- Tapentadol vs oxycodone/naloxone in the management of pain after total hip arthroplasty in the fast track setting: an observational study
- Comparison of the Risks of Opioid Abuse or Dependence Between Tapentadol and Oxycodone: Results From a Cohort Study
- Strongest Pain Pills
- Opioids Weaker than Morphine
- Opioids Equivalent to Morphine
- Opioids Stronger than Morphine
- Oxycodone (OxyContin, Percocet, Percodan, Roxicodone)
- Methadone (Methadose, Dolophine)
- Hydromorphone (Dilaudid)
- Oxymorphone (Opana)
- Buprenorphine (Subutex)
- Fentanyl (Sublimaze, Duragesic, Subsys)
- Brand Names: US
- Brand Names: Canada
- What is this drug used for?
- What do I need to tell my doctor BEFORE I take this drug?
- What are some things I need to know or do while I take this drug?
- What are some side effects that I need to call my doctor about right away?
- What are some other side effects of this drug?
- How is this drug best taken?
- What do I do if I miss a dose?
- How do I store and/or throw out this drug?
- General drug facts
- Consumer Information Use and Disclaimer
- Last Reviewed Date
- Is Tapentadol a Glorified Tramadol?
- NUCYNTA® (tapentadol): ONE SOURCE OF RELIEF IN THE ACUTE SETTING1
- Narcotics & Breakthrough Pain Relief
Tapentadol vs oxycodone/naloxone in the management of pain after total hip arthroplasty in the fast track setting: an observational study
The aim of the present study was to evaluate outcomes in THR patients in terms of pain management within 96 h after surgery, following the administration of tapentadol or naloxone/oxycodone in combination with ketoprofen. From the results it is clear that patients in the tapentadol group experienced a decrease in pain intensity and collateral effects compared to the control group, with statistically significant differences both in terms of NRS (at rest and during movement) and collateral effects. Consequently, these benefits helped patients adhere to the fast track protocol of rehabilitation better, which nowadays is one of the main goals in joint replacement surgery.
In particular, in the field of hip disease, the ‘experience of pain’ with its neuropathic and inflammatory components often represents a physical and mental burden to patients, to the point that it might condition their approach to surgical intervention first, and subsequently to the rehabilitation process. Tapentadol’s nociceptive and neuropathic components, that reduce the ascendant component of pain while strengthening descending inhibitory stimulation, could represent an effective option in the management of post-op pain, with a good tolerability profile (Tzschentke et al., 2014; Langford, 2016; Pergolizzi et al., 2016). Post-op management has always represented a challenge in major orthopaedic procedures such as joint replacement, and many analgesic protocols have been tested over time: in many cases opioids have been among the drugs of choice to control pain in the very first phases following surgery, but (despite providing satisfactory pain reduction) the unfavorable rate of adverse events typically associated to many opioids has been regarded as their greatest disadvantage. The search for the “ideal opioid”, i.e. a drug with sufficient analgesic power and a low rate of side effects, led to the development of new molecules: tapentadol has been recently proposed as an effective and well tolerated pain killer, suitable for use in many orthopaedic situations, including surgical-related settings (Lee et al., 2014; Lockwood & Dickenson, 2019; Chen et al., 2015).
In particular, tapentadol has reduced pharmacological interactions (low binding to plasma proteins and no impact on CPY450, no active metabolites), which makes the drug more appealing for elderly patients, who represent the majority of the THR patient population admitted to our facility, and often displaying comorbidities and/or concomitant treatments (Tzschentke et al., 2014; Biondi et al., 2015). Another relevant advantage of tapentadol is the low rate of complications associated to its use (Vadivelu et al., 2017), which is inferior to that of other similar molecules. In the present study we used oxycodone/naloxone as a comparator. Oxycodone is a traditional and “popular” opiod, whose use in the field of muscolo-skeletal diseases is well established and reported in many trials so far (Kim et al., 2018; Oppermann et al., 2016), and its combination with naloxone has been developed and marketed more recently, in the attempt of diminishing the well-known gastro-intestinal side effects reported when administering oxycodone alone (Scardino et al., 2015).
In our experience, a dosage of 100 mg twice daily (following surgery), resulted in a satisfactory management of pain for the majority of patients (250 mg being the maximum daily recommended dose).
Post-op pain, both at rest and during movement, throughout T1-T4 was always reported as being bearable, with a NRS < 2. This has certainly contributed to the quick recovery of the patients after surgery as confirmed by the fact that 50% of patients were able to stand on T0 (that is within 4 h from surgery) a value which increased to 90% on T1. Patients treated with tapentadol also displayed a better post-operative recovery, which is not only represented by lower pain scores compared to patients who received oxycodone/naloxone, but also by the absence of recurring acute pain episodes. Specifically, the lower NRS both at rest and in motion was the main factor responsible for the well being of the tapentadol patients, a factor which allowed them to perform physical rehabilitation activities early, bringing with it all the inherent advantages in terms of functional recovery.
Indeed our results are comparable to those reported by Panella et al. (Panella, 2016) who assessed pain treatment following THA in 144 patients with either tapentadol PR (50 mg twice daily) versus paracetamol (1000 mg three times daily). Patients were treated throughout rehabilitation and followed-up for three weeks, showing (in addition to a satisfactory functional recovery) a 4.3 point decrease (83%) in patients treated with tapentadol vs 2.4 points (48%) in those treated with paracetamol. Conversely another study described the administration of tapentadol starting the day before surgery, but in this case, this did not result in statistically significant advantages compared to the standard treatment with oxycodone (Haesler et al., 2017).
