphanol
  • Carbamazepine
  • Chloral hydrate
  • Cholestyramine
  • Dasatinib
  • Dexamethasone
  • Dextroamphetamine
  • Imatinib
  • Isoniazid
  • Lamotrigine
  • Macrolide antibiotics
  • Methocarbamol
  • Monoamine oxidase inhibitors
  • Other narcotic analgesics
  • Pentazocine
  • Phenothiazines
  • Phenytoin
  • Primidone
  • Protease inhibitors
  • Quinidine
  • Rifabutin
  • Rifampin
  • Selective Serotonin Reuptake Inhibitors
  • St. John’s Wort
  • Thiazide diuretics
  • Tricyclic antidepressants
  • Warfarin

Use Only as Prescribed

Various products on shelves at storeInteractions between drugs in the body system is vital information that protects one from making wrong decisions that may be fatal to one’s health. This painkiller should only be used as prescribed and when prescribed by the physician. However, if one is feeling addicted to the prescribed painkiller, it can be challenging to adhere to the doctor’s instructions. Nonetheless, there are known ways to resolve such addiction. Seek professional addiction treatment from health specialists.

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Published on: November 1st, 2018

Updated on: June 24th, 2020

About Author

Roger Weiss, MD

Dr. Roger Weiss is a practicing mental health specialist at the hospital. Dr. Weiss combines his clinical practice and medical writing career since 2009. Apart from these activities, Dr. Weiss also delivers lectures for youth, former addicts, and everyone interested in topics such as substance abuse and treatment.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.


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