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?
Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the body senses pain.
How should this medicine be used?
Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use rectal morphine 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 morphine exactly as directed.
Your doctor may adjust your dose of morphine during your treatment to control your pain as well as possible. 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.
Morphine may be habit-forming. Do not use a larger dose, use it more often, or use it for a longer period of time than prescribed by your doctor.
Do not stop using morphine without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop using morphine, you may experience withdrawal symptoms such as anxiety; sweating; difficulty falling asleep or staying asleep; chills; shaking of a part of your body that you cannot control; nausea; diarrhea; runny nose, sneezing or coughing; hair on your skin standing on end; or hallucinating (seeing things or hearing voices that do not exist).
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 rectal morphine,
- tell your doctor and pharmacist if you are allergic to morphine, any other medications, or any of the ingredients in morphine suppositories. Ask your pharmacist for a list of the ingredients.
- do not use rectal morphine if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), procarbazine (Matulane), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate) or if you have stopped taking any of these medications within the past 2 weeks. Your doctor will probably tell you not to use rectal morphine if you are taking one or more of these medications.
- 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 any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); antidepressants such as amitriptyline , amoxapine, clomipramine (Anafranil), cyclobenzaprine (Amrix), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Surmontil, Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); antihistamines (found in cold and allergy medications); medications for anxiety, mental illness, pain, seizures, or nausea; barbiturates such as phenobarbital and primidone (Mysoline); beta-blockers such as propranolol (Hemangeol, Inderal, InnoPran); butorphanol ; chloral hydrate, chlorpromazine, dextromethorphan (found in many cough medications; in Nuedexta); lithium (Lithobid), medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); methocarbamol (Robaxin), mirtazapine (Remeron); muscle relaxants; nalbuphine; pentazocine (Talwin); 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; tramadol (Conzip, Ulltram, in Ultracet), tranquilizers; trazodone; and tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with rectal morphine, 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 drink or have ever drunk large amounts of alcohol or have had biliary tract or stomach surgery. Also tell your doctor if you have or have ever had a head injury; a brain tumor or any condition that increases the amount of pressure in your brain; seizures; serious or life-threatening breathing problems; asthma; an irregular heartbeat; or heart failure. Your doctor will probably tell you not to use rectal morphine.
- tell your doctor if you have ever had major surgery. Also tell your doctor if you have or have ever had mental illness; chronic obstructive pulmonary disease (COPD; a group of diseases that cause gradual loss of lung function) or other breathing problems; prostatic hypertrophy (enlargement of a male reproductive gland); urethral stricture (blockage of the tube that allows urine to leave the body); urinary problems; low blood pressure; Addison's disease (condition in which the body does not make enough of certain natural substances); or thyroid, liver, kidney, pancreatic, intestinal, or gallbladder disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using morphine, 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 rectal morphine.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using morphine.
- you should know that morphine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- ask your doctor about the safe use of alcoholic beverages while you are using morphine.
What special dietary instructions should I follow?
Drink plenty of fluids while you are using this medication.
What should I do if I forget a dose?
Insert 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 insert a double dose to make up for a missed one.
What side effects can this medication cause?
Morphine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty falling asleep or staying asleep
- stomach pain
- dry mouth
- vision problems
- decreased urination
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- slowed, shallow, or irregular breathing
- changes in heartbeat
- 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
- blue or purple color to the skin
- swelling of the arms, hands, feet, ankles, or lower legs
Morphine may cause other side effects. Call your doctor if you have any unusual problems while 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 at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
Store rectal morphine in a safe place so that no one else can use it 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, 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:
- slow, shallow, or irregular breathing
- blue or purple color to the skin
- loss of consciousness
- limp muscles
- cold, clammy skin
- slow heartbeat
- blurred vision
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 morphine.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using morphine.
This prescription is not refillable. If you are using morphine to control your pain on a long-term basis, be sure to schedule appointments with your doctor so that you do not run out of medication. If you are using morphine on a short term basis, call your doctor if you continue to experience 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.
- RMS® Suppository¶
¶ This branded product is no longer on the market. Generic alternatives may be available.