In our study, patients treated with tapentadol and ketoprofen on T1 reported no pain, but they did report a higher incidence of symptoms such as nausea and vomiting than on the following days thus suggesting that, at least partially, these symptoms are related to the anesthesia and post-operative analgesia. Furthermore, a higher occurrence of nausea and vomit was described in the control group at T1 and T2, which again, emphasizes the better tolerability of tapentadol compared to oxycodone/naloxone.
This observation was confirmed by the presence of a few fainting episodes, all of which occurred on T1, linked to hypotension following local anesthesia. Additionally, hemodynamic parameters of patients treated with tapentadol, such as oxygen saturation and heart rate remained stable throughout the four days of observation. Overall, the typical collateral effects of opioids such as nausea, vomiting and constipation resulted to be greatly reduced in number in the tapentadol group compared to the oxycodone/naloxone group, an observation which is supported by data present in medical literature (Coluzzi & Ruggeri, 2014; Pergolizzi et al., 2016; Sanchez de Aguila et al., 2015). The higher incidence of PONV in the oxycodone/naloxone group may also be related to the higher request for morphine as rescue-analgesia in the control group.
In brief, results from our study support the use of tapentadol in combination with ketoprofen for the management of moderate-severe pain following major orthopedic surgeries, given its effectiveness in reducing intensity of pain and its satisfactory tolerance, allowing patients to perform post-operative rehabilitation activities early, and resume ambulation quickly after surgery. Indeed, forced immobilization due to pain, post-operative fasting, nausea and vomiting all contribute to comorbidities flares and increase the onset of complications which can compromise post-operative recovery and lengthen hospital stay.
The main limitation of the present study is its retrospective design, which warrants future randomized controlled trials to confirm the findings emerged from the present analysis. Despite data being retrospectively collected, we are confident about their reliability since our Department’s dedicated personnel (i.e. anesthesiology nurses) are in charge of evaluating patient pain NRS, daily, at the same hour. Among other study limitations, the lack of a long-term follow-up is of particular note, since it does not provide any information on the treatment’s long-term outcome. It is currently thought, as suggested by data in the literature, that tapentadol offers a longer-term efficacy compared to other opioids, featuring complete tolerance at 51 days compared to 21 days with morphine (Pergolizzi et al., 2016), with no risk of addiction in the medium-long term (Buynak et al., 2015). However, there is still a substantial paucity in long-term data within the literature, with the longest studies being limited to a maximum of 2 years. Another limitation is the lack of data concerning different post-op dosages of tapentadol, since it might be argued that variations in the dose could have yielded a significantly different therapeutic response and perhaps different incidence of adverse events. Additional randomized studies are therefore needed to understand the best administration protocols to maximize the benefit/risk ratio.
Comparison of the Risks of Opioid Abuse or Dependence Between Tapentadol and Oxycodone: Results From a Cohort Study
Tapentadol may have a lower abuse risk than other opioids because it has a relatively low affinity for the mu-opioid receptor. The aim of this retrospective cohort study was to compare the risk of opioid abuse between tapentadol immediate release (IR) and oxycodone IR using 2 claims databases (Optum and MarketScan). Subjects with no recent opioid use exposed to tapentadol IR or oxycodone IR in 2010 were followed for 1 year. The outcome was the proportion of subjects who developed opioid abuse, defined as subjects with International Classification of Diseases, 9th revision, codes for opioid abuse, addiction, or dependence. The relative odds of abuse were estimated using a logistic regression model with propensity-score stratification. The estimates from the 2 databases were pooled using a random effects model. There were 13,814 subjects in Optum (11,378 exposed to oxycodone, 2,436 exposed to tapentadol) and 25,553 in MarketScan (21,728 exposed to oxycodone, 3,825 exposed to tapentadol). The risk of abuse was higher in the oxycodone group than in the tapentadol group in each database. The pooled adjusted estimate for the odds of abuse was 65% lower with tapentadol than with oxycodone (odds ratio = .35, 95% confidence interval = .21–.58). The risk of receiving an abuse diagnosis with tapentadol was lower than the risk with oxycodone. Continued monitoring is warranted because opioid desirability can change over time.
One of the bright new changes in pain medications over the last few years were two medications: Ultram (tramadol) and now Nucynta (tapentadol). These are different from Vicodin (hydrocodone/acetaminophen), Percocet (oxycodone/acetaminophen), and Tylenol #3 (codeine/acetaminophen) in many ways and are considered much “gentler.” So, is Nucynta better? Lets look.
Ten points about Nucynta and Ultram you need to know:
1. Nucynta (Tapentadol) and Ultram (tramadol) are similar in that they are considered “different” than the classic opioid meds: Vicodin, Percocet, or Tylenol with codeine.
2. tramadol is like a baby Nucynta (tapentadol). tramadol works as a relatively weak opioid receptor agonist. tramadol also inhibits norepinephrine and serotonin reuptake which contributes to pain relief. It’s not as “strong” as Nucynta.
