The main difference between fentanyl vs. hydrocodone lies in their potency. Although both medications are classified as opioids and have powerful analgesic effects, fentanyl is significantly more potent than hydrocodone. Still, both drugs carry similar risks, including that of dependence, addiction, and overdose.
This fentanyl vs. hydrocodone comparison guide will explore the major differences and similarities between these medications, covering their effectiveness, chemical compositions, and more.
What Is Fentanyl, and How Does It Work?

Fentanyl is an extremely potent synthetic opioid analgesic prescribed to control severe pain that cannot be managed with milder pain medications. It is also sometimes used as an anesthetic agent.
As one of the most potent opioids, fentanyl comes as an immediate- or extended-release drug in numerous forms, including:
- Nasal sprays (Lazanda®)
- Injectable solution (Sublimaze®)
- Transmucosal lozenges (Actiq®)
- Transdermal patches (Duragesic®)
- Buccal films (Onsolis®) and tablets (Fentora®)
Fentanyl works by interacting with the opioid receptors located throughout the central nervous system (CNS). Upon binding to these receptors, it disrupts the transmission of pain signals between the body and the brain, altering pain perception. It also floods the brain with dopamine, inducing euphoria and deep relaxation.
Although fentanyl is among the most effective prescription opioids, it exposes patients to a high risk of opioid abuse, dependence, addiction, and overdose. Prolonged medication use increases these risks. For this reason, it’s in your best interest to limit fentanyl use to a minimum and carefully follow your doctor’s instructions while taking this drug.
In recent years, fentanyl has become a very popular street drug. In 2023, the U.S. Drug Enforcement Administration seized almost 12,000 pounds of fentanyl powder and over 80,000 counterfeit fentanyl pills. On the streets, this drug is known as Dance Fever, Murder 8, Goodfellas, Friend, and Jackpot, among other names.
What Is Hydrocodone, and How Does It Work?
Hydrocodone is a potent semi-synthetic opioid prescribed to manage moderate-to-severe pain when non-opioid pain relievers are ineffective or cannot be used. It is also sometimes used as a combination drug for cough suppression. It works by acting on opioid receptors, thereby preventing pain signals from reaching the brain.
Like fentanyl, hydrocodone triggers dopamine release, leading to euphoria. Due to a high potential for misuse, dependence, and addiction, it should be taken strictly as prescribed.
In the United States, single-entity hydrocodone (Zohydro® ER, Hysingla® ER) is only available as an extended-release capsule or an extended-release abuse-deterrent tablet.
However, it is typically prescribed as a combination medication containing a non-opioid painkiller, usually acetaminophen. Currently, this drug combination is only available in its generic version. It was previously marketed under Vicodin®, Lortab®, Lorcet®, and Norco® brands, among others.
Hydrocodone/acetaminophen is the most frequently prescribed opioid medication in the U.S., with over 23.5 million prescriptions issued to nearly 8 million Americans in 2022 alone.
Hydrocodone products are also the most misused prescription painkillers among Americans. According to SAMHSA’s National Survey on Drug Use and Health, more than 45% of those abusing prescription pain relievers misused them in 2022. Common street names for hydrocodone include Fluff, Hydros, and Vikes.
Now that we’ve discussed the basics, it’s time to compare hydrocodone vs. fentanyl.
Key Differences Between Fentanyl vs. Hydrocodone

The key difference between fentanyl vs. hydrocodone is potency, as fentanyl is significantly more powerful. Compared to morphine, it is 100 times more potent, and hydrocodone is only 1.5 times more potent.
With this in mind, let’s compare fentanyl vs. hydrocodone chemical structures, effectiveness, cost, and potential for overdose and addiction:
Fentanyl vs. Hydrocodone: Effectiveness
Fentanyl and hydrocodone are both highly effective analgesics. However, fentanyl is the more potent of the two, which is why it is primarily prescribed for severe pain, usually during and after surgery. Meanwhile, hydrocodone can also be used to relieve moderate pain.
