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.
AUDIENCE: Family Practice, Psychiatry, Pain Management, Nursing, Endocrinology
ISSUE: FDA is warning about several safety issues with the entire class of opioid pain medicines. See the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm for a complete listing. These safety risks are potentially harmful interactions with numerous other medications, problems with the adrenal glands, and decreased sex hormone levels. We are requiring changes to the labels of all opioid drugs to warn about these risks.
BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief (see List of Opioid Medicines in the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm). However, opioids also carry serious risks, including of misuse and abuse, addiction, overdose, and death.
Prescription opioids are divided into two main categories – immediate-release (IR) products, usually intended for use every 4 to 6 hours; and extended release/long acting (ER/LA) products, intended to be taken once or twice a day, depending on the individual product and patient.
See the http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm for additional information, including a listing of opioids, serotonergic medicines, and a data summary.
Health care professionals should discontinue opioid treatment and/or use of the other medicine if serotonin syndrome is suspected.
Health care professionals should perform diagnostic testing if adrenal insufficiency is suspected. If diagnosed, treat with corticosteroids and wean the patient off of the opioid, if appropriate. If the opioid can be discontinued, follow-up assessment of adrenal function should be performed to determine if treatment with corticosteroids can be discontinued.
Decreased sex hormone levels:
Health care professionals should conduct laboratory evaluation in patients presenting with such signs or symptoms.
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?
Meperidine is used to relieve moderate to severe pain. Meperidine is in a class of medications called narcotic analgesics, a group of pain medications similar to morphine. It works by changing the way the body senses pain.
How should this medicine be used?
Meperidine comes as a tablet and a syrup (liquid) to take by mouth. It is usually taken with or without food every 3 to 4 hours as needed for pain. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Swallow the tablets whole: do not chew or crush them.
If you are taking meperidine syrup, use a dose-measuring spoon or cup to measure the correct amount of liquid for each dose, not a regular household spoon. Mix your dose with half a glass of water and swallow the mixture. Swallowing undiluted meperidine syrup may numb the mouth.
Your doctor will probably adjust your dose of meperidine during your treatment. Be sure to tell your doctor about any pain and side effects you experience while taking this medication. This will help your doctor find the dose that is best for you.
Meperidine can be habit-forming. Take meperidine exactly as directed. Do not take a larger dose, or take it more often or for a longer period of time than you were told by your doctor. Do not snort or try to inject the tablets. Meperidine may cause serious side effects or death if it is taken or used in these ways.
If you have taken meperidine for longer than a few weeks, do not stop taking the medication without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking meperidine, you may experience withdrawal symptoms. Withdrawal symptoms may include: restlessness, watery eyes, stuffy nose, yawning, sweating, chills, muscle pain, irritability, nervousness, stomach pain, upset stomach, vomiting, loss of appetite, diarrhea, fast breathing, fast heartbeat, and back pain.
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 meperidine,
- tell your doctor and pharmacist if you are allergic to meperidine, any other medications, or any of the ingredients in meperidine tablets or syrup. Ask your doctor or 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: acyclovir (Zovirax); antidepressants; butorphanol (Stadol NS); cimetidine (Tagamet); chlorpromazine (Thorazine); fluphenazine (Permitil, Prolixin); medications for anxiety, mental illness, pain, nausea, vomiting, and seizures; mesoridazine (Serentil); muscle relaxants such as baclofen (Lioresal), carisoprodol (Soma), cyclobenzaprine (Flexeril), methocarbamol (Robaxin), and tizanidine (Zanaflex); pentazocine (Talwin); perphenazine (Trilafon); phenytoin (Dilantin); prochlorperazine (Compazine); ritonavir (Norvir); sedatives; sleeping pills; thioridazine (Mellaril); trifluoperazine (Stelazine); triflupromazine (Vesprin); and tranquilizers. Also tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past 2 weeks: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you use or have ever used street drugs, if you drink or have ever drunk large amounts of alcohol, and if you recently had surgery. Also tell your doctor if you have or have ever had Addison's disease (a condition in which the body does not produce certain important chemicals); a head injury or a problem with pressure in your head or brain; mental illness; asthma, chronic obstructive pulmonary disease (COPD), or other conditions that affect your breathing; sickle cell anemia (a blood disease); pheochromocytoma (a type of tumor); an abnormally curved spine, especially if it causes breathing problems; enlarged prostate; urethral stricture (narrowing of the opening through which urine leaves the body); irregular heartbeat; seizures; stomach problems; or thyroid, liver, kidney, or lung disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking meperidine, call your doctor.
- talk to your doctor about the risks and benefits of taking meperidine if you are 65 years of age or older. Older adults should not usually take meperidine because it is not as safe or as effective as other medications that can be used to treat the same condition.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking meperidine.
- 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.
- ask your doctor about the safe use of alcoholic beverages while you are taking meperidine. Alcohol and street drugs can make the side effects of meperidine worse and can cause serious harm or death.
- you should know that meperidine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking meperidine. 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?
This medication is usually taken as needed. If your doctor has told you to take meperidine regularly, 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?
Meperidine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- extreme calm
- mood changes
- stomach pain or cramps
- dry mouth
- changes in vision
Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- slow or difficult breathing
- shaking hands that you cannot control
- muscle twitches or stiffening
- hallucination (seeing things or hearing voices that do not exist)
- slow, fast, or pounding heartbeat
- difficulty urinating
Meperidine 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). Protect this medication from theft. Medication that is outdated or no longer needed should be flushed down the toilet. 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:
- slowed breathing
- extreme sleepiness
- loose, floppy muscles
- cold, clammy skin
- slow heartbeat
- blurred vision
What other information should I know?
Keep all appointments with your doctor.
Do not let anyone else take your medication. It is against the law to give this medication to anyone else. Ask your pharmacist any questions you have about refilling your prescription.
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.