Nucynta ER

Keep all appointments with your doctor and laboratory. Your doctor may order certain lab tests to check your body's response to tapentadol.

Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking tapentadol.

This prescription is not refillable. If you continue to have pain after you finish the medication, call your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Since tapentadol is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Nucynta ER can cause serious side effects including:

• Life-threatening breathing problems. Call your doctor right away or get emergency medical help if you:
  • have trouble breathing, or have slow or shallow breathing
  • have a slow heartbeat 
  • have severe sleepiness 
  • have cold, clammy skin 
  • feel faint, dizzy, confused, or can not think, walk or talk normally 
  • have a seizure 
  • have hallucinations
• Physical Dependence. Nucynta ER can cause physical dependence. Talk to your doctor about slowly stopping Nucynta ER to avoid getting sick with withdrawal symptoms. You could become sick with uncomfortable symptoms because your body has become used to the medicine. Tell your doctor if you have any of these symptoms of withdrawal: feeling anxious, sweating, sleep problems, shivering, pain, nausea, tremors, diarrhea, upper respiratory symptoms, hallucinations, hair "standing on end." Physical dependence is not the same as drug addiction. Your doctor can tell you more about the differences between physical dependence and drug addiction. 
• Serotonin syndrome. Serotonin syndrome is a rare, life-threatening problem that could happen if you take Nucynta ER with Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), Monoamine Oxidase Inhibitors (MAOIs), triptans or certain other medicines. Call your doctor or get medical help right away if you have any one or more of the these symptoms: you feel agitated, have hallucinations, coma, rapid heart beat, feel overheated, loss of coordination, over active reflexes, nausea, vomiting, or diarrhea. 
• Seizures. Nucynta ER can cause seizures in people who are at risk for seizures or who have epilepsy. Tell your doctor right away if you have a seizure and stop taking Nucynta ER. 
• Low blood pressure. This can make you feel dizzy if you get up too fast from sitting or lying down.

Do not drive, operate machinery, or participate in any other possibly dangerous activities until you know how you react to this medicine. Nucynta ER can make you sleepy. 

Do not take Nucynta ER if you:

• have severe asthma, trouble breathing, or other lung problems
• a bowel blockage or have narrowing of the stomach or intestines.
• taken a monoamine oxidase inhibitor (MAOI) medicine or have taken a MAOI medicine within the last 14 days.

You should not drink alcohol while using Nucynta ER. Alcohol increases your chance of having dangerous side effects.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Tapentadol can slow or stop your breathing, and may be habit-forming. MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription.

You should not use this medicine if you have severe breathing problems, or a bowel obstruction called paralytic ileus.

Do not use this medicine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine.

Taking this medicine during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Fatal side effects can occur if you use this medicine with alcohol, or with other drugs that cause drowsiness or slow your breathing.

Narcotic (opioid) medication can interact with many other drugs and cause dangerous side effects or death. Be sure your doctor knows if you also use:

• other narcotic medications--opioid pain medicine or prescription cough medicine;

• drugs that make you sleepy or slow your breathing--a sleeping pill, muscle relaxer, sedative, tranquilizer, or antipsychotic medicine; or

• drugs that affect serotonin levels in your body--medicine for depression, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting.

This list is not complete. Other drugs may interact with tapentadol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

• Tell all of your health care providers that you take this medicine. 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 Nucynta ER (tapentadol extended-release tablets) 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 medicine with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
• This medicine 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 Nucynta ER.
• Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of signs of withdrawal. If you need to stop Nucynta ER, you will want to slowly stop it as ordered by your doctor.
• If you have been taking this medicine 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 Nucynta ER stops working well. Do not take more than ordered.
• Long-term use of an opioid drug like this medicine may lead to lower sex hormone levels. This may lead to signs like change in sex ability in men, no menstrual period in women, lowered interest in sex, or fertility problems. Call your doctor if you have any of these signs.
• If you are 65 or older, use Nucynta ER with care. You could have more side effects.
• This medicine 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 medicine, call your doctor right away.

• 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.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Nucynta ER, please talk with the doctor, 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.

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 Nucynta ER. 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 Nucynta ER.

Review Date: October 4, 2017

Nucynta ER 50 mg, 100 mg, 150 mg, 200 mg and 250 mg extended-release tablets are available in the following colors and prints:

• 50 mg extended-release tablets are white oblong-shaped with a black print “OMJ 50” on one side
• 100 mg extended-release tablets are light-blue oblong-shaped with a black print “OMJ 100” on one side
• 150 mg extended-release tablets are blue-green oblong-shaped with a black print “OMJ 150” on one side
• 200 mg extended-release tablets are blue oblong-shaped with a depression in the middle running lengthwise on each side and a black print “OMJ 200” on one side
• 250 mg extended-release tablets are dark blue oblong-shaped with a depression in the middle running lengthwise on each side and a white print “OMJ 250” on one side.

