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 nasal spray 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 nasal spray 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 nasal spray 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.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with diazepam nasal spray and each time you refill your prescription. 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?
Diazepam nasal spray is used for emergency situations to stop cluster seizures (episodes of increased seizure activity) in adults and children 6 years of age and older 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 spray to inhale through the nose. It is used when needed, according to your doctor's directions. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use diazepam nasal spray exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Before diazepam nasal spray is prescribed, the doctor will talk to you and 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 nasal spray.
Keep diazepam nasal spray with you or available at all times so that you will be able to use it to control your seizures when they occur.
If used regularly, diazepam may be habit forming. Do not use a larger dose than your doctor tells you to. Diazepam nasal spray is not meant to be used on a daily basis. Diazepam nasal spray 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 nasal spray more often than this, talk to your doctor.
- Read all of the manufacturer's instructions for using the nasal spray before you use your first dose.
- Put the person having seizures on their side in a place where they cannot fall.
- The person can be on their side or back to receive diazepam nasal spray.
- Remove the device from the blister pack.
- Hold the sprayer between your fingers and thumb, but be careful not to press the plunger.
- Put the tip of the sprayer into one nostril until your fingers are against the bottom of the person's nose.
- Press the plunger firmly with your thumb.
- Remove the tip from the nose.
- The sprayer contains only one dose of medication. After you have used it, dispose of it safely, so that is out of the reach of children and pets.
- Keep the person on their side. Take note of what time diazepam nasal spray was given, and continue to watch the person.
- the seizures seem different or worse than usual.
- you are worried about how often seizures are happening or how long seizures are lasting.
- you are worried about a change in skin color or breathing of the person with seizures.
- the person is having unusual or serious problems.
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 nasal spray,
- tell your doctor and pharmacist if you are allergic to diazepam (Diastat, Valium), any other medications, or any of the ingredients in diazepam nasal spray. 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); carbamazepine (Carbatrol, Epitol, Tegretol, others); cimetidine (Tagamet); clotrimazole (Lotrimin), cyclosporine (Gengraf, Neoral, Sandimmune); dexamethasone; imipramine (Tofranil); ketoconazole (Nizoral); medications for anxiety, mental illness, or nausea; omeprazole (Prilosec, Zegerid, in Yosprala); paclitaxel (Abraxane); phenobarbital; phenytoin (Dilantin, Phenytek); propranolol (Hemangeol, Inderal, Innopran); quinidine (in Nuedexta); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); sedatives; sleeping pills; terfenadine (not available in the US); theophylline (Elixophyllin, Theo-24, Theochron); tranquilizers; tranylcypromine (Parnate); troleandomycin (no longer available in the U.S.; TAO); and valproic acid (Depakote). Many other medications may also interact with diazepam nasal spray, 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 if you have narrow angle glaucoma (a serious eye condition that may cause loss of vision). Your doctor will probably tell you not to use diazepam nasal spray.
- 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 lung problems such as asthma, chronic obstructive pulmonary disease (COPD), or pneumonia; depression or other mental illness; 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 nasal spray, call your doctor.
- you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are using diazepam nasal spray for the treatment of epilepsy. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as diazepam to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as one week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as diazepam, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.
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 nasal spray may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- sore or irritated nose
- nasal congestion
- unusual taste in the mouth
- abnormal 'high' mood
- lack of coordination
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- trouble breathing
- hallucinating (seeing things or hearing voices that do not exist)
Diazepam nasal spray 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 light, excess heat, and moisture (not in the bathroom).
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
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
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:
- slow reflexes
What other information should I know?
Keep all appointments with your doctor and the laboratory.
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.