Fentanyl vs. Hydrocodone: Chemical Composition
The main difference between fentanyl vs. hydrocodone chemical compositions is that the former is a synthetic opioid, whereas the latter is semi-synthetic.
Synthetic vs. natural opioids differ in terms of how they are derived. Fentanyl, a synthetic compound, is entirely artificial. Unlike natural opioids—or opiates—like morphine, which are extracted directly from the opium poppy plant, it is produced in labs. Hydrocodone stands in the middle, as it is made by synthesizing the opium alkaloids codeine or thebaine.
Fentanyl vs. Hydrocodone: Addictiveness
Fentanyl and hydrocodone have a high potential for dependence and addiction. As such, they are both treated as Schedule II controlled substances and require a prescription.
Nonetheless, anyone taking fentanyl or hydrocodone for a prolonged time can become dependent, as these drugs gradually alter brain chemistry. Taking them as prescribed can reduce the risk of dependence and addiction, but it doesn’t eliminate it.
Fentanyl vs. Hydrocodone: Cost
Fentanyl vs. hydrocodone cost differs based on the drug’s formulation, prescription strength, and other factors. Both medications are available in generic versions, which tend to be more affordable and covered by insurance.
For example, a generic oral tablet containing 20 mg of extended-release hydrocodone costs around $7, whereas that of Hysingla® ER costs about $13.50. Meanwhile, 200 mcg of fentanyl oral transmucosal lozenges cost roughly $7 per unit, but you might have to pay around $115 for Actiq® of the same strength.
Fentanyl vs. Hydrocodone: Overdose
While fentanyl and hydrocodone can both cause a potentially fatal opioid overdose, fentanyl has a significantly higher overdose potential. Even a tiny amount of this drug can be deadly because of its extraordinary potency.
Synthetic opioids have claimed the lives of nearly 74,000 Americans in 2022; most of these deaths were caused by a fentanyl overdose. By contrast, close to 12,000 Americans lost their lives to an overdose involving hydrocodone and other natural or semi-synthetic opioids that year.
Next, let’s compare fentanyl vs. hydrocodone side effect profiles.
Fentanyl vs. Hydrocodone Side Effects
Fentanyl and hydrocodone side effects are very similar since both medications belong to the class of opioids.
Most commonly, they cause the following side effects:
- Confusion
- Headache
- Dry mouth
- Drowsiness
- Constipation
- Lightheadedness
- Nausea and vomiting
Talk to your doctor if you experience any side effects while taking fentanyl or hydrocodone. In the event of allergic reactions (hives, itching, etc.) or other severe reactions, seek medical attention immediately.
Furthermore, prolonged use of fentanyl or hydrocodone can lead to tolerance, dependence, and opioid use disorder (OUD). Taking these medications for an extended time and abusing them also increases the risk of organ damage, fertility problems, and similar adverse effects.
Do not mix opioids with other substances without your doctor’s permission, as this can increase the risk of serious adverse effects, including opioid overdose.
On this note, let’s examine fentanyl vs. hydrocodone drug interactions.
Fentanyl and Hydrocodone Drug Interactions

Fentanyl and hydrocodone can interact with various drugs, including but not limited to:
- Other opioids
- Antipsychotics
- Muscle relaxers
- Antidepressants
- Benzodiazepines
- Antifungal medications
- Anti-seizure medications
- Certain antibiotics, such as clarithromycin
- Alcohol
If you are taking any medications, supplements, or herbal medicines, inform your doctor about them before initiating opioid therapy to reduce the risk of drug interactions. Mixing fentanyl or hydrocodone with other substances, including alcohol, can considerably elevate the risk of respiratory depression, overdose, and other potentially life-threatening adverse events.
Other Risk Factors of Fentanyl and Hydrocodone
Other risk factors that can make you more susceptible to the adverse effects associated with fentanyl and hydrocodone include:
- Head injury
- Liver damage
- Kidney problems
- Respiratory issues
- Low blood pressure
- Cardiovascular disease
- Allergy to fentanyl or hydrocodone
Furthermore, fentanyl patches and other forms of this drug are generally not recommended for opioid-naïve patients. Before using either of these opioids, disclose your complete medical history to your doctor to ensure you can safely take opioids.
