AUDIENCE: Pharmacy, Internal Medicine, Psychiatry, Neurology, Family Practice
ISSUE: FDA review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, FDA is adding Boxed Warnings, our strongest warnings, to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines. See the Drug Safety Communication, available at: http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm, for a listing of all approved prescription opioid pain and cough medicines, and benzodiazepines and other CNS depressants.
FDA conducted and reviewed several studies showing that serious risks are associated with the combined use of opioids and benzodiazepines, other drugs that depress the CNS, or alcohol (see the FDA Drug Safety Communication, available at: http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm, for a Data Summary). Based on these data, FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed Warnings and revisions to the Warnings and Precautions, Drug Interactions, and Patient Counseling Information sections of the labeling.
FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy (MAT) drugs used to treat opioid addiction and dependence. FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will update the public when more information is available.
BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines cannot be taken or are not able to provide enough pain relief. Benzodiazepines are a class of medicines that are widely used to treat conditions including anxiety, insomnia, and seizures.
RECOMMENDATION: Health care professionalsshould limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate. If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.
Patients taking opioids with benzodiazepines, other CNS depressant medicines, or alcohol, and caregivers of these patients, should seek medical attention immediately if they or someone they are caring for experiences symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Oxymorphone may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. Your doctor will monitor you carefully during your treatment. Tell your doctor if you have or have ever had slowed breathing or asthma. Your doctor will probably tell you not to take oxymorphone extended-release tablets. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema), a head injury, any condition that increases the amount of pressure in your brain, sleep apnea (condition in which breathing stops or becomes shallow during sleep);or kyphoscoliosis (curving of the spine that may cause breathing problems). The risk that you will develop breathing problems may be higher if you are an older adult or are weak or malnourished due to disease. If you experience any of the following symptoms, call your doctor immediately or get emergency medical treatment: slowed breathing, long pauses between breaths, or shortness of breath.
Taking certain medications other medications with oxymorphone may increase the risk that you will develop serious or life-threatening breathing problems. Tell your doctor and pharmacist if you are taking or plan to take any of the following medications: antidepressants; cimetidine (Tagamet); other narcotic pain medications; medications for anxiety, seizures, mental illness, or nausea; muscle relaxants; sedatives; sleeping pills; and tranquilizers.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with oxycodone increases the risk that you will experience serious, life-threatening side effects. Talk to your doctor about the risks of drinking alcohol during your treatment.
Swallow oxymorphone extended-release tablets whole; do not break, chew, dissolve, or crush them. If you take broken, chewed, dissolved, or crushed extended-release tablets, you may receive the entire dose of oxymorphone at once, instead of slowly over 12 hours. This may cause serious problems, including overdose and death. Tell your doctor if you are unable to swallow the tablets whole. Your doctor may prescribe a different medication.
Oxymorphone may be habit forming. Do not take a larger dose, take it more often, or take it for a longer period of time, or in a different way than prescribed by your doctor. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse oxymorphone if you have or have ever had any of these conditions.
Do not allow anyone else to take your medication. Oxymorphone may harm or cause death to other people who take your medication, especially children. Store oxymorphone in a safe place so that no one else can take it accidentally or on purpose. Be especially careful to keep oxymorphone out of the reach of children. Keep track of how many tablets, or capsules are left so you will know if any medication is missing. Dispose of any unneeded tablets and extended-release tablets properly according to instructions. (See STORAGE and DISPOSAL).
Tell your doctor if you are pregnant or plan to become pregnant. If you take oxymorphone regularly during your pregnancy, your baby may experience life-threatening withdrawal symptoms after birth. Tell your baby's doctor right away if your baby experiences any of the following symptoms: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.
Talk to your doctor about the risks of taking oxymorphone.
If you are taking the extended-release tablets, your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with oxymorphone and each time you fill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Why is this medication prescribed?
Oxymorphone is used to relieve moderate to severe pain. Oxymorphone extended-release tablets are used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. Oxymorphone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the body responds to pain.
How should this medicine be used?
