"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Respiratory Depression [see WARNINGS AND PRECAUTIONS]
- Interaction with Alcohol [see WARNINGS AND PRECAUTIONS]
- Chronic Pulmonary Disease [see WARNINGS AND PRECAUTIONS]
- Hypotensive Effects [see WARNINGS AND PRECAUTIONS]
- Interactions with Other CNS Depressants [see WARNINGS AND PRECAUTIONS]
- Drug abuse, addiction, and dependence [see Drug Abuse and Dependence]
- Gastrointestinal Effects [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Based on data from nine Phase 2/3 studies that administered multiple doses (seven placebo-and/or active-controlled, one noncontrolled and one Phase 3 active-controlled safety study) the most common adverse reactions (reported by ≥ 10% in any NUCYNTA® dose group) were: nausea, dizziness, vomiting and somnolence.
The most common reasons for discontinuation due to adverse reactions in the studies described above (reported by ≥ 1% in any NUCYNTA® dose group) were dizziness (2.6% vs. 0.5%), nausea (2.3% vs. 0.6%), vomiting (1.4% vs. 0.2%), somnolence (1.3% vs. 0.2%) and headache (0.9% vs. 0.2%) for NUCYNTA®- and placebo-treated patients, respectively.
Seventy-six percent of NUCYNTA®-treated patients from the nine studies experienced adverse events.
NUCYNTA® was studied in multiple-dose, active- or placebo-controlled studies, or noncontrolled studies (n = 2178), in single-dose studies (n = 870), in open-label study extension (n = 483) and in Phase 1 studies (n = 597). Of these, 2034 patients were treated with doses of 50 mg to 100 mg of NUCYNTA® dosed every 4 to 6 hours.
The data described below reflect exposure to NUCYNTA® in 3161 patients, including 449 exposed for 45 days. NUCYNTA® was studied primarily in placebo- and active-controlled studies (n = 2266, and n = 2944, respectively). The population was 18 to 85 years old (mean age 46 years), 68% were female, 75% white and 67% were postoperative. Most patients received NUCYNTA® doses of 50 mg, 75 mg, or 100 mg every 4 to 6 hours.
Table 1 : Adverse Reactions Reported by ≥ 1%
of NUCYNTA®-Treated Patients In Seven Phase 2/3 Placebo- and/or
Oxycodone-Controlled, One Non-controlled, and One Phase 3 Oxycodone-Controlled
Safety, Multiple-Dose Clinical Studies
MedDRA Preferred Term
|NUCYNTA® 21 mg – 120 mg
|Dry mouth||4||< 1|
|General disorders and administration site conditions|
|Feeling hot||1||< 1|
|Infections and infestations|
|Upper respiratory tract infection||1||< 1|
|Urinary tract infection||1||< 1|
|Metabolism and nutrition disorders|
|Nervous system disorders|
|Abnormal dreams||1||< 1|
|Skin and subcutaneous tissue disorders|
|Pruritus generalized||3||< 1|
|Hot flush||1||< 1|
The following adverse drug reactions occurred in less than 1% of NUCYNTA®-treated patients in the pooled safety data from nine Phase 2/3 clinical studies:
Cardiac disorders: heart rate increased, heart rate decreased
Eye disorders: visual disturbance
Gastrointestinal disorders: abdominal discomfort, impaired gastric emptying
General disorders and administration site conditions: irritability, edema, drug withdrawal syndrome, feeling drunk
Immune system disorders: hypersensitivity
Musculoskeletal and connective tissue disorders: involuntary muscle contractions, sensation of heaviness
Nervous system disorders: hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, depressed level of consciousness, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure
Psychiatric disorders: euphoric mood, disorientation, restlessness, agitation, nervousness, thinking abnormal
Renal and urinary disorders: urinary hesitation, pollakiuria
Respiratory, thoracic and mediastinal disorders: oxygen saturation decreased, cough, dyspnea, respiratory depression
Skin and subcutaneous tissue disorders: urticaria
Vascular disorders: blood pressure decreased
In the pooled safety data, the overall incidence of adverse reactions increased with increased dose of NUCYNTA®, as did the percentage of patients with adverse reactions of nausea, dizziness, vomiting, somnolence, and pruritus.
The following additional adverse reactions have been identified during post-approval use of NUCYNTA®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably.
Gastrointestinal disorders: diarrhea
Nervous system disorders: headache
Psychiatric disorders: hallucination, suicidal ideation
Cardiac disorders: palpitations
Read the Nucynta (tapentadol immediate-release oral tablets) Side Effects Center for a complete guide to possible side effects
NUCYNTA® is mainly metabolized by glucuronidation. The following substances have been included in a set of interaction studies without any clinically significant finding: acetaminophen, acetylsalicylic acid, naproxen and probenecid [see CLINICAL PHARMACOLOGY].
The pharmacokinetics of tapentadol were not affected when gastric pH or gastrointestinal motility were increased by omeprazole and metoclopramide, respectively [see CLINICAL PHARMACOLOGY].
Alcohol, Other Opioids, and Drugs of Abuse
Due to its mu-opioid agonist activity, NUCYNTA® 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® therapy [see WARNINGS AND PRECAUTIONS].
Monoamine Oxidase Inhibitors
NUCYNTA® is contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitors or who have taken them within the last 14 days due to potential additive effects on norepinephrine levels which may result in adverse cardiovascular events [see CONTRAINDICATIONS].
Concurrent use of NUCYNTA® and other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol can increase the risk of respiratory depression, hypotension, profound sedation or coma. Monitor patients receiving CNS depressants and NUCYNTA® for signs of respiratory depression and hypotension. When such combined therapy is contemplated, start NUCYNTA® at 1/3 to ½ of the usual dosage and consider using a lower dose of the concomitant CNS depressant [see WARNINGS AND PRECAUTIONS].
There have been post-marketing reports of serotonin syndrome with the concomitant use of tapentadol and serotonergic drugs (e.g., SSRIs and SNRIs). Caution is advised when NUCYNTA® is co-administered with other drugs that may affect serotonergic neurotransmitter systems such as SSRIs, SNRIs, MAOIs, and triptans. If concomitant treatment of NUCYNTA® with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised [see WARNINGS AND PRECAUTIONS].
Mixed Agonist/Antagonist Opioid Analgesics
The concomitant use of NUCYNTA® with mixed agonist/antagonists (e.g., butorphanol, nalbuphine, and pentazocine) and partial agonists (e.g., buprenorphine) may precipitate withdrawal symptoms. Avoid the use of agonist/antagonists and partial agonists with NUCYNTA® .
Drug Abuse And Dependence
NUCYNTA® contains tapentadol, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA® is subject to misuse, abuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].
All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug seeking” behavior is very common in addicts, and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Healthcare professional shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, people suffering from untreated addiction and criminals seeking drugs to sell.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.
NUCYNTA® can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics (pentazocine, butorphanol, buprenorphine, nalbuphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate. Withdrawal symptoms may be reduced by tapering NUCYNTA® .
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use In Specific Populations].
Read the Nucynta Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 7/24/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Nucynta Information
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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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