3. Nucynta (tapentadol) comes in an immediate or extended release pill (Nucynta ER). Nucynta’s effect on the opioid receptor is several-fold greater than tramadol’s, with more prominent norepinephrine reuptake inhibition.
4. tramadol is perfect for pain conditions where a strong opioid component is not needed—and it has the benefit of a low abuse potential. Nucynta, a schedule II controlled substance, is well-suited for pain conditions requiring a strong opioid component (post-operative pain, pain where other medications have failed you) and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids.
5. Is Nucynta (tapentadol) as good as oxycodone? Studies have shown that Nucynta works as well as oxycodone for spinal compression fractures and the pain relief provided is similar to oxycodone and morphine.
6. Nucynta has been well studied and shown to be effective for chronic back pain, diabetic neuropathy, and post-operative pain.
7. Less nausea and vomiting? Yep. Nucynta scores points too for being better tolerated by the gut, so it has less nausea and vomiting compared to other opioids like Dilaudid, morphine or fentanyl.
8. Is it less addictive? Yes. Nucynta appears to have a low level of abuse in post-marketing studies.
9. Nucynta is a schedule II drug, so it requires a triplicate prescription, whereas tramadol (Ultram) does not, so tramadol is easier to refill and easier to acquire from the doctor.
10. Cost, not SO bad. Nucynta and Nucynta ER are new and brand-name-only drugs so they will be pricey and more expensive than tramadol, which is the generic form of Ultram.
Worth considering . . .
Strongest Pain Pills
Author: Amy Keller, RN, BSN | Last Updated: 6/05/18 | 26 sources
Two hundred years after its discovery, morphine remains one of the most popular opioid painkillers in use — but it’s far from the strongest. Synthetic opioids hundreds to thousands of times stronger than morphine are now turning up on America’s streets and contributing to a wave of overdoses and deaths.
Opioid abuse is not a new phenomenon, but it has become a worsening epidemic. Opioid-related overdose deaths have doubled since 2000, making drug overdose the leading cause of death for Americans under the age of 50.
Among the factors fueling this deadly epidemic is the exploding popularity of potent synthetic opioids such as fentanyl, which is 50 to 100 times stronger than morphine, and its chemical cousin carfentanil, an elephant tranquilizer that is 10,000 times more powerful than morphine.
Every day, 91 Americans die from an opioid overdose and more than 1,000 people are treated in emergency departments for not using prescription opioids as directed.
Source: Centers for Disease Control and Prevention
Most opioids work in roughly the same way. They attach to receptors in the brain that send signals to block pain, slow breathing and create a sense of euphoria. But what makes one drug more powerful or euphoric than another is its unique chemical structure — and how quickly and tightly it binds to those pain receptors.
As one of the faster prescription opioids, fentanyl zooms through the blood-brain barrier to the brain’s opioid receptors with remarkable efficiency and hugs those receptors more tightly than many other drugs. These characteristics make fentanyl particularly deadly among opioids.
Of the 60,000 drug overdose deaths recorded in 2016 in the United States, 20,000 involved fentanyl. The death rate increased more than fivefold since 2013, when fentanyl was implicated in 3,105 fatalities.
In medical literature, the analgesic strength, or potency, of most painkillers is measured as a comparison to morphine. For example, oxycodone is roughly 50 percent stronger than morphine. Therefore, researchers might say the drug is 1.5 times as strong as morphine. A single dose of Tylenol or aspirin is about 360 times weaker than a dose of morphine.
Opioids Weaker than Morphine
While morphine is the pharmacologic standard bearer in the lineup of prescription opioids, there are several milder prescription painkillers on the market. These range from codeine, a common ingredient in many cough syrups, to tapentadol, a relatively new drug that is being marketed to patients requiring long-term opioid treatment, such as those suffering from diabetic leg pain.
Like morphine and heroin, codeine comes directly from the opium poppy plant. The drug is an ingredient in many cough syrups and is also prescribed to treat mild to moderate pain and diarrhea. Codeine, which is seven to 14 times less potent than morphine, comes in a variety of dosages. The opioid is often combined with Tylenol to increase both drugs’ analgesic effects.
Meperidine (Demerol, Meperitab)
A synthetic opioid similar to morphine, Demerol has been used to treat pain since the early 1940s. It is sometimes used for post-surgical pain relief. While it is about seven to 10 times less potent than morphine, caution must be exercised because Demerol produces a toxic byproduct in the body that can cause tremors and seizures, particularly in patients with kidney problems. For this reason, meperidine should only be used by patients with normal renal function. Because of its relatively short half-life, meperidine doesn’t work well for acute or chronic pain.
Tramadol (Ultram, Ultram ER)
This synthetic opioid was a popular prescription painkiller for decades before it made its debut in the United States in the 1990s. Tramadol, which is about one-tenth as potent as morphine, works similarly to morphine, targeting the brain’s mu-opioid receptors to block pain signals. While it is considered to be less addictive than other opioids, the potential for addiction still exists.
Stronger than tramadol but two to three times less potent than morphine, tapentadol can be used to treat moderate to severe pain that is acute or chronic. A relatively new drug that was first approved for use in the United States in 2008, tapentadol is frequently prescribed for controlling pain related to diabetic neuropathy. It comes in both immediate-release and extended-release formulations. Studies have shown lower rates of abuse with tapentadol than with similar narcotics.
