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 rectal gel is used in emergency situations to stop cluster seizures (episodes of increased seizure activity) in people who are taking other medications to treat epilepsy (seizures). Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.
How should this medicine be used?
Diazepam comes as a gel to instill rectally using a prefilled syringe with a special plastic tip. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Before diazepam rectal gel is prescribed, the doctor will talk to your caregiver about how to recognize signs of the type of seizure activity that should be treated with this medication. Your caregiver will also be taught how to administer the rectal gel.
If used regularly, diazepam may be habit forming. Do not use a larger dose than your doctor tells you to. Diazepam rectal gel is not meant to be used on a daily basis. Diazepam rectal gel should not be used more than 5 times a month or more often than every 5 days. If you or your caregiver think that you need diazepam rectal gel more often than this, talk to your doctor.
- Put the person having seizures on his/her side in a place where he/she cannot fall.
- Remove the protective cover from the syringe by pushing it up with your thumb and then pulling it off.
- Put lubricating jelly on the rectal tip.
- Turn the person on his/her side facing you, bend his/her upper leg forward, and separate his/her buttocks to expose the rectum.
- Gently insert the syringe tip into the rectum until the rim is snug against the rectal opening.
- Slowly count to 3 while pushing in the plunger until it stops.
- Slowly count to 3 again, and then remove the syringe from the rectum.
- Hold the buttocks together so the gel doesn't leak from the rectum, and slowly count to 3 before letting go.
- Keep the person on his/her side. Take note of what time diazepam rectal gel was given, and continue to watch the person.
- seizures continue for 15 minutes after diazepam rectal gel was given (or follow the doctor's instructions).
- the seizures seem different or worse than usual.
- you are worried about how often seizures are happening.
- you are worried about the skin color or breathing of the person with seizures.
- the person is having unusual or serious problems.
Ask your pharmacist or doctor for a copy of the manufacturer's administration instructions.
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 diazepam rectal gel,
- tell your doctor and pharmacist if you are allergic to diazepam (Valium) or any other medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (blood thinners) such as warfarin (Coumadin); antidepressants ('mood elevators') including imipramine (Tofranil); antihistamines; carbamazepine (Carbatrol, Epitol, Tegretol); certain antifungals such as clotrimazole (Lotrimin), fluconazole (Diflucan),itraconazole (Sporanox), and ketoconazole (Nizoral); cimetidine (Tagamet); cyclosporine (Neoral, Sandimmune); dexamethasone (Decadron, Dexpak); medications for anxiety, mental illness, nausea, or pain; monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); omeprazole (Prilosec); paclitaxel (Taxol); phenobarbital; phenytoin (Dilantin, Phenytek); propranolol (Inderal); quinidine (Quinidex); rifampin (Rifadin, Rimactane, in Rifamate); sedatives; sleeping pills; theophylline (Theo-Dur, Theo-24); tranquilizers; and troleandomycin (TAO). Many other medications may also interact with diazepam, 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.
- tell your doctor if you drink large amounts of alcohol or use or have used street drugs and if you have or have ever had glaucoma, lung problems such as asthma or pneumonia, or liver or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using diazepam rectal gel, call your doctor.
- talk to your doctor about the risks and benefits of using diazepam rectal gel if you are 65 years of age or older. Older adults should not usually use diazepam rectal gel because it is not as safe as other medications that can be used to treat the same condition.
- you should know that diazepam rectal gel may make you drowsy. Do not drive a car, operate machinery, or ride a bicycle until the effects of diazepam rectal gel have passed.
- remember that alcohol can add to the drowsiness caused by this medication.
What special dietary instructions should I follow?
Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.
What side effects can this medication cause?
Diazepam rectal gel may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- abnormal 'high' mood
- lack of coordination
- runny nose
- problems falling asleep or staying asleep
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:
- trouble breathing
- hallucinating (seeing things or hearing voices that do not exist)
Diazepam rectal gel 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). To dispose of the diazepam gel, remove the plunger from the syringe body and point the tip over a sink or toilet. Insert the plunger into the syringe and gently push it to release the medication into the toilet or sink. Then flush the toilet or rinse the sink with water until the diazepam gel is no longer visible. 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 the following:
- slow reflexes
What other information should I know?
Keep all appointments with your doctor. Your doctor will need to examine you about every 6 months to check if your dose of diazepam rectal should be changed.
If you have symptoms that are different from your usual seizures, you or your caregiver should call your doctor immediately.
Do not let anyone else use 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.