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.
Meperidine injection 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 use meperidine injection. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways), a head injury, or any condition that increases the amount of pressure in your brain. 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.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with meperidine 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.
Meperidine injection may be habit-forming. Do not use more of it, use it more often, or use it in a different way than directed 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, if you need to take narcotic pain medications regularly in order to feel well or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse meperidine if you have or have ever had any of these conditions.
Do not allow anyone else to use your medication. Meperidine injection may harm or cause death to other people who use your medication, especially children.
Tell your doctor if you are pregnant or plan to become pregnant. If you using meperidine injection 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 using meperidine injection.
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?
Meperidine injection is used to relieve moderate to severe pain. It may also be used before and during surgery or other medical procedures. Meperidine injection 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?
Meperidine injection comes as a solution (liquid) to inject subcutaneously (just under the skin), intramuscularly (into a muscle), or intravenously (into a vein). It is usually injected subcutaneously or intramuscularly once every 3 to 4 hours as needed. Use meperidine injection exactly as directed.
Your doctor may adjust your dose of meperidine injection during your treatment, depending on how well your pain is controlled and on the side effects that you experience. Talk to your doctor about how you are feeling during your treatment with meperidine injection.
If you have used meperidine injection for longer than a few days, do not stop using it suddenly. If you suddenly stop using meperidine injection, you may experience withdrawal symptoms including restlessness; teary eyes; runny nose; yawning; sweating; chills; muscle, back or joint pain; widening of the pupils; irritability; anxiety; 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.
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 meperidine injection
- tell your doctor and pharmacist if you are allergic to meperidine, any other medications, or ingredients in meperidine injection. Ask your pharmacist for a list of the ingredients.
- do not use meperidine injection 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), or 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 meperidine injection if you are taking one or more of these medications.
- 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: cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); medications for anxiety, mental illness, or seizures; 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); mirtazapine (Remeron); 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 duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); sleeping pills; tramadol (Conzip, Ultram); tranquilizers; trazodone (Oleptro); or 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 meperidine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Also tell your doctor or pharmacist if you are taking narcotic medications for pain or if you have recently taken these medications. 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 or have ever had problems urinating; Addison's disease (a condition in which the body does not produce certain important chemicals); prostatic hypertrophy (enlargement of a male reproductive gland called the prostate); urethral stricture (narrowing of the opening through which urine leaves the body); seizures; or thyroid, heart, kidney, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using meperidine injection, 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 meperidine.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using meperidine injection.
- you should know that meperidine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that meperidine 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.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What side effects can this medication cause?
Meperidine injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- uncontrollable shaking of a part of your body
- blurred vision
- dry mouth
- pain or redness at injection site
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:
- slowed breathing
- 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
- decreased sexual desire
- irregular menstruation
- intense happiness
- sad mood
Meperidine injection 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).
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:
- slowed breathing
- extreme sleepiness
- loose, floppy muscles
- cold, clammy skin
- slow heartbeat
What other information should I know?
Keep all appointments with your doctor. Your doctor may order certain lab tests to check your body's response to meperidine.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using meperidine.
This prescription is not refillable. If you continue to have pain after you finish meperidine, 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.