Opioids Equivalent to Morphine
Morphine and its chemically similar cousin hydrocodone might be equal in strength — but they haven’t always been treated as such. For years, Vicodin and other drugs containing a mixture of hydrocodone and acetaminophen had less stringent prescribing regulations than other opioids.
Originally a Schedule III drug, Vicodin was once deemed to have a moderate to low potential for dependence and a lower abuse potential than other narcotics. Unfortunately, those laxer standards helped propel the combination opioid to become the most prescribed drug in the United States, contributing to widespread abuse of the substance.
In 2014, the federal government tightened its controls on hydrocodone/acetaminophen, elevating the combination drug to Schedule II status. This category is for substances considered to have a high potential for harm and abuse.
Vicodin’s popularity hasn’t waned much though. In 2016, American pharmacies and long-term care facilities dispensed 90 million prescriptions for Vicodin, making it the fourth most prescribed medicine in the nation, according to a report by the IQVIA Institute for Human Data Science.
Hydrocodone (Vicodin, Lorcet, Norco)
Equal in strength to morphine, hydrocodone is one of the most popular opioid medications on the market. As such, it’s also the most commonly abused substance in the nation, with 24 million Americans reporting they use hydrocodone for nonmedical purposes. Some of the most popular formulations of the drug, including Norco, Vicodin and Lorcet, contain hydrocodone in combination with acetaminophen.
Morphine (MS Contin, Avinza, Kadian, Oramorph)
Two centuries after it was first discovered, morphine remains one of the most widely used painkillers in the world, with more than 230 tons of morphine prescribed legally each year. Morphine is approximately three times as strong as codeine and “remains the standard against which all new medications for postoperative pain relief are compared,” according to Dr. Jonathan Moss, a professor of anesthesia and critical care at the University of Chicago.
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Opioids Stronger than Morphine
The opioid death toll in this country is growing rapidly, and increased use of the drugs is not solely to blame. It’s also because people are taking increasingly strong opioids recreationally. Among them is the potent painkiller fentanyl. Stronger still is carfentanil, an elephant tranquilizer so powerful that sometimes Narcan cannot even counter its effects.
Oxycodone (OxyContin, Percocet, Percodan, Roxicodone)
Milligram for milligram, oxycodone is about 50 percent stronger than morphine. At one time, oxycodone was rarely used in settings outside of hospice or cancer treatment. That changed, however, in 1995, when Purdue Pharma released a new extended-release formulation of the drug called OxyContin.
While the drug manufacturer touted OxyContin as nonaddictive and safe, the opposite was true. Amid Purdue’s aggressive marketing campaign, OxyContin prescriptions soared. The drug made its way onto the streets and into the hands of abusers who snorted and injected it, methods that increase the potency of the time-release medication.
Methadone (Methadose, Dolophine)
Three times stronger than morphine, methadone is often prescribed to help people recover from addiction to heroin and other opioid pain medications. It lessens the painful symptoms of opioid withdrawal, and it is effective at reducing cravings. It also lacks the euphoric effects of other opioids. Methadone can be taken in the form of a pill, a liquid or a wafer. It is sometimes used for pain management in cancer patients and others with chronic pain.
Though it has a comparatively shorter duration of effect than morphine, Dilaudid is five to 10 times stronger. Hydromorphone is a popular second-line treatment for pain after morphine, but it has a high potential for abuse and dependence. An extended-release version of hydromorphone called Palladone was pulled from the market in 2005 amid safety concerns when several patients died after mixing the medication with alcohol.
Depending on who is using it and how it’s consumed, heroin is approximately two to five times stronger than morphine. Heroin is a naturally occurring substance that comes from the seed pod of certain types of poppy plants. When it’s snorted, smoked or injected, heroin users experience a euphoric rush lasting several hours. The rush is followed by a state of stupor or sleep that may also last multiple hours. Though heroin’s heyday was in the 1960s and 1970s, there’s been a resurgence in heroin use in recent years — particularly among young people — as prescription painkillers have become increasingly expensive and harder to obtain.
This controversial opioid is 10 times stronger than morphine when taken intravenously and about three times more potent than morphine in pill form. In 2017, Opana manufacturer Endo Pharmaceuticals agreed to pull the extended-release formulation of drug, Opana ER, from the market at the request of the Food and Drug Administration because of its high abuse potential. Individuals found ways to crush and inject the medication despite its hard coating, and intravenous use of the medication was associated with in a 2015 outbreak of HIV in Indiana and a 2011 outbreak of hepatitis C in New York.
Buprenorphine is an opioid doctors prescribe to help treat opioid addition. It can be 25 to 100 times stronger than morphine depending on the formulation and other factors. It suppresses withdrawal symptoms and cravings, but unlike methadone, which is dispensed through clinics, buprenorphine can be prescribed and dispensed at a physician’s office.
Fentanyl (Sublimaze, Duragesic, Subsys)
This synthetic opioid that killed pop icon Prince is 100 times stronger than morphine. It moves quickly from the blood stream into the brain and binds tightly to pain receptors, making a fentanyl overdose extremely difficult to counteract. Rescue attempts may require multiple administrations of the reversal agent Narcan. A side effect known as “wooden chest syndrome,” which causes rigidity of the chest wall, can make doing CPR compressions on an overdose victim impossible.