If you are pregnant or planning to have a baby, discuss alternative pain management options with your doctor. Using hydrocodone or fentanyl during pregnancy amplifies the risk of neonatal abstinence syndrome (NAS), stillbirth, congenital disabilities, and other complications.
Physical Dependence and Addiction to Opioids
Physical dependence and addiction to opioids are two of the greatest risks of opioid pain management. Although they may co-occur, these conditions are distinct; you can be dependent on fentanyl or hydrocodone without being addicted.
Opioid dependence is the physical reliance people develop due to prolonged opioid use. It happens because repeated opioid exposure causes a decrease in the production of endorphins and an increase in opioid receptors.
If left untreated, physical dependence can evolve into opioid addiction. This condition is predominantly psychological; it is characterized by a loss of control over opioid use.
Those addicted experience an overwhelming urge to take opioids, struggling to quit these drugs, even when they wreck their relationships, careers, and health. Luckily, opioid addiction can be conquered with professional opioid use disorder treatment.
Signs and Symptoms of Opioid Dependence
Seek opioid dependence treatment if you or a loved one displays the following signs of opioid dependence:
- Tolerance. Tolerance to opioids develops as the number of opioid receptors in the nervous system increases. Subsequently, people who use fentanyl or hydrocodone eventually need higher doses to feel their effects. If this happens to you, do not take more medication than prescribed. Instead, discuss your concerns with your doctor.
- Opioid withdrawal symptoms. Opioid-dependent people suffer from anxiety, cravings, muscle aches, diarrhea, and other uncomfortable withdrawal symptoms upon drug cessation. This can make it nearly impossible to quit opioids. Because of this, your best option is to seek professional help as soon as you suspect you might be dependent.
ANR Treatment for Fentanyl or Hydrocodone Dependence

Accelerated Neuro-Regulation (ANR) is an ultra-modern method developed by Dr. Andre Waismann that revolutionized opioid dependence treatment by identifying and addressing its root.
Unlike traditional treatments, ANR treatment takes a medical, scientifically backed perspective by re-regulating the endorphin-receptor system imbalance. In other words, it repairs the damage opioid exposure causes to the central nervous system, eradicating opioid dependence together with cravings and other withdrawal symptoms. As such, it negates the risk of relapse.
Benefits of Undergoing ANR Treatment
The key benefits of undergoing ANR treatment include:
- Safety. ANR is very safe, as it is performed by board-certified healthcare professionals in an ICU setting of fully accredited state-of-the-art hospitals. Plus, the treatment plan is tailored to each patient’s medical history and needs, making it suitable even for those with co-occurring health conditions.
- Speed. By opting for ANR, you won’t have to worry about making time in your busy schedule for opioid dependence treatment or missing out on important life events. With an average hospital stay of just 36 hours, most patients can return home within 3-4 days of hospitalization. This groundbreaking treatment can help you achieve lasting success within a matter of days.
- High success rate. As the only treatment that attacks opioid dependence at its core, ANR has an unmatched success rate. It has helped over 25,000 people worldwide reclaim their lives from opioid dependence.
Meet Amanda, who defeated opioid dependence—including that on fentanyl—with ANR treatment:
Take the first step toward an opioid-free life today by reaching out to us and scheduling a free, 100% confidential consultation.
Key Takeaways
Hopefully, our fentanyl vs. hydrocodone guide helped you gain a deeper understanding of the differences and similarities between these two opioid medications.
Before you leave, let’s go over the key points we covered:
- Fentanyl is a synthetic opioid prescribed for severe pain, whereas hydrocodone is a semi-synthetic opioid used for moderate-to-severe pain.
- Due to its extreme potency, fentanyl can lead to dependence, addiction, and overdose at lower doses than hydrocodone.
- ANR is a revolutionary treatment that eradicates opioid dependence through endorphin-receptor modulation, facilitating long-lasting recovery.