TOPIC: Benzodiazepine Drug Class: Drug Safety Communication - Boxed Warning Updated to Improve Safe Use
AUDIENCE: Patient, Health Professional, Pharmacy
ISSUE: The FDA is requiring the Boxed Warning, FDA's most prominent warning, be updated by adding other information to the prescribing information for all benzodiazepine medicines. This information will describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. The FDA is also requiring updates to the existing patient Medication Guides to help educate patients and caregivers about these risks.
Other changes are also being required to several sections of the prescribing information, including to the Warnings and Precautions, Drug Abuse and Dependence, and Patient Counseling Information sections.
BACKGROUND: Benzodiazepines are a class of medicines approved to treat generalized anxiety disorder, insomnia, seizures, social phobia, and panic disorder.
Health Care Professionals
- Consider the patient's condition and the other medicines being taken, and assess the risk of abuse, misuse, and addiction, available at: http://bit.ly/3lfHUIG.
- Limit the dosage and duration of each medicine to the minimum needed to achieve the desired clinical effect when prescribing benzodiazepines, alone or in combination with other medicines.
- Use a gradual taper to reduce the dosage or to discontinue benzodiazepines to reduce the risk of acute withdrawal reactions.
- Take precautions when benzodiazepines are used in combination with opioid addiction medications, available at: http://bit.ly/3eNL9ET.
Patients, Parents, and Caregivers
- Always tell your health care professionals about all the prescription and over-the-counter (OTC) medicines you are taking or any other substances you are using, including alcohol.
- Take benzodiazepines and all medicines exactly as prescribed by your health care professional
- Discuss a plan for slowly decreasing the dose and frequency of your benzodiazepine(s) with your health care professional.
- Contact your health care professional if you experience withdrawal symptoms or your medical condition worsens.
- Go to an emergency room or call 911 if you have trouble breathing or other serious side effects such as seizures.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Diazepam rectal may increase the risk of serious or life-threatening breathing problems, sedation, or coma if used along with certain medications. Tell your doctor if you are taking or plan to take certain opiate medications for cough such as codeine (in Triacin-C, in Tuzistra XR) or hydrocodone (in Anexsia, in Norco, in Zyfrel) or for pain such as codeine (in Fiorinal), fentanyl (Actiq, Duragesic, Subsys, others), hydromorphone (Dilaudid, Exalgo), meperidine (Demerol), methadone (Dolophine, Methadose), morphine (Astramorph, Duramorph PF, Kadian), oxycodone (in Oxycet, in Percocet, in Roxicet, others), and tramadol (Conzip, Ultram, in Ultracet). Your doctor may need to change the dosages of your medications and will monitor you carefully. If you use diazepam rectal with any of these medications and you develop any of the following symptoms, call your doctor immediately or seek emergency medical care immediately: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Be sure that your caregiver or family members know which symptoms may be serious so they can call the doctor or emergency medical care if you are unable to seek treatment on your own.
Drinking alcohol or using street drugs during your treatment with diazepam rectal also increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol or use street drugs during your treatment.
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.
- To dispose of the remaining 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. Discard all used materials in the trash away from children and pets.
- 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), any other medications, or any of the ingredients in diazepam rectal. Ask your pharmacist for a list of the ingredients.
- 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, Jantoven); antidepressants ('mood elevators') including imipramine (Surmontil, Tofranil); antihistamines; carbamazepine (Carbatrol, Epitol, Tegretol); certain antifungals such as clotrimazole (Lotrimin), fluconazole (Diflucan), itraconazole (Onmel, Sporanox), and ketoconazole (Nizoral); cimetidine (Tagamet); cyclosporine (Gengraf, Neoral, Sandimmune); dexamethasone; medications for anxiety, mental illness, or nausea; monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); omeprazole (Prilosec); paclitaxel (Abraxane, Taxol); phenobarbital; phenytoin (Dilantin, Phenytek); propranolol (Hemangeol, Inderal, Innopran); quinidine (in Nuedexta); rifampin (Rifadin, Rimactane, in Rifamate); sedatives; sleeping pills; theophylline (Elixophyllin, Theo-24, Theochron); tranquilizers; and troleandomycin (no longer available in the U.S.; TAO). Many other medications may also interact with diazepam rectal, 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 breastfeeding. 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.
What special dietary instructions should I follow?
Talk to your doctor about eating grapefruit and drinking grapefruit juice while using 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 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). Talk to your pharmacist about the proper disposal of your medication.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call 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.