Approximately 2 to 3 milligrams of fentanyl — which is roughly the same size as two to three grains of table salt — can cause respiratory depression, respiratory arrest and even death.
Source: Drug Enforcement Administration
Prescription fentanyl comes in many forms, including lozenges, lollipops and transdermal patches that are applied to the skin. The drug is also created illicitly and sold on the street. Fentanyl is commonly mixed with heroin, cocaine and other chemicals in counterfeit pills.
Though molecularly similar to fentanyl, this synthetic opioid is 100 times stronger than its chemical cousin and 10,000 times more potent than morphine.
Carfentanil was never intended for use in humans. It is so lethal, in fact, that it’s been classified as a chemical weapon in international arms control treaties. The only legitimate use of the drug is as a tranquilizer for elephants and other large animals. Nevertheless, the lethal substance has made its way from labs in China onto American streets.
“Carfentanil is 1000 times more powerful than morphine, and we’ve seen a lot of carfentanil on the streets.”
Carfentanil is just one of the substances — along with fentanyl, heroin and a synthetic opioid called U-47700 — that’s been turning up in a deadly new street drug called “Gray Death.” A minuscule grain of the combination drug, which resembles a chunk of concrete, can kill someone instantly. Gray death was associated with 50 overdoses in Georgia over a three-month span in the first half of 2017, and the DEA confirmed that U-47700 caused 46 deaths nationwide in 2015 and 2016.
While powerful opioids may carry a high risk of accidental overdose and death, weaker opioids are not necessarily safer than stronger ones. All opioids are addictive and carry significant risks and potential side effects. If you are prescribed an opioid pain reliever, take it only as directed. If you are unsure how to take your medication, contact your doctor or pharmacist.
Author Amy Keller, RN, BSN, Content Writer, DrugRehab.com As a former journalist and a registered nurse, Amy draws on her clinical experience, compassion and storytelling skills to provide insight into the disease of addiction and treatment options. Amy has completed the American Psychiatric Nurses Association’s course on Effective Treatments for Opioid Use Disorder and continuing education on Screening, Brief Intervention and Referral to Treatment (SBIRT). Amy is an advocate for patient- and family-centered care. She previously participated in Moffitt Cancer Center’s patient and family advisory program and was a speaker at the Institute of Patient-and Family-Centered Care’s 2015 national conference. @DrugRehabAmy
This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.
Brand Names: US
Nucynta; Nucynta ER
Brand Names: Canada
Nucynta ER; Nucynta IR
- This drug is a strong pain drug that can put you at risk for addiction, abuse, and misuse. Misuse or abuse of this drug can lead to overdose and death. Talk with your doctor.
- You will be watched closely to make sure you do not misuse, abuse, or become addicted to this drug.
- This drug may cause very bad and sometimes deadly breathing problems. Call your doctor right away if you have slow, shallow, or trouble breathing.
- The chance of very bad and sometimes deadly breathing problems may be greater when you first start this drug or anytime your dose is raised.
- Even one dose of this drug may be deadly if it is taken by someone else or by accident, especially in children. If this drug is taken by someone else or by accident, get medical help right away.
- Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
- Using this drug for a long time during pregnancy may lead to withdrawal in the newborn baby. This can be life-threatening. Talk with the doctor.
- This drug has an opioid drug in it. Severe side effects have happened when opioid drugs were used with benzodiazepines or other drugs that may make you drowsy or slow your actions. This includes slow or troubled breathing and death. Benzodiazepines include drugs like alprazolam, diazepam, and lorazepam. Benzodiazepines may be used to treat many health problems like anxiety, trouble sleeping, or seizures. If you have questions, talk with your doctor.
- Many drugs interact with this drug and can raise the chance of side effects like deadly breathing problems. Talk with your doctor and pharmacist to make sure it is safe to use this drug with all of your drugs.
- Do not take with alcohol or products that have alcohol. Unsafe and sometimes deadly effects may happen.
- Get medical help right away if you feel very sleepy, very dizzy, or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up.
- Swallow whole. Do not chew, break, crush, or dissolve before swallowing. Doing these things can cause very bad side effects and death.
What is this drug used for?
- It is used to ease pain.
What do I need to tell my doctor BEFORE I take this drug?
- If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
- If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
- If you have any of these health problems: Kidney disease or liver disease.
- If you have taken certain drugs for depression or Parkinson’s disease in the last 14 days. This includes isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline. Very high blood pressure may happen.
- If you are taking any of these drugs: Linezolid or methylene blue.
- If you are taking any of these drugs: Buprenorphine, butorphanol, nalbuphine, pentazocine, or tramadol.
- If you are taking another drug that has the same drug in it.
- If you are breast-feeding or plan to breast-feed.
This is not a list of all drugs or health problems that interact with this drug.
Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
- Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
- Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
- To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
- Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
- Do not take this drug with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
- This drug may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking this drug.
- If you have been taking this drug for a long time or at high doses, it may not work as well and you may need higher doses to get the same effect. This is known as tolerance. Call your doctor if this drug stops working well. Do not take more than ordered.
- Long-term or regular use of opioid drugs like this drug may lead to dependence. Lowering the dose or stopping this drug all of a sudden may cause a greater risk of withdrawal or other severe problems. Talk to your doctor before you lower the dose or stop this drug. You will need to follow your doctor’s instructions. Tell your doctor if you have more pain, mood changes, thoughts of suicide, or any other bad effects.
