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?
Diazepam is used to relieve anxiety, muscle spasms, and seizures and to control agitation caused by alcohol withdrawal.
How should this medicine be used?
Diazepam comes as a tablet, extended-release (long-acting) capsule, and concentrate (liquid) to take by mouth. Do not open, chew, or crush the extended-release capsules; swallow them whole. It is usually taken 1 to 4 times a day and may be taken with or without food. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take diazepam exactly as directed.
Diazepam concentrate (liquid) comes with a specially marked dropper for measuring the dose. Ask your pharmacist to show you how to use the dropper. Dilute the concentrate in water, juice, or carbonated beverages just before taking it. It also may be mixed with applesauce or pudding just before taking the dose.
Diazepam can be habit-forming. Do not take a larger dose, take it more often, or for a longer time than your doctor tells you to. Tolerance may develop with long-term or excessive use, making the drug less effective. This medication must be taken regularly to be effective. Do not skip doses even if you feel that you do not need them. Do not take diazepam for more than 4 months or stop taking this medication without talking to your doctor. Stopping the drug suddenly can worsen your condition and cause withdrawal symptoms (anxiousness, sleeplessness, and irritability). Your doctor probably will decrease your dose gradually.
Other uses for this medicine
Diazepam is also used to treat irritable bowel syndrome and panic attacks. Talk to your doctor about the possible risks of using this drug for your condition.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking diazepam,
- tell your doctor and pharmacist if you are allergic to diazepam, alprazolam (Xanax), chlordiazepoxide (Librium, Librax), clonazepam (Klonopin), clorazepate (Tranxene), estazolam (ProSom), flurazepam (Dalmane), lorazepam (Ativan), oxazepam (Serax), prazepam (Centrax), temazepam (Restoril), triazolam (Halcion), or any other drugs.
- tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially antihistamines; cimetidine (Tagamet); digoxin (Lanoxin); disulfiram (Antabuse); fluoxetine (Prozac); isoniazid (INH, Laniazid, Nydrazid); ketoconazole (Nizoral); levodopa (Larodopa, Sinemet); medications for depression, seizures, pain, Parkinson's disease, asthma, colds, or allergies; metoprolol (Lopressor, Toprol XL); muscle relaxants; oral contraceptives; probenecid (Benemid); propoxyphene (Darvon); propranolol (Inderal); ranitidine (Zantac); rifampin (Rifadin); sedatives; sleeping pills; theophylline (Theo-Dur); tranquilizers; valproic acid (Depakene); and vitamins. These medications may add to the drowsiness caused by diazepam.
- if you use antacids, take diazepam first, then wait 1 hour before taking the antacid.
- tell your doctor if you have or have ever had glaucoma; seizures; or lung, heart, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking diazepam, call your doctor immediately.
- talk to your doctor about the risks and benefits of taking diazepam if you are 65 years of age or older. Older adults should not usually take diazepam because it is not as safe as other medications that can be used to treat the same conditions.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking diazepam.
- you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this drug affects you.
- remember that alcohol can add to the drowsiness caused by this drug.
- tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this drug.
What should I do if I forget a dose?
If you take several doses per day and miss a 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?
Side effects from diazepam are common and include the following:
- dry mouth
- changes in appetite
Tell your doctor if any of these symptoms are severe or do not go away:
- restlessness or excitement
- difficulty urinating
- frequent urination
- blurred vision
- changes in sex drive or ability
If you experience any of the following symptoms, call your doctor immediately:
- shuffling walk
- persistent, fine tremor or inability to sit still
- difficulty breathing or swallowing
- severe skin rash
- yellowing of the skin or eyes
- irregular heartbeat
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.
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.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to diazepam.
Diazepam can cause false results in urine tests for sugar using Clinistix and Diastix. Diabetic patients should use TesTape to test their urine for sugar.
If you are taking diazepam to control seizures and have an increase in their frequency or severity, call your doctor. Your dose may need to be adjusted. If you use diazepam for seizures, carry identification (Medic Alert) stating that you have epilepsy and that you are taking diazepam.
Do not let anyone else take your medication. 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.