Oxymorphone comes as a tablet and an extended-release tablet to take by mouth on an empty stomach, at least 1 hour before or 2 hours after meals. The regular tablet is usually taken every 4 to 6 hours. The extended-release tablet is usually taken every 12 hours. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take oxymorphone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
If you are taking the extended-release tablets, swallow them one at a time with plenty of water. Swallow each extended-release tablet right after putting it in your mouth. Do not presoak, wet, or lick the tablets before you put them in your mouth.
Your doctor will probably start you on a low dose of oxymorphone and gradually increase your dose until your pain is controlled. Your doctor may adjust your dose at any time during your treatment if your pain is not controlled. If you feel that your pain is not controlled, call your doctor. Do not change the dose of your medication without talking to your doctor.
Do not stop taking oxymorphone without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking oxymorphone, you may experience withdrawal symptoms such as restlessness; watery eyes; runny nose; yawning; sweating; chills; muscle, joint, or back pain; enlarged pupils (black circles in the centers of the eyes); irritability; anxiety; weakness; stomach cramps; difficulty falling asleep or staying asleep; nausea; vomiting; diarrhea; loss of appetite; fast heartbeat; and fast breathing.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking oxymorphone,
- tell your doctor and pharmacist if you are allergic to oxymorphone, oxycodone (OxyContin, Oxaydo, Xtampza, in Percocet, in Roxicet, others), codeine (in many pain relievers and cough medications), hydrocodone (Zohydro, Hysingla, in Anexsia, in Norco, in Reprexain, in Rezira, in Vicoprofen, in Vituz, others), dihydrocodeine (in Synalgos-DC, in Trezix), hydromorphone (Dilaudid, Exalgo), any other medications, or any of the ingredients in oxymorphone tablets or extended-release tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antihistamines; buprenorphine (Buprenex, Butrans, Zubsolv, in Suboxone); butorphanol (Stadol); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); ipratropium (Atrovent, in Combivent); lithium (Lithobid); medications for irritable bowel disease, mental illness, motion sickness, nausea, Parkinson's disease, ulcers, or urinary problems; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); nalbuphine;pentazocine (Talwin); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ulltram, in Ultracet), trazodone; or tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking any of the following medications or have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), rasagiline (Azilect), selegiline (Emsam, Eldepryl, Zelapar), and tranylcypromine (Parnate). Many other medications may also interact with oxymorphone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John's wort and tryptophan.
- tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, liver disease, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take oxymorphone.
- tell your doctor if you have or have ever a blockage in your stomach or intestine, low blood pressure; Addison's disease (condition in which the adrenal gland does not produce enough hormone); seizures; urethral stricture (blockage of the tube that allows urine to leave the body); problems urinating; enlarged prostate (a male reproductive gland); or heart, kidney, pancreas, thyroid, or gall bladder disease.
- tell your doctor if you are breastfeeding.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking oxymorphone.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking oxymorphone.
- you should know that oxymorphone may make you drowsy, dizzy, or lightheaded. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that oxymorphone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- you should know that oxymorphone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are using oxymorphone.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Oxymorphone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- dry mouth
- stomach pain
- extreme tiredness
- difficulty falling asleep or staying asleep
Some side effects can be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately:
- chest pain
- agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
- nausea, vomiting, loss of appetite, weakness, or dizziness
- inability to get or keep an erection
- irregular menstruation
- decreased sexual desire
- changes in heartbeat
- swelling of the eyes, face, lips, mouth, tongue or throat
- difficulty breathing or swallowing
- extreme drowsiness
- lightheadedness when changing positions
Oxymorphone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Flush any medication that is outdated or no longer needed down the toilet so that others will not take it. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include the following:
- difficulty breathing or slowed or stopped breathing
- bluish-tinged skin, lips, or fingernails
- cold, clammy skin
- increase or decrease in pupil (dark circle in the eye) size
- limp or weak muscles
- extreme sleepiness
- loss of consciousness
What other information should I know?
Keep all appointments with your doctor and laboratory. Your doctor may order certain lab tests to check your body's response to oxymorphone.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking oxymorphone.
This prescription is not refillable. If you are taking oxymorphone to control your pain on a long term basis, be sure to schedule appointments with your doctor regularly so that you do not run out of medication. If you are taking oxymorphone on a short term basis, call your doctor if you continue to have pain after you finish the medication.
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.
- Opana® ER