- Long-term use of an opioid drug may lead to lower sex hormone levels. Call your doctor if you have a lowered interest in sex, fertility problems, no menstrual period (women), or change in sex ability (men).
- If you are 65 or older, use this drug with care. You could have more side effects.
- This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
What are some side effects that I need to call my doctor about right away?
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
- Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
- Very bad dizziness or passing out.
- Severe constipation or stomach pain. These may be signs of a severe bowel problem.
- Chest pain or pressure or a fast heartbeat.
- Feeling confused.
- Mood changes.
- Shortness of breath.
- Trouble walking.
- Feeling overheated.
- A severe and sometimes deadly problem called serotonin syndrome may happen if you take this drug with certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; severe diarrhea, upset stomach, or throwing up; or severe headache.
- Taking an opioid drug like this drug may lead to a rare but very bad adrenal gland problem. Call your doctor right away if you have very bad dizziness or passing out, very bad upset stomach or throwing up, or if you feel less hungry, very tired, or very weak.
What are some other side effects of this drug?
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
- Feeling dizzy, sleepy, tired, or weak.
- Upset stomach or throwing up.
- Dry mouth.
- Stomach pain.
- Not hungry.
These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
You may report side effects to your national health agency.
How is this drug best taken?
Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
- Take with or without food. Take with food if it causes an upset stomach.
- Take by mouth only.
- Do not inject or snort this drug. Doing any of these things can cause very bad side effects like trouble breathing and death from overdose.
- Do not use for fast pain relief or on an as needed basis.
- Do not use for pain relief after surgery if you have not been taking drugs like this drug.
- Swallow whole. Do not chew, break, or crush.
- Take 1 tablet at a time if your dose is more than 1 tablet. Do not lick or wet the tablet before putting it in your mouth. Swallow the tablet with lots of water right after putting it in your mouth.
- If you have trouble swallowing, talk with your doctor.
What do I do if I miss a dose?
- Take a missed dose as soon as you think about it.
- If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
- Some products are to be taken to ease pain as needed. If you are taking this drug as needed, do not take more often than told by your doctor.
How do I store and/or throw out this drug?
- Store at room temperature in a dry place. Do not store in a bathroom.
- Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
- Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
- If your symptoms or health problems do not get better or if they become worse, call your doctor.
- Do not share your drugs with others and do not take anyone else’s drugs.
- Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
- If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Consumer Information Use and Disclaimer
This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
Last Reviewed Date
Is Tapentadol a Glorified Tramadol?
Ask The Expert from January/February 2016
In 1995, Janssen Pharmaceutical released a chemical entity known as tramadol (Ultram). In 2009, Janssen released a similar entity, tapentadol (Nucynta), as a Schedule II analgesic that was the first new opioid entity with controlled substance status approved by the U.S. Food and Drug Administration (FDA) in several decades. The drug was sold to DepoMed in April 2015.1 In 2014, the Drug Enforcement Administration (DEA) officially changed tramadol from a schedule V to a schedule IV drug.1 Both tramadol and tapentadol are phenylpropylamines (Figure 1).
Although both compounds are mu opioid receptors agonists, they differ in their mu binding affinity: tramadol has a mu binding affinity 6,000 times less than that of morphine. In fact, tramadol is pharmacologically a “partial agonist.”2 In contrast, tapentadol is a full mu agonist with a binding affinity 18 times less than that of morphine, but is only 2- to 3-times less potent than morphine. This is presumably because of its dual mechanism—a mu receptor agonist and norepinephrine reuptake inhibitor.3
Both tramadol and tapentadol inhibit the reuptake of norepinephrine from the synaptic cleft, which has been shown to have analgesic properties separate from opiate activity.2,4,5 Tramadol has been shown to inhibit serotonin reuptake, but tapentadol has not been shown to have any therapeutic serotonin activity.3
Despite this, the FDA-approved labeling requires both compounds to include the standard warning for risk of seizure and serotonin syndrome—especially when they are taken with antidepressants, other opioids, or neuroleptics, or are used in patients with a history of epilepsy or head injury.6,7
Without a doubt, tapentadol is far from a “glorified tramadol,” which has been suggested to one of the authors (JF) by many medical and pharmacy colleagues. But an important question remains: Are all of these warnings warranted for tapentadol?
