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.
Why is this medication prescribed?
Hydromorphone suppositories are used to relieve moderate to severe pain. Hydromorphone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
How should this medicine be used?
Hydromorphone comes as a suppository to insert in the rectum. It is inserted usually once every 6 to 8 hours. Insert hydromorphone at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use hydromorphone suppositories exactly as directed.
Hydromorphone suppositories may be habit forming. Do not use a larger dose, use them more often, or use them for a longer period of time than prescribed by your doctor.
Do not stop using hydromorphone suppositories without talking to your doctor. If you suddenly stop using hydromorphone suppositories, you may experience withdrawal symptoms including restlessness, teary eyes, runny nose, yawning, sweating, chills, hair standing on end, muscle and joint pain, widening of the pupils (black circles in the middle of the eyes), irritability, anxiety, backache, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, loss of appetite, vomiting, diarrhea, fast breathing, or fast heartbeat. Your doctor will probably decrease your dose gradually.
To use the suppositories, follow these steps:
- Remove the wrapper.
- Dip the tip of the suppository in water.
- Lie down on your left side and raise your right knee to your chest (a left-handed person should lie on the right side and raise the left knee).
- Using your finger, insert the suppository about 1 inch (2.5 centimeters) into the rectum.
- Hold it in place with your finger for a few moments.
- Stand up after about 15 minutes. Wash your hands thoroughly and resume normal activities.
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 using hydromorphone suppositories,
- tell your doctor and pharmacist if you are allergic to hydromorphone, any other medications, or any of the ingredients in hydromorphone suppositories. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antidepressants ('mood elevators') such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); lithium (Lithobid); medications for anxiety, seizures, mental illness or nausea; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); narcotic medications for pain other than hydromorphone; sedatives; 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); sleeping pills;, tranquilizers,, trazodone (Oleptro); and 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 or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with hydromorphone, 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 or tryptophan.
- tell your doctor if you have or have ever had a head injury or any condition that caused damage to your brain, any condition that increases the pressure in your brain; slowed breathing; or any condition that affects your breathing such as asthma, chronic obstructive pulmonary disease (COPD; a group of diseases including chronic bronchitis and emphysema that affect the lungs and airways), or kyphoscoliosis (curving of the spine that may cause breathing problems). Your doctor may tell you not to use hydromorphone suppositories.
- tell your doctor if you are an older adult or if you are weakened or malnourished by disease. Also tell your doctor if you have or have ever had hypothyroidism (condition in which the thyroid gland produces less hormone than normal); Addison's disease (condition in which the adrenal gland produces less hormone than normal); any condition that causes difficulty urinating such as an enlarged prostate (a male reproductive gland) or urethral stricture (blockage of the tube that allows urine to leave the body); or liver or kidney disease.
tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using hydromorphone suppositories, call your doctor.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of using hydromorphone suppositories.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using hydromorphone suppositories.
- you should know that hydromorphone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that drinking alcohol during your treatment with hydromorphone suppositories increases the risk that you will experience serious or life-threatening side effects. Talk to your doctor about the risks of drinking alcohol during your treatment with hydromorphone suppositories.
- you should know that hydromorphone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start using hydromorphone suppositories. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
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?
Use 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 use a double dose to make up for a missed one.
What side effects can this medication cause?
Hydromorphone suppositories may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- mood changes
- difficulty urinating
- narrowing of the pupils (dark circles in the center of the eyes)
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:
- slowed or stopped breathing
- breathing that is irregular or that stops and starts
- 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
Hydromorphone suppositories may cause other side effects. Call your doctor if you have any unusual problems while you are using 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 in the refrigerator. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
Store hydromorphone suppositories in a refrigerator in a safe place so that no one else can take the medication accidentally or on purpose. Keep track of how many suppositories are left so you will know if any are missing.
In case of emergency/overdose
In case of overdose or if someone swallows hydromorphone suppositories, 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:
- slowed or stopped breathing
- coma (loss of consciousness for a period of time)
- muscle weakness
- cold, clammy skin
- narrowing or widening of the pupils (dark circle in the middle of the eye)
- slowed or stopped heartbeat
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 hydromorphone.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using hydromorphone.
This prescription is not refillable. If you continue to have pain after you finish the hydromorphone suppositories, 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.
- available generically