The following serious adverse reactions are described, or described in greater detail, in other sections:

• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)]
• Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)]
• Interaction with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.4)]
• Serotonin Syndrome [see Warnings and Precautions 5.6]
• Adrenal Insufficiency [see Warnings and Precautions (5.7)]
• Severe Hypotension [see Warnings and Precautions (5.8)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.10)]
• Seizures [see Warnings and Precautions (5.11)]
• Withdrawal [see Warnings and Precautions (5.12)]

Clinical Trial 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.

Commonly-Observed Adverse Reactions in Clinical Studies with Nucynta ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis

The safety data described in Table 1 below are based on three pooled, randomized, double-blind, placebo- controlled, parallel group, 15-week studies of Nucynta ER (dosed 100 to 250 mg BID after a 50 mg BID starting dose) in patients with chronic pain due to low back pain (LBP) and osteoarthritis (OA). These trials included 980 Nucynta ER-treated patients and 993 placebo-treated patients. The mean age was 57 years old; 63% were female and 37% were male; 83% were White, 10% were Black, and 5% were Hispanic.The most common adverse reactions (reported by ≥10% in any Nucynta ER dose group) were: nausea, constipation, dizziness, headache, and somnolence.

The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any Nucynta ER dose group for Nucynta ER- and placebo-treated patients were nausea (4% vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively.

Commonly-Observed Adverse Reactions in Clinical Studies with Nucynta ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy

The types of adverse reactions seen in the studies of patients with painful diabetic peripheral neuropathy (DPN) were similar to what was seen in the low back pain and osteoarthritis trials. The safety data described in Table 2 below are based on two pooled, randomized withdrawal, double-blind, placebo-controlled, 12-week studies of Nucynta ER (dosed 100 to 250 mg BID) in patients with neuropathic pain associated with diabetic peripheral neuropathy. These trials included 1040 Nucynta ER-treated patients and 343 placebo- treated patients. The mean age was 60 years old; 40% were female and 60% were male; 76% were White, 12% were Black, and 12% were “Other”. The most commonly reported ADRs (incidence ≥10% in Nucynta ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache.

Table 2 lists the common adverse reactions reported in 1% or more of Nucynta ER-treated patients and greater than placebo-treated patients with neuropathic pain associated with diabetic peripheral neuropathy in the two pooled studies.

Other Adverse Reactions Observed During the Premarketing Evaluation of Nucynta ER

The following additional adverse drug reactions occurred in less than 1% of Nucynta ER-treated patients in ten Phase 2/3 clinical studies:

Nervous system disorders: paresthesia, balance disorder, syncope, memory impairment, mental impairment, depressed level of consciousness, dysarthria, presyncope, coordination abnormal

Gastrointestinal disorders: impaired gastric emptying

General disorders and administration site conditions: feeling abnormal, feeling drunk

Psychiatric disorders: perception disturbances, disorientation, confusional state, agitation, euphoric mood, drug dependence, thinking abnormal, nightmare

Skin and subcutaneous tissue disorders: urticaria

Metabolism and nutrition disorders: weight decreased

Cardiac disorders: heart rate increased, palpitations, heart rate decreased, left bundle branch block

Vascular disorder: blood pressure decreased

Respiratory, thoracic and mediastinal disorders: respiratory depression

Renal and urinary disorders: urinary hesitation, pollakiuria

Reproductive system and breast disorders: sexual dysfunction

Eye disorders: visual disturbance

Immune system disorders: drug hypersensitivity

Postmarketing Experience

The following adverse reactions have been identified during post approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Psychiatric disorders: hallucination, suicidal ideation, panic attack

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Nucynta ER.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2)].

Applies to tapentadol: oral solution, oral tablet, oral tablet extended release

Along with its needed effects, tapentadol (the active ingredient contained in Nucynta ER) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tapentadol:

• Bladder pain
• bloody or cloudy urine
• body aches or pain
• chills
• cough
• difficult, burning, or painful urination
• difficulty with breathing
• fever
• headache
• loss of voice
• lower back or side pain
• muscle aches
• unusual tiredness or weakness

• Anxiety
• being forgetful or confused
• clumsiness or unsteadiness
• convulsions
• drowsiness
• fast or irregular heartbeat
• feeling drunk
• irritability or restlessness
• joint pain, stiffness, or swelling
• pale or blue lips, fingernails, or skin
• rash, hives, or itching
• sensation of heaviness
• shakiness or trembling
• slurred speech
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• trouble with speaking or hoarseness
• troubled breathing or swallowing

• Changes in behavior
• dizziness
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seeing, hearing, or feeling things that are not there
• thoughts of killing oneself

Some side effects of tapentadol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• nausea
• vomiting

• Abnormal dreams
• decreased appetite
• difficulty with moving
• heartburn or indigestion
• increased sweating
• muscle pain or stiffness
• redness of the face, neck, arms, and occasionally, upper chest
• stomach discomfort, upset, or pain
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

• Change in vision