Tapentadol is metabolized hepatically by Phase 2 pathways, primarily conjugating with glucuronic acid to form glucuronides, and by a minor Phase 1 oxidative pathway through cytochrome P (CYP) 2C19 (13%) and CYP2D6 (2%) enzymes.2,6 The terminal half-life of tapentadol is approximately 4.25 hours, and it is excreted through the kidneys.6,8 This means that tapentadol has no active metabolites, and, therefore, possesses less risk of drug-drug and cytochrome P450 interactions.3,9
In contrast, tramadol is metabolized by CYP2D6 and CYP3A4, with 2D6 producing the O-demethylated metabolite (M1) that has more analgesic properties than tramadol itself but interestingly doesn’t impact the pain relief.2,10-12 Here’s why: Although M1 is a more potent analgesic than tramadol, the metabolite has more difficulty passing into the central nervous system (CNS).3 Additionally, as the dose of tramadol is increased, so too is the M1 metabolite; however, the ratio of tramadol to M1 entering the CNS increases. This means that more of the weaker parent compound binds to the mu receptors.2
If a patient taking tramadol is classified as a “poor” metabolizer of 2D6 or is taking 2D6 inhibitors, it can result in decreased analgesia and metabolism—20% higher blood concentration and 40% decreased M1 compared with “extensive” metabolizers (ie, normal metabolic rate).7,12
Common 2D6 inhibitors include citalopram, doxepin, escitalopram, fluoxetine, paroxetine, and sertraline; common 3A4 inhibitors include amiodarone, amlodipine, cimetidine, ciprofloxacin, clarithromycin, diltiazem, erythromycin, and fluoxetine.6,7,11,13-16
In fact, studies have found that poor metabolizers of 2D6 had higher concentrations of tramadol (4.4 mcg/mL) than extensive metabolizers (0.8 mcg/mL), confirming that 2D6 was an important factor in drug metabolism.17 The mean half-life of tramadol is approximately 6 hours, whereas the mean half-life for the M1 metabolite is 7.4 hours—tramadol is metabolized by the liver and M1 is excreted by the kidneys.7,12 Compared with extensive metabolizers, ultra-rapid metabolizers are able to convert tramadol into M1 more quickly, yielding improved analgesia, but also can cause toxicity at lower doses.12
Other studies show another interesting difference between tramadol, M1, and tapentadol when evaluating the binding of recombinantly expressed human mu opioid receptor (hMOR). Tramadol has 15 times less binding affinity for the hMOR than tapentadol and about 700 times less than M1. Yet, functional activity studies indicate that tapentadol is analogous to M1, whereas tramadol showed no activity in an agonist-stimulated GTPγS binding assay in cells recombinantly expressing hMOR.2
In another words, although the binding affinity of the M1 is greater than that of tapentadol and the parent compound tramadol, the actual effect of M1 on mu opioid receptors is approximately the same as that of tapentadol. The parent drug tramadol itself has no activity, and therefore tramadol has 2 to 5 times less potency compared to tapentadol across various animal pain models.2
Serotonin Syndrome Risk Examined
What is the relative risk of seizure and serotonin syndrome between tramadol and tapentadol? Serotonin syndrome occurs when there is a buildup of serotonin in the central and the peripheral nervous systems or the serotonin receptors are activated. This buildup in serotonin can be due to a combination of the following: increased serotonin synthesis or release, or decreased serotonin metabolism or reuptake.11 The symptoms of serotonin syndrome include neuromuscular hyperactivity, autonomic hyperactivity, altered mental status, and seizures.11
Human affinity (measured by Ki values) of tapentadol and tramadol for human norepinephrine receptors (hNET) were 8.8 mcM and 14.6 mcM, respectively, wherease values for human serotonin (hSERT) were 5.28 mcM and 1.19 mcM, respectively. According to Raffa et al, this shows that tapentadol is slightly more potent than tramadol in blocking hNET and nearly 5-fold less potent than tramadol in blocking hSERT.2 In rats given an analgesic dose, tramadol increases norepinephrine 5 times baseline levels and serotonin 5 to 6 times baseline levels, whereas tapentadol increases norepinephrine 5 to 6 times and serotonin 2 times baseline levels.2 According to the authors, these changes would be equivalent in humans. Of note, another study of rats found that tapentadol only increased the cerebral spinal fluid (CSF) concentration of norepinephrine 50% to 60%, whereas the serotonin norepinephrine reuptake inhibitor duloxetine doubled the concentration.18
Most commonly, tramadol-induced seizures appear to be generalized tonic-clonic seizures that occur within 24 hours of medication ingestion. These seizures have occurred predominantly in patients ingesting alcohol, illicit drugs, antipsychotics, or antidepressant medications or some combination of these along with tramadol.19
Other groups that have been shown to have frequent seizures when taking tramadol at the recommended daily dose are patients with epilepsy and those who have suffered head trauma.11,19 In one study, 50% of patients who had a seizure were taking another prescribed medication, half of those being antidepressants.11 Additionally, countries with a high incidence of ultra-rapid metabolizers, such as Iran and Middle Eastern countries (genetic predisposition), are seeing higher incidence of abuse of tramadol resulting in more opioid side effects and seizures.20
The 15% of Caucasians who have a problem in the CYP pathway may require higher doses of tramadol to manage pain because less M1 is being produced.5 In such individuals, higher concentrations of tramadol enters the CNS without competition from M1, more serotonin reuptake inhibition occurs and therefore elevated intra-neuronal serotonin; this leads to lower analgesia and a higher risk of serotonin syndrome. Drugs that are CYP inhibitors and inhibit serotonin themselves, such as fluoxetine, sertraline, paroxetine, and citalopram, can elevate the risk of serotonin syndrome.11
Tramadol is a Schedule IV analgesic. Its designation was changed from Schedule V to Schedule IV on August 18, 2014, due to concerns regarding abuse. At the time, it was the only non-controlled opioid on the market indicated for the management of moderate to moderately severe pain.21
Tapentadol, by comparison, is a Schedule II drug indicated for the management of moderate to severe acute pain that undergoes hepatic Phase 2 metabolism primarily, and is devoid of any active metabolites.
Both medications are considered opioid agonists, but tramadol is significantly weaker than tapentadol. Tramadol and tapentadol both inhibit reuptake of norepinephrine to roughly the same degree, but tramadol inhibits serotonin reuptake 3 times more than tapentadol. For these reasons, tapentadol should be associated with a lower incidence of serotonin-related toxicities and superior analgesia.
View Sources Last updated on: February 9, 2016 Continue Reading: New Research Into Psoriatic Arthritis
NUCYNTA® (tapentadol): ONE SOURCE OF RELIEF IN THE ACUTE SETTING1
INDICATIONS AND USAGE
NUCYNTA tablets are contraindicated in patients with:
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including suspected paralytic ileus
Hypersensitivity to tapentadol (eg, anaphylaxis, angioedema) or to any other ingredients of the product
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
WARNINGS AND PRECAUTIONS:
Addiction, Abuse, and Misuse
NUCYNTA tablets contain tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA tablets expose users to the risks of addiction, abuse, and misuse.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA tablets and monitor all patients receiving NUCYNTA tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA tablets, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA tablets along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
IMPORTANT SAFETY INFORMATION
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
NUCYNTA tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing NUCYNTA tablets, and monitor all patients regularly for the development of these behaviors and conditions.
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
complete a REMS‑compliant education program,
counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
consider other tools to improve patient, household, and community safety.
Life‑Threatening Respiratory Depression
Serious, life‑threatening, or fatal respiratory depression may occur with use of NUCYNTA tablets. Monitor for respiratory depression, especially during initiation of NUCYNTA tablets or following a dose increase.
Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in a fatal overdose of tapentadol.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of NUCYNTA tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life‑threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of NUCYNTA tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain
Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA tablets.
To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA tablets are essential. Overestimating the NUCYNTA tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.
Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of NUCYNTA tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life‑threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA tablets with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.
Life-Threatening Respiratory Depression in Patients With Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients
The use of NUCYNTA tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: NUCYNTA tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA tablets.
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
Monitor such patients closely, particularly when initiating and titrating NUCYNTA tablets and when NUCYNTA tablets are given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.
Serotonin Syndrome With Concomitant Use of Serotonergic Drugs
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concurrent use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), certain muscle relaxants (ie, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.
Serotonin syndrome symptoms may include mental-status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) and can be fatal. The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue NUCYNTA tablets if serotonin syndrome is suspected.
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
NUCYNTA tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA tablets. In patients with circulatory shock, NUCYNTA tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA tablets in patients with circulatory shock.
Risks of Use in Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury or Impaired Consciousness
In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), NUCYNTA tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA tablets in patients with impaired consciousness or coma.
Risks of Use in Patients With Gastrointestinal Conditions
NUCYNTA tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The tapentadol in NUCYNTA tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
Increased Risk of Seizures in Patients With Seizure Disorders
The tapentadol in NUCYNTA tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA tablets therapy.
Do not abruptly discontinue NUCYNTA tablets in a patient physically dependent on opioids. When discontinuing NUCYNTA tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.
Additionally, avoid the use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NUCYNTA tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.
Risks of Driving and Operating Machinery
NUCYNTA tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA tablets and know how they will react to the medication.
Interactions With Alcohol, Other Opioids, and Drugs of Abuse
Due to its mu-opioid agonist activity, NUCYNTA tablets may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, respiratory depression, hypotension, and profound sedation, coma or death. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol, other opioids, or drugs of abuse while on NUCYNTA tablets therapy.
Risk of Toxicity in Patients With Hepatic Impairment
A study with NUCYNTA tablets in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA tablets in patients with severe hepatic impairment. Reduce the dose of NUCYNTA tablets in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when receiving NUCYNTA tablets.
Risk of Toxicity in Patients With Renal Impairment
Use of NUCYNTA tablets in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.
In clinical studies, the most common (≥10%) adverse reactions were nausea, dizziness, vomiting, and somnolence.
Please see full Prescribing Information, including Boxed Warning.
Narcotics & Breakthrough Pain Relief
For those taking narcotics, breakthrough pain might be a sign that the body is developing tolerance to the narcotic, Ferrante says. “Tolerance means you need to take more of the drug over time to achieve the same pain relief.”
When a patient develops a narcotic tolerance, the doctor can increase the dosage to provide the same pain relief — but the risk of side effects gets higher with the higher dose, explains Salahadin Abdi, MD, PhD, chief of pain medicine at the University of Miami School of Medicine.
“Instead of increasing the dosage of that narcotic, a good solution is to change to a different narcotic,” Abdi tells WebMD. “You can then use a relatively small dose of the new narcotic to get the same effect. You can switch to yet another narcotic later on if you need to.”
Drugs called NMDA antagonists (N-methyl-D-aspartate) have been another advance in narcotics for pain relief, says Rollin M. Gallagher, MD, MPH, director of pain management at the Philadelphia VA Medical Center. NMDA antagonists block NMDA receptors to stop or minimize opioid drug tolerance.
“NMDAs allow us to provide pain relief with a lower dose of a narcotic drug,” Gallagher tells WebMD. “Opioids are very effective, very safe, because they don’t damage organs like other drugs do — but you can develop tolerance. NMDAs can help prevent tolerance.” Meaning less drugs and better pain relief.